Lamotrigine rivals Lithium in Effectiveness for Acute Mania. (Randomized, Controlled Trial).
These findings were somewhat at odds with earlier findings from open trials and case reports, which had suggested that lamotrigine has more antidepressant than antimanic properties, said Dr. Ichim of the University of Witwatersrand in Johannesburg, South Africa.
Lamotrigine, a novel anticonvulsant, appears to have diverse mechanisms of action, including inhibition of the release of the excitatory neurotransmitter glutamate, calcium channel blockade, and an effect on voltage-sensitive sodium channels, which are believed to play a role in bipolar disorder.
The study, which received the George Winokur Clinical Research Award from the AACP, involved 30 patients who were hospitalized for acute mania and randomized to receive lamotrigine (titrated up to 100 mg/day) or lithium (400 mg/day) for 4 weeks. Most had had two or more prior episodes and were severely ill when they entered the study.
Patients also received lorazepam (4-12 mg/day) and biperidin (2-6 mg/day) as needed for control of aggression and acute dystonia, he said.
Changes in various measures of illness severity were comparable and highly significant with both drugs: Mania Rating Scale scores, for example, declined from 31.6 to 13.1 with lithium and from 37.4 to 14.3 with lamotrigine. Global Assessment of Functioning scores rose from around 45 to about 60, and there were no significant differences in Clinical Global Impression of Severity of Illness or Improvement scores between the groups, Dr. Ichim said.
The use of lorazepam was comparable whether lithium or lamotrigine were used, and biperiden use was negligible.
By the end of the study, "patients were better but not well," he said.
No significant adverse effects were seen in either group. In addition, there were no rashes in the lamotrigine group even though titration had been more rapid than the manufacturer advises, Dr. Ichim said.