Quetiapine in the Successful Combination Treatment of an Assaultive Patient With Treatment-Resistant Schizoaffective Disorder

Written By: Sam Savage

Published Date: May 30, 2007 Last Edited: May 30, 2007

By Post, David Edward

Abstract. The author relates the case study of a 38-year-old man with schizoaffective disorder (bipolar type) refractory to multiple medications. This patient had a long history of psychiatric illness and had been hospitalized at least 15 times because of aggression, hostility, and psychosis. Two separate trials of risperidone and olanzapine resulted in adverse effects, including possible neuroleptic malignant syndrome. Quetiapine, as part of combination therapy, led to substantial reductions in the patient’s schizoaffective disorder symptoms and problematic behaviors. The patient tolerated quetiapine and did not experience any adverse effects. Quetiapine may be a suitable treatment option in patients with schizoaffective disorder.

Index terms: adverse effects, atypical antipsychotic, neuroleptic malignant syndrome, quetiapine, schizoaffective disorder

Schizoaffective disorder, a common, chronic, and frequently disabling psychiatric disorder, manifests prominent symptoms of both schizophrenia and mood disorder.1 Over the past decade, atypical antipsychotic drugs (eg, risperidone, quetiapine, olanzapine) have replaced typical antipsychotic drugs (eg, haloperidol, chlorpromazine) as the treatment of choice for schizophrenia and now are indicated for a number of psychiatric conditions, with target symptoms including aggression, hostility, suicidality, and substance abuse.2 Because atypical psychotic drugs have a better adverse effect profile, fewer extrapyramidal symptoms, a lower risk of tardive dyskinesia, and improved negative symptoms and certain parameters of cognition, researchers have found these drugs to be beneficial in the treatment of patients with schizoaffective disorder. 2,3 In this article, I describe the case report of an assaultive patient with schizoaffective disorder (bipolar type) refractory to multiple medications who improved significantly when high-dose quetiapine was added to his treatment regimen.

CASE REPORT

In May 1997, a 38-year-old muscular man of impressive size and strength (6 feet 1 inch tall and 240 lbs) was admitted for the third time to the tertiary state hospital where I practiced general and forensic psychiatry. Physicians at an intermediate state hospital where he had been an inpatient 6 times referred him to us because of his hostility, extreme mania, and demanding behavior. The referring hospital staff frequently used locked seclusion and 4-point restraints as part of the patient’s treatment protocol. The physicians at the intermediate state hospital diagnosed him with schizoaffective disorder and alcohol dependence in remission and recommended long-term hospitalization in a closed environment. During his stay at our tertiary state hospital, I also added a diagnosis of personality disorder not otherwise specified (with prominent antisocial traits).4 The admitting physician’s emergency certificate stated that the patient threatened to kill his family members and police officers, had destroyed his home, exhibited pressured speech, and was noncompliant with his medication regimen. He faced criminal charges for trespassing in his grandmother’s house, and his family experienced difficulty in restraining him from being a public nuisance (eg, confronting and assaulting people without provocation) and vandalizing public and private property with his fists (eg, parked cars). His family members were finding it increasingly difficult to live with and care for him.

His family history was notable for psychotic disorder in his grandmother, who required several hospitalizations for exacerbations of psychosis. School records and family statements show that he demonstrated behavioral problems during his early adolescence. He began smoking cigarettes at age 11 years and started to drink alcohol excessively.

Soon after, at age 12 years, he also began drinking alcohol in an excessive fashion. In his late 20s, he experimented with phenylcyclohexyl piperidine (PCP) and marijuana. He had never been gainfully employed, and Social Security payments were his only source of income. Over a 6-year period, he had been admitted approximately 15 times to the local acute care hospital and twice to our hospital for behavioral problems. During his most recent hospital admission, he exhibited symptoms of paranoia without evidence of substance abuse.

Previous physicians had administered a number of psychotropic medications to the patient in an attempt to control his hostile and aggressive behavior without causing excessive sedation or cognitive decline. These agents included haloperidol 30 mg/d, valproic acid 2500 mg/d, mesoridazine 100 mg/d, risperidone 4 mg/d, olanzapine 10 mg/d, buproprion 200 mg/d, gabapentin 1200 mg/d, lithium 1500 mg/d, and fluphenazine 10 mg/d. During trials of the atypical antipsychotic drugs risperidone and olanzapine, he developed some symptoms that raised concern about possible neuroleptic malignant syndrome (NMS). Despite trials with various psychotropic medications, the patient remained intimidating, boisterous, and difficult to redirect. At one point, he became severely agitated, and in a fit of rage, he self-inflicted a compound fracture of his left humerus.

His state hospital chart listed numerous physical, verbal, and psychological behavioral altercations, including repeatedly throwing furniture, threatening peers, screaming obscenities, slamming himself into inanimate objects, beating on walls and windows, swinging his fists wildly, and harassing female hospital staff members. He experienced auditory hallucinations, whereby he had unintelligible conversations with imaginary children he called “the kids.” He also acknowledged excessive energy, decreased need for sleep, sadness (especially over the death of his mother), and guilt (from not listening to his parents). In contrast to his agitation, however, he would often be euthymic and apologetic, and he would express a genuine sense of regret for his uncontrolled behaviors.

On his third admittance to our hospital, physicians initially administered risperidone 2 mg/d and titrated him to 4 mg/d over a period of a few days; however, he experienced a body temperature of 102.6F, unsteady gait, substantial lethargy, and urinary incontinence. During physical examination, the physician found an abscess on the patient’s buttock, which may have exacerbated development of symptoms. Because of the acute symptoms, the physician admitted him to the intensive care unit, and risperidone was discontinued as a precaution because its administration was temporally correlated with the onset of symptoms. On return to my ward, physicians switched him to olanzapine and increased his dosage to 10 mg/d within 7 days; however, the patient redeveloped disturbing symptoms, including a body temperature of 102.0F, pulse rate of 120 bpm, lethargy, and confusion. Physicians discontinued olanzapine as a precaution because of the close correlation of its administration with the subsequent acute symptoms.

Two months later, my colleagues and I initiated quetiapine 50 mg/ d and titrated to 250 mg/d. We used quetiapine as part of a combination therapy that included chlorpromazine 700 mg/d, thiamine 300 mg/d, and benztropine 4 mg/d. Over the next few months, because of incomplete symptom resolution, we increased the dosage of quetiapine several times, eventually reaching 750 mg/d. At a dosage of quetiapine 750 mg/d, he appeared more cooperative and attentive, and he was less hostile and aggressive. During the 3-month quetiapine titration, we also added propranolol hydrochloride 40 mg/ d and clonazepam 4 mg/d to the treatment regimen because of anxiety, nervous tension, and residual aggressive behavior. We increased propranolol hydrochloride to 100 mg/d (60 mg in the morning and 40 mg at night), and he no longer exhibited unprovoked aggression. He became actively involved in recreational therapy activities and anger management classes and had meaningful visits with his sister and father.

Although the patient exhibited periodic anger and irritability, he recognized that he had more control over his behavior than he had before receiving quetiapine. It was clinically notable that he responded well to a medication regimen that included quetiapine

750 mg/d and that he no longer experienced NMS-like symptoms. His treatment regimen resulted in a substantial calming effect, in addition to improved attention, concentration, and sociability. As a result of his continuing improvement, he was discharged to a less restrictive inpatient hospital. He continued to improve substantially at the other facility, and after a 4-month period he was discharged home. His medication regimen on discharge included quetiapine 750 mg/d, chlorpromazine 900 mg/d, propranolol hydrochloride 100 mg/d, thiamine 300 mg/d, clonazepam 4 mg/d, and benztropine 4 mg/d.

COMMENT

Because individuals with schizoaffective disorder exhibit symptoms of both schizophrenia and mood disorder, their illness has a prominent affective component, in addition to chronic psychosis, and they usually require maintenance antipsychotic medication and psychotropic medication for affective symptoms.5 In the present case, the patient had been prescribed numerous medications with ind\ications ranging from treatment of psychosis and control of extrapyramidal symptoms (induced by neuroleptic drugs) to treatment of depression and management of manic episodes of bipolar disorder. Several of these medications, including risperidone and olanzapine, caused symptoms of NMS, an unpredictable and rare, but potentially fatal, complication of antipsychotic medications.6

Although the patient did not respond positively to a number of medications, he did improve significantly while taking quetiapine, which has been proven in clinical studies to treat both the positive and negative symptoms of schizophrenia effectively.7-9 Quetiapine is well tolerated and has a low propensity for causing adverse events during acute and long-term treatment in adult populations.10

The success of this patient is in line with a randomized, placebo- controlled trial in which Goldstein11 found that quetiapine reduced hostility and aggression markedly in patients with schizophrenia. Our patient’s improvement is also consistent with the results of an open-label trial5 involving 10 patients with bipolar disorder and 10 patients with schizoaffective disorder who received quetiapine therapy. Overall, these patients with serious mood disorders tolerated quetiapine well, suggesting that this atypical antipsychotic may be beneficial when treating individuals with serious mood disorders who have suboptimal responses to mood stabilizers alone.

Our patient improved greatly with high-dose quetiapine, reinforcing the notion that patients who have been resistant to other agents may need a higher dose of the drug, which is typically well tolerated across the dose range.12 Although the present case suggests that physicians should use quetiapine in the treatment of patients with schizoaffective disorder, further studies involving atypical antipsychotic drugs in combination with other medications or as monotherapy are needed.

ACKNOWLEDGMENT

The author independently identified this case to report and received no financial compensation with respect to this article. As well, the author does not have any financial relationship with respect to any medical/pharmaceutical company. Astra Zeneca did provide editorial assistance.

REFERENCES

1. McElroy SL, Keck PE Jr, Strakowski SM. An overview of the treatment of schizoaffective disorder. J Clin Psychiatry. 1999;60:16- 22.

2. Glick ID, Murray SR, Vasudevan P, Marder SR, Hu RJ. (2001). Treatment with atypical antipsychotics: New indications and new populations. J Psychiatr Res. 2001;35:187-191.

3. Grieger TA, Benedek DM, Flynn J. Pharmacologic treatment of patients hospitalized with the diagnosis of schizoaffective disorder. J Clin Psychiatry. 2001;62:59-60.

4. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, 4th ed. Washington, DC: APA;1994.

5. Sajatovic M, Brescan DW, Perez et al. Quetiapine alone and added to a mood stabilizer for serious mood disorders. J Clin Psychiatry. 2001;62:728-732.

6. Susman VL. Clinical management of neuroleptic malignant syndrome. Psychiatr Q. 2001;72:325-336.

7. Arvanitis LA, Miller BG. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Biol Psychiatry. 1997;42:233-246.

8. Borison RL, Arvanitis LA, Miller BG. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo- controlled trial in patients with schizophrenia. US SEROQUEL Study Group. J Clin Psychopharmacol. 1996;16: 158-169.

9. Meats P. Quetiapine (‘Seroquel’): an effective and well- tolerated atypical antipsychotic. Int J Psych Clin Pract. 1997;1:231- 239.

10. Dev V, Raniwalla J. Quetiapine: a review of its safety in the management of schizophrenia. Drug Saf. 2000;23:295-307.

11. Goldstein JM. “Seroquel” (quetiapine fumarate) reduces hostility and aggression in patients with acute schizophrenia. Paper presented at: American Psychiatric Association 151st Annual Meeting; May 30-June 4, 1998; Toronto, Canada.

12. Brooks JO III. Successful outcome using quetiapine in a case of treatment-resistant schizophrenia with assaultive behavior. Schizophr Res. 2001;50:133-134.

David Edward Post, MD

Dr. Post is a general and forensic psychiatrist with Capital Area Human Services District in Baton Rouge, LA.

NOTE

For comments and further information, address correspondence to Dr. David Edward Post, Capital Area Human Services District, 4615 Government St / Bldg #2, Baton Rouge, LA 70806 (e-mail: [email protected]).

Comments

comments