Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo. Opioid antagonist effects on self-injury in adults with mental retardation: response form and location as determinants of medication effects. An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior. Sequential analysis of the effects of naltrexone on the environmental mediation of self-injurious behavior. Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies.
The efficacy of the serotonin (5-HT) uptake inhibitor clomipramine in the treatment of self-injurious behavior (SIB) was tested in individuals with severe and profound mental retardation. Six of the 8 subjects who completed a double-blind, placebo-controlled crossover trial exhibited a clinically significant improvement (50% or greater reduction from placebo) in the frequency of SIB. Clomipramine treatment was also associated with improvement in SIB intensity, frequency of stereotypy and compulsions, teacher ratings of stereotypy and social withdrawal, and frequency of staff intervention required for problem behaviors. Adverse effects (seizure and tachycardia/agitation) occurred in 2 of the 8 subjects. These results represent the first controlled trial of a 5-HT uptake inhibitor in the treatment of SIB in mental retardation. The opioid antagonist naltrexone was administered to 8 adults with severe or profound mental retardation and extensive histories of self-injurious behavior. Five-minute behavioral samples were observed randomly out of every hour from 8 a.m. through 3 p.m., Monday through Friday, for four 2-week phases (baseline, placebo, 50 mg, and 100 mg). During naltrexone administration, there were fewer days with frequent head-banging and self-biting, whereas there were more days on which blows to the head or self-biting were infrequent. Self-injurious participants slept 1.38 hours less per night during baseline, which was unaffected by naltrexone. Several recent reports have indicated that opioid blockers are effective in attenuating self-injurious behavior (SIB). In the present study, four patients with SIB were challenged with four fixed doses (0, 25, 50, 100 mg) of naltrexone. In a double-blind procedure, all patients received each dose on a different week as determined by latin square design. Naltrexone was given on Monday and Wednesday of each week, and patients were videotaped daily for 10 minutes in the morning and afternoon. The tapes were scored for incidents of SIB, stereotypy, and activity, with interrater reliability of 0.93. The Conners Teacher Rating Scale was administered by staff in the morning and afternoon each day. The Vineland was completed each week (Thursday). All patients had decreased SIB when treated with naltrexone. Three patients decreased their SIB as dose of naltrexone increased. There were no consistent effects of naltrexone on stereotypy, activity, or performance on the Conners or the Vineland. These results suggest that endogenous opioids are implicated in SIB and that naltrexone is a powerful tool for examination of this treatment-resistant behavior. Accumulated evidence shows that biology and the environment can mediate self-injurious behavior (SIB) in persons with mental retardation. Whether pharmacological treatment alters the environmental mediation of self-injury is unclear. Opioid antagonist effects on sequential dependencies for self-injury were studied in the context of experimental single-subject double-blind placebo-controlled designs. Direct observational data were collected for 4 adult subjects in real time on daily rate of SIB and staff interactions. Clinically significant reductions (i.e., > or = 33%) in SIB rate were observed for 3 of the 4 subjects. For all subjects, the magnitude of the sequential dependency between staff behavior and self-injury was significantly greater during treatment with naltrexone than during treatment with a placebo. Results are discussed in relation to behavioral mechanisms of action regulating medication effects for self-injury. It is hypothesized that self-injurious behavior (SIB) and symptoms of autism may be due to overactivity in some opioid systems in the brain. We examined the efficacy and safety of naltrexone hydrochloride, an opioid antagonist, in the treatment of SIB and autism in mentally retarded adults.
                Thirty-three mentally retarded adults with autism and/or SIB participated in double-blind, placebo-controlled crossover studies. Active treatment was first a single 100-mg dose of naltrexone hydrochloride. Subsequently, 19 subjects were treated with 50 mg/d and 14 with 150 mg/d of naltrexone hydrochloride for 4 weeks. The outcome was assessed by means of direct observations (n = 11) and on the basis of scores on a list of target behaviors, the Aberrant Behavior Checklist, and the Clinical Global Impression Scale.
                Thirty-two subjects (seven with autism, 16 with autism and SIB, and nine with SIB) completed the trial. Naltrexone treatment failed to have therapeutic effects on SIB and autism. On the contrary, naltrexone increased the incidence of stereotypic behavior on the Aberrant Behavior Checklist, and the care staff evaluated the effect of the 50-mg/d treatment as being significantly worse than that of the placebo treatment as measured by the Clinical Global Impression Scale.
                Our findings suggest that naltrexone has no clinical value for a broad group of mentally retarded subjects with SIB and/or autism.
There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating SIB. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo.