Olanzapine More Effective for Preventing Mania Relapse

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							May 19, 2004

Mark Lewis

June 18, 2003 (Pittsburgh) — Olanzapine was tolerated better and prevented mania relapse more effectively than lithium, a recent study showed.

Mauricio Tohen, MD, PhD, from Harvard Medical School's Department of Psychiatry, Cambridge, Massachusetts, presented the results here at the 5th International Conference on Bipolar Disorders.

"When you have a new drug, you compare it to the gold standard and certainly lithium is that gold standard, Dr. Tohen told Medscape. "Lithium is thought to be quite effective at preventing mania," he added. "What was interesting," Dr. Tohen emphasized, "...was that olanzapine was more effective."

Olanzapine also was better than lithium at preventing mixed episodes. But, Dr. Tohen noted, "We found no difference in the prevention of depression."

Dr. Tohen said that overall "olanzapine appears to be more effective in the prevention of relapses in bipolar disorder as compared to lithium."

The study included 543 patients diagnosed with bipolar I, either manic or mixed types. All patients had a history of two manic episodes or two mixed episodes in last six years and a Young Mania Rating Scale (YMRS) total score 20 or higher. Prior to randomization, all patients received an open-label combination therapy of olanzapine and lithium for six to 12 weeks.

Symptomatic remission was achieved by 431 patients, who were then randomized in a double-blind fashion to monotherapy with either olanzapine or lithium for 52 weeks. Remission criteria were a YMRS score of 12 or less and a Hamilton Depression Rating Scale (HAM-D-21) score of 8 or less. The olanzapine group (n = 217) received 5 to 20 mg/day, and the lithium group (n = 214) had a target serum drug level of 0.6 to 1.2 mEq/L, with doses ranging from 300 to 1800 mg/day.

More olanzapine patients finished the trial — 46.5% compared with 32.7% of the lithium patients (P = .004). Relapse to affective episode (defined as a YMRS total score 15 or higher or a HAMD-21 total score of 15 or higher) occurred in 30.0% of olanzapine patients and in 38.8% of lithium patients (P = .055).

The difference in incidence of relapse into manic episode between the olanzapine group and the lithium group was significant (14.3% vs. 28.0%, respectively; P < .001). The two groups had similar incidences of relapse into depressive episode (16.1% vs. 15.4%; P = .895). There was not a significant difference between rates of discontinuation due to adverse events between the two groups (18.9% vs. 25.7%; P = .105).

During the two phases of the study period, the olanzapine group showed significant weight gain compared with the lithium group (1.79 kg vs. 1.38 kg, respectively; P < .001).

Tom Brown, a psychiatrist from Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina, told Medscape that he was "not surprised" by the findings. "The half-life of olanzapine is very long. It has a mean half-life of 30 hours." Dr. Brown said that a missed dose would not affect blood levels much, likely increasing tolerance.

Regarding the popularity of lithium, Dr. Brown said, "Lithium just happened to be the first one on the scene" and that there are a number of agents that are likely to be superior to lithium.

Olanzapine, however, still may have some problems, said Dr. Brown, including weight gain and diabetes. "It's a topic open to discussion," he said.

A far-reaching impact of the study, Dr. Tohen noted, is that "the overall prevention of hospitalization was larger in the olanzapine-treated patients than the lithium-treated patients" for both manic and depressive episodes. "And prevention of hospitalization is a big cost [savings] to the family and to society."

Dr. Tohen said he plans to compare olanzapine to other new agents as well as look into the neuroprotective effects of olanzapine.

Eli Lilly and Company funded this research.

5th ICBD: Abstract P201. Presented June 13, 2003.

Reviewed by Gary D. Vogin, MD

Mark Lewis is a freelance writer for Medscape.

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