Treatment of Aggression in Schizophrenia

To the Editor: Aggression in schizophrenia is an important clinical problem. We report a case of an aggressive patient with schizophrenia who improved when fluvoxamine was added to her regimen of risperidone.

Ms. A, a 25-year-old single woman, had been hospitalized for the last 8 years. At the age of 14 years, she became socially withdrawn and developed thought disorder, odd behaviors, and angry outbursts. She stopped school, stayed home in her room believing that people in the street were laughing at her, and often intentionally injured herself. Outpatient treatment with perphenazine was initially helpful, but then she deteriorated, developing insomnia, auditory hallucinations, delusions, and aggression toward family members. These symptoms led to her first admission at the age of 16. Schizophrenia was diagnosed, and Ms. A was treated with haloperidol, carbamazepine, and ECT with some improvement. After discharge, she remained isolated at home. There were frequent aggressive outbursts without obvious precipitants. She would scream, throw objects, and physically attack family members. These outbursts were followed by remorse and apologies.

At 17, Ms. A was admitted to our hospital with marked agitation, delusions, and derogatory auditory hallucinations. After admission, she fluctuated between quieter periods when she could be treated in an open ward and, more frequently, periods of aggressive and bizarre behavior necessitating transferal to a secure ward.

Treatment including levopromazine, haloperidol, perphenazine, carbamazepine, chlorpromazine, fluphenazine decanoate, haloperidol decanoate, ECT, and clozapine was of limited benefit. Results of physical, neurological, and laboratory investigations, including EEG, were normal.

In the summer, Ms. A was again transferred to the secure ward because of severe agitation, auditory hallucinations, and verbal and physical aggression toward others. She would burn herself in scalding water and would refuse to remove her rings, causing sores to develop on her fingers.

She began a regimen of risperidone, up to 8 mg/day, with no improvement after 4 weeks. Fluvoxamine, 50 mg/day, was added, and 2 days later, the dose was increased to 100 mg/day. Improvement, noted 1 week later, progressed: Ms. A became quieter, more relaxed, and more organized in her thinking and behavior. Her delusions and hallucinations became less prominent; her violent outbursts ceased. She returned to work in occupational therapy and went out on leave with her family. Her scores on the Brief Psychiatric Rating Scale (rating range: 0–6) changed from 42 at baseline to 17, 14, 13, 9, and 10, respectively, over the next 5 weeks. Her Clinical Global Impression score was rated much improved after 1 week. No side effects appeared.

Serotonergic dysfunction is implicated in aggression, and several receptors may be involved (1, 2). Risperidone, which was not effective in Ms. B’s case when given alone, can improve aggression in some patients with schizophrenia (3). Fluvoxamine can also improve aggression (4). It is likely that the interaction between the two was important in producing the rapid response in our patient. We postulated that fluvoxamine may act by modulating the balance both within the complex serotonergic system and between it and other neurotransmitter systems (5). Alternatively (or additionally), since fluvoxamine interacts with cytochrome P450 enzymes, the mechanism may involve an increase in risperidone concentration.