Three cases of schizophrenia for which olanzapine was effective after early acute phase
Nobutomo Yamamoto, MD, Department of Psychiatry, Shimofusa Psychiatric Medical Center, 578, Heta-cho, Chiba City, Chiba 266-0007, Japan. Email: email@example.com
Aims: It clarifies a difference between early acute phase and late acute phase in medication.
Methods: The present report describes three patients with schizophrenia who presented with restlessness and excitement requiring hospitalization.
Results: Treatment with risperidone solution orally or parenteral haloperidol until the day after admission, followed by olanzapine, successfully improved the clinical condition of the patients. In the early stage of hospitalization, selection of fast-acting drugs that can be administered to uncooperative patients is considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after this early stage, olanzapine is preferable for improving patient compliance in addition to stabilizing symptoms.
Conclusions: Because the target symptoms differ between the early and late acute phases, the term ‘acute phase’ used in the broad sense should be divided into two units, each requiring a different therapeutic strategy, and independent clinical approaches should be considered in order to provide more suitable treatment.
THE PRESENT STUDY describes three patients with schizophrenia who presented with restlessness and excitement requiring hospitalization. Treatment with risperidone solution orally (RIS-OS) or parenteral haloperidol (HPD) until the day after admission, followed by olanzapine, successfully improved the clinical condition of the patients. In the early stage of hospitalization, fast-acting drugs that can be administered to uncooperative patients are considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after this early stage, olanzapine (OZP) is preferable for improving patient compliance in addition to stabilizing the symptoms. Because the target symptoms differ between the early and late acute phases, the term ‘acute phase’ used in the broad sense should be divided into two units, each requiring a different therapeutic strategy, and for which independent clinical approaches should be considered in order to provide more suitable treatment.
In the initial treatment of schizophrenia patients with severe restlessness and excitement, RIS-OS and HPD are used extensively for sedation. Currently, however, there is no systematized strategy of subsequent treatment in terms of the type, sequence, and duration of use of second-generation antipsychotic drugs, although the US guidelines recommend their use as first-line agents for patients presenting with a first episode. Herein we describe the treatment strategy used for the present three patients, and discuss the systematic treatment strategy for acute-phase schizophrenia on the basis of these experiences.
Patient 1: 33-year-old man diagnosed as having hebephrenic schizophrenia (ICD-10: F20.1)
The patient was one of two siblings with neither a relevant clinical history nor hereditary negative psychiatric factors. He had an introverted personality, and few friends. Trouble with a friend triggered stupor status in the year of X-19 (at the age of 14 years), from which he recovered in approximately 3 days. Thereafter, psychological stress triggered hallucination and delusion once a year or biennially, leading to stupor status, although remission occurred within 3–7 days each time. After the year X-15 (at the age of 18 years), the patient visited a local physician complaining of insomnia. He was diagnosed as having anxiety neurosis and treated with an anti-anxiety drug, although the patient had been unaware of any symptoms and was not treated with antipsychotic drugs. After graduation from a vocational technical school, the patient worked part-time for approximately 1 year, and then helped with the family business. However, he did little work and his initiative declined. He lived an isolated life at home, and his family noted monologia and an inappropriate smile. In the first half of July in the year of the present episode, the patient developed serious anxiety when mulling over the future, and 4 days later developed auditory hallucinations in which voices urged him to go to North Korea. He then showed behavior such as storming out of the house and roaming about outside. The patient was eventually admitted to Shimofusa Psychiatric Medical Center for his own protection.
The patient was strongly excited on admission, rejected any medication, and was put under restraint to receive i.v. HPD 10 mg/day on the first and second hospital days. On the second hospital day, without recurrence of excitement, the auditory hallucinations were resolved and the physical restraint was removed, after which the patient lay inactive on the bed throughout the day. Laboratory tests and body mass index (BMI) measurement conducted on the second hospital day indicated that the fasting blood glucose and cholesterol levels were within the normal ranges, and that BMI was 20.6. Treatment with OZP 5 mg/day from the third hospital day followed by 10 mg/day from the 10th hospital day resulted in improvement of spontaneity from the 12th hospital day, and by the 14th hospital day the patient claimed that his head had become clearer and his haziness of thought had disappeared. After several stays out of the hospital, the patient was allowed to be discharged on the 23rd hospital day with a prescription of OZP 10 mg/day. Upon discharge, his 10-item Drug Attitude Inventory (DAI-10) score was 9. This is a scale ranging from −10 points to +10 points, and indicates good drug compliance if the total score is high.1 The patient is currently receiving regular outpatient treatment, and he continues to have a clear head, allowing him to help with the family business. His initiative is also improving.
Patient 2: 38-year-old man diagnosed as having paranoid schizophrenia (ICD-10: F20.0) and pathological gambling (ICD-10: F63.0)
The patient was one of two siblings and had neither a relevant clinical history nor hereditary negative psychiatric factors. Obsessive-compulsive symptoms such as frequent hand-washing began from the year Y-23 (at the age of 15 years). From the year Y-18 (at the age of 20 years), the patient suffered an auditory hallucination in which someone was giving him orders. In the year Y-16 (at the age of 22 years), he visited a local physician and was diagnosed as having schizophrenia. His condition was treated with HPD and RIS tablets, but the auditory hallucinations persisted, and were exacerbated by psychological stresses. From the year Y-13 (at the age of 25 years) the patient began to waste excessive amounts of money playing Japanese pinball, which often left him penniless, and was additionally diagnosed as having a pathological gambling habit. The patient subsequently lived on welfare but moved to Shimofusa Psychiatric Medical Center in the year Y-2 (at the age of 36 years). His symptoms remained unchanged under treatment with RIS-OS 4–6 mL/day (1 mL RIS-OS contains 1 mg RIS) and valproic acid (VPA) 400 mg/day, and the patient was sometimes hospitalized because he had spent all his welfare payments, making it impossible for him to live independently. Due to his financial hardship he borrowed money from moneylenders and, when subjected to violent threats from debt collectors his auditory hallucinations were exacerbated. At one point his medication was discontinued for approximately 2 weeks because he had been too scared to go outside the hospital to obtain the drugs. The patient was eventually admitted to Shimofusa Psychiatric Medical Center from July in the year Y. Slight remission from the auditory hallucinations was obtained on 4 mL RIS-OS on the day of admission. On physical examination and laboratory tests conducted by the second hospital day a BMI of 21.7 was obtained, confirming that the fasting levels of blood glucose and cholesterol were within the normal range. Treatment with OZP 5 mg/day was started on the second hospital day in addition to VPA 400 mg/day, which was gradually increased to 10 mg/day on the ninth hospital day, and 15 mg/day on the 17th hospital day. The auditory hallucinations began to disappear from the 10th hospital day, and on the 21st hospital day he stated that they seemed to be reduced to approximately one-third, allowing him to concentrate on things and follow the content of TV programs. The patient was discharged on the 25th hospital day with a prescription of OZP 15 mg/day and VPA 400 mg/day. Upon discharge his DAI-10 score was 8. The patient is receiving regular outpatient treatment at present, and his auditory hallucinations remain under control, allowing him to concentrate on tasks.
Patient 3: 63-year-old woman diagnosed as having paranoid schizophrenia (ICD-10: F20.0)
The patient had no siblings, and no contributory medical history or hereditary negative psychiatric factors. She had married at the age of 22 years, had three children, and had lost her husband at the age of 55 years. While details of her disease symptoms were unknown, around the year Z-30 (at the age of 33 years) she had claimed to be the illegitimate child of the Emperor of Ethiopia, to possess several national treasures that she loaned out to a temple for a living, and that ‘God was guiding her life’. However, her personality had remained intact, and she had worked as an accountant in the iron foundry run by her husband, subsequently working as a canteen lady after his death. However, people around her had always considered her strange, and she had frequent troubles because of her words and paranoid behavior. Although her family had consulted a public health center in the year Z-3, the patient had received no treatment. In November of the year Z, the patient had become blindly agitated, claiming that her daughter abroad had become a prostitute and was in danger of dying due to HIV transmission. She was therefore eventually admitted to Shimofusa Psychiatric Medical Center for protection. Because of her severe excitement the patient was isolated, and treated with RIS-OS 6 mL/day on the day of admission and 4 mL/day on the second hospital day. The excitement was resolved, and the patient was released from isolation on the second hospital day. Laboratory tests and BMI measurement conducted on the second hospital day showed that the fasting blood glucose and cholesterol levels were within the normal range, with a BMI of 23.1. Treatment with OZP 10 mg/day starting from the third hospital day eliminated her daughter-centered delusion and eliminated her auditory hallucination of God's voice. From the seventh hospital day she conceded that her claim to own national treasures was possibly imaginary, and her auditory hallucinations disappeared completely on the 30th hospital day. At this time she claimed that the medication had made her feel refreshed, and that something like a fog appeared to have lifted from her consciousness. Nonetheless, she persisted in her delusion of being a child of the Emperor of Ethiopia. The patient was discharged from hospital on the 62nd hospital day with a prescription of OZP 10 mg/day. Upon discharge, her DAI-10 score was 9. She is still receiving regular outpatient treatment, and her systematized delusion is still maintained in a status of double orientation, although her feeling of being refreshed continues.
In the three case studies presented here, the antipsychotic drugs used until the day after admission were different from those used thereafter. This is because, in the early stage of hospitalization, fast-acting drugs that can be administered to uncooperative patients are considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after the early stage of hospitalization, drugs to encourage patient compliance are preferable to ensure continuity of treatment in addition to symptom stabilization. The principal antipsychotic drugs used for treatment in the acute phase are often switched to others in the subsequent stage.
When hallucination and delusion are severe or if behavior is hard to control, it is essential to calm the patient as soon as possible to facilitate subsequent stable medical treatment. Although, in such cases, many guidelines have recommended using first-line second-generation antipsychotic drugs in combination with benzodiazepine etc.,2 fast-acting drugs that can be administered without fail for sedation are preferable in this early phase.
In contrast, medication with antipsychotic drugs should focus on stabilization of symptoms and improvement of drug compliance after the early symptoms have been resolved. Because the more the patient is stabilized, the better drug compliance becomes, continuous treatment should also be considered to prevent recurrence and recrudescence. The purpose of medication at this time-point differs from that in the early phase, which is aimed at sedation, and therefore different types of antipsychotic drugs should be selected.
In many guidelines the phase until resolution of the severe symptoms and behavioral disorders (early acute phase) is not clearly distinguished from the subsequent phase in which treatment is maintained until the patient's condition has stabilized (late acute phase). Both phases are broadly interpreted as the ‘acute phase’ and differential use of antipsychotic drugs is not described. However, the target symptoms differ between the early and late acute phases, and therefore the term ‘acute phase’ used in the broad sense should be divided into two units of different therapeutic strategy, and independent clinical approaches should be considered in order to provide more suitable clinical treatment.
If use of an isolation room or physical restraint is inevitable in the early acute phase, it is necessary to control the psychiatric symptoms until these approaches are no longer required. The first candidate drug during the early acute phase is RIS-OS, which has been proved to be as equally effective as HPD,3 and parenteral HPD can be administered without fail to patients who refuse oral medication. Among the three case studies presented here, the symptoms in the early acute phase in patient 1 were resolved on the first to second hospital day on i.v. HPD, and in patients 2 and 3 by oral administration of RIS-OS.
Once treatment has been successful in the early acute phase, it is then necessary to improve drug compliance to stabilize the symptoms. The American Psychiatric Association Practice Guidelines recommend using antipsychotic drugs by classifying the symptoms into suicidal ideation/behavior, hostility/aggression, metabolic syndrome, extrapyramidal symptoms, increased prolactin, and poor drug compliance.2 However, it is considered preferable to use atypical antipsychotic drugs with long-term effectiveness in the late acute phase of an independent therapeutic unit where sustained-action drugs are recommended to prevent poor drug compliance after the treatment of the first episode in the early acute phase.
Recently, a large-scale double-blind Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was conducted by the National Institute of Mental Health in patients with chronic schizophrenia, excluding those who were therapy resistant or who had had a first-episode acute case, and OZP was reported to be associated with a significantly low rate of treatment dropout compared with other second-generation antipsychotic drugs and perphenazine.4–6 In addition, OZP has a high 5HT2a/D2 ratio and good compatibility with other neurotransmitters7,8. OZP also has a low incidence of tardive dyskinesia with prolonged administration.9 For these reasons, OZP is an attractive treatment option in the late acute phase.
In the three presented case studies, the patients were first sedated with RIS-OS or parenteral HPD until the day after admission, allowing us to confirm that there were no risk factors in terms of BMI or abnormal metabolism of glucose and lipids on blood sampling and physical examination, before proceeding to treatment with OZP. Considering the results of the CATIE study, switching to OZP, which has a low treatment dropout rate, seems to be an acceptable therapeutic option in the late acute phase, after sedation has been achieved with fast-acting and strongly sedative antipsychotic drugs such as RIS-OS and parenteral HPD in the early acute phase, as shown in the present patients. The DAI-10 score was high in all of the present patients at discharge, and the patients were able to actively comply with medication. Nevertheless, before treatment with OZP it is necessary to confirm that there are no risk factors such as an unfavorable BMI or abnormal glucose and lipid metabolism, and to continue observing the patients. However, in the present patients no effects on BMI or glucose and lipid metabolism have been observed to date.