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Bipolar Disorder: Increasing the Effectiveness and Decreasing the Side Effects of Treatment: Page 7 of 11

Bipolar Disorder: Increasing the Effectiveness and Decreasing the Side Effects of Treatment: Page 7 of 11

Three relatively recent studies have compared lithium with placebo. One included 175 patients with a recent manic or hypomanic episode,44 another included 463 patients with a recent episode of bipolar depression,45 and the third included 372 patients in symptomatic remission from a manic episode.8 Lithium mean serum levels ranged from 0.8 to 1.0 mEq/L. Study discontinuations were notable. Only 2% of subjects treated with lithium in the study by Bowden and colleagues44 and 17% of patients treated with lithium in the study by Calabrese and colleagues45 completed the trials. Lithium significantly delayed time to intervention for a mood episode and time to intervention for a manic episode in the first 2 studies44,45 but did not separate from placebo on these parameters in the third.8 Lithium failed to delay time to a depressive episode in all 3 studies. Treatment emergent adverse events were more prevalent in the lithium group, including nausea, diarrhea, tremor, and somnolence.

A meta-analysis of randomized controlled trials that compared lithium with placebo, excluding trials that abruptly discontinued lithium, found 5 studies ranging in length from 11 months to 4 years.7 Overall, study withdrawal was lower with lithium relative to placebo. Lithium was more effective in preventing a new affective episode, with an average relapse rate of 40% over 1 to 2 years compared with 60% in the placebo group. In addition, lithium had a lower rate of manic or mixed recurrences. There was no difference in the rate of depressive episodes. The side effects seen more frequently with lithium were somnolence, nausea, and diarrhea.

Studies have also focused on the relationship between lithium treatment and suicidal acts. Findings have consistently demonstrated a reduced rate of suicide attempts and completions during lithium maintenance treatment compared with patients who did not take lithium.46-49 An analysis of 34 trials that included 17,491 patients with major affective illnesses found that the overall rate of suicidal acts in the group without lithium was 3.1% per year compared with 0.2% per year among patients who received lithium treatment.46 In a subgroup analysis, the rate of suicidal acts in patients with bipolar disorder decreased from 6.1% per year without lithium to 0.295% per year with lithium, a 95% risk reduction.

Lamotrigine. Two randomized controlled trials compared lamotrigine with placebo.44,45 Dosing of lamotrigine ranged from 50 to 400 mg. Patients recovering from manic episodes had a 5% study completion rate, compared with 0% in the placebo group. Patients recovering from a depressive episode had a 17% completion rate versus 10% in the placebo group. Lamotrigine was superior to placebo in delaying time to intervention for any mood episode and time to intervention for a depressive episode. Lamotrigine did not separate from placebo in delaying time to intervention for a manic episode in either study, but a combined analysis of both studies found a significant difference.50 In the combined analysis, lamotrigine did not separate from placebo on any adverse event.

 
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