Fluvoxamine and Aggression in Mental Retardation

To the Editor: Among adults with mental retardation, aggressive behavior—directed against self and others—and challenging behavior are common obstacles to all types of treatment. Research on the usefulness of various medications to control aggressivity in this population has raised concerns about the efficacy and safety of all the agents studied.

Changes in serotonin levels in the central nervous system are a critical factor in the pathophysiology of aggressivity. Selective serotonin reuptake inhibitors (SSRIs) have been used successfully to control aggressive behavior (1,2). Fluvoxamine has particularly useful characteristics. It has a mild sedative effect, and it seems to be more selective for serotonergic pathways than most other SSRIs.

We sought to obtain preliminary data on the efficacy and safety of fluvoxamine in controlling aggressive behavior among adults with mental retardation.

Study participants were 60 aggressive inpatients with a DSM-IV diagnosis of mental retardation—40 with mild and 20 with moderate retardation. The mean±SD age of the participants was 30.6±2.5 years. Twenty-nine were men (48 percent), and 31 were women (51 percent). Fifty-five patients (92 percent) lived in an institution, and five (8 percent) lived with their family. All the participants were Caucasian. Patients gave written consent to take part in the study.

The participants were treated for three weeks with fluvoxamine, which was initiated after a run-in period of three weeks—one week of no medication and two weeks of placebo. Over the three-week treatment period, the daily dose of fluvoxamine was gradually increased to a range of 200 to 300 mg, depending on individual response. The mean±SD dosage at the end of the treatment period was 250±41 mg a day.

Aggressivity was assessed with the Handicaps, Behavior, and Skills Schedule (HBSS) (3) at three time points—at the end of the week without medication, at the end of the placebo period, and at the end of three weeks of fluvoxamine treatment. Side effects were assessed with the Dosage Record and Treatment Emergent Symptom Scale (DOTES) (4) at the end of the placebo period and after fluvoxamine.

The HBSS is a 12-item scale for measuring aggressive and aversive behavior among people with a mental handicap. The score on each item ranges from 0 to 2, with 0 indicating no abnormal behaviors and 1 and 2 indicating moderate and severe abnormal behaviors, respectively. The DOTES is a checklist that includes 33 possible side effects. The patient is assessed for the presence and severity of each side effect. The DOTES score ranges from 0 to 4, with higher scores indicating more severe side effects.

Two experienced psychiatrists administered the instruments to all patients. Before the study began, their interrater reliability, as measured by Cohen's kappa, was greater than .8 for both instruments. Student's t test was used to compare scores at the different time points. The significance level was set at .05.

The mean±SD HBSS score at the end of the week without medication was not significantly different from the score at the end of the placebo period (20.9±1.8 and 20.2±1.6, respectively). The DOTES score at the end of the placebo period was not significantly different from the score after fluvoxamine treatment (1.1±.2 and 1.1±.4). However, the HBSS score after fluvoxamine was significantly lower than the score at the end of the placebo period (10.9±.8 and 20.2±1.6; t=34.82, df=59, p< .001), indicating a reduction in the severity of aggressive behaviors.

Because of ethical and practical considerations, we could not conduct a more rigorous study. The findings must be considered preliminary because participants were not randomly assigned to treatment condition, the psychiatrists who administered the instruments were not blinded to the patients' treatment condition, and no control group was used. However, our results suggest that fluvoxamine is a well-tolerated treatment that is more effective than placebo in controlling aggression among adults with mental retardation.

The authors are affiliated with the study group for mental retardation in the department of neurological and psychiatric sciences at the University of Florence in Italy.