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. Tianeptine: a novel strategy of psychopharmacological treatment of children with autistic disorder.
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. Many autistic children have problems of eye contact and expressive language that limit the effectiveness of educational and behavioural interventions. Few controlled psychopharmacological trials have been conducted in autistic children to determine which agents may be effective for these associated features.
                Twelve male children (7.3 +/- 3.3 years) with autistic disorder, diagnosed by ICD-10 criteria, completed a placebo-controlled, double-blind crossover trial of tianeptine, which lasted for 12 weeks. Subjects were included in the study if their eye contact and expressive language was inadaequate for their developmental level. Subjects had not tolerated or responded to other psychopharmacological treatments (neuroleptics, methylphenidate, clonidine or desipramine).
                Teacher ratings on the aberrant behaviour checklist irritability, stereotypy and inappropriate speech factors were lower during treatment with tianeptine than during treatment with placebo. Clinician ratings (children's psychiatric rating scale autism, anger and speech deviance factors; children's global assessment scale; clinical global impressions efficacy) of videotaped sessions were not significantly different between tianeptine and placebo.
                Tianeptine were modestly effective in the short-term treatment of irritability in some children with autistic disorder.
                Copyright 2003 John Wiley & Sons, Ltd.
Clinicians considering the use of TCAs need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have ASD and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD.