In the past several years, two new studies have been published examining the efficacy (in pristine, experimental conditions; rigorous selection criteria, minimal comorbid conditions) and effectiveness (real world variability) of lamotrigine (Lamictal) in the treatment of acute bipolar depression [1, 2]. These and other studies were recently summarized in a review paper by Amann and colleagues in the Journal of Psychopharmacology[3]. Attempting to synthesize disparate findings, Amann concludes that “…the antidepressant effect of LTG in acute bipolar depression, if it exists, is small.”
These data support our own clinical work with this anticonvulsant, where we consistently find its acute antidepressant effects quite limited. In our practice, we now reserve lamotrigine for use with residual depressive symptoms, which either fail to respond to primary mood stabilizers or other antidepressant treatment, or that fail to clear with the remission of the depressive episode. We are less pessimistic but still uncertain about lamotrigine’s efficacy in the long-term prevention of depressive episodes.
This emerging profile of lamotrigine as a marginal antidepressant stands in stark contrast to the fanfare announcing its arrival in the late 1990’s when it was viewed as the Holy Grail for the treatment and prevention of bipolar depression. This recalibration parallels our growing recognition of the limited potential of standard antidepressants, in general, in the therapy of the depressed phase of this illness[4].