Dean Elbe1, Zaahira Lalani. 1. Children's and Women's Mental Health Programs, BC Children's Hospital, Vancouver, British Columbia.
Abstract
OBJECTIVE: To review the randomized controlled trial data regarding pharmacotherapy of irritability of autism. METHOD: A LITERATURE REVIEW WAS CONDUCTED USING THE MEDLINE SEARCH TERMS: 'autism' OR 'autism spectrum disorder' with the following limits: Randomized Controlled Trials (RCTs), human trials, English language. Additional articles were identified from reference information. Trials involving nutritional supplements, hormones or drugs not approved by either Health Canada or the US Food and Drug Administration (FDA) were excluded from analysis. RESULTS: Twenty-three RCTs that met criteria were identified. The greatest number of RCTs involved risperidone, with six of seven placebo-controlled risperidone trials reporting statistically significant improvements on the primary outcome measure. Two aripiprazole RCTs and one olanzapine RCT reported statistically significant improvement in primary outcome measures. Haloperidol was superior to both clomipramine and placebo in a head-to-head crossover trial, while risperidone was superior to haloperidol for treatment of behavioural symptoms in a separate head-to-head trial. Clonidine, methylphenidate, valproate and levocarnitine monotherapy were superior to placebo in single RCTs, while adjunctive treatments cyproheptadine, pentoxifylline and topiramate were superior to placebo in small studies when given in combination with an antipsychotic. Adverse events from RCTs were summarized, including weight gain and metabolic effects, if available. CONCLUSION: The bulk of positive RCT evidence for the pharmacotherapy of irritability of autism pertains to FDA approved antipsychotics risperidone and aripiprazole. RCTs supporting efficacy of several alternative and adjunctive agents may afford additional treatment options when optimal antipsychotic doses fail to control symptoms or cause intolerable adverse effects. Behavioural therapy should be employed where possible either before, or in addition to pharmacotherapy.
OBJECTIVE: To review the randomized controlled trial data regarding pharmacotherapy of irritability of autism. METHOD: A LITERATURE REVIEW WAS CONDUCTED USING THE MEDLINE SEARCH TERMS: 'autism' OR 'autism spectrum disorder' with the following limits: Randomized Controlled Trials (RCTs), human trials, English language. Additional articles were identified from reference information. Trials involving nutritional supplements, hormones or drugs not approved by either Health Canada or the US Food and Drug Administration (FDA) were excluded from analysis. RESULTS: Twenty-three RCTs that met criteria were identified. The greatest number of RCTs involved risperidone, with six of seven placebo-controlled risperidone trials reporting statistically significant improvements on the primary outcome measure. Two aripiprazole RCTs and one olanzapine RCT reported statistically significant improvement in primary outcome measures. Haloperidol was superior to both clomipramine and placebo in a head-to-head crossover trial, while risperidone was superior to haloperidol for treatment of behavioural symptoms in a separate head-to-head trial. Clonidine, methylphenidate, valproate and levocarnitine monotherapy were superior to placebo in single RCTs, while adjunctive treatments cyproheptadine, pentoxifylline and topiramate were superior to placebo in small studies when given in combination with an antipsychotic. Adverse events from RCTs were summarized, including weight gain and metabolic effects, if available. CONCLUSION: The bulk of positive RCT evidence for the pharmacotherapy of irritability of autism pertains to FDA approved antipsychotics risperidone and aripiprazole. RCTs supporting efficacy of several alternative and adjunctive agents may afford additional treatment options when optimal antipsychotic doses fail to control symptoms or cause intolerable adverse effects. Behavioural therapy should be employed where possible either before, or in addition to pharmacotherapy.
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