The anticonvulsant lamotrigine in treatment-resistant manic-depressive illness.

Anticonvulsants are used extensively in the treatment of bipolar disorder. Treating depression in bipolar disorder can be difficult because of the limited antidepressant effects of the standard mood stabilizers and the tendency of antidepressants to induce mania or decrease cycle length. Lamotrigine is a new anticonvulsant with few side effects that may have mood-stabilizing and elevating effects. Its mechanism of action probably involves the inhibition of excessive release of excitatory amino acids such as glutamate. Antiglutamatergic agents may be antidepressant and mood stabilizing. A case series of 16 patients treated with lamotrigine (dose range 50 mg to 250 mg, mean dose of responders = 141 mg) is presented along with two case reports. All patients were considered treatment-resistant bipolar type I or II. Patients were rated on average 5 weeks after starting lamotrigine using a semistructured follow-up form that included symptom rating, Clinical Global Impressions (CGI), and Global Assessment of Functioning (GAF) scores. Eight of 16 patients were rated as "responders" (CGI < or = 2) and had a mean increase of 16 in their GAF scores. Lamotrigine seems to have antidepressant and mood-stabilizing effects, but this requires confirmation in randomized, controlled trials.