A number of randomized-controlled trials (RCTs) have been conducted comparing the efficacy of piracetam with placebo and other medications in children with breath-holding spells (BHS). However, no systematic review has yet collated all this evidence. All RCTs comparing the efficacy and/or safety of piracetam with placebo or other medications in children with BHS were included. The pooled estimates were compared for the number of participants with a favorable response, the change in monthly frequency of BHS, compliance, and adverse effects in both groups. The ROB 2.0 tool was used to assess the risk of bias, and the GRADE system was used to determine the certainty of the collated evidence. We included 5 RCTs (437 participants) in the review. Piracetam group had significantly more participants with favorable responses at 1, 2 and 3 months after randomization, as compared to placebo group (RR: 6.5 (95% CI-1.8–23.2), I2 = 75%, p = 0.004, RR: 4.7 (95% CI-3.3–6.7), I2 = 49%, p < 0.0001, RR: 5.4 (95% CI-3.4–8.5), I2 = 0%, p < 0.0001 respectively). Number of participants with complete response or total cessation of attacks was more in the piracetam group compared to placebo (RR: 5.7 (95% CI-1.4–23.2), I2 = 88%, p = 0.01). Change in the average number of BHS was significantly more in the piracetam group, as compared to the placebo group (mean difference-4.9 (95% CI-0.7–9.0), I2 = 99%, p = 0.02). Number of participants with treatment-emergent adverse effects were comparable in both piracetam and placebo groups (RR: 1.9 (95% CI-0.5–7.6), I2 = 0%, p = 0.33).

Conclusion: Oral piracetam is efficacious and safe in children with BHS, and its efficacy may further increase by co-administration of oral docosahexaenoic acid.

What is known?

• Breath-holding spells (BHS) are a common pediatric condition, affecting 0.1% to 4.6% of otherwise healthy children.

• Several studies have investigated the efficacy of piracetam in reducing the frequency and severity of BHS, with mixed results.

What is new?

• Oral piracetam is efficacious and safe in children with BHS.

• Its efficacy is further increased by co-administration of oral docosahexaenoic acid.