Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia

Background Lamotrigine, a novel anticonvulsant drug having modulatory effects on glutamatergic neurotransmission, improves mood and cognition parameters in bipolar disorder. Recent studies suggest that when added to clozapine, lamotrigine treatment may result in significant positive symptoms reductions in schizophrenia. Similar effects were not observed in an open trial in which lamotrigine was used as adjuvant to nonclozapine antipsychotics. Methods Thirty-eight treatment-resistant schizophrenia inpatients receiving conventional and atypical antipsychotics enrolled in a 10-week, double-blind, placebo-controlled study, in which they were randomized in a 2:1 ratio to receive adjuvant treatment with lamotrigine, gradually titrated to a 400 mg/day dose, or placebo. Of these, 31 completed the trial. Measures of clinical efficacy and side effects were determined every other week. Serum levels of amino acids were assessed at the beginning and end of the study. Results In primary last observation carried forward analysis, no statistically significant between-group differences were observed; however, the completersʹ analyses revealed that lamotrigine treatment resulted in significant (p ≤ .05) reductions in positive and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale. No significant differences in lamotrigine effects were noted between conventional versus atypical antipsychotics. Lamotrigine treatment was well tolerated, and glutamate serum levels remained stable throughout the study. Conclusions These preliminary findings 1) support the hypothesis that lamotrigine adjuvant treatment may improve positive symptoms and general psychopathology in schizophrenia, 2) suggest that beneficial effects may be achieved when lamotrigine is added to both conventional and atypical antipsychotics, and 3) warrant additional, larger scale trials.