A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders

There is a pressing need for additional treatment options for refractory mo od disorders. This controlled comparative study evaluated the efficacy of l amotrigine (LTG) and gabapentin (GBP) monotherapy versus placebo (PLC). Thi rty-one patients with refractory bipolar and unipolar mood disorders partic ipated in a double-blind, randomized, crossover series of three 6-week mono therapy evaluations including LTG, GBP, and PLC. There was a standardized b linded titration to assess clinical efficacy or to determine the maximum to lerated daily dose (LTG 500 mg or GBP 4,800 mg). The primary outcome measur e was the Clinical Global Impressions Scale (CGI) for Bipolar Illness as su pplemented by other standard rating instruments. The mean doses at week 6 w ere 274 +/- 128 mg for LTG and 3,987 +/- 856 mg for GBP. Response rates (CG I ratings of much or very much improved) were the following: LTG, 52% (16/3 1); GBP, 26% (8/31); and PLC, 23% (7/31) (Cochran's Q = 6.952, df = 2, N = 31, p = 0.031). Post hoc Q differences (df = 1, N = 31) were the following: LTG versus GBP (Q, 5.33, p = 0.011); LTG versus PLC (Q(diff) = 4.76, p = 0 .022); and GBP versus PLC (Q(diff) = 0.08,p = 0.70). With respect to antico nvulsant dose and gender, there was no difference between the responders an d the nonresponders. The agents mere generally well tolerated. This control led investigation preliminarily suggests the efficacy of LTG in treatment-r efractory affectively ill patients. Further definition of responsive subtyp es and the role of these medications in the treatment of mood disorders req uires additional study.