A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo. Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.
Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD. 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. 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. To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride.
                Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine.
                Outpatient clinic.
                A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study.
                Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale.
                Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity.
                Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored. Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.
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.