ANTIDEPRESSANTS FOR REPETITIVE RESTRICTED BEHAVIORS IN AUTISM SPECTRUM DISORDER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Maneeton *Benchalak , Maneeton Prapinpatch , Winichaikul Yanisa , Kawilapat Suttipong , Kienngam Nongluck , Maneeton Narong 
Published: February 2025

Background

Although previous randomized controlled trials (RCTs) illustrated the efficacy of antidepressants in repetitive restricted behaviors (RRBs) in autism spectrum disorder (ASD), the outcome determining the efficacy of antidepressants in RRBs in ASD remains inconsistent 1-4

Aims & Objectives

We aimed to systematically review the efficacy, acceptability, and tolerability of antidepressants in the treatment of RRBs in patients with ASD.

Method

The authors searched relevant RCTs in the CINAHL, Cochrane Library, PubMed, and Scopus databases from inception to August 16, 2023. The primary outcomes of this review were efficacy, acceptability, and tolerability. The difference in the pooled mean endpoint scores of standardized rating scales for ASD RRBs was estimated to evaluate the efficacious outcomes. An inverse variance, weighing the effect of individual RCT was applied to estimate the pooled mean endpoint scores with 95% confidence intervals (CIs). The RRs with 95% CIs were thoroughly applied for discontinuation rates. All pooled RRs with 95% CIs were calculated using Mantel-Haenszel.

Results

We included 599 randomized participants from eight RCTs for the synthesis in this review. The overall pooled mean-end score of the RRBs between the antidepressant and placebo-treated groups was not significantly different [SMD (95% CI) of -0.27(-0.56, 0.02), I2=59%]. The pooled mean endpoint for RBB in ASD patients of the clomipramine-treated group was significantly less than desipramine-treated group [SMD (95% CI) of -1.11(-1.80, -0.41), I2=0%]. Considered individually, only clomipramine and fluvoxamine illustrated some efficacy over placebo. There were no significant differences in the overall discontinuation rates and discontinuation due to adverse events. Additionally, adverse events were not significantly different between the antidepressant and placebo-treated groups.

Discussion & Conclusion

The synthesis of results shows the various outcomes of antidepressants in the treatment of RRB symptoms. Clomipramine and fluvoxamine appear to have some efficacy in the reduction of RRBs in ASD but are not found in other antidepressants. Although antidepressants are well tolerated with minimal side effects, their acceptability is not better than placebo. Further well-defined and large sample-size studies could verify these outcomes.

References

1.GORDON, C. T., NELSON, J. E., HAMBURGER, S. D. &RAPOPORT, J. L. 1993. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Archives of General Psychiatry, 50, 441-447.

2.HERSCU, P., HANDEN, B. L., ARNOLD, L. E., SNAPE, M. F., BREGMAN, J. D., GINSBERG, L., HENDREN, R., KOLEVZON, A., MELMED, R. &MINTZ, M. 2020. The SOFIA study: negative multi-center study of low dose fluoxetine on repetitive behaviors in children and adolescents with autistic disorder. Journal of autism and developmental disorders, 50, 3233-3244.

3.KING, B. H., HOLLANDER, E., SIKICH, L., MCCRACKEN, J. T., SCAHILL, L., BREGMAN, J. D., DONNELLY, C. L., ANAGNOSTOU, E., DUKES, K. &SULLIVAN, L. 2009. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Archives of general psychiatry, 66, 583-590.

4.MCDOUGLE, C. J., NAYLOR, S. T., COHEN, D. J., VOLKMAR, F. R., HENINGER, G. R. &PRICE, L. H. 1996. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Archives of general psychiatry, 53, 1001-1008.