N-acetylcysteine is effective as add-on therapy to risperidone-based combination for children with autistic disorders

We read with great interest a recent meta-analysis by Lee et al. (2021) that investigated the effectiveness of N-acetylcysteine in patients with autism spectrum disorders (ASD). The authors of that study showed that N-acetylcysteine (NAC) supplementation was effective for treating irritability and hyperactive in this patient population with an overall improvement in the aberrant behavior checklist (ABC) total score, thereby concluding that NAC is safe, tolerable and effective in improving ASD’s comorbid symptoms (Lee et al., 2021). However, there is a potential concern regarding how the results of individual studies were pooled to produce total effect sizes. Among those five randomized controlled trials included in that meta-analysis, three used NAC in addition to existing treatments without controlling for the use of other medications (Dean et al., 2017; Hardan et al., 2012; Wink et al., 2016), while two studies compared NAC plus risperidone versus risperidone treatment alone (Ghanizadeh and Moghimi-Sarani, 2013; Nikoo et al., 2015). Taking into account potential fundamental differences between the use of NAC as supplementation to other treatments and as a component of the NAC-risperidone combination, grouping all five studies together may give misleading results guiding clinical practice.

Therefore, we conducted a meta-analysis in a different way by putting NAC-risperidone combination as one group and grouping NAC supplementation to other treatments as another. Our results, which were quite different from those of that meta-analysis (Lee et al., 2021), failed to show effectiveness of NAC supplementation for improving irritability in patients with ASD (Figure 1[a]). Instead, NAC was only effective when used as add-on therapy to risperidone when compared with risperidone treatment alone in respect of improving irritability among patients with ASD (Figure 1[b]). Our findings suggest that current evidence only support the use of NAC as add-on therapy to risperidone for irritability in patients with ASD rather than as supplementation to other treatments.

Figure 1.

Forest plots comparing the changes in severity of irritability of autistic spectrum disorder between (a) N-acetylcysteine and placebo groups, (b) N-acetylcysteine /risperidone and placebo/risperidone groups.