Treatment for autism

FENFLURAMINE

The finding of hyperserotonemia in one third of autistic children led to the hypothesis that autistic symptoms may be due to increased brain serotonin levels. That hypothesis in turn led to the study of fenfluramine, a serotonin depleter, in autistic children. In several studies fenfluramine was reported to decrease stereotypies and hyperactivity, increase intellectual functioning, foster language development, and improve social relatedness. However, those studies had serious methodological flaws. One well-designed double-blind, placebo-controlled study with random assignment of children having a narrow age range and which assessed cognition in a learning laboratory failed to show a difference for fenfluramine (optimal daily dosage range, 1.250 to 2.068 mg/kg) over placebo in reducing problem behaviors; learning was adversely affected by fenfluramine.

Similarities between the behaviors of autistic children and the behaviors of opiate addicts while intoxicated and during withdrawal led to the theory of opioid dysregulation in autism. Case reports and open trials involving a small number of children suggested that naltrexone, an opioid antagonist, reduced stereotypies, withdrawal, and hyperactivity and increased language production. In a recently completed double-blind, placebo-controlled study of naltrexone, the only significant finding in 41 autistic children, aged 2.9 to 7.8 years, who received dosages of 0.5 to 1.0 mg/kg a day of naltrexone was a decrease in hyperactivity; naltrexone had no adverse effect on learning in the laboratory, and the side effects of drowsiness, nausea, and vomiting were mild and transient. There was a suggestion that naltrexone might decrease self-injurious behavior.

SYMPATHOMIMETICS

The efficacy of amphetamines was investigated in autistic children because hyperactivity and inattention, frequently seen in such children, are ameliorated by amphetamines in nonautistic children with attention-deficit/hyperactivity disorder. Early studies of a large number of autistic children reported decreases in hyperactivity and increases in attention span, although severe behavioral toxicity and worsening of stereotypies were also observed. More recently, an open trial of methylphenidate (Ritalin) (optimal daily dose range, 10.0 to 50.0 mg) in nine autistic children resulted in a marked decrease in hyperactivity without major side effects.

CLOMIPRAMINE

Clomipramine (Anafranil online), an antidepressant, inhibits the reuptake of serotonin, which has been implicated in the pathogenesis of autistic disorder. A recent double-blind, placebo-controlled crossover study found clomipramine to be superior to both desipramine (Norpramin) and placebo in decreasing obsessive-compulsive symptoms, anger, and core autistic symptoms, including withdrawal and abnormal object relations. The sample consisted of 7 autistic individuals aged 6 to 18 years. The mean dosage of clomipramine was 129 mg a day (4.3 mg/kg a day). However, in a recent pilot study conducted on eight hospitalized children, aged 3.5 to 8.7 years, clomipramine yielded therapeutic changes in only one child. Untoward effects were numerous and included acute urine retention, constipation, and behavioral effects indicating toxicity; the daily dosage ranged from 2.50 to 4.64 mg/kg (mean, 3.14 mg/kg a day).

CLONIDINE

The possibility that some symptoms of autism reflect hyperarousal and dysregulation of the adrenergic system led to the study of clonidine (Catapres), an alpha2 -adrenergic agonist that reduces noradrenergic activity. In one recent double-blind, placebo-controlled study, clonidine was found to be superior to placebo in decreasing certain problem behaviors. The transdermal administration of clonidine at a mean dosage of 0.005 mg/kg a day was associated with a decrease in stereotypies, withdrawal, hyperactivity, and temper outbursts in nine autistic male patients aged 5 to 33 years. A second double-blind, placebo-controlled study on eight autistic boys aged 5 to 13 years who were hyperactive and impulsive found modest decreases in teacher and parent ratings of hyperactivity and irritability; clinicians’ ratings, however, failed to support an effect for clonidine.

The efficacy of various other psychopharmacological agents, including buspirone (BuSpar online), propranolol (Inderal), and fluoxetine, in a few autistic persons has been reported.

Leave a Reply

Your email address will not be published. Required fields are marked *