The surgical treatment of pharmacoresistant epilepsy continues to gain acceptance around the world. Although the achievement of seizure remission is the primary aim of this treatment modality, epilepsy surgery has been associated with a remission of presurgical psychiatric comorbidity in up to 30–50% of patients, in particularly mood and anxiety disorders (Devinsky et al., 2005). After all, the prevalence of psychiatric comorbidity in patients evaluated for epilepsy surgery is relatively high, ranging from 30% to 70%, depending on the series (Koch-Stoecker, 2002; Kanner & Balabanov, 2008). By the same token, postsurgical psychiatric complications (PSPCs) have been reported, including exacerbation of presurgical conditions and de novo development of depressive and/or anxiety or psychotic disorders, as well of psychogenic nonepileptic seizures (Kanner & Balabanov, 2008). Although all epilepsy centers include a neuropsychological evaluation to identify patients at risk for postsurgical cognitive disturbances, few have incorporated a presurgical psychiatric evaluation to recognize those patients at risk of PSPCs. These can be classified by the type of psychiatric disorder (e.g., depression, anxiety, psychosis), by the timing of PSPCs after surgery (e.g., complications in the immediate postsurgical period, and those occurring within the first year after surgery) and, as stated above, whether they represent an exacerbation of a presurgical psychiatric comorbidity or the development of a de novo condition. The purpose of this article is to review practical strategies that can be followed in the prevention and treatment of postsurgical psychiatric complications.
We describe the physical, psychological, and social complications and adaptation demands after epilepsy surgery and the risks of the development of psychiatric disorders when adequate stress processing fails. Practical strategies that can be followed in the prevention and treatment of postsurgical psychiatric complications are reviewed. The postoperative period is divided in three phases: (1) the early postoperative phase of stress processing until discharge from hospital; (2) the coping phase during the first months after discharge; and (3) the reorientation phase. The early postoperative course is often dominated by physical problems that hamper success in convalescence. They may initiate early psychiatric disturbances especially in patients with preoperative psychiatric comorbidity. The second phase after discharge from hospital is the typical time in which various psychiatric disorders may develop (either de novo or exacerbations of known disorders). At this time it is mandatory to keep in contact with patients, to start psychiatric treatments if necessary, and to assess for suicidal risk. The course of the third phase of reorientation depends on seizure outcome and on psychiatric state. Seizure-free persons without psychiatric comorbidities start to forget their epilepsy; those with less successful outcome conditions may need further support, especially for vocational integration. Epilepsy surgery brings about an overall strong improvement of psychiatric morbidity and quality of patients' life. Nevertheless, the first postoperative year is a fragile period that includes multiple physical, psychological, and social adaptation tasks. Patients with a history of psychiatric disorders are at a special risk of failing to cope with those health-related demands, but also for nonpsychiatric patients the months after epilepsy surgery are often stressful and exhausting. Professional help must be available during the postoperative coping time.
Complications during the Postsurgical Period
One of every two to three patients who undergo epilepsy surgery has a lifetime (or current) history of psychiatric comorbidities, most of which includes depressive and anxiety disorders (Kanner & Balabanov, 2008) and to a lesser degree personality disorders (Koch-Stoecker, 2002). These psychiatric comorbidities, particularly if present at the time of surgery, may impact negatively on the immediate postsurgical period of recovery. After all, the time after epilepsy surgery with its pain, expectations, hopes, and fears is a stressful, critical life phase for most patients.
Stress is experienced when a person feels that the situational demands exceed his coping resources (Lazarus & Alfert, 1964). Therefore, stress is no objective condition but refers to what a person has experienced before, how he perceives the current situation, and how he is able to mobilize coping energies for its management. How stress is involved in the development of mental disorders is explained by the diathesis-stress model. Each person has a specific inherited and biographically shaped mental vulnerability that interacts with life stressors. The greater a person's vulnerability the less stress is needed for a psychiatric disorder to emerge. Firstly described to explain the development of schizophrenia (Zubin & Spring, 1977), this model and the prominent role of stress have been applied to a variety of mental disorders. Therefore, the risk of psychiatric complications during the postoperative time may vary extremely depending on vulnerability, expectations, and coping capacities of a patient.
Clearly, given all of the above-cited considerations, any treatment strategy for PSPCs has to start with establishing whether the patient is actively depressed or experiencing any type of psychiatric disorder that can interfere or worsen the ability to cope with the postsurgical common discomforts (e.g., headache, fatigue, nausea, vomiting). In patients who are symptomatic, postponement of the surgical procedure should be considered until such time as the patient is considered to be sufficiently stable to withstand the stressors of the surgical procedure. With respect to PSPCs, we know that preexisting psychiatric disorders complicate the postoperative course because (1) of postoperative exacerbations (depression, psychosis) (Anhoury et al., 2000); (2) their existence can compromise adaptation necessities (personality disorders) (Koch-Stoecker, 2002); and (3) they predict negative prognoses of seizure outcome (Kanner et al., 2009).
In addition, preoperative expectations have an influence on the postoperative course. The more concrete, practical, and realistic the postsurgical expectations are, the better is the outcome in terms of quality of life (Wilson et al., 1999). Preoperative reflections about the postoperative situation have an influence on perception of and suffering from stress, and adequate use of coping strategies (Wheelock et al., 1998).
In our context, the acute stress reaction is represented by the direct postoperative time span until discharge from hospital; the second, the coping time span, may last until 6–12 months after surgery; and finally the reorientation takes place during the second postoperative year. We will focus on three domains within these three phases of PSPC: physical, psychological, and socioenvironmental. These differentiations go back to the definition of health in the World Health Organization (WHO) constitution (“Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.”) (), and the biopsychosocial model of treatment (Engel, 1977). It is obvious that the physical domain will play a more prominent role in the early postoperative phase, whereas environmental and social processes, such as vocational developments, will dominate the later course.
The Phase of Acute Postoperative Stress Processing
Physical problems and their effect on psychiatric complications
Headache and associated sleep disorders, nausea, or vomiting due to anesthesia are among the most common early postsurgical physical complaints of epilepsy surgery. Postsurgical language disturbances are not infrequent during the first days (or 2 weeks) that follow a resection in the dominant hemisphere. They may impede convalescence and elicit psychiatric complications in those without appropriate strategies of stress coping. Patients and family members need to be informed before the surgical procedure of their potential occurrence, their natural course, and how these symptoms are treated. Implementation of “promised” interventions (especially in pain management) is of the essence in any patient, but in particular in patients with presurgical psychiatric comorbidities.
De novo early psychiatric complications
Acute encephalopathic processes associated with cognitive and psychiatric symptomatology can occur in patients with and without presurgical psychiatric history. These may present with various clinical manifestations, ranging from sole disturbances in states of alertness and orientation to delirium associated with visual and auditory hallucinations. Often these events are iatrogenic, resulting from excessive use of narcotic drugs. Yet, in some patients (particularly those with a previous psychiatric history) it is necessary to exclude causes such as alcohol withdrawal, or withdrawal of benzodiazepines.
Treatment of delirium contains
Monitoring of patients for potential (self-)harmful behavior; reorientation of patients to person, place, time, and circumstances by all who come into contact; information for family members especially about the transient character of symptoms; reduction of exacerbating factors by environmental interventions (e.g., change of the lighting to cue day and night, reduction of monotony, and of overstimulation); and correction of visual and auditory impairments (e.g., retrieve glasses, hearing aids) (1999). High-potency antipsychotics like haloperidol are the pharmacologic treatment of choice in a dosage that ranges from 1 to 2 mg every 2–4 h. The cardiac risks that may add to those of antiepileptic drugs have to be kept in mind. Benzodiazepines (e.g., lorazepam as a short-term agent, without active metabolites) may be used as an alternative to antipsychotic drugs to reduce the risk of seizure relapse.
Early postoperative adaptation needs
In this early postoperative time adaptation tasks are often related to physical disturbances. Some find it difficult to adapt to their hairless shapes, in this case some creative animation by the staff how to drape colorful scarves may help.
Activity level during convalescence varies widely between patients. Some show asthenic behavior that often cannot be determined as either psychogenic-regressive or organic-exhausted. Best treatment of regressive tendencies is to instruct the patient to focus on every small progress from day to day, to implement reinforcing steps, to support any coping activity, and to increase the sensation of self-worth.
After Discharge from the Hospital—The Coping Phase
Typically, back home after surgery psychiatric complications come to the foreground, either as exacerbations of preoperative existing disorders or as de novo depressive or anxiety episodes. Beyond this, adaptation disorders that affect the whole psychosocial network need professional support (Kerr et al., 2011).
If possible a follow-up visit should be scheduled within 2 weeks after discharge from the hospital in all patients, but in particular in those with known psychiatric history or those who displayed new psychiatric symptoms before discharge from the hospital. Furthermore, telephone contact should be maintained on a monthly basis during the first 3 months to investigate the occurrence of de novo psychiatric symptoms, or exacerbation of previous psychiatric comorbidities, in which case a visit should be scheduled immediately to delay the progression of symptoms, particularly, the development of suicidal ideation that has been reported to progress to complete suicide in these patients. In fact, suicide is the most frequent cause of death in postsurgical patients.
In most centers, postsurgical outpatient appointments focus on neurologic issues. Given all the data discussed earlier, a psychiatric evaluation must be incorporated into these visits. Of note, reliable detection of postoperative suicidality after surgery is not possible with the sole administration of self-report instruments (e.g., Beck Depression Inventory) (Hamid et al., 2011a).
Physical problems during the coping phase—psychiatric treatment approaches
Postsurgical neuropsychological deficits are not unusual, particularly following epilepsy surgery performed in the dominant hemisphere. Yet, psychiatric comorbidity and in particular depressive disorders are known to exacerbate (and at times account for) these deficits. In fact, presurgical depressive symptomatology may be associated with an increased risk of postsurgical memory decline (Busch et al., 2011). In such cases, antidepressant medication should be considered in combination with specific neuropsychological rehabilitation training.
Persistent sleep disturbances
Fatigue is a common occurrence after surgery, which can persist for some months following a temporal lobectomy. Accordingly daytime naps are not infrequent, but these may result in a shift of the sleep cycle. By the same token, insomnia and/or excessive daytime somnolence are frequent expressions of depressive and/or anxiety disorders that can appear within the first 6 weeks after surgery. Clearly, a careful investigation of these variables is necessary to identify the cause(s) and plan the treatment for postsurgical sleep disturbances.
Postsurgical psychiatric disorders
In some patients a change of elevated mood can be detected a few days after surgery. It may begin with an excessive feeling of gratefulness for the surgeon who is denoted as the savior and responsible for the patient's new life. Although this affection is partly comprehensible the mood may switch into a socially inappropriate euphoric state, including seeking emotional closeness to rather distant persons, and finally the development of classic hypomanic symptoms (e.g., increased levels of energy, insomnia, pressured speech, flight of ideas, marked irritability, and increased sexual activity). Risk factors have included right temporal resection and bilateral electrographic ictal foci (Carran et al., 2003).
In most cases hypomanic symptoms are identified in the early postsurgical period and typically are short-lived. Pharmacotherapy is rarely required, lest the patient does not respond to redirection over the euphoric mood and limit setting of inappropriate behavior. Low doses of atypical antipsychotic medication for a few days or up to 2 weeks may be sufficient. Of note, postsurgical hypomanic episodes may herald an undetected bipolar disorder and should alert the clinician to the cautious use of antidepressant drugs.
Anxiety symptoms occur in the early postoperative period, often before manifest depression develops (Ring et al., 1998). In fact, symptoms of anxiety and fear of variable severity have been reported to occur in about 40% of patients. In many patients anxiety is a reasonable expression of uncertainty about the future perspective of a life without epilepsy, or of fear of recurrent seizures. Postoperative anxiety, thus, is a mixed psychoreactive and organic problem, a typical constellation of many psychiatric syndromes in epilepsy patients.
The treatment of anxiety episodes includes the use of benzodiazepines (e.g., clobazam, lorazepam) for a short time period. When anxiety is accompanied with depressive symptoms an antidepressant treatment is indicated. Some of the selective serotonin reuptake inhibitors (SSRIs) are approved for the use in anxiety disorders as well, which should be considered for long-term treatment of a pure anxiety disorder.
Depression and organic asthenic disorders
A depressive disorder may be identified about 3 months after surgery and in some patients earlier in about 10–30% of patients, independent of seizure outcome. Although preoperatively depressed mood in epilepsy patients often appears with dysthymic or dysphoric affect, with short-term mood changes lasting hours or days, as described in the interictal dysphoric disorder (IDD) by Blumer (Blumer et al., 2004), the postoperative mood changes have a different quality: persisting, more severe, associated with loss of interest and pleasure, feelings of hopelessness, and decreased energy and self-drive. Therefore, postoperative depression can present as a major depressive episode, and in patients with presurgical interictal dysphoric disorder, display more severe characteristics.
Overlapping with depression many patients have a physical and mental asthenia, which is an organic sequel of the surgical procedure, as described by Malmgren et al. (2002). This kind of fatigue and lack of psychophysical energy goes along with avoidance of social contacts because communications seem arduous, stimulus-selection fails, and high sensitivity to noise leads to withdrawal from interaction.
According to the American Psychiatric Association (APA) guidelines, depression requires multimodal treatment. Of course this applies to patients with depressive disorder in epilepsy as well. Generally, to promote good disease management it is important to assess impairment of quality of life at the beginning of treatment and set adequate goals for the course of recovery. A good coordination of care with other health professionals is necessary. The use of self-rating and clinician-rating scales to monitor symptom development is recommended.
An important basis for the treatment of depression is providing information about the disease as well as an education about treatment strategies for patient and family, including an explanation of all symptoms (including emotional withdrawal from close persons) and their transient character (e.g., positive prognosis), despite the actual feelings of hopelessness. Patients should be advised not to make life-changing decisions during a depressive episode (including no definite breakup with partner). Patients and family members should also be informed about associated cognitive complaints (poor concentration, distractibility, loss of attention) as they may also be signs of depression.
Before the start of any pharmacotherapy, medical factors facilitating the depressive episode should be identified and treated. Antiepileptic drugs (AEDs) may have to be changed (e.g., AEDs with negative psychotropic properties started after surgery, such as levetiracetam, topiramate, zonisamide, and barbiturates). No changes are required, however, if patients had been taking these AEDs before the surgical intervention without any psychiatric symptoms.
The next treatment step is to introduce antidepressant medication, which has been proved to be effective in depression accompanying neurologic disorders (Price & Rayner, 2011), although no controlled placebo-controlled trials have been published in patients with epilepsy. Yet, there is a consensus that the use of antidepressants in patients with epilepsy yields a therapeutic effect and drugs of the selective serotonin reuptake inhibitor (SSRI) family have been suggested as first choice (e.g., citalopram, escitalopram, or sertraline) (Kerr et al., 2011; see also the article on Treatment of Depression in this issue).
Some patients may be reluctant to take additional medication, especially those who had been told previously that psychotropic drugs are associated with a potential proconvulsant risk. It is important to inform patients that several studies have demonstrated clinical improvement of the depressive episodes without an increased risk of seizure occurrence when using antidepressant drugs at therapeutic doses (and in some cases, a decrease in seizure frequency associated with improvement of mood has been suggested by several authors) (Hovorka et al., 2000; Kühn et al., 2003; Specchio et al., 2004).
The use of SSRIs may at times cause insomnia, in which case the drug should be administered in the mornings. Although mirtazapine has been suggested as an alternative (Noe et al., 2011), this antidepressant has been shown to have an increased proconvulsant risk (Münchau et al., 2005). In the Bielefeld surgery program, two cases of a first seizure occurrence after surgery were associated with the introduction of mirtazapine. Agomelatine, a melatonin-activating agent, may be used with sleep disorders as primary symptoms, although the magnitude of the antidepressant effect seems to be limited (Singh et al., 2011).
After remission of the depressive episode, treatment must be continued for 6 months (Kerr et al., 2011; 1999, 2010) and when discontinuation is planned, the dose of the medication should be tapered down over the course of several weeks.
If SSRIs are ineffective, a switch to a serotonin-norepinephrine reuptake inhibitor should be considered. Tricyclic antidepressants are another option, although this class of drugs is associated with a lower tolerability and higher cardiotoxicity, which can facilitate a successful suicide attempt in case of an overdose.
If depression is accompanied by delusional symptoms, antipsychotic medication should be added to the pharmacologic regimen. Blumer (Blumer et al., 1998) recommended the use of low-dose risperidone.
In treatment-resistant severe depression after epilepsy surgery, especially when suicidal risk requires rapid therapeutic changes, electroconvulsion therapy (ECT) has been used safely (Kaufman et al., 1996; Aksoy-Poyraz et al., 2008).
With respect to psychotherapy, cognitive behavior therapy (CBT) is indicated (and has been found to be as effective as antidepressant medications) for mild or moderate depression (2010). Typically, 12–16 treatment sessions are sufficient to address the obstacles posed by the depressive disorder. CBT has been successfully tested in patients with epilepsy (Macrodimitris et al., 2011; Crail-Meléndez et al., 2012). In addition, the psychodynamic approach Interpersonal Psychotherapy (IPT) has proven to be effective in the treatment of depression (Jakobsen et al., 2012). It includes four major treatment areas all of which seem highly appropriate for treatment of depressed patients with epilepsy after epilepsy surgery: grief, conflicts in relationships, problems with change of life circumstances, and social isolation. Unfortunately, limited or no access to CBT and IPT is a common problem in most countries.
The rate of de novo postoperative psychoses is low, but it is an eminently harmful condition that affects about 2% of patients after epilepsy surgery (Koch-Stoecker & Kanemoto, 2008). Postsurgical psychotic episodes often develop later than depressive episodes (>6 months after surgery), independently of seizure outcome. Their severity may range from worried-skeptical mistrust to paranoid-hallucinatory schizophrenia-like syndromes compromising survival by self-harmful actions or aggression toward others.
In some cases, psychotic episodes may evolve from a severe depressive episode, which may delay the recognition of the psychotic features. Family members need to be instructed on the natural course of the psychotic episode, while the need for inpatient hospitalization may need to be considered.
With respect to the treatment, the use of the newer atypical antipsychotic agents is indicated and should be maintained for half a year after symptom remission at a minimum. In complicated patients with a suspected thought disorder, Blumer (Blumer et al., 1998) recommends adding a low dose of risperidone (1–2 mg/day) even before overt psychotic symptoms appear.
In the case of persistent psychotic episodes, the patient should be referred to day-hospital programs, which should include family members in the therapeutic process. In addition, vocational evaluations and training in sheltered workshops can be planned before discharge.
As in the case of severe depression, there have been reports of the effective use of ECT in severe postoperative psychoses (Maixner et al., 2010). In these cases the concept of alternative psychosis associated with the surgery-related phenomenon of forced normalization (Wolf & Trimble, 1985; Schmitz, 1998) should be considered.
Adaptation needs and efforts during the coping phase
Surgery is a “crucial ‘turning point’ in an individual's development” (Wrench et al., 2011). Even for psychiatrically unimpaired persons, the first postoperative months are accompanied by various adaptive processes. For example, a patient may fail to abandon the role of “learned helplessness” typical in chronic epilepsy patients, (Hermann et al., 1996) and may maintain a dependency on others. Other patients may overestimate new possibilities and expect unrealistically big life changes, like better options for partnership or professional standing.
The family plays an important role in the adaptation process. Family members may continue to react in an overprotective manner, even when the patient wants to expand his role in the family affairs (e.g., financial decisions) or may pressure the patient to fulfill expectations of now being healthy (burden of normality, Wilson et al., 2007). Particularly patients with personality disorders report disrupted family dynamics and difficulties adjusting to seizure freedom (Wilson et al., 2010). Attenuation of this type of problems can be achieved by having before and after surgery family meetings so as to identify the “dynamics,” the expectations from surgery and prepare them for the impact of a life without seizures. Finally some patients and families need support to deal with the disappointment of ongoing seizures if surgery failed to be successful.
Reorientation—The Second Year after Surgery
For many patients, 1 year after surgery the surgical procedure, the seizures, and postoperative adaptation time belong to the past. The need to continue taking AEDs is the only reminder of the presurgical period. The quality of life has improved and new roles have been adopted. Mood and other psychiatric symptoms have remitted, but this positive applies only to those patients with an excellent seizure outcome (Hamid et al., 2011b). Yet, besides the enduring, reliable seizure-free outcome, good quality of life is in the long run determined by a lack of psychiatric complications and a good employment status (Elsharkawy et al., 2009). Both areas are relevant in the second postoperative year. Although depression and anxiety disorders may improve and even remit after epilepsy surgery in those who are seizure-free (Devinsky et al., 2005), many persons with severe adaptation disorders, postoperative depression, or psychosis continue to struggle with new postoperative demands. In some cases, especially in those with presurgical psychiatric handicaps, the maladaptive coping mechanisms tend to persist. For this patient group professional support in vocational reintegration is necessary, either in sheltered workshops or in regular employment. In older patients the rehabilitation into work needs long-lasting supervision, as cognitive flexibility may be reduced and elderly patients tend to become depressed more easily (Barbieri et al., 2011).
Despite the overall improvement of psychiatric morbidity and quality of life in patients after epilepsy surgery, the first postoperative year is a fragile period that includes multiple physical, psychological, and social adaptation tasks. Patients with a history of psychiatric disorders are at a special risk of failing to cope with those health-related demands. Psychiatric exacerbations or new disorders may develop and need specific treatment. But also for numerous nonpsychiatric patients the months after epilepsy surgery—perceived as a turning point toward a better life—are stressful and exhausting. Preoperative psychiatric consultations with patients and families should detect risk factors for postsurgical complications. They should also focus on families' postsurgical expectations and must prepare for the possibility of obstacles during the process of convalescence.
The authors report no conflicts of interest. The contents of this supplement reflect the opinions of the individual authors and do not necessarily represent official policy or position of the ILAE. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.