Levetiracetam for treatment of premenstrual dysphoric disorder: a pilot, open-label study

Kindling and impaired electroencephalophysiology have been suggested to play a role in the pathophysiology of premenstrual dysphoric disorder (PMDD). Levetiracetam is a novel antiepileptic drug which has shown strong anti-kindling activity in animal models of epilepsy. In this preliminary prospective study we examined the safety and efficacy of levetiracetam for the treatment of PMDD. One hundred twenty-three potential patients were prospectively screened to enroll seven patients into the open-label treatment phase of the study. PMDD was diagnosed per DSM-IV-TR criteria and two consecutive months of prospective ratings of Daily Record of Severity of Problems (DRSP). The Mini International Neuropsychiatric Interview (MINI) was used to exclude any co-morbid conditions. Levetiracetam was started at 250 mg qhs at the end of the first week of the follicular phase. Dosage was gradually increased up to 1,500 mg bid as tolerated or clinically effective. The treatment phase lasted 4 months. Response to treatment was evaluated by Clinical Global Impression (CGI) and DRSP scores. Six out of seven patients experienced a considerable decrease in their DRSP scores with levetiracetam, starting from the first treatment cycle. One patient dropped out of the study due to lack of efficacy after one cycle. Medication was fairly well tolerated. Improvements in food cravings and premenstrual headaches were also noted as unexpected benefits. Anticonvulsant medications, specifically levetiracetam, could be effective in the treatment of PMDD. Future double-blind, placebo controlled, randomized studies are warranted and should include larger number of patients.