Long-Term Combination Therapy Versus Monotherapy With Lithium and Carbamazepine in 46 Bipolar I Patients

Harvard University, Cambridge, Massachusetts, United States
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 03/2005; 66(2):174-82. DOI: 10.4088/JCP.v66n0204
Source: PubMed


Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies.
In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression.
Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%.
Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

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    • "A naturalistic study of bipolar I patients followed for 2 years after a mean of 4.5 years after hospitalization found that, those treated with lithium monotherapy had fewer relapses, as well as better adjustment and work performance (Goldberg et al., 1996). Other studies have found that lithium monotherapy has not been successful at improving quality of life for those with bipolar disorder (Tohen et al., 1990; Baethge et al., 2005; Bocchetta et al., 1997). These mixed results may be due to variable definitions of functioning and quality of life assessments. "
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