Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder

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Abstract

Objective:

To test the efficacy of venlafaxine at a dose of 18.75 mg/day on the reduction of behavioral problems such as irritability and hyperactivity/noncompliance in patients with intellectual disabilities and autism spectrum disorder (ASD). Our secondary hypothesis was that the usual doses of zuclopenthixol and/or clonazepam would decrease in the venlafaxine-treated group.

Methods:

In a randomized double-blind study, we compared six patients who received venlafaxine along with their usual treatment (zuclopenthixol and/or clonazepam) with seven patients who received placebo plus usual care. Irritability, hyperactivity/noncompliance, and overall clinical improvement were measured after 2 and 8 weeks, using validated clinical scales.

Results:

Univariate analyses showed that the symptom of irritability improved in the entire sample (p = 0.023 after 2 weeks, p = 0.061 at study endpoint), although no difference was observed between the venlafaxine and placebo groups. No significant decrease in hyperactivity/noncompliance was observed during the study. At the end of the study, global improvement was observed in 33% of participants treated with venlafaxine and in 71% of participants in the placebo group (p = 0.29). The study found that decreased cumulative doses of clonazepam and zuclopenthixol were required for the venlafaxine group. Multivariate analyses (principal component analyses) with at least three combinations of variables showed that the two populations could be clearly separated (p < 0.05). Moreover, in all cases, the venlafaxine population had lower values for the Aberrant Behavior Checklist (ABC), Behavior Problems Inventory (BPI), and levels of urea with respect to the placebo group. In one case, a reduction in the dosage of clonazepam was also suggested. For an additional set of variables (ABC factor 2, BPI frequency of aggressive behaviors, hematic ammonia at Day 28, and zuclopenthixol and clonazepam intake), the separation between the two samples was statistically significant as was the Bartlett's test, but the Kaiser–Meyer–Olkin Measure of Sampling Adequacy was below the accepted threshold. This set of variables showed a reduction in the cumulative intake of both zuclopenthixol and clonazepam.

Conclusion:

Despite the small sample sizes, this study documented a statistically significant effect of venlafaxine. Moreover, we showed that lower doses of zuclopenthixol and clonazepam were needed in the venlafaxine group, although this difference was not statistically significant. This was confirmed by multivariate analyses, where this difference reached statistical significance when using a combination of variables involving zuclopenthixol. Larger-scale studies are recommended to better investigate the effectiveness of venlafaxine treatment in patients with intellectual disabilities and ASD.

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