To evaluate the effectiveness of vigabatrin (VGB) compared to hormonal therapy (HRT), placebo, ketogenic diet, or combination therapy in achieving seizure freedom in infantile spasms (IS).

VGB is widely used for IS, but its comparative efficacy remains debated. We synthesized evidence from randomized controlled trials (RCTs) and observational studies (OS) to clarify its role in clinical practice.

We conducted a meta-analysis of 23 PubMed-indexed studies (n ≈ 2,000) reporting seizure freedom in IS patients without tuberous sclerosis complex. Random-effects models (DerSimonian-Laird) were applied using the Mantel-Haenszel method to pool risk ratios (RR) with 95% confidence intervals (CI). Heterogeneity was assessed with I² and Cochran’s Q. Publication bias was evaluated using Egger’s and Begg’s tests, trim-and-fill, and fail-safe N analyses.

The random-effects model demonstrated a significant benefit of VGB: log RR = -0.16 (95% CI: -0.32 to -0.006; p = 0.04), corresponding to RR ≈ 0.85. Prediction interval ranged from -0.73 to 0.41. Heterogeneity was low (I² = 0.6%). Subgroup analyses showed consistent effects: RCTs comparing VGB vs HRT (log RR = -0.20; 95% CI: -0.41 to -0.003) and observational studies (log RR = -0.24; 95% CI: -0.40 to -0.08). Combination therapy (VGB + HRT) showed no clear advantage (log RR = 0.13; 95% CI: -0.28 to 0.53). Egger’s test indicated small-study effects (p = 0.019), and trim-and-fill suggested six missing studies, reducing the effect size by 66%. Fail-safe N was 12, indicating susceptibility to publication bias.

VGB significantly improves seizure freedom compared to other therapies, with consistent effects across RCTs and observational studies. However, evidence of small-study effects and potential publication bias warrants cautious interpretation. Further large-scale trials are needed to confirm these findings.