Five trials (n=161) were included. Sample size ranged from four to 60. All studies were rated as low risk of bias for allocation concealment. Two studies were funded by industry. No statistically significant heterogeneity was observed and so all results were from fixed-effect models.
Lamotrigine augmentation was superior to placebo for total symptom scores (SMD 0.57, 95% CI 0.25 to 0.89, I2= 37%), positive symptoms (SMD 0.34, 95% CI 0.02 to 0.65) and negative symptoms (SMD 0.43, 95% CI 0.11 to 0.76). Lamotrigine was associated with a higher proportion of patients who responded (OR 0.19, 95% CI 0.09 to 0.43; number needed to treat=4, 95% CI 3 to 6). There were three reports of severe adverse events that involved psychiatric symptoms after lamotrigine (with facial pain and gingival infection in one case) and two cases that involved psychiatric symptoms for placebo. Rash was reported in four lamotrigine and two placebo patients. There was no difference in drop-out rate.