Rediscovering catatonia: the biography of a treatable syndrome

Abstract

Objective

Catatonia, a disorder of movement and mood, was described and named in 1874. Other observers quickly made the same recognition. By the turn of the century, however, catatonia was incorporated as a type within a conjured syndrome of schizophrenia. There, catatonia has lain in the psychiatric classification for more than a century.

Method

We review the history of catatonia and its present status. In the 1970s, the tie was questioned when catatonia was recognized among those with mood disorders. The recognition of catatonia within the neuroleptic malignant syndrome offered effective treatments of high doses of benzodiazepines and electroconvulsive therapy (ECT), again questioning the tie. A verifying test for catatonia (the lorazepam sedation test) was developed. Soon the syndromes of delirious mania, toxic serotonin syndrome, and the repetitive behaviors in adolescents with autism were recognized as treatable variations of catatonia.

Results

Ongoing studies now recognize catatonia among patients labeled as suffering from the Gilles de la Tourette's syndrome, anti-NMDAR encephalitis, obsessive–compulsive disease, and various mutisms.

Conclusion

Applying the treatments for catatonia to patients with these syndromes offers opportunities for clinical relief. Catatonia is a recognizable and effectively treatable neuropsychiatric syndrome. It has many faces. It warrants recognition outside schizophrenia in the psychiatric disease classification.

Introduction: liberating catatonia from schizophrenia

The ultimate court of appeal is observation and experiment, and not authority.

Thomas H. Huxley [1]

For an illness to be effectively treated, it has first to be recognized; only then can physicians apply their knowledge and skills. Catatonia is an identifiable syndrome of abnormal movement and emotion first described by the German psychiatrist Karl Kahlbaum in 1874 among the patients in his psychiatric asylum. His description was soon affirmed by other physicians and broadly accepted as an identifiable syndrome among psychiatric disorders. Within two decades, another German psychiatrist, Emil Kraepelin also recognized catatonia. But Kraepelin included catatonia and two other syndromes, hebephrenia and paranoia, as markers within a grand scheme that he labeled dementia praecox (later, schizophrenia).

Kraepelin was a prolific writer of textbooks widely regarded as gospel truth. As a result, for more than a century, catatonia was buried within schizophrenia as one of many types. To this day, when clinicians recognize catatonia, they immediately see schizophrenia and reflexively prescribe neuroleptic drugs even when the signs of psychosis are absent. The Kraepelin equation of ‘catatonia = schizophrenia’ dominates clinical thought and writing. Such prescription is not helpful; indeed, it is often harmful as neuroleptic drugs often precipitate a toxic syndrome in patients with catatonia that is recognized as the neuroleptic malignant syndrome. More egregious, however, is the failure to prescribe the specific and effective treatments for catatonia as they are not recognized as treatments for schizophrenia. This mistaken conception has plagued patients for more than a century and has distorted the classification of psychiatric diseases.

These chapters of Rediscovering Catatonia trace the biography of catatonia, relate how it is identified, describe its many forms, look forward to identifying other forms of catatonia that are now not recognized and inadequately treated, discuss the fear hypothesis that explains catatonia's origin, and discuss catatonia's history within psychiatric classifications with the present promise of relief in the DSM-5 iteration.

Catatonia is a syndrome of body movement and speech related to disorders of emotion. Mutism (not speaking), negativism (refusing commands), posturing and rigidity (holding unusual bodily postures), and repetitive speech and acts (repeating meaningless words, phrases, or motor movements, often self-injurious) are its main signs. The characteristic delusions, hallucinations, and disturbances in thought that are central to the image of schizophrenia are not features of catatonia. Catatonia is a distinct syndrome that in the past half century has been increasingly reported outside schizophrenia.

Effective treatments for catatonia were developed in the 1930s – first the barbiturates and then electroconvulsive therapy (ECT). In the 1980s, the barbiturates were replaced by the benzodiazepines for clinical use. Neither the sedative drugs nor ECT are considered effective in schizophrenia and are therefore not applied in cases of catatonia when it is presumed to be a manifestation of schizophrenia. Inadequate treatment and prolonged illness result when this error of diagnosis is made. The neuroleptic drugs that are promoted as treatments for schizophrenia are ineffective for catatonia; indeed, they increase toxicity and occasionally lead to death.

I was trained as a neurologist and psychiatrist and began my academic career as a researcher in 1954. Like many of my peers, only occasionally did I recognize catatonia in practice. I was not awakened to the extent of catatonia until the 1980s when as an Attending Physician at the University Hospital of Stony Brook University on Long Island I supervised the care of hospitalized patients and its ECT treatment unit.

Neuroleptic drugs such as chlorpromazine and haloperidol, the drugs used to relieve psychosis, affect the body's motor functions. They induce tremors, peculiar rhythmic movements of mouth and tongue (dyskinesia), and stiffen and slow body movement (rigidity). They induce acute toxic states of fever and delirium that are accompanied by the catatonia signs of mutism, repetitive acts, and rigidities. These toxic signs were increasingly recognized during the 1970s as the reports of fatalities grew; by 1980, the toxic consequences were named the neuroleptic malignant syndrome (NMS).

By 1984 at Stony Brook, we had identified three patients with NMS, and each exhibited signs of catatonia. We applied the promoted treatments of the time; one slowly recovered but two did not. The lifesaving benefits of ECT in these conditions had been described in 1952 and repeatedly confirmed [2]. When the two patients who had not responded to medications were treated with ECT, they recovered quickly [3].

Although we lacked understanding of the causes of malignant catatonia, we did know that ECT relieved it. Relatively few hospitals had ECT treatment units, but all could prescribe agents like bromocriptine that increased the brain levels of the dopamine neurotransmitter that is directly inhibited by neuroleptic drugs. A national debate ensued, carried on for more than two decades, whether the neuroleptic-induced malignant syndrome was an abnormality of dopamine metabolism and best treated with dopamine agonists or an example of malignant catatonia that was best treated with ECT. The debate focused my interest in catatonia [4-6].

Two former students, Michael A. Taylor and Richard Abrams, had been instrumental in reporting catatonia in patients with manic–depressive illnesses and in 1976 had questioned the teaching that catatonia was necessarily an aspect of schizophrenia [7, 8]. In 1990, I began to collaborate with Taylor, and in our first essay, we argued that catatonia was best seen as a distinct syndrome independent of schizophrenia, arguing for their separation [9]. At the time, the Diagnostic and Statistical Manual of psychiatric disorders of the American Psychiatric Association was undergoing its fourth revision, and we urged that catatonia be separated from schizophrenia. To accommodate our view, although still beholden to the dominant perspective of catatonia as a form of schizophrenia, the DSM-IV committees added a class of ‘Catatonia secondary to a medical condition’ with a distinct code of 293.89 [10].

Our interest in catatonia – its main features, how it is found, in what forms, and how best treated – led us to publish the textbook Catatonia: A Clinician's Guide to Diagnosis and Treatment in 2003 [11] and to urge again that catatonia warranted a home of its own in the classification [12]. This publication was the first text on catatonia since the original publication by Karl Kahlbaum 130 years earlier [13].

Much has changed since then – catatonia is more often recognized, effective treatments are commonly applied, favorable outcomes are increasingly reported, and death rates for medication-induced neurotoxic syndromes have fallen. Increasing numbers of citations to catatonia in the medical literature are reflected in the NIH Pub-Med indices (Fig. 1).

Figure 1. Average annual number of citations marked as “catatonia” in each 5-year period.

Two new forms of catatonia have been recognized since our publication. In 2007 the syndrome of ‘anti-NMDAR encephalitis’ was described as a neuropsychiatric disorder of diverse manifestations connected to an autoimmune etiology. More than 70% of the diagnosed patients exhibit catatonia that is neither recognized nor properly treated. Instead, patients are subjected to intensive searches for hidden tumors, offered surgery if a silent tumor is recognized, and prescribed potent steroids, immunotherapy, and plasma exchange with minimal benefit.

A more dramatic impetus to tracing this history has been the recognition that the self-injurious behaviors of children and adolescents suffering from autism spectrum disorders may be signs of catatonia that are responsive to catatonia treatments. The recognition of catatonia in these disorders and demonstrations of the efficacy of catatonia treatments are largely the efforts of Drs. Lee Wachtel at Johns Hopkins Medical Center and Dirk Dhossche at the University of Mississippi [14].

As the connection to schizophrenia has been loosened, catatonia is increasingly recognized among the childhood disorders of Gilles de la Tourette's syndrome, obsessive–compulsive disorder, and diverse mutisms – the ‘selective’ or ‘elective’ and the pervasive refusal syndrome recognized in the classification of diseases. Catatonia is also seen in patients with post-traumatic stress disorders, passive acceptance of rape assault, and fear-induced freezing in urban violence and military disasters. These connections support a hypothesis of catatonia as a residual response to fear of imminent doom from the time when humans feared predators [15].

Most psychiatric disorders are identified by the presence of symptoms from symptom checklists. No laboratory tests, common in clinical medicine, are used. But catatonia is among the few psychiatric diagnoses that are operationally defined. In the chapters that follow, catatonia is defined as published by Michael Taylor and myself in 2003: Patients who exhibit two or more motor signs of catatonia (recognized in Catatonia Rating Scales) for more than 24 h and that quickly improve with test doses of lorazepam are presumptively diagnosed as suffering from catatonia. Recovery of the illness with relief of the motor and vegetative signs after treatment with benzodiazepines and ECT validates the diagnosis.

An operational diagnostic procedure assures recognition of the syndrome and offers patients typically effective and prompt relief. For those who are misidentified as catatonic when they are not, the principal hazard is the delay in instituting a more appropriate treatment, if there is one. The benzodiazepines are not hazardous, and the test doses are well within clinical experience for safety. Although ECT is widely stigmatized as brain damaging and capable of erasing memories, these hazards pale before the risks to life inherent in the more malignant forms of catatonia and the prolonged illness that follows inappropriate diagnosis and ineffective treatment.

The American Psychiatric Association DSM-5 Psychosis Work Group presented its recommendations on catatonia online in May 2012, listing many proposed changes. When these are published in DSM-5, the much needed separation of catatonia from schizophrenia will be accomplished. Much will then need to be done in professional and public education to assure recognition and treatment of catatonia as an independent psychiatric syndrome.

Chapter 1: catatonia is discovered

In some ways disease does not exist until we have agreed that it does – by perceiving, naming, and responding to it.

CE Rosenberg 1986 [16]

Catatonia is a syndrome of dysfunctions in movement and emotion. It was first culled in the 1870s from the welter of behaviors that are common in every asylum. Unlike diseases of a single body organ and narrowly defined functions, abnormal behaviors encompass the whole organism. What did practitioners see when they entered an asylum in the mid-1800s and tried to make sense of what they encountered?

The entrance door is locked, and one of a ring of large keys is used to enter. The moment the door opens, the entrance is filled with a cacophony of cries and the pungent odors of urine, sweat, and the medicine paraldehyde (a liquid sedative with the odor of vinegar). Loud voices, some sing-song and some cackling, and occasional screams fill the entranceway. Some patients are tied down on a pallet, while others sit motionless seemingly unaware of the activities around them, unresponsive to questions and even to painful stimuli; and yet, others are rocking, posturing Christ-like, staring, and pacing. When they do respond, many are sad and despondent, or frightened, or grandiose, or angry. Speech may be normal, but more often it is repetitive and meaningless. Occasionally a patient has an epileptic seizure.

Trying to distinguish causes and predict the course of an illness in an individual patient was challenging. Over time, the behaviors of individual patients may remain the same day after day but more often the symptoms evolve, sadness and despondency alternating with excitement and mania, for example, deteriorating to ever poorer self-care, until dementia and a vegetative state ensues.

How was one to extract a recognizable ‘disease’ from this welter of dysfunctions? No help was likely to be gleaned from studies of the brain after death, either in the search for abnormal tissues in the sliced brain or cellular changes in stained brain tissues, even when examined with the finest microscopes. At the time, dementia paralytica had been described as the neurological consequence of syphilis. It was recognized during life by progressive paralyses accompanied by grandiose thoughts, impaired memory, and silly comments. After death, thickened brain coverings were found as evidence of the fatal disease. But such direct pathological evidence was the exception. Also demarcated and generally accepted at the time were mania and melancholia, the stupidities (mental retardation), epilepsies, and the dementias of aging, as a result of head trauma or alcoholism.

Among the patients were some who postured and stared, frequently mute but occasionally repetitive in speech and movement, occasionally appearing in stupor as if dead, or in delirious furor and unresponsive to painful stimuli. In 1874, Karl Kahlbaum, the 46-year-old director of a private psychiatric sanitarium in the German town of Görlitz, described his experience with such patients in a small book of 104 pages that he labeled Die Katatonie. It was his third attempt to classify the behaviors of his patients [17].

From an extensive clinical practice, Kahlbaum described 26 case histories that included disabling disorders of movement and speech among their symptoms. The patients were immobile and posturing, remaining in one position for hours; or moving continually, pacing, or hitting a wall or themselves; or standing and staring, unblinking, repeating words or phrases over and over again, sometimes in whispers or in repetitive shouts. They had other signs of mental illness – melancholia (depression, withdrawal to stupor, and suicide risk), mania (continuous movement, grandiosity, delirium), psychosis (peculiar thoughts that brought forth unusual speech), and dementia (poor memory, disorientation, poor self-care). Many were also suffering the systemic diseases of syphilis, tuberculosis, or epilepsy. Onsets and courses of illness fluctuated with sudden changes in retardation and withdrawal, or mania and excitement, or delusional and suicidal thoughts, so much so that one school of professional thought described the behaviors as expressions of a single disease of many causes. Before specific syndromes were described, the variations in symptoms seemed to appear and disappear but no single pattern was discerned. The term Einheitspsychose – unitary psychosis – was in common use until Kahlbaum and his colleague Hecker's description of hebephrenia and catatonia and Kraepelin's images of dementia praecox and manic–depressive insanity were accepted.

Kahlbaum describes a young man admitted to the sanitarium who becomes intensely fearful when he is told that he has syphilis. (This case record is paraphrased from Case #2 of the English translation of the Kahlbaum text by George Mora on the publication's 100th anniversary. Mora was a pediatric psychiatrist lecturing at Yale and New York Universities.)

A 33-year-old peasant terminates a love affair, becomes depressed and is reluctant to talk or participate in social activity. His depressed moods become constant after he develops a syphilitic infection. Muscular twitching in the face and extremities and severe tonic contractions of the back muscles follow. He retires to his bed without interest in his surroundings; his eyes remain shut, refuses to reply when addressed or even to speak. He eats little. On admission to the sanitarium he is inactive, lies prone in bed, giving no answer to questions put to him. He maintains any posture he is made to assume for long periods. It is possible to place his extremities in the most extravagant postures that he changes gradually to an original passive position. When induced to walk, he moves forward slowly, leaning to the right and extending his right leg stiffly. Sensory responses are greatly reduced over the entire body with little reaction to needle pricking.

Three months later he suddenly begins to speak incessantly, expressing a few monotonous phrases over and over as ‘Love is God, Love, Love, Love is God, Love is God’ with permutations, adding short phrases as ‘Is it so?’ or ‘I say’, spoken softly or at times shouting loudly. While voicing these phrases he sometimes lies flat on his back; at times the upper part of his body is raised and head bent stiffly back. He becomes hoarse, speaking softly with intermittent shouting. This condition persisted with brief interruptions. He died a year later after contracting tuberculosis [13].

A detailed analysis of Kahlbaum's cases was undertaken by Daniel Rogers who finds 25 case vignettes [18]. Rogers analyzes 21 vignettes for motor signs characterized as signs of catatonia. Kahlbaum recognized 17 motor signs. Since then, additional signs, altogether about 40, have been listed in Catatonia Rating Scales. The most recent addition to the recognized catatonia signs is the repetitive self-injuries seen in children and adolescents suffering from autism spectrum disorders [19].

Consider the effort entailed by Kahlbaum's attempt at classification. No catalog of psychiatric diseases existed nor had criteria been described with which to label an illness or to predict a person's fate. No effective treatments were known, and persons recovered, remained ill, or died independent of physicians’ efforts. Some patients suddenly recovered after a severe systemic infection or after an epileptic seizure and could leave the asylum. At best, physical restraints and sedation with opiates were prescribed for the unruly, and feeding was forced to maintain life in the stuporous and negativistic. By providing a clean, protected home, the physicians hoped that recovery would be spontaneous.

Attempts at classification were being made in other branches of medicine, especially in bacteriology. Unique infectious diseases were identified by the patterns of clinical symptoms and the course of the illness. Pathogens were identified in body fluids, and illnesses were labeled by the name of the invading pathogen, offering opportunities to test treatments in homogeneous samples of one illness type. These efforts in clinical medicine were models for Kahlbaum. He saw his efforts as similar to those that described the motor disorders of tabes dorsalis, the loss of motor control of the limbs when syphilis affected the spinal cord and the paranoia and dementia of dementia paralytica. Kahlbaum's descriptions and demarcations of catatonia were so well defined that others soon recognized similar cases.

Kahlbaum's first classification of psychiatric disorders

Born in eastern Germany on December 28, 1828, Kahlbaum had been schooled at the universities of Königsberg, Würzburg, and Leipzig. He was awarded an MD in Berlin with a thesis on the anatomy and histology of the intestinal tract of birds in 1854. After joining the faculty at Königsberg, he established training courses in psychiatry for medical students and published a monograph on sensory delusions. By 1863, he had developed a complex glossary of mental disorders that he published as Die Gruppierung der psychischen Krankheiten und die Einteilung der Seelenstörungen [20].

He listed many peculiar behaviors and clustered the symptoms into disorders according to their principal features (depression, mania, psychosis) and course of illness (continuous, recurrent, and episodic). In an obsessively detailed organization, he gave each form a unique name. ‘Vesania typica’ anticipated the manic–depressive illness of Kraepelin and ‘vesania progressiva’ described a deterioration in mood to delirium and dementia. ‘Vecordia’ were disorders beginning in puberty, including ‘paraphrenia hebetica’, a disorder that later was labeled ‘hebephrenia’. A disorder in mood labeled ‘dysthymia’ exhibited a retarded form ‘dysthymia atra’ and an agitated form, ‘dysthymia elata’. In that burst of creativity, he had not yet described the concept of catatonia.

Kahlbaum's first classification was filled with obsessive details and not based on any logical principle that could be explained to others, so it is no surprise that this creation was deemed too complex to be understood and was not accepted by his colleagues. In similar fashion, the iterations of the DSM classification describe illnesses without a basis in biological or medical principles. The class names and descriptions are committee-driven, and depending on the skills and enthusiasm of vocal leaders, a diagnosis is either included or eliminated from the accepted list. The criteria are descriptive based on the presence of symptoms, with some attention to course. The few biological criteria that have been developed are excluded.

Kahlbaum left the university faculty in 1866 to become a staff physician at the Reimer Sanitarium, a private sanitarium in Görlitz, a village in eastern Germany that bordered Poland. A year later, he bought the hospital, became its director, and maintained it until his death in 1899.

In his personal life, Kahlbaum was liberal in politics, ascetic in not using tobacco or alcohol, regular in church attendance, and active in the church choir. He traveled frequently to meetings and to art museums. In 1866, he married the cousin of his colleague Ewald Hecker. The union produced three sons and one daughter. Kahlbaum's wife died in 1884 and he remarried in 1888, producing two more sons. After his death, his son Siegfried, who had trained in psychiatry with Carl Wernicke, directed the sanitarium until 1943 when it was taken over by the government for military uses.

Hebephrenia

In 1866, the same year that he became hospital director, Kahlbaum was joined by Ewald Hecker as a staff physician. Together, they continued an interest in classification. In Die Gruppierung Kahlbaum had described a syndrome of ‘paraphrenia hebetica’, and together, they described the syndrome that became a model for the description of catatonia. It began as a disorder in thought and speech with an onset in adolescence. By early adulthood, it had progressed to dementia. Child-like, often imbecilic behaviors limited the ability of the patients to take part in normal schooling and even in adequate self-care. In 1871, Ewald Hecker described these conditions in seven cases in the 35-page essay ‘Die Hebephrenie’ [21].

The illness begins its progressive course with melancholia and mania between the ages of 18 and 22 years. Over time, thinking becomes confused and speech becomes silly and repetitive, a course that ends in dementia. Hecker said:

In most cases the disease apparently begins as a sequel to a profound alteration in emotions with decidedly melancholic symptoms….

The melancholia expresses itself first as a sadness and depression of mood that gradually consolidates into delusions … ending in a brooding persecutory mania or a delusion of injury. A shallowness of affect appears …

Side by side with his morbid lamentations of his terrible misery … [the patient] frequently cannot suppress an impulse to laughter and silly jokes.

Of special importance are disturbances of form [of speech] … First there is a peculiar deviation from logical sentence formation… [with] a noticeable tendency to remain stuck on a topic once he has taken it up…

The mode of speech and expression … sinks well below his level of education [and] we see a propensity to gush, a preference for sentimental descriptions, a seemingly poetic diction, and consequently an overflow of empty misshapen phrases.

On etiology, Hecker wrote:

the first striking fact is that we are mostly (although not always) dealing with individuals who have been slightly retarded in their physical and in their mental development from early on … a certain weakness of intellect, laziness, and inability to do mental work is already noticed in childhood, but this is not as extreme or as noticeable as in idiotism.

The condition was commonly recognized among patients in the asylums. A few decades later, hebephrenia, like catatonia, was co-opted by the German psychiatrist Emil Kraepelin within his conjured disorder of ‘dementia praecox’. Hebephrenia was the principal form of the syndrome later labeled schizophrenia. In successive psychiatric disease classifications, hebephrenia has often been relabeled. The present term ‘disorganized schizophrenia’ is one of the five recognized types of schizophrenia [22, 23].

At one time, hebephrenia was frequently seen in chronic care institutions. The illness was considered progressive, poorly responsive to treatments, often ending in silly behaviors and dementia. Patients became lifelong wards of society as they were unable to care for themselves. The processes of deinstitutionalization that closed the sanitaria in the last quarter of the twentieth century shifted patients with hebephrenia to adult homes and chronic disease institutions.

Catatonia

As Hecker and Kahlbaum were collaborating at Görlitz, we can picture their discussions of each patient and their search for other examples of hebephrenia. And just as Hecker was riveted by hebephrenia, Kahlbaum focused his attention upon what is now recognized as catatonia. His first public discussion of catatonia was before an audience at the University of Königsberg in 1866 [24]. At Innsbruck 3 years later, he described two cases of melancholia with stupor that exhibited the signs of catatonia. The discussion after his presentation was sparse, but a published comment noted that enlarging the classification with a new diagnosis focused on a ‘muscular tension psychosis’ would not be helpful. [25]

In 1874, 3 years after Hecker's 1871 article on hebephrenia, Kahlbaum formally introduced catatonia to psychiatry. His description is valid today.

Catatonia is a brain disease with a cyclic, alternating course, in which the mental symptoms are, consecutively, melancholy, mania, stupor, confusion, and eventually dementia. One or more of these symptoms may be absent from the complete series of psychic ‘symptom complexes’. In addition to the mental symptoms, locomotor neural processes with the general character of convulsions occur as typical symptoms.

Lacking effective treatment, Kahlbaum observed the full course that marked the disease:

The typical signs of the condition termed atonic melancholia [a depressive illness with the characteristic motor signs of catatonia] may be described as a state in which the patient remains entirely motionless, without speaking, and with a rigid, masklike facies; the eyes focused at a distance; he seems devoid of any will to move or react to any stimuli; there may be fully developed ‘waxen’ flexibility, as in cataleptic states, or only indications, distinct, nevertheless, of this striking phenomenon.

The motor-inhibited form of the illness is distinguishable from its excited forms, often resolving dramatically and suddenly, a resolution that clearly distinguished catatonia from an association with schizophrenia.

The general impression conveyed by such patients is one of profound mental anguish, or an immobility induced by severe mental shock; it has been classified either among the states of depression (which explains the term atonic melancholia) or among the conditions of feeblemindedness (stupor or dementia stupida); others have regarded it as a combination of the two.

Here Kahlbaum offers a clue to his thinking of the cause of catatonia. His patients appeared to be ‘astonished’ or ‘thunderstruck’. The syndrome appeared:

after very severe physical or mental stress … such as a terrifying experience…. The patient remains motionless, without speaking, and with a rigid masklike facies, the eyes focused at a distance …. The general impression conveyed … is one of profound mental anguish, or an immobility induced by severe mental shock [13].

Citing fear as central to the syndrome, Kahlbaum titled his book Die Katatonie, oder das Spannungs-Irresein, translated as ‘Catatonia, the tension insanity’.

Other observers wrote that a subject suffering Kahlbaum's disease might ‘lay like a log of wood, stretched out, able to behold with his eyes but unable to speak a word for several days…. The malady occurs suddenly and he stops as if he were frozen, his eyes open, fixed and motionless’ [26]. On recovery, patients say that they desired to speak but were unable to do so, sensing impending doom. Persons in catatonic stupor are ‘frozen’, ‘petrified’, and ‘experience extreme fear’ [27]. Recent authors also describe patients as giving the appearance of intense anxiety [28-30].

Kahlbaum compared his image of catatonia to what at that time had recently been demarcated as ‘dementia paralytica,’ the general paralysis of the insane associated with syphilis:

In this newly defined group of disorders, similar to general paralysis of the insane (GPI) – with or without delusions of grandeur – clinical changes in the locomotor apparatus form the main and typical features of the disease; in addition, each disease (GPI and this disease) exhibits manifold patterns of symptoms. In GPI the paralytic components are of many varying grades of severity and type; one or other may be absent in any particular case…. In the same way as in GPI, the spastic signs in the newly described clinical form of the disease are also manifold and varied… These muscular symptoms … display alterations in muscular tone … and I would like to name this disease entity the tonic mental disorder (Spannungs-Irresein) or vesania katatonica (catatonia) [13].

In this progressive understanding, we see Kahlbaum identifying the principal signs of the disorder, the emotional basis, and the progressive course. His model was the developing understanding of neurosyphilis. Although no connection to an infection had been made, a search for brain lesions in anatomy and histology for each psychiatric disorder was ongoing. New techniques for staining brain tissues identified different cellular forms (e.g., neurons and glia), and many authors searched for brain lesions and cell forms to associate with behaviors. Kahlbaum was not enthusiastic about this search:

This anatomicopathological work produced much valuable material but contributed nothing to the basic views on the origin of mental illness or on the anatomical locus of their diverse and significant manifestations; the view is now spreading that only comprehensive clinical observation of cases can bring order and clarity into the material by using the method of clinical pathology…. It is futile to search for an anatomy of melancholy or mania, etc. because each of these forms occurs under the most varied relationships and combinations with other states, and they are just as little the expressions of an inner pathological process as the complex of symptoms called fever…. How wrong it inevitably was to expect pathological anatomy alone to reform the obsolete psychiatric framework.

In the final chapter, Kahlbaum, finding no beneficial treatments, argued for supportive and non-punitive hospital care at a time when the debilitating treatments of bleeding, purging, and dunking sped many persons to untimely deaths. An interest in electricity as a source of treatments for psychiatric diseases – both the symptoms of the patients and the characteristics of electricity were ephemeral – led to many imaginative experimental applications. Kahlbaum ends his discussion of treatments, possibly anticipating the role of electricity:

On the other hand it seems we have methods of very great therapeutic importance in faradic and galvanic electricity, although for the time being the indications have not yet been worked out, and in many cases the action might be explained more on the basis of mental than of physiopathological effects.

The catatonia that we envision today is not the result of structural tissue changes (as in strokes, tumors, traumatic injury) nor infections or singular systemic disorders, but as extensions of physiological functions. The signs of catatonia are not novel behaviors but exaggerations of every human's repertoire of tics, mannerisms, compulsions, rituals, speech interjections, and postures. So long as these habits do not interfere with normal living, the subjects and the observers adjust, considering the peculiarities as part of the individual's personality. When the changes in behavior are acute and by their severity impede normal living, an illness is perceived and relief is sought. Many patients, including some severely ill, recover normal functions and do so rapidly, without permanent effects, an indication that the catatonia motor signs result from variations in physiology and not from changes in structures or tissues. We do not view catatonia as similar to neurosyphilis as Kahlbaum conjectured. But when the repetitive behavior is self-injurious, when the withdrawal is to stupor or to delirious mania, and when the changes in autonomic activity are severe, catatonia becomes life-threatening. In most instances, the signs are well tolerated, and with the effective treatments known today, the subject returns to the state of functioning before the onset of the illness.

Kahlbaum after catatonia

As a hospital director, Kahlbaum shared the belief in ‘moral treatment’ for the psychiatric ill – the benevolent, supportive, non-punitive, socially encouraging environment that emphasized rehabilitation measures. By 1887, his hospital consisted of 18 buildings with 130 patient rooms; large dining and recreation halls; theater, library, and reading rooms; tennis and croquet courts, and an indoor-heated gymnasium, all in a park-like setting with gardens and a farm. He developed a special child treatment unit, the Pädagogicum, with schoolrooms, employed trained teachers, and specialists in handicrafts and educational programs. His asylum became a model for the care of children and adolescents.

Kahlbaum's interest in the psychiatric care of children was enduring. In 1883, he published an essay on child psychiatry, refining the concept of hebephrenia and arguing for special treatment for juveniles, much as he had developed in his Pädagogicum. ‘His refined description of the condition [hebephrenia or pubertal neurosis]’, wrote Ernest Harms in 1962,

‘must be designated the first realistically established concept of child psychiatry’. [31]

What is Kahlbaum's place in the history of psychiatry? In celebrating the centenary of the publication of Die Katatonie, Rafael Katzenstein cited Kahlbaum as

‘the first German psychiatrist to systematically elaborate forms of mental diseases from the pure clinical viewpoint. He identified the defects in earlier formulations [ie, the Einheitspsychose] and sought to organize psychiatric states according to observations of onset, course, and outcome’ [25].

Late in life, Emil Kraepelin assessed Kahlbaum's role in clinical medicine in this way:

He [Kahlbaum] was the first to stress the necessity of juxtaposing the condition of the patient, his transitory symptoms and the basic pattern underlying his disease. The condition of a patient may change often and in diverse ways, with the result that in the absence of other clues any attempt to rescue him from his plight is doomed to failure. Moreover, identical or remarkably similar symptoms may accompany different diseases. Their inner nature may only be revealed through their progress and termination and, in some instances, at post mortem.

On the basis of such considerations Kahlbaum sought to delineate a second pattern of illness similar to that of [general] paralysis and, like it, including both mental disorders and physical concomitants: catatonia, in which muscular tension provided a basis for comparison with [general] paralysis. Although his interpretation is open to criticism, Kahlbaum deserves credit for having suggested the right approach. Careful attention to the progress and termination of mental disorders, information gleaned in some instances from autopsies, and insight into underlying causes have made possible the juxtaposition of a vast array of evidence and often diagnosis on the basis of symptom pattern. We can today formulate in specific terms what earlier doctors could surmise but not prove [32].

Kahlbaum's work was praised by Karl Jaspers, a German psychopathologist and author of the definitive text of psychiatry after Kraepelin:

Kahlbaum formulated two fundamental requirements: firstly, the entire course of the mental illness must be taken as basically the most important thing for any formulation of disease entities and, secondly, one must base oneself on the total picture of the psychosis as obtained by comprehensive clinical observation. In emphasizing the course of the illness, he added a new viewpoint [33].

By the end of the twentieth century, Kahlbaum's contribution in extracting catatonia from the welter of altered behaviors was increasingly appreciated and biographies appeared [34-36].

In my view, as a clinician, Kahlbaum made the best of the knowledge of his time and extracted two clinical entities that are still appreciated by clinicians today. He had the misfortune, however, to have his work co-opted by a fellow German psychiatrist whose skill as a textbook writer (that went through eight editions) hid Kahlbaum's work within the shadow of a poorly defined abnormal behavior syndrome that even today, after more than a century, lacks any measurable and verifiable characteristics and also lacks effective treatment. In the past few decades, a few intrepid clinicians have resurrected Kahlbaum's image of catatonia and refined its characteristics in a way that are both objectively verifiable and eminently treatable. Present-day clinical skills indicate that many syndromes that are actually forms of catatonia are hidden in plain sight. As these are reframed as treatable aspects of catatonia, the place of Karl Kahlbaum as a father of modern clinical psychiatry will be assured.

Chapter 2: catatonia disappears

It is true that man is still, as he has always been, subject to error; his judgments are often incorrect, his beliefs false, his opinions changeable from age to age. But experience of error is his best guide to truth, often dearly bought, and therefore, the more to be relied upon.

Alfred Russel Wallace, 1905 [37]

Kahlbaum's 1874 account of catatonia was delineated so well that others quickly recognized the disorder that he described. Within 3 years, catatonia as Kahlbaum delineated was reported in four patients with depression and mania [38]. From New York City's Ward's Island in 1883, catatonia was recognized in patients with melancholia [39]. Four years later, a German report cited catatonia in manic patients [40]. By 1898, six subtypes of catatonia had been described [41], and catatonia had been distinguished from dementia paralytica (neurosyphilis) in a study of 227 psychiatric patients [42].

An active academic industry commenting on catatonia quickly followed among German, French, and American authors [11]. Each effort, in samples of 1–12 patients, confirmed Kahlbaum's descriptions and took a position on whether the syndrome was best explained by systemic medical or by psychologic mechanisms. As each recognition sharpened the image of the syndrome, catatonia became more strongly established as an identifiable psychiatric entity, making the eventual development of treatments increasingly likely.

Then catatonia was recognized by the German psychiatrist Emil Kraepelin (1856–1926), the head of psychiatry at Heidelberg and then at Munich. As an asylum physician, Kraepelin cared for chronically ill psychiatric patients whose prognosis was poor. In the absence of effective treatments, the illness of many patients ended in dementia. In the nineteenth-century tradition of the study of diseases, Kraepelin sought to classify his patients’ illnesses. He adopted Kahlbaum's ‘course of illness’ as a defining characteristic for his own diagnostic formulations [43]. He periodically organized and re-organized his case records into clusters of similar symptoms and outcome. After much shuffling of the file cards describing the observations in his patients, by 1899, he described two main groups with different courses of illness, dementia praecox and manic–depressive insanity.

Dementia praecox, as he described it, was a disorder in thought, speech, and affect that began in adolescence and progressed to dementia. Kraepelin lumped together Hecker's hebephrenia, Kahlbaum's catatonia, and a paranoid psychosis (a delusional fear of impending harm) as one disease, a position that under the later name of schizophrenia has persisted in psychiatric classifications until the present.

Manic–depressive insanity began later in life, Kraepelin said, with fluctuations into relative health and recurrent illness without progressing to dementia. Although he found instances of catatonia in both the dementia praecox and manic–depressive populations, he marked catatonia as a principal sign of dementia praecox. He established a categorical firewall in his system between these two disorders, a firewall that persists to this day in the world's principal psychiatric classifications.

For neither illness did Kraepelin offer defining characteristics. Nor were his descriptions improved upon in the succeeding century to develop a well-defined disease description, or to define specific tests, or to identify effective treatments. In psychiatric manuals, schizophrenia remains a heterogeneous conglomeration of disturbances of speech, thought, and affect. Manic–depressive illness has undergone greater development into two major syndromes, one characterized by depressive mood disorder and one by mania. Each has been divided into non-specific overlapping types without defining characteristics, without effective treatments, and ignoring the extensive evidence that the two syndromes appear in the same subjects as their illnesses progress [44].

Kraepelin regarded catatonia only as a type within his concept of dementia praecox. The demotion of catatonia from an individual syndrome to that of a subtype, a marker, and in the present classifications as a specifier of dementia praecox has hidden catatonia from recognition as a unique syndrome for more than a century. This is in no small part a tribute to the enormous influence Kraepelin has had in the history of psychiatry. A prolific writer of psychiatric textbooks, Kraepelin was the most prominent German psychiatrist up to World War I. He published his first textbook in 1883 [45] with revisions through an 8th edition, which appeared in four volumes between 1909 and 1915. It is little wonder that Kraepelin's image of catatonia overwhelmed that of Kahlbaum. Kahlbaum published his small book of 104 pages in 1874, but the voices of the many authors who endorsed his work were faint compared with the booming of Kraepelin, Eugen Bleuler, and Adolf Meyer, among many others. It was not until 1973 that the English translation of Kahlbaum's book became available and sparked the studies that found catatonia outside schizophrenia.

Kraepelin received his MD in 1878 and begun his academic travels first as Professor at Dorpat (Estonia) in 1886, then at Heidelberg in 1890. He moved to Munich in 1903 where he founded a German Institute for Psychiatric Research with extensive funds from American philanthropists, the banker James Loeb, and the Rockefeller Foundation. The Institute established Kraepelin and Munich as a world center for biological psychiatric research.

Kraepelin was nurtured in a world that saw the brain as the seat of psychiatric illness. At the opposite end of the psychopathology spectrum stood Sigmund Freud with an emphasis on individual psychology. Psychiatric symptoms typically arose from the mental experience of the patient rather than as a result of a brain disorder, a seductive paradigm that captivated clinicians’ interest especially in the United States. An image of dementia praecox as a brain disease was replaced by an image of disorganization induced by childhood experiences and memories, best relieved by individual psychoanalysis, a philosophy enthusiastically adopted by Paul Eugen Bleuler (1857–1939).

Bleuler obtained his MD in Zurich in 1881 and, after various positions in psychiatric hospitals, became a professor in Zurich and head of the Burghölzli Sanitarium in 1898. He studied hypnotism with Sigmund Freud, published a textbook on schizophrenia in 1911 and a general psychiatry text in 1918.

Bleuler restructured Kraepelin's image of dementia praecox using psychological theory and terms. It was he who created the name schizophrenia, the favored name that reifies the syndrome to this day. He described mutism, negativism, and rigidity as ‘generalised and persistent blocking – an exaggeration of the phenomenon seen in healthy individuals when they are overwhelmed by emotional disturbance’. [46]. The patient with catatonia was suppressing unpleasant memories by silence (mutism), by tenseness and rigidity (holds back acts that are compelled by memories), by refusal to obey commands, and by displacing rising emotions and tension into motor acts that shut out reality (posturing, grimacing, staring, stereotypes).

By the end of World War I, the writings of Kraepelin and Bleuler dominated psychiatric thinking until the philosophy of Sigmund Freud achieved dominance in America during and after World War II. Kahlbaum's perception of catatonia as an independent syndrome was buried. Until the end of the twentieth century, Kahlbaum's catatonia was viewed within Kraepelin's conjured formulation of dementia praecox and subsequently within Bleuler's concept of schizophrenia.

Conflict of paradigms in psychiatry

As catatonia was incorporated as a feature within more severe chronic psychoses, a new influence in its recognition was the worldwide influenza pandemic of 1917–1919. Many who survived the infections developed chronic illnesses. Stupors were common with active periods of slow movements, shuffling gait, rigid posturing, fixed facies, decreased eye blinking, and extended staring. (In retrospect, these signs are better seen as examples of infection-induced catatonia.)

Labeled encephalitis lethargica, the syndrome was classified and treated as a form of Parkinson's disease that is commonly found in the elderly [47]. But these signs were also identical to those of catatonia, which by this time was accepted as an aspect of schizophrenia, leading the Viennese psychiatrist Cosimo von Economo to describe the patients as suffering the same schizophrenia illness that Kraepelin had described [48]. For many patients, the illness was progressive, leading to long-term hospitalization either in neurologic centers or in psychiatric sanitaria. Whether the label of encephalitis lethargica or of catatonic schizophrenia was applied in an individual patient depended not on any distinguishing findings but on the attitude and experience of the observer and the setting.

The lesson that catatonia is a treatable syndrome in postencephalitic states is still ignored. In the successful book and film Awakenings, the neurologist Oliver Sacks describes the patients exhibiting prolonged and severe motor inhibition, posturing, rigidity, and mutism that began during the encephalitis epidemic [49]. The patients resided in a home for the elderly chronic ill. Their syndrome was labeled ‘parkinsonism’, and the newly heralded treatment of high-dose l-dopa was applied. Limited relief occurred but was hailed in the book and film as a revolutionary discovery. At a meeting of the Society of Biological Psychiatry in 1996, I asked Dr. Sacks whether he had considered the patients to have catatonia. He averred that they did not, nor had he considered using the treatments for catatonia for these patients [50].

The conflict of paradigms between clinical neurology and psychiatry is ongoing, to the detriment of the clinical sciences and the welfare of the patients. [51] Examples are discussed in the assessment and treatment of the neuroleptic malignant syndrome (Chapter 3) and anti-NMDAR encephalitis (Chapter 5).

Daniel Rogers, in an excellent recent review of motor disorders in psychiatry, presents portraits of patients with dementia praecox by Kraepelin and comparable portraits of postencephalitic motor signs. The pictures are indistinguishable [18]. The label of schizophrenia or of a neurological disease again depends not on objective findings but on the accident whether the referral was to the neurologic or the psychiatric clinic. And the outcomes are determined by the treatments associated with each diagnosis – parkinsonism with l-dopa and similar medications and schizophrenia with neuroleptic drugs.

A retrospective note on the increasing dominance of psychology during the first half of the twentieth century stated ‘The fact that an undoubted neurological disease, encephalitis lethargica, could produce a wide spectrum of psychiatric illness challenged the central idea of the so-called ‘functional psychoses’ [i.e., not derived from brain pathology] in an era that had come to be dominated by the teachings of psychoanalysis’ [52].

The identification of catatonia within and outside schizophrenia varied in the twentieth century. In 1912, catatonia was described in 30 patients with infectious diseases, toxic states, depression, mania, and delirium, encouraging the belief that catatonia occurred outside schizophrenia [53]. The prognoses varied, being good when episodes were few and worsening as the episodes increased in number. In a 1922 study of 200 patients who met Kraepelin's constructs, catatonia was found more often among the manic–depressive patients than among those with dementia praecox [54].

August Hoch's 1921 monograph Benign Stupors described 25 psychiatric patients treated at the Ward's Island Hospital in New York City. Their behaviors, motor signs, course, and outcomes are similar to the patients described by Kahlbaum. Classifying the patients using the Kraepelin/Bleuler distinctions, Hoch reported the prognoses were favorable with remission of symptoms and return to the community in 13 manic–depressive patients. The outcomes were poor in the 12 patients with general medical illnesses or schizophrenia [55]. (Hoch lacked the effective treatments for catatonia developed a decade later.)

Reviewing the twentieth-century psychiatric literature finds many articles both in Europe and the United States that describe catatonia as an independent entity, but many more accept the Kraepelin/Bleuler incorporation within schizophrenia. Interest in catatonia as an identifiable independent syndrome waned so much that when the American Psychiatric Association presented its classifications of psychiatric illnesses in 1952, catatonia was only recognized as a type of schizophrenia and remained so in the succeeding revisions in 1968, 1980, and 1994.

Psychiatry leaves the asylum

Catatonia was further pushed into the background by changes in psychiatry. First, the enthusiasm for the psychodynamic philosophy that blossomed during World War II decreased interest in systemic medical illnesses and moved the focus of psychiatric practice from the asylum to the private office and clinic. A principal influence was the rapid expansion of the numbers of physicians trained in psychiatry.

Involuntary military conscription of millions of men brought many who were not fit for such service, leading to an expansion of the need for physicians trained in psychiatry to evaluate and treat those who became ill. Many physicians entering military service without prior psychiatric experience, myself included, were trained in schools of military neuropsychiatry. That training was dominated by the psychodynamic philosophy.

William Menninger, a confirmed Freudian analyst, was the head of the US Army's Department of Psychiatry. Schools for military neuropsychiatry were established in San Antonio, Texas, and in Topeka, Kansas. I was a field medical officer in the US Army in 1946 when I was assigned to the school in Texas. For 4 months, I attended daily classes in psychoanalysis, clinical psychiatry, and clinical neurology. Diagnosis and treatments were almost wholly psychodynamic. Lip service was played to the teaching of the biological treatments of ECT, insulin coma, and lobotomy. In that prepsychopharmacology era, pharmacology was focused on the used of sedating drugs. When I left military service, I was helped by the Serviceman's Readjustment Act, known as the GI Bill, to pay tuition to attend the William Alanson White Institute of Psychoanalysis in New York City during my postgraduate residency training in neurology and psychiatry at Montefiore, Bellevue, and Hillside Hospitals. When the war ended, many physicians used government education benefits to extend their training in psychoanalysis and then to open private offices separate from hospitals for their clinical practices.

Few connected with the large sanitaria where the more severely ill were housed, and psychiatry increasingly became an out-patient office practice focused on psychotherapy. A few clinicians applied their skills among those who were in hospital care, but it was soon clear that the severely ill were no longer of interest to most practitioners as their attention was focused on the young, alert, intelligent, attractive, emotionally ill who did not require institutional care. The acute illnesses of catatonia did not lend themselves to office care, and as interest shifted from the psychoses to the less ill, interest in catatonia dissipated.

A second factor in the virtual disappearance of catatonia from the psychiatric radar screen was the development in the 1930s of treatments that could effectively and quickly relieve it. In 1930, William Bleckwenn demonstrated the immediate relief of catatonia by injections of sodium amobarbital, a medication that decreases anxiety and induces sleep [56, 57]. The effects ended mutism, relieved posturing and staring, and encouraged speech, feeding, drinking, and self-care. For some, relief was immediate and complete. For others, the benefits were transient and treatments had to be continued. The ease with which a retarded and excited patient with catatonia could be relieved by a single chemical injection made the sodium amytal glass vials in wooden cylinders ubiquitous features of clinical care in psychiatric hospitals and emergency rooms.

During my medical school training in psychiatry at Bellevue Psychiatric Hospital in 1945, and again during neurology and psychiatry residency training between 1948 and 1951, I was equipped with vials of sodium amytal and sterile water and was frequently called upon to treat mutism and negativism for feeding and to relieve excited catatonic states by these injections. In retrospect, the relief of catatonia by amobarbital was the first sign of the approaching era of psychopharmacology.

Treatments for the most seriously ill psychiatric patients appeared next – insulin coma therapy in 1933, chemically induced seizures in 1934, frontal leucotomy in 1936, and electrically induced seizures in 1938.

Insulin coma patients were injected with large doses of the hormone insulin that reduced blood sugar to minimal survival levels, inducing coma until blood sugar levels were normalized by intravenous injections or tube-feeding into the stomach of high concentrations of glucose sugars. In treatment programs, comas were induced daily for 40–50 comas over 3 months. Seizures occurred in up to 20% of the treatments, and for those who were not responding rapidly, electric-induced seizures were added during the coma.

Seizures were first induced chemically using intramuscular injections of camphor, later with intravenous pentylenetetrazol (metrazol). Other chemical methods of inducing seizures were examined. In the 1950s, the inhalant flurothyl (Indoklon) was tested in random assignment studies vis a vis ECT. Flurothyl, an ether with the ether aroma and volatility, was presented to the patient by way of a mask that covered mouth and nose. Within three to four breaths, the patient was asleep and a seizure quickly followed. These treatments were as effective as ECT, but the complexity of the administration and chemical cost limited the interest, and the method was discarded. These chemical inductions were replaced by electricity in what is now electroconvulsive treatment (ECT). In each treatment, the benefit accrues to the number and frequency of seizures induced.

Frontal leucotomy was the surgical procedure that severed the connections between the frontal lobes and the rest of the brain, inducing changes in thought, reducing obsessions, and often inducing seizures. Leucotomy was introduced as a full neurosurgical procedure under sterile operating room conditions. But one of the proponents, Walter Freeman, introduced a quick method using an ECT-induced seizure as anesthetic and cutting the brain via an ‘ice-pick-like’ device introduced through the thin plate over the eyeball. [58] Public and professional distaste for this procedure is illustrated in the book and film One Flew Over the Cuckoo's Nest by Ken Kesey [59]. Interest in lobotomy ended when chlorpromazine and other neuroleptic drugs were introduced and shown to be safer and more effective.

These treatments typically relieved the more severe and malignant catatonias. The physicians prescribing the treatments most often labeled the patients as suffering from schizophrenia and only occasionally focused interest on catatonia. While continuing treatments were needed to sustain the benefits, the prognosis for full relief became excellent, making catatonia among the most successfully treatable conditions in psychiatry. Interest remained weak as the patients were quickly returned to their homes and no longer were clinical challenges.

In the discovery that induced seizures relieved schizophrenia, it was most fortuitous that Ladislas Meduna selected patients with catatonia for his first experiments. Nine of the first 11 patients were catatonic requiring nursing care and naso-gastric feedings. Had he selected subjects from among those with hebephrenia, his experiences would not have been encouraging [60].

Were these treatments, lobotomy, insulin coma, and ECT effective in relieving schizophrenia? The answer depends on the populations selected and the settings from which they came. For the more acutely ill patients, mainly from out-patient settings that included those with catatonia and those with the mixed syndromes of depression and psychosis (labeled schizoaffective illness), the treatments offered dramatic relief. For the more chronically ill, especially those with long-standing illness diagnosed as the paranoid, hebephrenic, and non-catatonic forms of schizophrenia, neither ECT nor the other biological treatments were beneficial. The site of the assessment, whether in a long-stay hospital population or in a general hospital acute treatment center, influenced the evaluation [61, 62].

In 1981, the neurologist B. Mahendra posed the question, ‘Where have all the catatonics gone?’ [63]. Noting that the psychiatric texts had commented on the decline in the recognition of catatonic schizophrenia and that the decline had preceded the influence of neuroleptic drugs, Mahendra doubted that the disorder of catatonic schizophrenia ever existed. The frequency of association of catatonia and schizophrenia depended on the incidence of the many ways in which catatonia was elicited. He cited examples of catatonia secondary to infections (as in encephalitis) and in the excitement and retardation of the mood disorders. As an analogy, he noted that tuberculosis had been frequently found among severely ill psychiatric patients but had not been reified as a ‘tuberculous schizophrenia’. Catatonia had not disappeared, but the connection to psychosis had been prematurely reified.

An example is the 1969 study published by B. Pauleikhoff based on 35 years of experience with 552 hospitalized psychiatric patients [24]. Pauleikhoff identified stupor in 100 patients and excitement in 51 patients with catatonia. In 26 patients, catatonia was malignant, that is, life-threatening and severe. Presenting his data in 5-year increments, he reported a drop in the frequency of the diagnoses after 1953, ascribing the reduced numbers to changes in clinic administration and diagnostic styles and not to changes in the incidence of catatonia. In 12 patient histories, he illustrated catatonia variants that are readily recognizable today as a syndrome distinct from schizophrenia.

In the 1970s, James Morrison at the University of Iowa examined hospital chart records and reported an increased incidence of catatonia in patients with mood disorders, chiefly those with mania [64, 65]. An examination of patients admitted to a New York City hospital psychiatric unit in the same period found a higher prevalence of catatonia among the patients with mania and depression than in those with schizophrenia [7, 66]. The same higher concentration of catatonia among manic patients than in those with schizophrenia was reported from Germany [67]. These reappraisals had little immediate effect but set the stage for liberating catatonia from schizophrenia. As we will see, they made it possible for the appearance of an acute, often lethal syndrome associated with high-potency neuroleptic drugs to rekindle interest in catatonia as independent of schizophrenia.

Chapter 3: the neuroleptic malignant syndrome

With all these disadvantages of re-examination, I can only expect to dig my new species [of clinical case] from the mass of rubbish – of confused, irregular conglomerations of amorphous appearance, to separate it from the encumbrance of incidental matters, and so present it, that others may be able to satisfy themselves of its individuality, and then enter upon the critical and exact analysis of its true and essential essence; or else to decide that it is only an old variety with some accidental and illusive peculiarities.

Luther V. Bell, 1849 [68]

Catatonia faded from psychiatry's awareness until the hazards of the neuroleptic malignant syndrome brought it to professional attention. Frequently fatal, the stupor, rigid posturing, mutism, and repetitive speech of critically ill delirious patients renewed interest in catatonia, especially when the treatments for catatonia were found to relieve the neurotoxic syndrome.

Chlorpromazine (CPZ), the first of the neuroleptic drugs, was introduced in 1954 as a sedating agent for excited psychotic patients. The aggression, screaming, fire setting, breaking furniture, and physical injuries that were common in the sanitaria were quickly reduced, benefits that were recognized in every psychiatric center where it was used. As the director of psychiatric research at Hillside Hospital in Long Island, New York, a 200-bed sanitarium, I also studied its effects. Within a few weeks, the nurses who first saw the benefits eagerly referred their most disturbed patients for the experimental treatment. By 1957, the antidepressant imipramine was introduced followed by a flood of new chemicals for the relief of anxiety, depression, and psychosis. The enthusiasms of psychopharmacology soon dominated both the profession and the public media and have done so to the present.

But patients paid heavily for these benefits. Motor movements slowed and gait became ungainly. Stiff and rigid posturing was accompanied by tremors. Drooling slathered their clothing. Their faces were emotionally flat, without smiles or laughter. Some became jaundiced, itched, and scratched leaving long red trails on their arms and legs. Patients refused their medicines, and in that era of paternalism and involuntary treatment, the new drugs were often administered forcibly.

We had no knowledge of how to prevent these effects. Many chemicals thought to be prophylactic for these effects were prescribed, but with little relief. Despite the increasingly severe impacts on movement and speech, the balance between the reduction in expressed delusions and hallucinations, aggressive acts, screaming behaviors, and frightening thoughts was considered favorably by administrators, so that continued prescription was widely endorsed.

The benefits were also considered sufficient to replace insulin coma (ICT), a more dangerous and unpleasant treatment then in use. In 1933, the Austrian psychiatrist Manfred Sakel proposed treating schizophrenia by daily injection of increasing high doses of the hormone insulin to lower blood glucose levels to states of coma [69]. After an hour of observed coma, an intravenous injection or nasogastric gavage of concentrated glucose quickly returned the patient to consciousness. Within an hour, patients were alert having showered, toileted, and been fed, able to return to their treatment ward. Psychotic thoughts and aggressive behaviors were inhibited so that about one-third of the patients left the hospital and returned to their families after courses of up to 50 comas.

In the 1940s and 1950s, about 40 patients were treated with ICT each year at Hillside Hospital. In the 5 years, I treated about 200 patients. Prolonged coma, the failure of the patient to recover consciousness as glucose was administered, occurred in 3% of the treatments. The patients required intensive nursing care and careful management of fluids and blood electrolytes. We tried many medications, including the newly introduced steroids, with none proving useful. Three patients died. Spontaneous seizures occurred in up to 20% of the treatments, and when no benefits were apparent after a month of comas, we added ECT to the comas. ICT was a laborious and riskful treatment of marginal benefit.

We soon recognized that the patients who improved with ICT were also relieved by CPZ. Beginning in 1957, the patients referred for ICT were randomly assigned to either a 50-coma treatment course of ICT or to daily oral dosing with CPZ. In the prior 3 years of experience, we had learned that about 1200 mg/day of CPZ was the effective dosing schedule. In the study, patients received doses beginning at 300 mg/day rising weekly to 1200 mg/day. The median dosage was 800 mg/day for the 10-week course.

Within 15 months, we had treated 50 patients, half with CPZ and half with ICT. A seminal 1958 paper in the Journal of the American Medical Association reported similar reductions in psychosis and aggression with both treatments [70]. But the risks for prolonged coma and death, weight gain, and nursing care costs of ICT were greater than the risks and costs of CPZ. By the end of 1958, the hospital discontinued its use, and soon ICT had been widely abandoned throughout the nation.

An interesting footnote to the ICT history is described by the author Sylvia Nasar in the biography and film A Beautiful Mind, the story of the 1994 Nobel Economics Prize winner John Nash. He had become psychotic soon after completing his degree at Princeton and had begun a teaching career. By 1961, he required hospital care for a paranoid psychosis and was admitted to the Trenton State Hospital where ICT was still available. His treatment with ICT relieved the principal symptoms, but he remained chronically ill. [71]

Suppression of interest in movement disorders

More potent neuroleptic drugs, such as fluphenazine, trifluoperazine, and haloperidol, were next introduced to the psychiatric community and widely prescribed. Hospital wards became quieter, and increasing numbers of patients moved from in-patient to out-patient care. The rapid discharge of patients and the closing of the asylums, the process soon labeled deinstitutionalization, began as a trickle and soon became a flood, closing the majority of the sanitaria in the United States and throughout the world by the end of the century.

Neuroleptic drugs suppress psychosis but do not cure. Their effects are more like that of steroids that suppress symptoms than like those of an antibiotic in relieving an infection by destroying the invading agent. Neuroleptic drugs require continued prescription to maintain health. As the dosages of neuroleptic drugs are reduced or withdrawn, symptoms flare. We did not know then, nor do we know now, for how long treatments should be sustained nor did we understand the risks. Medication treatments, month after month and year after year are accepted clinical practice.

As more patients exhibited peculiar motor movements, the association with neuroleptic drugs was increasingly recognized. Tremors interfered with writing and speaking, gait became slow and shuffling, and as eyelids did not blink, patients appeared to be constantly staring. After long exposures, especially in older patients, voices became husky. Feeding and talking were made difficult by worm-like writhing mouth movements. Labeled tardive dyskinesia and tardive dystonia, the movements were uncontrollable, becoming progressively more severe and unsightly. No effective treatment or prevention was known as patients risked the Scylla of psychosis or the Charybdis of dyskinesia. The sanitaria were soon filled by slow, shuffling, trembling, shadows of human beings, occasionally laughing or giggling uncontrollably [72]. The motor effects of the neuroleptic drugs were so commonly recognized that measuring the severity of tremors in handwriting was suggested as a criterion to identify an active clinical agent [73].

The enthusiasm for prescribing these agents would be severely lessened if the effects on movement were widely discussed. The pharmaceutical industry, frightened that their sales would be impeded, encouraged leading psychiatrists (‘known opinion leaders’) to publicly opine that the motor changes were inconsequential and tolerable. The movement effects were widely denied and pushed out of professional and public awareness. In hospital settings where physicians examined patients at their bedsides, the measuring and recording of the motor signs were feasible. But in office settings, physicians sat behind their desks, and physical examinations were not carried out, further minimizing the recognition of motor signs of illness.

When newly introduced the second-generation or atypical neuroleptic drugs – clozapine, risperidone, olanzapine, and quetiapine – were marketed in the 1990s, the banner argument for their use was their lesser motor effects. It took more than two decades after the first appreciation of the motor toxicity of neuroleptic drugs for these effects to be publicly acknowledged and then mainly as an advertising strategy to encourage prescription of the second-generation neuroleptics. It took another two decades to recognize that the lesser movement effects were tied to the lesser antipsychotic potency of the new agents: their benefits were only slightly better than those of placebos [74].

The active suppression of the recognition of abnormal movements with neuroleptic drugs also suppressed the recognition of catatonia. The belief that catatonia had disappeared was further encouraged by the segregation of the severe psychiatrically ill outside the experience of community physicians and the many psychiatrists now active only in their office settings. The full range of motor signs of parkinsonism, tardive dyskinesias, and catatonia was only identified in long-stay facilities [75].

The neuroleptic malignant syndrome enables recognition of catatonia

The recognition of catatonia was energized by the awareness that the more potent neuroleptic drugs risked inducing acute febrile catatonic syndromes. Described within the decade after CPZ was introduced and labeled, the syndrom malin des neuroleptiques – an acute neuroleptic toxic syndrome – patients suddenly became feverish, stuporous, and delirious [76, 77]. Heart rate, blood pressure, breathing rate, and sweating increased without evidence of infection. Catatonic signs became prominent. This life-threatening syndrome appeared without warning, often following a transient influenza-like syndrome of malaise, fever, and weakness [78-80].

As agents with greater neuroleptic potency than CPZ were marketed, severity of the toxicity increased. Evidence of the syndrome in eight patients treated with high-potency neuroleptic drugs described by Alan Gelenberg of Boston's Massachusetts General Hospital compelled attention, and clinicians became frantic to understand these phenomena [81, 82].

The cause was puzzling. Were these acute symptoms evidence of the blockade of dopamine neurotransmission that was reported in laboratory studies and considered the basis for the relief of thought disorders? Dopamine was one of the brain's principal intercellular communication systems impaired by the new drugs. Perhaps prescription of dopamine agonists, drugs that increased brain dopamine levels, would reverse toxicity?

A 1980 review of more than 60 published cases brought particular attention to the syndrome that was labeled the neuroleptic malignant syndrome (NMS), a name that was widely accepted [83]. The syndrome was labeled ‘malignant’ in recognition that many patients died in an acute autonomic storm of high fever, elevated blood pressure, increased heart rate, irregular heart rhythms, and sweating. Each case report recognized rigidity, dyskinesia (abnormal motor movements), posturing, mutism, and negativism, the classic signs of catatonia. This publication cited dopamine blockade as the cause of NMS and endorsed treatment with the dopamine agonists bromocriptine and amantadine.

When it was realized that the same neuroleptic drugs that inadvertently led to the appearance of these catatonic signs were used to relieve schizophrenia, including the cases labeled as the catatonic form of schizophrenia, treatment options became confused. When patients exhibited signs of psychosis, physicians prescribed neuroleptic drugs. But these also increased neurotoxicity. It took some time to realize that discontinuation of neuroleptics was essential to relieve the toxic syndrome.

Matters were not helped by an assertion that increased motor rigidity and fever were signs of malignant hyperthermia (MH), a syndrome of muscle weakness and fever that follows the use of inhalation anesthetics [83]. This syndrome is restricted to a few patients with an identifiable genetic fault. For symptomatic relief of MH, the muscle relaxant dantrolene is prescribed. As a result of this confused association, dantrolene was added to the recommended prescriptions for NMS. In 1997, the newly established NMS Internet Hotline made prescription of both bromocriptine and dantrolene and withdrawal of the offending neuroleptic the cornerstones of the recommended management.

Neuroleptic malignant syndrome was soon sensed as clinically identical to malignant (that is, lethal) catatonia (MC) that had been described before the neuroleptic drugs were introduced. Many forms of MC had been recognized, and the efficacy of ECT in its relief was reported by 1952 [2].

By 1984, we had recognized NMS in three patients at the University Hospital at Stony Brook, each with prominent signs of catatonia [3]. We first summarized the prior reports of 17 similar cases; 11 had been precipitated by haloperidol, a finding that since has been repeatedly confirmed. Two patients had died with the others slowly recovering after extended nursing care. Different psychoactive agents had been prescribed – benztropine, dantrolene, amantadine, bromocriptine, and diphenhydramine – but none were effective.

Among our patients, a 30-year-old woman had been treated with the neuroleptic fluphenazine and then admitted to the hospital in an acute state of rigidity, posturing, mask-like facies, profuse sweating, and fever. She was treated with the antihistamine diphenhydramine, the dopamine agonist bromocriptine, the antimanic lithium, and the antipsychotic mesoridazine, each selected to relieve one of her symptoms. She received little benefit, and only after all medications were discontinued and weeks of nursing care did the toxic syndrome slowly resolve and she was able to return home.

In a 45-year-old disorganized and psychotic woman with depressed mood, the neuroleptic haloperidol and then fluphenazine had been prescribed. NMS was precipitated. A 5 mg diazepam dose administered intravenously as a sedative resolved the motor syndrome quickly but transiently. Continued treatment with bromocriptine and lorazepam offered little benefit. In another patient, a 26-year-old man with bizarre thinking, slow speech and movement, and the catatonic signs of posturing and rigidity had been transferred from a state hospital for treatment with ECT. An intramuscular injection of the long-acting neuroleptic fluphenazine decanoate was given and within 72 h NMS was recognized.

Electroconvulsive therapy was prescribed for both patients, and within 1 day, the toxic syndrome had resolved dramatically for each. Their ECT treatment courses were continued until the toxic states had fully resolved without residual motor or toxic signs. We concluded that NMS was a physician-induced form of malignant catatonia treatable by ECT.

Over the next few years, other patients with NMS were successfully treated. We described our awareness that the neuroleptic drugs, particularly the high-potency drugs, were also toxic in eliciting syndromes of catatonia and fever and that the toxicity resolved with neuroleptic drug withdrawal; and if withdrawal alone was not sufficient, ECT was a definitive treatment.

This awareness was documented hesitantly as ECT was the most stigmatized treatment in psychiatry. Yet, by 1990, the recognition of catatonia warranted immediate treatment with ECT even before medication trials [4]. By 1991, Denise White reported that catatonia was a risk factor for neurotoxic development [84] and then catatonia was seen as integral to the diagnosis [85]. These reports crystallized the integral role of catatonia in NMS.

That same year, collaborating with Michael Taylor, we suggested to the American Psychiatric Association DSM-IV commission, then revising the classification criteria, that catatonia warranted a place distinct from its role as a type of schizophrenia [9]. Increasingly, the argument was made that NMS was best regarded and treated as a form of malignant catatonia and that effective relief was assured when treatments for catatonia were applied rather than those considered useful for an aberration of neurotransmitter activity [5, 86]. By 1996, a rating scale was developed for catatonia and a systematic study established the lorazepam sedative test as a diagnostic verification of catatonia. Treatment with high doses of lorazepam was shown to be effective for 80% of the patients with catatonia and ECT effective for the remainder [87, 88].

In the next decade, numerous reports found NMS rapidly responsive to ECT, and in 2003, Michael Taylor and I summarized the extensive evidence in the textbook Catatonia: A clinician's guide to diagnosis and treatment [11]. But ECT is much stigmatized, and many institutions lacked the physical facility or the trained personnel for its use leading to ethically troubling reports of prolonged hospital care and unnecessary deaths in patients with NMS. Fortunately, the benzodiazepines, a less controversial and less invasive treatment than ECT, were also available to relieve NMS.

Catatonia and benzodiazepines

Catatonia had first been successfully treated with intravenous injections of the barbiturate amobarbital in 1930 by William Bleckwenn in Wisconsin [56]. Within 4 years, relief by inducing grand mal seizures was described by the Hungarian neuropsychiatrist Ladislas Meduna [89]. Both treatments were widely adopted when catatonia was recognized as such. Once NMS was pictured as a form of catatonia, the question was raised whether barbiturates would relieve NMS. Ever since its first description, amobarbital had been the accepted immediate treatment of catatonia in emergency room settings. By the 1980s, concerns about the toxicity and safety of the barbiturates led to their replacement by benzodiazepines that were used as sedatives, soporifics, and anticonvulsants.

In 1983, Gregory Fricchione and his colleagues at Massachusetts General Hospital described the rapid relief of NMS by intravenous lorazepam, a commonly used benzodiazepine [90]. Each of four patients they treated exhibited catatonia, fever, agitation, and delirium, with elevated blood pressures, rapid heart rates, and increased sweating. Haloperidol had been the toxic agent in three instances and trifluoperazine in one. After various prescribed medications and nursing care had failed to relieve the syndrome, intravenous lorazepam in 2-mg doses was administered. In each patient, NMS resolved within a day, with some symptoms resolving within hours. This dramatic experience established lorazepam as an effective treatment for catatonia.

In discussing this experience, Greg Fricchione relates: ‘I had treated a patient in postcardiotomy delirium with intramuscular and then intravenous haloperidol and he developed neuroleptic induced malignant catatonia. I brought my mentor Ned Cassem the Director of the MGH Consultation Psychiatry Service and both a physician and Jesuit priest with me around 8 pm to see the patient who had not responded to diphenhydramine or benztropine. Ned chose lorazepam and I injected 2 mg intravenously in the presence of several of the nurses. Catatonia lysed [disappeared] dramatically in about 1 min; the nurses who all knew Ned asked in wonderment: “What did you give him Dr Cassem?” And as he turned to leave, Ned said nonchalantly, “why holy water of course …”’

By 1990, Patricia Rosebush and her colleagues at McMaster University in Hamilton, Canada, also described complete and dramatic relief of NMS by lorazepam in a prospectively open trial in 1 mg or 2 mg doses in 12 episodes [29]. Other reports of the efficacy of lorazepam [91, 92] were followed by descriptions of the efficacy of other benzodiazepines, clonazepam [93], diazepam [94], and zolpidem [95].

At Stony Brook University Hospital in 1994, 28 patients with catatonia were systematically treated with injected and/or oral lorazepam for up to 5 days and with ECT when lorazepam failed. Outcomes were monitored quantitatively during the treatment phase with a Catatonia Rating Scale [87]. In 16 of the 21 patients (76%) who received a treatment trial of lorazepam, catatonia resolved within 1 day. Three cases were examples of NMS. In 11 patients to whom we had administered an intravenous dose of lorazepam, immediate relief of catatonia was the result, the harbinger of the full relief that followed treatment with high oral doses of lorazepam. Four patients who did not have an immediate response to intravenous lorazepam were successfully treated with ECT [88].

By 1990, two competing treatment protocols were prescribed for NMS – the bromocriptine–dantrolene model based on the dopamine/malignant hyperthermia association and the benzodiazepine–ECT model based on the recognition that NMS is the form of malignant catatonia. Although no direct comparisons between the two treatments were made, the efficacy of the benzodiazepine–ECT model assured its widespread use and acceptance. By 1991, doubts as to the merit of dopamine augmentation as the effective treatment for NMS were expressed [96]. By 1995, the hypothesized connection of NMS to malignant hyperthermia was also found wanting, and treatment with dantrolene was no longer recommended [97]. Thereafter, whether NMS was relieved or a fatality ensued depended not on the administration of dopamine agonists or dantrolene but whether the neuroleptic administration had been promptly discontinued and fluid and metabolic integrity re-established. Well-documented texts describing the neuroleptic malignant syndrome as a variant of malignant catatonia appeared in 2003 [11] and 2004 [98].

What delayed the recognition of NMS as drug-induced catatonia? The tie of catatonia to schizophrenia was so intimate that the prior recognition of schizophrenia was obligatory before catatonia could be considered. The recognition of catatonia outside schizophrenia reported in the 1970s had yet to become part of psychiatry's teaching. In the era of psychopharmacology, psychiatric disorders are perceived as errors in neurotransmitter physiology, favoring the belief that NMS was the result of a decrease in brain dopamine activity and making the prescription of dopamine agonists a logical treatment. The same beliefs would not support treatment with benzodiazepines (or ECT) as no theory of neurotransmitter action had been promoted for catatonia or malignant catatonia. Beliefs in dopamine aberration in NMS were very strongly held, and intense public debates were frequent for more than a decade.

Recognizing catatonia today

With the renewed interest in catatonia and the appreciation that catatonia often occurs independent of schizophrenia, it became important to develop criteria to define its many variations. In clinical medicine, a diagnosis is made, and treatment is offered after the patient relates his symptoms and recent history; the physician examines for signs of dysfunctions; laboratory tests are requested and assessed; and based on these findings, the clinician considers a diagnosis from his glossary of disorders. After identifying the most likely fit, treatment is prescribed. When a specific treatment leads to recovery, the diagnosis is considered validated. Patients with catatonia rarely complain of symptoms; the behaviors are observed or reported, and examination identifies the presence of identifiable catatonia signs. When motor signs are prominent, a checklist of catatonia signs sorted in a Catatonia Rating Scale becomes a useful guide to the examination [11].

Catatonia is an all-or-none phenomenon, so the presence of two or more catatonia signs for 24 h or longer is sufficient to consider it to be present. Surveys of populations in psychiatric hospital wards and emergency rooms find that 7–15% exhibit catatonia [11, 12].

Once the diagnosis is entertained, the clinician can confirm the diagnosis by employing a sedative relaxation test (‘lorazepam test’). William Bleckwenn's description of immediate relief of catatonia by the intravenous injection of amobarbital sodium in his article ‘The production of sleep and rest in psychotic cases’ presented both an effective treatment and a diagnostic test [56]. For patients who are mute, posturing, rigid, or with other catatonia signs, the return of speech and relaxation of posture and tension are prompt, usually within 10 min after an injection of sodium amobarbital or, more commonly today, after 1 mg or 2 mg lorazepam. The change may be transient or may persist, but the immediate relaxation confirms the presence of catatonia.

For many decades, amobarbital and other barbiturates were essential features of hospital emergency room care. As a medical student and resident in the 1940s, I was usually in the hospital carrying a small wooden cigar case with a glass vial of 500 mg amobarbital powder, syringe, needle, sterile water, and tourniquet – always prepared and often used. In his clinical review of the diagnosis and management of catatonia in 1975, James Morrison studied 250 patients with catatonia of whom 97 were examined by a ‘barbiturate interview’, the intravenous injection of up to 5 g of amobarbital [99]. He reported that 71 (73%) responded favorably, meaning a quick relief of mutism, tension, posturing, and stereotypy. He gives the example of a 23-year-old single man with a 2-year history of persecutory and grandiose delusions who exhibited waxy flexibility and posturing of the psychological pillow (head held elevated as if on a pillow) and not responding to antipsychotic treatments. After the intravenous administration of four grams of sodium amobarbital, the rigidity, tension, and posturing lessened and the patient ‘began to speak of the terror he had felt when he realized that the television was bugged and the FBI was gathering information about him’.

In the early 1980s, as discussed earlier, benzodiazepines were recommended as safer sedatives than the barbiturates, and lorazepam and diazepam were successfully tested in catatonia treatment. Numerous anecdotes cite the patient with mute catatonia being sent to a hospital laboratory for a procedure after an injection of lorazepam to assure cooperation, only for the ward nurse to be called with a complaint that the patient is overly talkative and uncooperative in the procedure room. Intravenous dosing in a mute, posturing, or stuporous patient typically relieves the syndrome within a few minutes.

How assured is the response to an intravenous injection of 1 mg lorazepam or 2.5 mg diazepam as verification of catatonia? Almost all patients with positive scores on the Catatonia Rating Scale are relieved. Occasionally, a second dose is required and applied within 10 min. It is not stretching the comparison too far to say that a sedative drug acts with the same dose-related speed as a concentrated acid or base reverses the pH balance of a chemical solution.

Once the presence of catatonia is verified, treatment today is remarkably effective. More than 80% of the patients are relieved by barbiturates or benzodiazepines, and when these fail, the others are relieved by ECT [11].

The availability of both a reliable and quick diagnosis method and effective treatment has enabled the discovery of additional forms of catatonia [14, 100]. Once catatonia was divorced from schizophrenia and the main motor signs were appreciated, other forms of catatonia, such as delirious mania, toxic serotonin syndrome, and pediatric catatonia, were recognized and their diagnostic criteria and treatment algorithms established.

Chapter 4: new forms are recognized

According to an old story, there are three types of baseball umpires. One says: ‘I call them [balls and strikes] as they are’. The second says ‘I call them as I see them’. And the third says ‘What I call them is what they become’.

Frederick Grinnell, 1992 [101]

Recognizing the neuroleptic malignant syndrome (NMS) as a form of malignant catatonia showed that catatonia was found outside schizophrenia. It also offered effective treatment for the patients and justified the challenge to the hypothesis that NMS was the result of dopamine blockade. Breaking the association with schizophrenia freed clinicians to see catatonia in broader samples of patients. It encouraged the development of Catatonia Rating Scales and exploration of an injection of lorazepam as a verifying diagnostic test. It stimulated the search for catatonia in other guises.

Among patients admitted to the hospital in a hyperactive agitated delirium, the fluctuating signs of catatonia were commonly recognized. The risk of death led to many descriptions of excited delirious states with prominent signs of catatonia, variously labeled malignant, pernicious, lethal, fatal, or mortal catatonia; or delirium becomes the focus as in delirious mania or manic delirium; or the eponym of Bell's mania or Stauder's lethal catatonia was used.

Acute signs of NMS were also identified in subjects who had not been treated with neuroleptics but with psychoactive drugs that affected the serotonin neurotransmitter system. These patients suffered what became known as the toxic serotonin syndrome, a parallel disorder to NMS.

Increasingly, the signs of catatonia were found among adolescents admitted to our facility, at first among those with peculiar behaviors associated with mental retardation and then those with delirious mania [102]. Many patients showed repetitive self-injurious behaviors (SIB), but we did not realize that this behavior was a form of catatonia until we read reports from other medical centers among their patients with neurobehavioral disorders. That the patients improved with ECT validated the association [19]. Such repetitive behaviors are now recognized within the catatonia spectrum.

Delirious mania as malignant catatonia

Our experience associating catatonia with delirium increased when an intermittently mute and screaming 25-year-old woman, ill with a 3-year history of lupus erythematosus (a highly varied systemic, often fatal autoimmune disease) was referred for ECT by Dr. Gregory Fricchione, the head of the hospital's Consultation & Liaison Service [103]. Her agitated manic behavior, facial grimacing, mutism, and rigidity were poorly controlled. She required high doses of sedative drugs and four-limb restraints to sustain her life in intensive nursing care. With the consent of her husband, her mother, and her physicians, the first ECT was given on the 27th day of hospital care.

Mania and delirium rapidly disappeared, speech and self-care improved, posturing, mutism, and screaming were allayed, so much so that after seven treatments the family and her physicians withdrew consent for further treatment. But treatment was incomplete and symptoms soon returned. The ECT course continued, and she received 10 more treatments. Her psychiatric and medical conditions were relieved, and she left the hospital in psychiatric and systemic remission.

On admission, she had exhibited the systemic signs of lupus erythematosus supported by positive antinuclear antibody tests. Treatments with intravenous methyl prednisolone and three plasmapheresis exchanges did little to improve her condition. Treatment with cyclophosphamide was begun but her delirium and excitement led to the referral for ECT. With ECT, her behavior normalized and she returned to her home. Cyclophosphamide continued monthly, and she was well on 1-year re-examination.

Similar cases of delirium are commonly found in medical, surgical, and emergency room settings. For more than two centuries, clinicians have described patients with the acute onset of an excited delirious state, dangerous to themselves and to others, frequently so severe as to result in death. In 1849, Luther Bell, in a 13-year review of 1700 admissions to Boston's McLean Hospital, described 40 patients with delirium, fever, and uncontrollable excitement that alternated with stupor. Three-quarters had died. The syndrome became known as Bell's mania [68].

In 1934, Karl Heinz Stauder described the sudden onset of intense excitement, delirium, high fever, and catalepsy in three young adults with a family history of psychiatric illness but who previously had been in good medical health. In a matter of minutes, each went from ‘well’ to extreme excitement and psychosis. During the illness, each injured himself by slamming repeatedly into the ground or walls. All three died. Stauder termed the syndrome tödliche katatonie (fatal catatonia) [104].

Similar descriptions by many authors confirm the characteristics of delirious mania as a form of malignant catatonia [2, 105-114]. The principal feature is the acute onset of a nightmarish, dream-like, overactive state that develops within a few hours or a few days. Voices, noises, and sights are misperceived, encouraging frightening thoughts. Patients hit out and thrash about, harming themselves and others. Grimacing, posturing, echolalia (repeating words), and echopraxia (repeating movements) are prominent. Negativism (refusing to obey commands) and automatic obedience (obeying commands that they are told not to obey) are almost always present. Patients sleep poorly and are unable to recall their recent experiences or the names of objects or numbers given to them. They are disoriented and they confabulate. Patients hide in small spaces, close the doors and blinds on windows, and remove their clothes running nude in and from their homes. Garrulousness, flights of ideas, and rambling speech alternate with mutism. Fever, rapid heart rate, elevated blood pressure, and rapid breathing are common. An example is abstracted from my review of delirious mania [109].

A 29-year-old man with a positive history for HIV had been found wandering on a beach, naked, confused, and unable to rationally answer questions. He was admitted to the psychiatric emergency room of Stony Brook University Hospital. Despondent about his illness, he stopped taking the prescribed medicines, and said that he wished to die. The day before admission, he had been slashing pictures of his friends and walking about the house with a bloody knife, muttering incoherently.

On admission, he was excited, screaming, confused, dehydrated, unkempt, and dirty. He required four-limb restraints and 0.5 mg of the antipsychotic chemical restraint haloperidol was administered intramuscularly. Within an hour he was rigid and mute, febrile, dehydrated, and urine showed evidence of cannabinoids.

An intravenous injection of 1 mg lorazepam quickly reduced the catatonia signs. Mutism, rigidity, staring, and periodic excitement persisted despite daily lorazepam dosages to 10 mg per day. Neuroleptic medication was precluded by his reaction to haloperidol.

Surrogate consent was obtained for ECT. On day 11, the first seizure was induced and within 24 h he no longer required protection. Mutism, rigidity, and staring disappeared. Within 2 h his temperature rose to 102°F and resolved to normal over the next 12 h.

After the second ECT 2 days later, he became better oriented and cooperative. The next day he came voluntarily for the third treatment. Delirium, catatonia signs, and excitement were fully relieved by the sixth treatment, and he was discharged to the care of his family. Lorazepam was discontinued, and lithium therapy was prescribed for persisting mania. Follow-up 2 months later showed him to be continuing his medical treatment without any persisting signs of psychiatric illness.

In this patient and in additional similar cases described in texts on ECT, the risks of precipitating a neuroleptic malignant syndrome precluded the prescription of haloperidol and other potent neuroleptic drugs to control behavior [70]. Benzodiazepines were preferred. While doses of lorazepam to 10 mg/day reduced manic and aggressive behavior, these did not relieve delirium. ECT, however, effectively resolved the delirious syndrome in each case. We had been encouraged to apply ECT in delirious patients by reports published in 1952 by the Austrian clinicians Otto Arnold and H. Stepan [115]. They were faced with patients with the life-threatening condition of malignant catatonia, and lacking any effective treatment risked the use of ECT. To induce grand mal seizures in acutely ill moribund patients was counterintuitive. Yet, 16 of 19 delirious patients survived when they were treated with ECT within 5 days of the onset of the illness; of the 14 whose treatment had been delayed, none survived. Daily ECT and up to three seizures a day were necessary to relieve the more severe conditions.

Although such published experiences were few, ECT became the accepted treatment. Not all the cases were associated with neuroleptic drugs, although these were the more common forms of physician-induced deliria [116-118].

In the French literature, a dreamy, stuporous syndrome is described as onirisme (translated as oneiroid state, oneiroid syndrome, or oneirophrenia) [119]. In a short delightful 1950 text, Ladislas Meduna, the developer of convulsive therapy, described such patients in sufficient detail to identify their syndrome as a form of malignant catatonia [120]. He distinguished the syndrome from schizophrenia and reported 64% full remission with ECT.

The cause of delirious mania is unknown, but the syndrome is often preceded by an acute infection, a traumatic incident or poisoning [121-123]. As delirium dominates the story, the connection to a prior illness is usually overlooked. A connection to bipolar disorder or manic–depressive illness is often assumed, but is rarely confirmed by the patient's history. Considering delirious mania as a form of catatonia rather than as a form of bipolar disorder offers a bridge to quick, effective relief with catatonia treatment.

The sudden appearance of delirious mania in a public place has been hazardous. One example, as described by Edward Shorter, is that of a non-English-speaking immigrant from Poland upon his arrival at a Canadian airport. Confused by the requirements of customs control, he could not find his mother whom he expected to meet. He became increasingly agitated, sweating, dehydrated, and aggressive. Police were called and sought to control his behavior by electric taser applied ‘… up to four times; he fell to the ground screaming and convulsing, and minutes later was dead’ [124]. Similar experiences dot the literature [125].

Toxic serotonin syndrome

Occasionally, an acute febrile and toxic reaction mimicking NMS follows the administration of drugs that affect the brain's serotonin system. In 1994, a woman was admitted to University Hospital at Stony Brook with the motor and vegetative signs of NMS. She had not been exposed to neuroleptics but had been treated with serotonergic drugs.

A 59-year-old married woman with a 21-year history of psychiatric disorder and three prior hospitalizations for agitation, mood swings, and psychosis was admitted to hospital following the addition of a single 25 mg dose of nortriptyline to a regimen of l-dopa and trazodone. The l-dopa was prescribed for signs of parkinsonism after many years of neuroleptic treatment. Trazodone was prescribed as an antidepressant of the serotonin antagonist and reuptake inhibitor class.

Within 5 h she became fearful, tremulous, sweating, and incontinent of urine. The systemic signs persisted with waxing and waning of motor restlessness, rigidity, and tremors. Four days later, she became confused and reported episodes of explosive diarrhea.

At the psychiatric emergency room, she was mute, rigid, sweating, and tremulous with rapid heart rate and elevated blood pressure. A single 1 mg intravenous dose of lorazepam was administered, without benefit. On admission to the psychiatric unit, she was afebrile, her posture was rigid and she did not obey simple commands. In the absence of exposure to neuroleptics a toxic serotonin syndrome (TSS) was diagnosed. Treatment with lorazepam did not offer relief. ECT was begun and a day after the first treatment, motor rigidity, mutism, and negativism became more prominent, and additional lorazepam was prescribed. The afternoon of her second treatment, motor rigidity and mutism were gone, she was more interactive and responsive, denied hallucinations, and attended unit activities. Three additional treatments resolved the psychosis, depressed mood, agitation, and motor and vegetative signs [126].

Her condition met the diagnostic criteria for the toxic serotonin syndrome (TSS) [127]. Serotonergic drugs are used widely to relieve depressed mood and may precipitate an acute febrile syndrome of twitching muscles, tremors, diarrhea, and mental changes. Such states follow a rapid increase in dosing or when a selective serotonin reuptake inhibitor (SSRI) is combined with a monoamine oxidase inhibitor (MAOI).

Patients become restless and sleep poorly, their sensorium is altered, the skin is flushed, and they complain of sweating, tremors, shivering, lethargy, salivation, nausea, diarrhea, and abdominal pain. Laboratory tests of body functions show signs of acute toxicity. Temperature and blood pressure are elevated, tendon reflexes are hyperactive, movements ataxic, and myoclonus appears. The ‘big picture’ is of a malignant catatonia/neuroleptic malignant syndrome with gastrointestinal symptoms [128-133].

Although most patients respond rapidly to withdrawal of the offending medicines and supportive care, ECT has been used successfully [134, 135]. The overlap in diagnosis of TSS and NMS is shown in a report of the calls to the NMS Information Service, an expert Internet referral service [136]. Of 29 calls requesting information about NMS, the symptoms of 22 (79%) met criteria for TSS and 25 (89%) met criteria for NMS [137]. The authors concluded that NMS and TSS are syndrome variants of malignant catatonia, a conclusion supported by their rapid relief by benzodiazepines and by ECT.

The pediatric catatonias

For many years, catatonia was not considered to exist in children and adolescents. Now we know differently. It was hidden under the global diagnosis of schizophrenia and the labels of stupor and catalepsy (muscular rigidity and fixity of posture regardless of external stimuli and decreased sensitivity to pain). The authoritative incorporation of catatonia as schizophrenia by Emil Kraepelin and Eugen Bleuler, as we have seen, blocked consideration of catatonia in other conditions. A detailed history by Edward Shorter of the vagaries of catatonia in children relates the various ways that catatonia has been regarded by psychiatrists. Often, catatonia has been hidden under diagnoses of encephalitis lethargica, hysteria, hebephrenia, schizophrenia, and, lately, autism [138].

Few childhood disorders were recognized in early psychiatric classifications and are usually defined as schizophrenia, mental retardation, and tics and mutisms. In recent classifications, conduct and attention deficit disorders have been added. In DSM-IV, what had been known as ‘mutism’ became ‘elective mutism’ and then ‘pervasive refusal syndrome’; echophenomena and stereotypy were relabeled ‘Tourette's syndrome’ or ‘obsessive–compulsive disorder’ (OCD); posturing and negativism were associated with ‘autism’ or ‘autism spectrum disorders’; and tantrums and excited states labeled ‘emotional behavior disorders’ or ‘conduct disorders’. No one of these behaviors is well defined, and for none has either an effective treatment or an understanding of the underlying pathophysiology been developed. When catatonia has been recognized, however, it has been possible to relieve the symptoms with treatments for catatonia [139]. Here we discuss the experience with children suffering autism spectrum disorders and mental retardation in whom the connection to catatonia is well defined; in the next chapter, we discuss other pediatric syndromes that meet criteria for catatonia and warrant further study.

Autism spectrum disorders

Autism, a disorder of socialization and speech with an onset in early childhood, was brought to professional attention by Leo Kanner in 1943 [140] and by Hans Asperger in 1944 [141]. They described children with delayed maturation, poor socialization, and a plethora of repetitive behaviors. Much debate ensued as to the distinction between childhood autism, mental retardation, and childhood schizophrenia. ‘Mainstreaming’ the education of these children, increased information on the Internet, and the rise of active parent organizations have established autism as a diagnosis for which special support is provided by many American school services. Children are offered aides in classrooms and psychological assistance and speech therapy at home. In communities with benefits for the children and their families, the number of children labeled ‘autistic’ has risen rapidly with recent estimates running as high as one of every eight children [142]. Severity of illness ranges from children who can be maintained at home and in community schools to those who require highly specialized institutional care.

Autism is marked by mutism, echolalia, echopraxia, odd hand postures, freezing of ongoing movements, rigidities, forced vocalizations, stereotypy, self-injurious behaviors, and insensitivity to pain. All are signs of catatonia. Two formal surveys find catatonia in 12–17% of adolescents otherwise labeled with autism [143, 144]. Although we lack systematic studies identifying and treating catatonia in autism, case reports now dot the literature indicating instances of relief for even the most severely ill [139, 145]. Children who are bound to their home, unable to participate in regular schooling, are relieved of their repetitive behaviors, especially those who are injurious to self and aggressive to their families. The behaviors are self re-enforcing and result in bodily harm with bone fractures or the loss of eyes, teeth, and fingers. Here is one of many case reports from the Stony Brook University Hospital:

A 14-year-old intellectually disadvantaged boy was admitted for persistent head-banging, which required him to wear a protective helmet and be restrained most of the day. Donald's mental age was measured as 4.3 years. He communicated by guttural sounds. The unusual behaviors began at age 10 and persisted despite various medications and both positive and negative reinforcement treatments. He wore large gloves in addition to the helmet, and was sedated to control his high-pitched wailing and prolonged screaming. After 4 years of failed treatment, Donald was evaluated for ECT. On admission to the hospital, examination found no bodily disorders to preclude further treatment. Consent was obtained from his legal guardian.

After the sixth of twice-weekly ECT, screaming, scratching, and head-banging were reduced. By the 10th treatment, Donald no longer needed the helmet, gloves, or restraints. Treatments were reduced to once weekly, and after 16 treatments he was returned to his residence. For another 2 months, treatments were given once every 2 weeks and then stopped, because the psychiatrists were satisfied with his progress. Anticonvulsants were prescribed and he participated in group activities without restraints or life-threatening behaviors [146].

Other reports cite the successful relief of catatonia in a child with Down syndrome [147], in autistic twins [148], and in malignant catatonia in an adolescent with a cerebellar malformation from birth [149]. Another report cites two adolescent patients with tics successfully treated with ECT [150]. The successful relief of self-inflicted injuries in youth with autism spectrum disorders is increasingly recognized [151-154]. While some relief occurs with high doses of lorazepam, ECT is more effective [155, 156]. The immediate changes are dramatic, and the benefits become persistent when treatments are continued over many weeks.

Another example of successful treatment is related by Dr. Lee Wachtel, the medical director of the Neurobehavioral Unit at the Kennedy Krieger Institute in Baltimore, Maryland.

Robert was the product of a full-term pregnancy and spontaneous vaginal delivery. Developmental milestones were within normal limits for the first 15 months of life, when he stopped interacting with others and lost acquired speech. A pervasive developmental disorder was diagnosed and he began intensive early intervention services at a private clinic, lived at home, and attended a specialized school for the next 15 years. He was estimated to have attained upper elementary school skills; at his best, he was learning the names of European capitals and completing multi-digit multiplication.

At age 14, Robert evinced grunting and other abrupt vocalizations, progressing to repetitive rocking, lunging, head shaking and finger flapping, multiple stereotypies and hair-combing echopraxia. The symptoms waxed and waned for the next 3 years. He continued to attend school.

Three years and 5 months after symptom onset, Robert suddenly stopped eating and required manual feeding by others. Food spooned onto his tongue would remain for several minutes until extensive prompting evoked swallowing. He lost about 50 lbs in weight in the next few months. Rigid posturing occurred intermittently throughout the day, particularly evident at mealtimes when utensils would remain suspended in his hand in the air, or he would clamp down so forcefully that staff members feared breaking his jaw to pry out the utensils. Periods of stupor, slow gait and shuffling steps became frequent. Aggression and self-injury ensued. Unprovoked physical attacks of his family and staff members necessitated physical holds frequently using canvas belts for limb immobilization. Self-injury included frenetic twisting movements of fingers deep into the nares, self-biting of hands, arms and tongue with wound formation. He was no longer able to attend school or to leave his home.

For lack of local inpatient services, Robert was only hospitalized 7 months after these symptoms began. Prior to hospitalization his days were spent sleeping from 4 am to 10 am, then lying or crouching unresponsive in his bed requiring full care in toileting, bathing and feeding, until early evening when agitation, self-injury, aggressive episodes, leaping, lunging, jumping, screeching and nonsensical vocalizations would commence.

Local psychiatric and neurological assessments offered no diagnosis or treatment. Extensive laboratory and imaging studies were within normal limits. Olanzapine 30 mg daily (a neuroleptic) was prescribed leading to further deterioration. Lorazepam 3 mg/day yielded mild improvement. Self-injury escalated to the frank loss of oral tissue and tongue bleeding.

Robert was admitted to hospital in January, 2012 with a diagnosis of delirious mania/agitated catatonia, and commenced ECT 2 days after admission. ECT thrice weekly was pursued with standard methohexital sedation, succinylcholine muscle relaxation, and bilateral electrode placement. Within 2 weeks self-injury, aggression and agitation ceased, (with the exception of a few episodes of slapping when redirected from masturbation) but other motor, vocal and behavioral symptoms of catatonia persisted. Tissue wounds healed.

ECT frequency was increased to 4–5 times weekly for the next 2 weeks, which led to overall symptom resolution. Lithium monotherapy was begun with ECT thrice weekly and Robert showed consistent improvement despite waxing and waning of symptoms.

On evaluation after ECT #26, Robert independently walked into the room at a normal pace, waved to the doctor, greeted her by name, and then began to read out loud from a book. He answered multiple questions with minimal hesitation in the same sing-song cadence he had demonstrated from an early age. He interacted appropriately with his mother and caregiver and independently selected multiple songs and videos on his IPad, deftly using the touch screen. The only abnormal physical movements observed were brief episodes of finger flapping. His father said that ECT ‘had released Robert from the shackles of Hell’.

At the time of writing Robert had received 44 treatments and was in the maintenance ECT phase with gradual tapering of the frequency. Medications included lithium 600 mg BID with a serum level of 0.8 meq/l, lorazepam 2 mg TID, and memantine 5 mg BID. Robert was still unable to transition to home for lack of appropriate ECT services in his home area.

An interesting feature of this boy's history and that of numerous other similar reports is the gradual onset of catatonia in childhood and then a rapid escalation during adolescence. Because ECT carries a heavy burden of stigma, however, families are extremely reluctant to consider ECT, despite the persistence of abnormal behaviors, poor maturation, and poor socialization. Parents who agree to treatment insist that only a minimum number of treatments be applied, withdrawing consent at the earliest favorable change. We now know that successful relief requires ECT continuation treatments. With effective care, adolescents are able to remain at home as a participating family member, manage their daily self-care, and participate in schooling and social activities.

Mental retardation

Before the recent enthusiasm for the autism diagnosis, patients with the same symptoms and signs of delayed speech and learning, poor socialization, and peculiar movements were labeled as suffering from ‘mental retardation’. Labels are sensitive to social acceptance and undergo change when they are deemed offensive. ‘Intellectual disability’, ‘intellectually challenged’,’ mental handicap’, and ‘learning disability’ are alternative terms. For a time, the scores under 70 on intelligence quotient tests were a measure of severity. The labels of autism or autism spectrum disorders include many of these subjects as well as a cluster of patients with high intellectual capacities that are seen as having Asperger syndrome.

But like normal persons, they develop mood disorders, acute excitements, deliria, and catatonia. They were often prescribed neuroleptic drugs to control aggressive behaviors, and from time to time, the neuroleptic malignant syndrome was induced. But even when these signs would have recommended treatment with ECT, the recommendation was precluded by the belief that these children were already suffering brain damage and that ECT would worsen the condition. From time to time, clinicians would treat such patients with ECT, often successfully and without a worsening of the subjects’ communication or language skills. In 1999, we reviewed chart records for the diagnosis of mental retardation of the patients admitted to Stony Brook University Hospital. We had treated five patients from ages 18–64: two with depressive mood, two with NMS, and one with a toxic response to hallucinogens. All responded well to ECT without worsening of their intellectual abilities [157].

The treatment for catatonia in a woman with a life history of mental retardation was also safe and successful.

On admission Claudia appeared her stated age of 23, not speaking for long periods. She would assume postures imitating others or after the examiner moved her limbs. The catatonic signs were accompanied by screaming and aggressive outbursts; she often required physical restraint. She appeared depressed, refused to eat, and was incontinent. Her speech was not intelligible to us but was interpretable by her mother.

High doses of lorazepam diminished the catatonia signs, but depressed mood, excitement, and incontinence continued as before. When ECT was recommended, both parents signed the consent form. After two treatments, Claudia's mood and sleep improved, her appetite returned, she was tractable, and she responded to questions and directions. After the third ECT, catatonia was gone and her behavior was easily manageable. She was discharged to her parents’ home for continuation treatment with lorazepam and weekly ECT. She took part in a day treatment programme for patients with mental handicaps and required no additional medications. After 5 months, ECT treatments were discontinued and Claudia remained in the community with lorazepam as her principal medication. [146]

A recent literature review in patients with intellectual disability treated with ECT found 72 reports with positive outcomes in 79% of the cases [158]. The patients include disabilities from mild to profound. Transient complications were cited in 13% of the reports; these included memory impairment, drowsiness, delirium, and spontaneous seizures. Relapse occurred in 32% despite continuing treatment with medications. The reviewers discuss the under-use of ECT because of ‘diagnostic overshadowing’ – the presence of the label of intellectual disability prejudiced caretakers against consideration of ECT as riskful and brain damaging. A second hurdle was that of informed consent as the disability calls into play legal issues of guardianship, surrogate consent, and judicial consent.

At this writing, delirious mania (malignant catatonia) in all its variations, toxic serotonin syndrome, and many forms of pediatric catatonia are widely considered among the diagnosable and treatable catatonia disorders. These recent recognitions are positive outcomes of our appreciation that catatonia is readily found outside schizophrenia and that we now are able to verify the diagnosis and have effective treatments to validate the diagnosis. The next challenge is to consider other disorders as possible forms of catatonia.

Chapter 5: are these forms of catatonia?

That a new disease should be manifested at this advanced day, in the calendar of medical history, is not without many precedents. That such should occur in the great family of maladies involving the nervous system, would be the least improbable, when we reflect how less than all others these have been studied, comprehended and treated, until within a comparatively recent period.

Luther V. Bell, 1849 [68]

The recognition that catatonia is the treatable core of the neuroleptic malignant syndrome released catatonia from its steel-bound tie to schizophrenia and encouraged questions whether other psychiatric syndromes were better considered catatonia in disguise and be brought under the same treatment umbrella. The life-threatening syndromes of delirious mania and the toxic serotonin syndrome were the first to be appreciated as forms of catatonia. Next, the self-injurious behaviors that are commonly described in children and adolescents with autism spectrum disorders were found to be part of a catatonia syndrome that responded to ECT. But that was just the beginning.

Within the DSM-IV classification of psychiatric disorders are many entities that readily meet catatonia criteria – selective (or elective) mutism; Gilles de la Tourette's syndrome, vocal, and transient tic disorders; the neuroleptic-induced Parkinson syndrome; stereotypic movement disorders; and obsessive–compulsive disorder. For none are defined biological markers nor effective treatments known. These mutisms and stereotypical behaviors bear sufficient characteristics of catatonia to warrant re-examination as catatonia variants.

In the past decade, a new diagnostic entity of anti-NMDAR encephalitis has been enthusiastically promoted as a unique neuropsychiatric disorder. Although catatonia is recognized in 70% of the subjects so diagnosed, the connection to catatonia is not credited in the disorder's evaluation nor in its treatment.

And, among neurologic syndromes, akinetic mutism, the prolonged state of stupor and paralysis with apparent vigilance, has many characteristics of catatonia, such that exploring its relation to catatonia would be useful.

Gilles de la Tourette's syndrome (GTS)

In 1885, the French neuropsychiatrist Georges Gilles de la Tourette described nine patients with multiple tics (sudden, repetitive, non-rhythmic motor movements or vocalizations), echolalia (repeating words), and coprolalia (repeating scatological words), a cluster of behaviors that is now known as the Gilles de la Tourette's syndrome (GTS). [159]. It was distinguished around the same time that Karl Kahlbaum described catatonia and was one of many attempts to identify psychopathological conditions with predictable outcomes.

GTS has a childhood age-of-onset and persists to adulthood. Repetitive vocalizations, antisocial and inappropriate sexual acts, self-injury, and sleep disturbances are the principal features. In a systematic examination of 55 adults with GTS, 87% exhibited echophenomena, perseveration, staring, grimacing, posturing, mannerisms, and stereotypy [160]. The signs of autism and GTS overlap, and in many cases, the choice of diagnosis is in the eyes of the beholder and not in any distinguishing criteria [161].

No fully effective treatment is known. For mild tics, the behavior is tolerated and treatment is considered unnecessary. For more severe forms, both negative and positive behavior re-enforcement rituals are prescribed, but success is limited [162, 163]. Reductions in the number of verbalizations are reported with treatment with the neuroleptics haloperidol and pimozide [164]. Recent industry-sponsored studies of olanzapine find decreases in symptoms with greater reduction of tics compared with placebo treatment [165]. For the more severely debilitating forms of the illness, experimental deep brain stimulation has been tried with teasingly favorable reports. The studies lack proper controls, however, so are considered exploratory [166].

From time to time, tics have been so severe as to warrant trials with ECT. A PubMed review found 10 reports of modest relief. In an 18-year-old man with depressed mood, facial tics, grimacing, repetitive hand-washing, and self-injurious behavior, ECT resolved both the mood and the tic disorders, a benefit that was sustained over the next year. When treatments stopped, he relapsed, but when ECT was re-instated, the tics did not return and he continued symptom-free while attending college. In the same review, the tics and self-injurious behavior of a 19-year-old autistic man were reduced but not fully relieved with ECT [150].

Another example comes from my own experience. A 64-year-old widowed woman with recurrent episodes of depressive illness relapsed with repetitive scatological expressions in response to any query. The tics disappeared quickly with ECT [167]. Individual case reports of the relief of GTS with ECT are frequent [168-172].

For all the similarity of GTS and catatonia – many descriptions of GTS meet the criteria for catatonia – reports of treatment with benzodiazepines are surprisingly sparse. When the benzodiazepine clonazepam was introduced to clinical trials, reductions in symptoms were reported [173-175]. The lack of interest in such experimentation is particularly surprising considering the persistence of GTS and the failure of recommended treatments. Given the safety and efficacy of benzodiazepines, further study of GTS as a form of catatonia certainly is warranted.

Elective mutism and pervasive refusal syndrome

In 1991, four young British girls between 9 and 14 years of age were described as suffering ‘a potentially life-threatening condition manifested by profound and pervasive refusal to eat, drink, walk, talk, or care of themselves in any way over a period of several months’. The children required nasogastric tube-feeding and spent such prolonged periods in bed that they were ‘occasionally requiring manipulations of the joints under general anesthetic to prevent contractures’ [176]. They eventually recovered after extended periods of hospital care.

The cases were labeled ‘pervasive refusal syndrome’ [177]. Since then <30 additional cases are cited in the literature, with a 3 : 1 ratio of girls to boys [178-180]. None of the reported cases had a fatal outcome, although each required prolonged hospital care. In the few patients who have been the subject of long-term follow-up, the recovery has been complete.

In discussing the four cases, Brian Lask and his colleagues specifically consider the diagnoses of anorexia nervosa, elective mutism, post-traumatic stress disorder, and stupor, but they do not list catatonia [176]. Yet, the children exhibit mutism, negativism, posturing, and rigidity and require parenteral feeding for survival. These are cardinal signs of catatonia, but no catatonia treatments had apparently been tried.

Separately, in one patient in Ireland, a diagnosis of catatonia was formally considered in an 11-year-old girl. Video images of her behavior clearly met the criteria for catatonia, but her parents refused a benzodiazepine treatment trial. She recovered after 18 months of nursing care in hospital [181].

Dirk Dhossche, a child psychiatrist in Jackson, Mississippi, has looked further into similar cases, applying the present criteria for catatonia. He describes children and adolescents diagnosed with childhood disintegrative disorder, Kleine-Levin syndrome (a disorder of excessive eating and sleeping), Prader–Willi syndrome (a disorder of low muscular tone, small stature, and incomplete sexual development), tic disorder, and autoimmune encephalitis as examples of catatonia [182]. In each case, the illness resolved safely once it was recognized and treated with benzodiazepines and ECT. The frequency of catatonia in such a wide range of child and adolescent disorders indicates that pediatric catatonias are not rare, particularly in eponymous disorders that are a principal part of pediatric medicine. Dhossche also cites deprivation, abuse, and trauma in the etiology of pediatric catatonia [183] and presents examples of catatonia among asylum-seeking children in Sweden [184, 185].

As with other pediatric syndromes that are poorly defined and difficult to treat, it behooves clinicians responsible for patients with persistent and severe forms of mutism to consider the connection to catatonia. But too few do so.

Anti-N-methyl-d-aspartate receptor encephalitis

Limbic encephalitis, an acute neurological disorder, was first described in the 1960s as a ‘paraneoplastic condition’ – one resulting from tissue changes induced by tumors that stimulate a form of self-poisoning. It is considered an autoimmune disorder, a condition in which the immune system mistakenly attacks and destroys healthy body tissue. More than 80 different autoimmune disorders are described in the medical literature. The pathophysiology is poorly understood, and the treatments are empiric and of limited efficacy.

The presumed connection to tumors sends patients to whole-body searches, but the syndrome is also accepted as a diagnosis without finding a tumor. In normal life, various tissue receptors, one of which is the n-methyl-d-aspartate receptor, are part of the body's natural physiology. In the words of enthusiasts, an ‘anti-NMDAR encephalitis’ reaction is present in patients who develop:

… an acute multistage illness that progresses from psychosis, memory deficits, seizures and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements and autonomic and breathing instability.

About 70% of patients have prodromal [early onset] symptoms consisting of headache, fever, nausea, vomiting, diarrhea or upper respiratory symptoms. [The psychiatric syndrome] … follows within a few days or a few weeks with a rapid disintegration of language, from reduction of verbal output and echolalia [and echopraxia] to frank mutism.

The initial phase of the illness is usually followed by decreased responsiveness that can alternate between periods of agitation and catatonia … [with] autonomic movements and autonomic instability… [186].

The descriptions readily meet the criteria for catatonia – disturbances of behavior marked by ‘unresponsiveness with catatonic features’, a febrile course, followed by ‘reduction in verbal output and echolalia to frank mutism’, followed by ‘periods of agitation and catatonia’, in which ‘patients resist eye opening but show … no response to painful stimuli’. Although experience with the syndrome is limited, the descriptions clearly fit within the present conception of catatonia as a systemic syndrome unrelated to psychosis and schizophrenia.

A 2008 case report in the New England Journal of Medicine describes a 26-year-old woman admitted for headache, behavioral changes, abnormal movements, and mutism of 7 weeks’ duration. After extensive laboratory test examinations, an anti-NMDAR encephalitis was diagnosed. Throughout her illness, signs of catatonia were recorded but neither recognized as such nor treated. An ovarian teratoma was found, surgically removed under anesthesia, and the syndrome resolved within a day. Was the removal of the tumor or the anesthesia the therapeutic agent? The rapidity of the resolution and her course favor the relief of catatonia from the sedation [187].

Another report, this one in the American Journal of Psychiatry, described a 16-year-old boy with protracted stupor, psychomotor retardation, mutism, posturing, stereotypical movement, refusal to eat and drink, and episodic agitation [188]. A positive blood test supported an anti-NMDAR diagnosis. No clear medical or toxic cause was found, nor were any of the prescribed psychotropic medications or immune therapies beneficial. The presence of catatonia was not recognized; as a consequence, no consideration was given to its treatments. Instead, after treatment with haloperidol and other antipsychotic agents, the symptoms worsened. The syndrome eventually abated with nursing care with the patient slowly returning to baseline function 7 months after the onset of symptoms. The failure to recognize catatonia or to consider its treatment was criticized as a disservice to the patient as well as unnecessary trumpeting of a poor clinical lesson [189].

The diagnosis of anti-NMDAR encephalitis depends on a specific positive serum or cerebrospinal fluid antibody test [186]. When the diagnosis is considered, much interest is paid to the coexistence of encapsulated teratoma tumors. The recommended treatments are tumor resection and non-specific immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) or immunotherapy medications (rituximab or cyclophosphamide).

A report of 100 cases of this syndrome exquisitely describes the signs of catatonia in the patients, but neither catatonia nor its treatments are discussed [190]. Case reports now dot the literature with most patients being female and with resolution after resection of ovarian teratomas when found. But the syndrome is also reported in males and among many patients without evidence of tumors [191].

The heightened enthusiasm for this diagnosis is reflected in an Editorial in the British Journal of Psychiatry in April 2012 calling for laboratory tests for anti-NMDAR encephalitis in ‘all individuals with a first presentation of psychosis, or people with psychosis and features of autonomic disturbance, movement disorder, disorientation, seizures, hyponatremia, or rapid deterioration … with the possibility of antibody-mediated encephalitis in mind’. The recommendation continues: ‘This assessment should include, as a minimum, a neurological and cognitive examination and early serum testing for antibodies against the NMDA receptor and voltage-gated potassium channel. All patients testing positive for these serum antibodies should be referred to neurological centers with expertise in managing these cases’ [192].

Support for the suggestion followed quickly with the unproven assertion that ‘NMDA receptor antibody encephalitis is a condition that responds to immunotherapy’ [193]. Such a recommendation is inconsistent with good medical practice, however, as the diagnosis directs attention to a treatment that has not been proven effective.

The popular enthusiasm for this diagnosis is illustrated by the rapidly increasing case report literature. The initial references to anti-NMDAR encephalitis cited in PubMed are dated 2007. By September 2011, 68 reports are listed with 2 coauthored by Josef Dalmau; by February 2012, the number has increased to 126 with 32 by Dalmau; and by October 24, 2012 the number of reports had increased to 166 with 40 co-authored by Dalmau.

Considering these cases as examples of catatonia is verified by the reported efficacy of ECT, cited in reports in five patients [194-197]. One example is described [198]:

An 11-year-old girl became uncooperative, confused, and agitated with slurred speech and hallucinations after an upper respiratory tract infection. She was admitted to the hospital with a diagnosis of acute psychosis and was prescribed a low dose of the atypical neuroleptic risperidone with little effect. After administration of chlorpromazine for agitation, she became febrile, with rapid pulse rates and body rigidity. Malignant catatonia was diagnosed, and a course of ECT was begun. After eight treatments she resumed normal functioning. Ongoing abdominal complaints prompted ultrasound and abdominal CT that revealed an ovarian tumor. Surgical removal of the ovarian teratoma may have contributed to the full recovery of the patient. Absent controlled studies, however, proof for this conclusion is lacking as the patient had already achieved near remission after an intensive 2-week course of ECT.

Clinical accounts of patients suffering from autoimmune limbic encephalitis commonly describe catatonia, but the syndrome is seldom so labeled nor are the effective treatments attempted. As catatonia is present in a majority of patients and we lack evidence of a specific treatable pathophysiology, it is prudent to consider catatonia in the differential diagnosis and offer its tests and treatments.

Obsessive–compulsive disorders

Obsessive–compulsive disorder is characterized by repetitive thoughts and persistent motor acts that interfere with normal life. The behaviors are similar to those of GTS except that the expressions are not scatological and onset occurs later in life. It is a persistent disorder for which no effective treatment is known. Suggested treatments, which vary with the severity of the symptoms, fill the full range of psychotherapy, negative and positive behavioral conditioning, medications, deep brain stimulation, and surgical ablation of brain regions. Historically, OCD has been interpreted as an anxiety disorder, and the syndrome is classified in the DSM under this umbrella. But the treatments for anxiety disorders are not effective in OCD, which throws the association into question.

Patients diagnosed with OCD exhibit signs of catatonia [199, 200], and when these patients have been treated with clonazepam [201-203] and with ECT ([204-208],) benefit has been reported. My personal experience is similar.

Faced with a severely incapacitated 24-year-old man with inability to leave his room, feed or toilet himself because of checking actions, a trial of ECT was undertaken, using a standard ECT protocol. After 2 weeks, the checking was reduced and he was able to leave his room, feed and care for himself. After 3 weeks, he left the ward and went to a meal at a restaurant accompanied by his mother. After 5 weeks he was discharged with a prescription for the selective serotonin reuptake inhibitor clomipramine. He was able to care for himself for 2 months and then the checking returned. A second ECT trial was less effective.

An additional seven patients I treated showed short-term benefits. Because we had not developed a protocol for out-patient ECT, we did not examine the merit of continuation ECT in these cases.

Considering the inefficacy of present treatments and the lack of understanding of the pathophysiology of obsessive–compulsive disorder, greater attention to the role of catatonia and its treatments is surely warranted.

Akinetic mutism

Neurologic texts describe patients who lie inert and mute, appear alert, and regarding the clinician by only moving their eyes. They may follow the movement of objects or be diverted by sound. Neither voluntary movements nor restlessness or negativism is seen. A painful stimulus may produce reflex withdrawal or no movement. Patients have to be fed and are incontinent of urine and feces [209]. They appear lifeless and may be mistaken for dead [124]. Initially labeled ‘akinetic mutism’, this condition has since been described under such names as ‘coma vigil’, ‘apallic syndrome’, ‘stiff-man syndrome’, ‘locked-in syndrome’, ‘encephale isolé’, and ‘stupor of unknown etiology’. The terms ‘vegetative state’ and ‘minimally conscious state’ are now used frequently. The symptoms differ little from those of the more severe forms of inhibited catatonia. Whether the subject is seen as a form of akinetic mutism on a neurologic medical service or as a form of catatonia on a psychiatric service is in the eyes of the beholder and not in any specific characteristic behavior [210].

Akinetic mutism was described in 1941 in a 14-year-old girl whose illness had lasted for 8 years. She experienced headaches localized over the left eye, disturbances in vision, and vomiting. A cyst had distended the third ventricle of the brain, and relief followed the removal of its fluid; permanent relief followed its excision [211]. Similar descriptions dot the medical literature in patients with tumors and blood vessel abnormalities in and around the brain's third ventricle and the basilar artery [212-218]. The stuporous state is thought to result from the direct structural involvement of the base of the brain [209]. States of stupor with the same neurologic signs are also found in the acute toxic states associated with hallucinogenic and other toxic drugs and in chronic infections [219-221].

Patients in chronic stupors or catatonia-like states form a portion of every chronic neurological medical service. When first seen, each patient is thoroughly examined for brain stem lesions, and when found, may be relieved medically or surgically. But in many cases, lesions are not found, and it is in such instances that the question arises whether the signs meet the criteria for catatonia.

One description of akinetic mutism describes the state as similar to that of catatonic schizophrenia. ‘In those catatonic schizophrenic states that simulate akinetic mutism, there is awareness, as these patients do have memory of the events happening during the catatonic state’ [213]. Another writer, discussing the range of etiologies, some with identified brain lesions and some without, noted: ‘Variations occur: the patient may be almost totally immobile and mute, or may have only a suggestion of hampering of speech and movement’ [208]. In each description, the signs of catatonia are among the physical signs noted in the examination, but because the accompanying behaviors, thoughts, or course are not those of schizophrenia, catatonia is not identified. The author of a detailed 1962 review of akinetic mutism and its symptoms from New York State Psychiatric Institute writes that these ‘simulate, in many respects, catatonic schizophrenia’ [214].

The following personal experience reflects the overlap between catatonia and one of the descriptive terms for akinetic mutism, that of a ‘stupor of unknown etiology’.

A 22-year-old woman, lying mute in stupor, not moving to sound or pinprick is seen in a bed filled with furry animal figures on the Neurology Service of an academic medical center. Her illness began a month earlier with acute malaise and somnolence followed by headaches and abnormal movements, and then a seizure. Medical and extensive neurologic examinations identified no cause, treatments for epilepsy were prescribed, with the diagnosis of record of ‘stupor of unknown etiology’. Plans for transfer to a long stay at a neurologic center were underway.

A psychiatric consultant suggested an intravenous lorazepam test to rule out catatonia. Within a few minutes of injection she opened her eyes, verbalized hoarsely, and then moved her hands to pick up an animal figure and to smile. Over the next few days increasing dosages of lorazepam resulted in some speech, and aided sitting, standing, and walking. With family consent, ECT was begun and after four treatments the patient was fully responsive, able to feed and care for herself, talking responsively. Within 2 weeks she was discharged to her home as recovered.

Early in the literature of this syndrome, relief was described by inducing phenobarbital coma [222]. Zolpidem brought back to life the motor movements and speech of a 48-year-old woman who developed akinetic mutism after a suicide attempt by hanging [223]. Failure to properly identify the locked-in syndrome as a form of catatonia in one instance resulted in a subject remaining in a paralyzed state for 16 years [224]. The tragedy of motor paralysis in a conscious state is not readily describable [225].

Descriptions of catatonia in the historical literature find many subjects at first believed to be ‘dead’ and their sudden revival fortuitously preventing their burial [124]. When a brain stem lesion is identified and is successfully treated surgically or medically, the outcome is determined by the site and pathology of the lesion and the efficacy of the treatments. But patients without an identifiable lesion who are residing on neurologic and medical hospital services in chronic care under any of the cluster of labels designating akinetic mutism warrant examination for catatonia.

We have explored the merits of separating catatonia from schizophrenia, seen its many clinical forms, and questioned whether other illnesses can be included under the catatonia umbrella. It is now useful to ask how the recognition of catatonia faltered and look at the recent developments that identify catatonia as an independent syndrome in the classification of psychiatric diseases. The process, while not complete, is well underway.

Chapter 6: classifying catatonia

The modern system of elevating every minor group, however trifling the characters by which it is distinguished, to the rank of genus, evinces, we think, a want of appreciation of the true value of classification.

Sir Joseph Dalton Hooker, 1855 [226]

How is catatonia recognized in psychiatric texts today? For a syndrome to be recognized, it must be identified in the classifications by a name, a description, and a coding number. Only then is it established as a disorder of professional interest. Two official classifications, the International Classification of Diseases (ICD) by the World Health Organisation [227] and the Diagnostic Statistical Manual (DSM) by the American Psychiatric Association [228], are mainstays of clinical recognition. The first classifications agreed on disease names and characteristics for statistical purposes of admissions, discharges, and deaths, but in the past half century, the labels have been increasingly used for selecting treatment, research studies, and physician and hospital payments. Guidelines for the prescription of treatments are tied to specific diagnoses. In evaluating the efficacy and safety of treatments, each subject is selected with narrow diagnostic criteria to assure homogeneity of the samples. As treatments are better defined, the payments for physician and hospital care are tied to specific procedures. Durations of hospital care can be matched against standard care experiences, allowing insurers and government agencies to evaluate the efficiency of treatment procedures and treatment teams. Indeed, the quality and applicability of the classification system is central to the concept of governmental control and insurance for health care.

When Karl Kahlbaum described catatonia, he saw many variations in the signs of the syndrome and in the associated disorders. He presented 26 cases that spanned a variety of illnesses, some that meet the present criteria for psychosis and mood disorder and some ill with the systemic diseases of tuberculosis and syphilis. As we have described, two decades later, Emil Kraepelin recognized catatonia just as Kahlbaum had described it. As Kraepelin shuffled his case record cards seeking patterns in the main signs, he saw catatonia in many instances, particularly in those who became models of dementia praecox. He also perceived catatonia among his other described diseases, in patients with manic–depressive insanity and with paranoia, but his belief that catatonia was a marker of dementia praecox dominated his writings. When Eugen Bleuler relabeled Kraepelin's image of dementia praecox as ‘schizophrenia’, he retained catatonia as its marker.

And there catatonia has lain, a marker for schizophrenia for a 100 years, in repeated editions of the official diagnostic classifications until the latest revision, the DSM-5, offers some relief.

The first Diagnostic and Statistical Manual of the American Psychiatric Association, published in 1952, designated catatonia simply as schizophrenic reactions, catatonic type. ‘These reactions are characterized by conspicuous motor behavior, exhibiting either generalized inhibition (stupor, mutism, negativism, and waxy flexibility) or excessive motor activity and excitement. The individual may regress to a state of vegetation’ [228].

The revision in 1968 (DSM-II) described two types of catatonia, both within the category of schizophrenia: ‘It is frequently possible and useful to distinguish two sub-types of catatonic schizophrenia. One is marked by excessive and sometime violent motor activity and excitement and the other by generalized inhibition manifested by stupor, mutism, negativism, or waxy flexibility. In time, some cases deteriorate to a vegetative state’ [229].

The third revision of 1980 mentioned catatonia under the classification ‘catatonic type of schizophrenia’ dominated by catatonic stupor, negativism, rigidity, excitement, or posturing [230]. By the time of this formulation, however, researchers had recognized many instances of catatonia outside schizophrenia, especially among the affectively ill.

For half a century, it was also known that catatonic patients responded well to barbiturates and to ECT, while patients identified as schizophrenic but without evidence of catatonia did not. Although members of the DSM-III committees were acquainted with this literature, they chose to ignore it [231].

Largely through the writings of intrepid catatonia scholars, the revision of 1994 (DSM-IV) added ‘catatonia secondary to a medical disorder’, a singular recognition outside schizophrenia [10]. For the mood disorders, a ‘catatonia specifier’ was added to encourage awareness of its possible association with mood disorders. The absence of a coding number, however, discouraged the use of a specifier term in diagnosis or in research studies. Literature searches now find few citations to a catatonia specifier.

These changes did not influence clinical practice. Catatonia was regarded as a sign of schizophrenia, and whenever catatonia was recognized, neuroleptic drugs were routinely prescribed even in patients showing no evidence of disturbed thought or speech.

Perhaps, the failure to recognize catatonia outside schizophrenia could be excused as the argument was lost in the growing cacophony of pleas by different constituencies. Each DSM revision expanded the numbers of principal diagnoses: DSM-I: 106; DSM-II: 182; DSM-III: 265; DSM-III-R: 292; and DSM-IV: 297 [232].

Recognition that the neuroleptic malignant syndrome (NMS) was more effectively relieved by benzodiazepines and by ECT, as we have seen, established catatonia as a well-defined syndrome outside schizophrenia. By 2003, Michael Taylor and I summarized the accumulated 130-year experience in Catatonia: A clinician's guide to diagnosis and treatment [11]. We argued that catatonia met the criteria for a distinct clinical syndrome; that the singular linkage to schizophrenia was not justified; that assigning catatonia to a separate DSM class in ‘a home of its own’ was consistent with the known experience; and that such a designation would optimize recognition and treatment [12].

Catatonia in DSM-5

In 2008, the American Psychiatric Association designated Work Groups of clinicians to examine the experience with the existing classifications and to recommend changes for a revision to be published as DSM-5 in 2013. Catatonia was assigned to the members of the Psychosis Work Group, still tying catatonia to the Kraepelin and Bleuler conceptual tradition, despite the extensive literature finding catatonia more often outside schizophrenia. As none of the Work Group members had been associated with the new learning on catatonia, any changes would necessarily be based on the effects of special pleadings from outside groups.

In 2010, 35 clinician–scholars, each with catatonia experience, joined together to urge simplification of catatonia as a unique, single diagnostic class and to discard the connection to schizophrenia [233]. The same-year child psychiatrists who had clinical experience with catatonia, especially among those patients with autism spectrum disorders, published their evidence in support of giving catatonia a classificatory home of its own [234].

Responding to these submissions, William Carpenter, the Psychosis Work Group chairman and editor of the Schizophrenia Bulletin, invited Michael Taylor, Edward Shorter, and me to argue the case for catatonia as an independent class [235]. He solicited comments from others [236, 237], and with these in hand, he published the responses and an overall critique by three members of the Psychosis Work Group [238].

In our submission, we reiterated the arguments for catatonia as an independent syndrome that we had documented in our writings of 2003 and throughout these essays [11, 12]. Patricia Rosebush and Michael Mazurek of the McMaster University in Canada had often written on the efficacy of benzodiazepines in malignant catatonia. They reported catatonia in about 10% of acutely ill psychiatric patients, only a minority having met criteria for schizophrenia. Among those with affective disorders, who comprise the largest subgroup of patients with catatonia, the catatonia signs typically resolve dramatically and completely with benzodiazepine therapy. Rosebush and Mazurek warned that failure to treat catatonia properly before administering neuroleptic medications increased the risk of inducing a malignant reaction. Establishing catatonia as a separate diagnostic entity, the researchers argued, would increase recognition of a treatable neuropsychiatric syndrome [236].

Gabor Ungvari, Stanley Caroff, and Jozsef Gerevich opined that catatonia was historically established, universally accepted as integral to schizophrenia, and the form should be retained. They cited the failure of benzodiazepines to relieve catatonia among chronic psychotic patients in Hong Kong. (ECT was not tried.) While these authors accepted that patients in stuporous catatonia did respond well to benzodiazepines and ECT, and could be distinguished from those with schizophrenia, the failure of patients with chronic catatonia to do so justified retention of catatonic schizophrenia as a unique entity in the classification [237]

Stephan Heckers, Tajiv Tandon, and Juan Bustillo, members of the DSM-5 Work Group, responded that a prominent position for catatonia would pave the way for better recognition of the syndrome, facilitate effective treatment, and catalyze studies of the neural and genetic mechanisms of catatonia. Although they encouraged better labeling of catatonia in the classification, they did not support the single designation. They see catatonia as a marker of other syndromes, of many entities in the psychiatric disease classification. They also noted that a single designation for catatonia would be beyond the limits of the charge given the Work Group [238].

These authors also offered the jarring note that ‘If such a consolidation does occur, it should likely be in the section on Psychotic Disorders because catatonia is a dimension of psychosis’ [238] Rosebush and Mazurek expressed the same conviction: ‘The majority of patients with catatonia have concurrent psychosis’ [236]. These assertions are beliefs, holdovers that catatonia is integral to schizophrenia for which the primary treatment is the prescription of neuroleptic drugs. Such association is unfortunate because many forms of catatonia are not accompanied by the delusions, hallucinations, and disorders of thought that characterize schizophrenia. Also, such patients respond to the specific treatments of catatonia without resort to those used in the relief of psychosis.

The proposed recommendations (Spring 2012)

Following consideration of various revisions, the latest proposal published on the American Psychiatric Association's DSM-5 Development website in May 2012 recommended [239]:

1. Catatonia as a type of schizophrenia is to be deleted.
2. The class of ‘Catatonia secondary to a general medical condition’ created in 1994 is to be retained.
3. A new class of ‘Catatonia Not Elsewhere Classified’ is to be created.
4. A catatonia specifier is to be added for 10 primary diagnoses with the coding of xxx.x5.
5. A list of catatonia signs is adopted from DSM-IV.

These recommendations were reviewed by the informal group of catatonia scholars in June 2012 and were endorsed as consistent with the ongoing experience. The elimination of the designation of schizophrenia, catatonic type, was hailed as necessary. The inclusion of a single class of ‘Catatonia Not Elsewhere Classified’ is responsive to the experience and publications repeatedly expressed by the catatonia scholars. It will serve the requests for a single catatonia term and do much to cut the tie between schizophrenia and catatonia.

The designation of ‘Catatonia Secondary to a Medical Disorder’ introduced in 1994 is to be maintained. The distinction between this label and that of Catatonia NEC is unclear, but the experience was considered insufficient to justify elimination. It is expected that the profession's experience will determine the relationship between these two diagnoses.

The designation of catatonia specifiers for 10 primary diagnoses sustains the secondary position of catatonia in the prior classifications. Whether such is necessary is unclear because as we describe in these essays, the recognition of catatonia identifies a syndrome for which effective treatments are known. Adopting a specifier model creates treatment dilemmas. For example, the present recommendations sustain a problematic inconsistency with a class of ‘Schizophrenia with catatonia specifier’. Is the prescription of a neuroleptic agent (the standard prescription for schizophrenia) to precede that of the benzodiazepine or are both to be prescribed simultaneously? We know that catatonia sets the stage for a malignant response when a patient is treated with neuroleptic drugs. Treatment consistent with the specifier label will subject patients to unnecessary risks.

For an excited and delirious patient with signs of catatonia, categorized as ‘Bipolar disorder with catatonia specifier’ is the treatment to be the commonly prescribed high-potency neuroleptic drug haloperidol for restraint, thereby risking a toxic response? Or is the effective prescription to be high doses of benzodiazepines and ECT, the treatments for catatonia? Or are both drugs to be prescribed simultaneously? Similar conflicts follow each designation of a catatonia specifier.

Despite these questions, the DSM-5 recommendation for catatonia as an independent syndrome not tied to schizophrenia corrects a long-standing error that has plagued patient care and clinical research for more than a century [235, 240]. The present recommendations are sufficiently broad to allow experience to refine the place of catatonia in clinical care. It may encourage clinicians to appreciate catatonia in the many syndromes cited in these pages, to do so early, and to offer the effective treatments that assure catatonia its unique place in medicine.

The changes recommended in the DSM-5 are impressive and are sufficient to significantly improve clinical diagnosis. With the known treatments, patient care will surely be improved. The main issue for these recommended changes will be their acceptance in guidelines for treatment and forthcoming textbooks. The known experience finds about 80% of the patients with catatonia respond to the benzodiazepines, but for the remainder, the consideration of ECT brings out the broad prejudice against its use, a prejudice that often blocks effective treatment.

Chapter 7: the fear response

Man's mind stretched to a new idea never goes back to its original dimension.

Oliver Wendell Holmes, Sr., 1859 [241]

How is catatonia related to other medical and psychiatric disorders? Catatonia usually has an acute onset and once expressed, persists for days, months, even years if not treated. It is as common in children and adolescents as it is in adults. Many forms are now recognized, some not ordinarily destructive but lethal when accompanied by fever and systemic distress. The behaviors are seen either as inhibited and retarded and regarded as stupor or as excited and aggressive and seen as delirium or delirious mania. Catatonia is mainly a disorder of body posture, movement, and speech, although some patients report intense anxiety and fear. Catatonia has not been traced to a defect in a single-body organ nor to a specific physiologic dysfunction. After catatonia is relieved, we see no residuals; it is as if the blackboard has been erased with a few smudges left at the corners. It is a behavior of the whole organism, more like waking and sleeping or like a child's crying.

The phenomenology is distinct from that of other psychiatric diagnoses. Some authors see catatonia as a common ‘end-state’ response to the feeling of imminent doom inherited from ancestral encounters with carnivores, an adaptation that has changed over the millennia of human development but remains a common feature of life [15]. In this ‘fear hypothesis’, catatonia is a whole-body phenomenon, and support for the hypothesis is found in the quick relief afforded by the anxiolytic qualities of drugs used to relieve its symptoms.

When Kahlbaum envisioned catatonia as a syndrome, he described his patients as ‘astonished’ or ‘thunderstruck’. The syndrome appeared ‘after very severe physical or mental stress … such as a terrifying experience’. He said that ‘the patient remains motionless, without speaking, and with a rigid masklike facies, the eyes focused at a distance … devoid of any will to move or to react to any stimulus’. He continues: ‘The general impression conveyed … is one of profound mental anguish, or an immobility induced by severe mental shock’ [13]. Citing fear as the central theme of the syndrome, Kahlbaum titled his book Die Katatonie, oder das Spannungs-Irresein, translated as Catatonia, The Tension Insanity.

A writer finds subjects who ‘lay like a log of wood, stretched out, able to behold with his eyes but unable to speak a word for several days’. ‘The malady occurs suddenly and he stops as if he were frozen, his eyes open, fixed and motionless’ [26]. On recovery, patients say that they desired to speak but were unable to do so, sensing impending doom. Persons in catatonic stupor are ‘frozen’, ‘petrified’, and ‘experience extreme fear’ [27]. They give the appearance of intense anxiety [28-30].

In discussing catatonia in children, the historian Edward Shorter cites an eighteenth-century French physician who ‘delayed the funeral services of a girl from the lower classes because her color had not changed at all. And she recovered a few hours later. The girl would already have been buried several times, if we had not been familiar with her attacks of hysterical vapors’ [138].

In a history of malignant catatonia, Shorter describes the progressively severe stages of catatonia, malignant catatonia, neuroleptic malignant syndrome, and delirious mania, the latter sometimes prompted by the horrors of war: ‘As the terrified civilian population of northern France fled the advancing German armies in 1940 … there was massive fear. Some of the worse afflicted found their way to the psychiatric hospital at Auxerre, where there were 17 cases of délire aigu [delirious mania], almost all with a fever and ending fatally’ [124].

In 1982, a perceptive Australian psychiatrist described four patients with systemic physical illness who exhibited catatonia in association with intense fear [242]. Although the patients were prescribed effective treatments for catatonia, recovery depended, he believed, on attention to and treatment of the psychological stressors. He regarded catatonia as regression to a primitive expression elicited by overwhelming fear.

In a systematic inquiry, Georg Northoff and his colleagues in Frankfurt, Germany, assessed the experiences 3 weeks after recovery of 24 patients (15 excited, 9 inhibited) who met the criteria of four or more catatonia signs [28]. The patients’ greatest fears were their inability to control their intense anxiety. They felt threatened and feared dying. They were less concerned about their lack of control of body movement or of self-care.

The association of the fear response with catatonia among children and adolescents with autism and with tics has recently been detailed by Dirk Dhossche. He reports deprivation, abuse, and trauma to be frequent in the expression of catatonia among them [148].

After cardiac surgery, immobilization reactions with the characteristics of catatonia have been encountered. One patient was ‘immobilized and almost like a statue’; another ‘was frozen and expressionless. She spoke barely audibly in a monotone with long pauses and made no spontaneous comments’. The postoperative reaction has been described as experiencing a catastrophe, the patients resembling ‘the photographed faces of survivors of civil disasters, and the countenances present staring and vacant expressions of seeming frozen terror. Immobile, apathetic, and completely indifferent to their fate, they respond to inquiries in monosyllables devoid of affect’ [243].

A one-person experimental study demonstrated the relation of catatonia to fear. A 42-year-old woman with a long history of recurring depressions was admitted to hospital for a recurrent episode. Treatment with the antidepressant maprotiline was discontinued, and the next day she was mute and stuporous. A single oral dose of 2.5 mg lorazepam relieved the stupor and the depressed mood, and she asked to be discharged. With her consent, an experiment was undertaken to verify the diagnosis of catatonia. She was given an intravenous bolus of 0.7 mg flumazenil, a benzodiazepine antagonist that blocks the receptor and reverses the actions of lorazepam. Almost immediately she became dizzy, nauseous, and anxious and feared impending accidents to family members. The fears quickly condensed to certainty, and within 2 min, she was again mute and stuporous and remained so for 2 h. She was treated with lorazepam and recovered. After the first treatment and reversal, the experiment was repeated with the same results. The patient was discharged from hospital with prescriptions for lorazepam and carbamazepine and remained well [244].

Seizures, whether naturally or experimentally induced, may immediately be followed by immobility and stupor. The sudden loss of consciousness, posture, and spontaneous motor acts with tongue biting and urinary wetting is a severely frightening experience. Consequences are often described as either rigid-catatonic or flaccid-cataleptic states that bear the characteristics of catatonia [245, 246].

Barbiturates and benzodiazepines that relieve anxious depression also relieve catatonia, an experience that, as previously noted, is consonant with the fear hypothesis. The rapid effect of these agents is demonstrated by reports that administering parenteral lorazepam to mute and negativistic patients en route to MRI or EEG laboratories makes them cooperative and talkative for the procedure.

Tonic Immobility

These diverse human experiences are found in animals described as ‘tonic immobility’ and ‘negative conditioning’. Tonic immobility is the elicitation of a fixed posture, usually rigid, that is elicited by quietly holding an animal down, slowly stroking, and then gradually releasing the hold. The animal remains immobile with limbs in the unusual postures that they are placed. The phenomenon is demonstrated in chickens and other fowl, frogs, snakes, guinea pigs, and rabbits [247]. A tradition of pretending to be dead is described as the behavior of the Virginia opossum – ‘playing possum’, as it is described in childhood play [248].

A loud noise terminates the imposed posture. The duration of the pose is lengthened when preceded by a frightening stimulus such as loud noise, electric shock, adrenalin injections, or simulated predation as when a chicken is held under the head of a model of a Cooper's Hawk for 15 s before immobilization. The duration is shortened in a dose-related fashion by pretreatment with tranquilizers that sedate and inhibit fear [247].

Intense fear is pictured as the evolutionary basis for both tonic immobilization and for catatonia. Recognition that catatonia is present in 10% of acutely ill psychiatric inpatients, that it is relieved by the potent anxiolytic drugs, and that patients give the appearance of intense anxiety, led the New Zealand psychologist Andrew Moskowitz to propose that catatonia is ‘a relic of ancient defensive strategies, developed during an extended period of evolution in which humans had to face predators in much the same way many animals do today and designed to maximize an individual's chances of surviving a potentially lethal attack’ [15].

Among the defenses of prey animals are flight, fight, and dissimulation. Flight is stimulated when the predator is seen at a distance; fight is an option when escape is not possible; and hiding, dissimulation, and lack of movement are encouraged when the predator is at a distance that would permit not seeing an immobile prey. The core catatonic symptoms of stupor, mutism, and immobility can be linked to tonic immobilization.

Fear conditioning, a form of emotional learning that connects a neutral stimulus to one eliciting fear, also suggests a link to catatonia. Repeated exposure to a neutral stimulus (e.g., ringing of a bell) with a painful shock stimulus ties the stimulus and response together so that ringing the bell elicits physiologic autonomic changes (e.g., catecholamine release from the adrenal medulla and sympathetic nerves) and endocrine release (e.g., glucocorticoids of the adrenal cortex) [249].

The most compelling daily life images of immobility in the face of intense fear are reported in accounts of rape assault. The actress Kelly McGillis presented a detailed description of being assaulted and raped by two men in an article on the film The Accused, noting that, although she was conscious, crying, and screaming, she was unable to move [250]. Studies of tonic immobility during rape and assault describe intense fear, inability to move, and perceived physical restraint [251, 252]. Fear-induced freezing is also reported in military disasters and in urban violence [253].

Cyber bullying, the sending of hostile denigrating messages through social media, is an increasing stressor among adolescents, severe enough to lead to withdrawal from school, hospital care, and suicide. A 14-year-old girl without prior psychiatric history was admitted to hospital with anxiety, tearfulness, and insomnia, which matured to an oneiroid state with mutism, immobility, waxy flexibility, posturing, and negativism. Treatment with daily ECT relieved the condition in 2 weeks [254].

The experiences with tonic immobility are relevant to our understanding of post-traumatic stress disorders (PTSD). In an experiment, both normal and PTSD subjects related their most disturbing experiences, and the stories were recorded and edited into 100-word scripts. A script was then read to the subject standing on a platform that measures body sway. The record of the sway is broad in normal subjects but very narrow in PTSD subjects reflecting increased immobility [255].

If tonic immobility is a human phenomenon, we would expect the signs to occur in patients with panic disorders. In a questionnaire study of 1118 community-based subjects with a history of panic attacks, 18% reported being immobilized ‘always’, 36% ‘sometimes’, and 16% ‘rarely’ during their attacks [256].

These many diverse experiences and descriptions encourage attention to the role of fear in our image of catatonia. Stupor, rigidity, posturing, and mutism are behaviors that are analogous to tonic immobilization. Repetitive words and acts, posturing, and grimacing are dissimulations – attempts to appear other than oneself. A child's fear and discomfort stimulates crying that brings nursing, cuddling, and relief. Older children develop a repertoire of calls, screams, cries, postures, hiding, throwing, and breaking of objects to bring similar relief. Being mute and not responding brings desired attention. The behaviors may be active or passive, and for each, the caretakers and other children respond, and soon postures, grimaces, repetitive acts, repetitive speech, and withholding of speech become learned behaviors that elicit reassuring responses.

Catatonia may be regarded as a relic of the period in human history in which being prey for aggressive animals led to the same defenses that are seen in prey animals. Such imagery is consistent with the efficacy of the anxiolytic treatments of barbiturates and benzodiazepines. The efficacy of ECT in relieving catatonia is a puzzlement, however. We do not understand the mechanism by which induced seizures alter behavior, although a viable hypothesis considers the brain's release of neuroendocrine hormones in the course of the seizure as instrumental [257]. Such hormone studies have not been of interest to catatonia scholars. It would be timely to study the neuroendocrine action of the effective treatments now that catatonia is appreciated as a unique behavior syndrome.

Catatonia is an abnormal behavior that is identified by observation alone. Changes in movement, posture, and speech are sufficient to identify the syndrome. No damage to the body remains after recovery, indicating that the abnormal behavior is an exaggeration of the normal state. Such observations allow the view of catatonia outside the conventional causes of the body's systemic disorders and encourage its consideration as an inherited adaptive syndrome.

Chapter 8: L'envoi

The art of drawing conclusions from experiments and observations consists in evaluating probabilities and estimating if they are large and numerous enough to constitute proofs. The type of calculation is more complicated and more difficult than we think; it demands great sagacity.

Antoine Lavoisier [258]

The birth of catatonia as a concept in 1874 was followed by a stormy childhood. Within two decades, it was abducted into the concept of dementia praecox and was hidden, like Cinderella, for almost a century. Despite the miraculous fitting slippers of sodium amobarbital and induced seizures, the effective treatments devised in the 1930s that should have been liberating, the sequestration of catatonia within schizophrenia remained all but complete until the 1970s when catatonia was again reported in patients with mood disorders and in neurotoxic states. The recognition that the neuroleptic malignant syndrome was a form of catatonia that could be effectively relieved by its treatments opened clinicians’ eyes to catatonia outside Kraepelin's schizophrenia.

Recognizing catatonia in NMS revived our interest in the unique syndrome and taught us its signs. When we perceived the signs of catatonia among our delirious manic patients, we were able to treat them effectively and save lives. Cases of NMS in patients who had not been exposed to neuroleptics led to recognition of the toxic serotonin syndrome as a treatable example of catatonia. The association of catatonia in patients in excited delirious states and the remarkable efficacy of induced seizures and benzodiazepines for rapid relief brought delirious mania within the catatonia tent.

The recognition that self-injurious behavior in patients with autism and neurodevelopmental defects were signs of catatonia argued for treatment trials that were successful. Catatonia was next appreciated in the repetitive behaviors of patients with Gilles de la Tourette and other tic disorders, obsessive–compulsive disorder, anti-NMDAR encephalitis, elective mutism, pervasive refusal syndrome, and akinetic mutism. The evidence for viewing these disorders as forms of catatonia is sufficiently compelling to revisit their classification, clarify their diagnostic criteria, and test alternate treatment possibilities.

The immediate relief of catatonia by intravenous injections of benzodiazepines offered a useful biological marker that verified the clinical diagnosis. Treatment with high doses of benzodiazepines (followed by ECT when the medications failed) relieved catatonia as effectively as do the treatments for neurosyphilis today.

We see immediate benefits in identifying catatonia as a unique syndrome outside schizophrenia. Ever since its creation, schizophrenia has been pictured as an illness of disorganized thought and speech associated with delusions, hallucinations, and emotional flattening. When catatonia was incorporated within schizophrenia, its recognition led physicians to interpret their patients’ peculiar movements and speech as ‘psychotic’ even when thought disorder, emotional flattening, and the other signs of psychosis were not present. The physicians reflexively prescribed neuroleptic drugs as treatment. Little merit has been found in this association; indeed, as we have seen, such prescription is fraught with the risk of precipitating a malignant syndrome and even death.

Patients meeting the criteria of catatonic schizophrenia respond to ECT with relief of catatonia. In most instances, the relief is accompanied with a disappearance of the signs that were interpreted as evidence of psychosis. But patients with other forms of schizophrenia, the paranoid, disorganized, undifferentiated, and residual forms, respond poorly to ECT. The benefit in the relief of catatonia clearly accrues to the signs of catatonia and not to those of schizophrenia.

In the first half of the twentieth century, catatonia was interpreted in psychologic terms, often labeled as ‘hysteria’. Once the syndrome was relieved by amobarbital and by ECT, however, a biological image took precedence. The efficacy of these treatments is now established, an experience that would be the envy of the clinicians who first recognized catatonia but whose knowledge provided no relief for their patients.

The appreciation of catatonia as an independent syndrome in clinical medicine is an example of the successful application of the medical model of diagnosis – the established method of disease identification by history, physical examination, laboratory tests, and validation by response to treatment [259]. Unfortunately, this medical diagnostic model is rejected for psychiatric classification and is replaced by an image match-up based on the main symptoms alone. After listening to the patient's history, the physician examines symptom checklists to find a comparable classified symptom pattern. No physical examination is made. No laboratory tests are applied. No reference to prior responses to treatments is considered. As a result, the DSM classification is a mélange of arbitrary and ill-defined labels, and each individual diagnosis is almost exclusively in the eyes of the beholder.

The melancholia error

Like the arbitrary classification of catatonia as a form of schizophrenia, melancholia is rejected in the DSM classification. Melancholia is a psychopathological syndrome that was well described throughout history, beginning in ancient Greek and Roman medical texts. In the 1850s, a circular insanity of severe depressions alternating with manic episodes was delineated by the French psychopathologists Jules-Gabriel Baillerger and Jean-Pierre Falret. Other authors confirmed their description, but it was the formulation by Emil Kraepelin of manic–depressive insanity that took hold and was appreciated throughout the twentieth century. In 1980, the DSM-III discarded the concept of a single illness of alternating phases and divided the mood disorders into ‘major depression’ and ‘bipolar disorder’. In splitting the disease entity by polarity, the classifiers sought to accommodate reports that the family patterns and the new treatments with anticonvulsants seemed to distinguish the entities. The label of manic–depressive reaction described in DSM-II was discarded, and melancholia was denigrated to a ‘specifier’ of mood disorders without a code number, thereby inhibiting its use [260].

Melancholia is a distinct identifiable syndrome with four consistent features [44]. The mood is of severe depression or mania or both. Suicide risk is high. Motor behavior is always altered with agitation and restlessness or retardation and stupor [261]. The vegetative signs of anorexia, weight loss, and insomnia are always present. And, cognitive inability to concentrate thoughts or recall memories is a common feature.

Extensive studies of cortisol, the adrenal gland hormone, find hypercortisolemia – elevated levels of cortisol in the blood – at the height of the illness and a return to normal levels with effective treatment and clinical relief. With relapse, the abnormality returns. Because systemic hormones exhibit diurnal rhythms, the abnormality is best measured by the dexamethasone suppression test, a measure of serum cortisol over 24 h. An abnormal test is considered a marker of melancholia and is used to verify the diagnosis [44].

Physiologic abnormality in melancholia is also reflected in abnormal sleep EEG studies and in dysfunction of thyroid metabolism. That melancholia is a specific form of mood disorder is reflected in its strong response to tricyclic antidepressants and to ECT, and the inefficacy of SSRI and SNRI antidepressants, various psychotherapies, and placebos [44, 262].

This error in the classification of melancholia parallels the error that plagued catatonia. Despite extensive writings justifying melancholia as a distinct medical syndrome [44, 261-264] and even pleadings [264], the members of the present DSM-5 Work Group on mood disorders have rejected any consideration of melancholia as a distinct entity. The present proposals for the mood disorders continue the classification much as developed for DSM-IV.

The position in the classification and treatment of the depressive mood disorders is reminiscent of the arguments that developed in the 1980s regarding the recommended treatments of the neuroleptic malignant syndrome. Once the syndrome was recognized as a toxic effect of neuroleptic drugs, the connection to the dopamine neurotransmitters was invoked and treatments with dopamine agonists recommended. It took two decades to replace the neurotransmitter model and treatment with that of catatonia and its specific treatment. Splitting the mood disorders according to the unipolar or bipolar model has yielded little benefit in either the understanding of mood disorders or effective treatments. The alternative model, that of melancholia as a defined entity with specific symptoms and signs, laboratory test evidence of cortisol abnormality as a diagnosis verifier, and rapidity of treatment response to tricyclic antidepressants and ECT as validating criteria, warrants better consideration in the classification.

The challenges

The relations of melancholia and catatonia is a challenge. The early reports of catatonia recognized its appearance in patients with disorders in mood, and the findings of catatonia among patients with manic and depressive mood disorders were the first awareness that the identity of catatonia with schizophrenia was false. As we have shown, patients with catatonia suffer intense emotions, often as severe as those with melancholia for which suicide is the major risk. Both catatonia and melancholia are rapidly resolved with ECT, suggesting an inherent commonality that is not understood and warrants exploration. Our lack of experimental evidence makes us believe that melancholia does not resolve with benzodiazepines or barbiturates and that catatonia does not resolve with tricyclic antidepressant drugs. But these assumptions are not secured by clinical trials; they may be wrong and testing is warranted. The neuroendocrine abnormality in melancholia is well documented, but that in catatonia is not. These questions need attention to clarify the relationship between melancholia and catatonia.

The connection of catatonia with seizures is another challenge. We know how to induce seizures and can offer effective treatment. We know that the benefit for the patient resides in the seizure and not in any aspect of the inducing agent – whether the stimulus is chemical, electrical, or magnetic is irrelevant. The effects are immediate, being appreciated within a day, but repeated seizures are required to sustain relief. Each seizure affects the neuroendocrine system, releasing a massive discharge of hormones into the brain and throughout the body. Some hormone effects are persistent and seem correlated with recovery and sustained benefit [257, 264]. While we have some information on the hormonal effects of induced seizures, we have very little on the hormone changes in catatonia. The relationships between seizures and catatonia warrant greater attention.

Another intriguing aspect of catatonia is its similarity to the animal condition of tonic immobility, a reflex that can be experimentally induced in prey animals under conditions of acute threat. Many authors, beginning with Kahlbaum, noted the fear and tension of patients with catatonia. The evidence for a relationship between fear and catatonia encourages more detailed study.

But while we have made much progress in identifying the patients who have catatonia and in our ability to help them, the position of patients with catatonia in our society is perilous. First, the recognition of catatonia and its teaching are poor. Catatonia is typically hidden in textbooks as a type of schizophrenia, nothing more, and its effective treatments are disregarded. Published case reports describe prolonged illness and even fatalities because catatonia was not appreciated and not appropriately treated.

The stigmatization of ECT is widely encouraged by the failure of medical school faculties and psychiatric and neurologic residency training programs to consider the treatment a necessary part of the education of their students. The failure of many psychiatric hospitals and medical schools to equip and maintain ECT treatment facilities is evidence of the stigma. Such failures are unethical in the principle of justice, the necessity for society to make known effective treatments available to all citizens regardless of their illness and social status [266].

Further, while the state has a duty to protect the interests of minors and the psychiatrically ill, special regulations have come to inhibit effective treatment for patients with catatonia. Patients who are mute, negativistic, and in stupor, delirium, or furor may be unable to give verbal or written consent for their care. In many treatment venues, the use of intravenous sedatives, and more so, the application of ECT is severely restricted; in some US states, it is even proscribed by law.

Two cases illustrate how legislative obstacles to appropriate treatment of catatonia can adversely affect individual patients and their families:

A 22-year-old woman, without any prior psychiatric illness, developed malignant catatonia following a Caesarean delivery. The legal hurdles to obtaining consent under the highly restrictive rules of California severely impeded her treatment for 33 days, risking her life and causing unnecessary additional expense for her and for society. Within 36 h of treatment she no longer required special nursing care and proceeded to full recovery [266].

A 16-year-old adolescent suffering from autism spectrum disorder developed life-threatening self-injurious behavior. After the failure of extensive psychological and medical treatment trials a course of ECT in Baltimore resolved the injurious behavior and allowed him to return to his home to be maintained by periodic continuation ECT. But the family lived in Los Angeles where ECT in children and adolescents under age 18 is legislatively interdicted. For his treatments the family had to fly every 7 to 10 days to Tucson, Arizona in order for the boy and the family to experience a more healthy home life.

Kahlbaum envisioned catatonia as a disorder of movement and mood, and in the more than a century since his description, we have learned to identify the syndrome as he saw it. We have added verifiable tests and developed effective and safe treatments. We are now able to detect many forms that catatonia takes in the clinic. The recognition of catatonia assures not only advances in wellbeing of patients but also offers personal gratification for clinicians as they restore a sick person, often moribund, to full health. In liberating catatonia as an independent treatable syndrome in the dictionary of psychiatric illnesses, we honor the vision of Karl Kahlbaum and bring his image of catatonia out of the shadows.

Acknowledgements

Michael Taylor brought catatonia out of the shadows of schizophrenia by his diagnostic studies in the 1970s. When my interest in catatonia was aroused in the 1980s, Mickey explained the many variations of the syndrome and together we challenged the DSM classification. We went on to collaborate in expanded texts on Catatonia (2003) and Melancholia (2006).

Edward Shorter dramatically extended my education in the history of psychiatry. His 1997 History of Psychiatry is the classic modern text. In 2007, with David Healy, he wrote Shock Therapy: A History of Electroconvulsive Treatment in Mental Illness. He went on to write Endocrine Psychiatry (Oxford 2010) and asked me to add a clinical chapter. Since then, he has written extensively on the history of malignant catatonia and delirious mania. He stimulated much of my enthusiasm for the stories of the clinicians who went before us, on whose eyes we depend for our images and on whose shoulders we stand.

Dirk Dhossche and Lee Wachtel are intrepid child and adolescent psychiatrists who broadened our concepts of catatonia to include many childhood disorders now labeled by eponymous names. The recognition of these behaviors as forms of catatonia has improved the lives of many disadvantaged and disabled youth.

When Taylor and I first described catatonia as a common medical syndrome, David Healy challenged our interpretation that catatonia was a frequently diagnosable illness. He sent out registrars to hospitals in Wales and India, used our rating scale, and found patients with the syndrome, as predicted. He also challenged us to defend catatonia as an independent identifiable and treatable syndrome.

Edward Shorter, David Healy, Jan-Otto Ottosson, Tom Bolwig, and Kennedy Cosgrove were readers and critics of early drafts of this biography. I am indebted to my wife Martha and the editor Jonathan Cobb who read each revision demanding increasing clarity and simplification. The text was ably copyedited by Susan Belanger. The index was assured by Kristin Nyitray and Lynn Toscano, archivists at the Stony Brook University Library.

I am grateful to the Directors of the Scion Natural Science Foundation and the predecessor International Association for Psychiatric Research who supported my studies of catatonia, melancholia, convulsive therapy, and quantitative electroencephalography.