For most of his life, the 12-year old autistic boy had uttered only single words or short phrases. A constant anxiety flared into panic if he noticed that the table was not see in just the right way for a meal. He flapped his arms for hours at a time, shunning toys of other children. A scar on his neck testified to the repeated scratching he inflicted on himself.
Then the boy entered a drug experiment in which he received clomimpramine, an antidepressant previously found to reduces the vexing rituals of obsessive-compulsive disorder (SN: 5/21/88, p.324), as well as compulsive hair pulling (SN: 9/9/89, p.175) and nail biting. Not only did the boy's arm flapping subside markedly within a few weeks of clomipramine treatment, but his anxiety, self-injury and social withdrawal lessened. Toys he had not touched for years now drew his interest. Although still saddled with language difficulties and other autism-related problems, his progress remains steady after 18 months on the drug.
This case illustrates the encouraging, but preliminary, results of the first controlled trials of clomipramine in autistic children. "We're not talking night-and-day improvement for autistic children on clomipramine," cautions psychiatrist Charles T. Gordon of the National Instititute of Mental Health in Bethesda, Md., who has directed two clomipramine studies with a total of 25 autistic youngsters. "But this drug produces clinically significant behavior improvement for many of the kids we've studies."
Clomipramine treatment also allowed some autistic children to benefit more from behavior therapy, in which adults offer immediate rewards for appropriate actions, Gordon says.
In 1990, his team studied seven youngsters, ages 6 to 18, with mild to severe autistic symptoms (the boy described above displayed moderate symptoms). Participants had taken no psychoactive drugs for at least three months prior to the trial. For two weeks, each child received placebo pills. The children were then assigned at random to five weeks of treatment with either clomipramine or desipramine, an antidepresant with different biochemical effects. Five weeks of treatment with one drug was followed by five weeks of therapy with the other.
Neither experiments nor parents knew when a child got clomipramine or desipramine, and parents did not know the initial phase involved placebos.
Youngsters received increasing doses for two to three weeks until a positive response or side effects appeared; they then remained at that dosage.
Clomipramine proved much superior to desipramine and placebo, Gordon's group reports in the March American Journal of Psychiatry. Ratings of compulsive behavior, social withdrawal, anxiety, angry outbursts and self-injurious actions improved significantly with clomipramine. Both active drugs caused minor side effects, such as mild sleep problems and dry mouth.
At their parents' behest, four youngsters still take clomipramine and have maintained their improvement with minimal or no side effects, Gordon says.
In an unpublished 10-week study of 18 more autistic children, his group found similar improvement with clomipramine, but not with desipramine or placebo.
Moderate or "remarkable" improvement occurred among 15 of the 25 participants in the two trials, Gordon says. A long-term study of clomipramine use by autistic must follow, he adds.
Clomipramine increases the availability of the specific effects on serotonin receptors in the brain remain unclear, Gordon notes. Fenfluramine, another drug that alters serotonin supplies, has yielded mixed results with autistics. Clinicians often prescribe the antipsychotic drug haloperidol for autism, but its purported effectiveness and sometimes severe side effects have proved controversial.
Based on Clomipramine's effects, Gordon's team theorizes that all ritualistic, impulsive behaviors--whether they occur with autism or any other disorder--may stem from a "core" disturbance of serotonin function in the brain.
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