BACKGROUND: The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD. METHODS: Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated. RESULTS: Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated. CONCLUSIONS: Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.