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

Department of Psychiatry, Harvard Medical School, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA.
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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    ABSTRACT: Objectives The aims of this study were to evaluate correlates and predictors of life functioning and quality of life in bipolar disorder during a comparative effectiveness trial of moderate doses of lithium. Methods In the Lithium treatment moderate-dose use study (LiTMUS), 283 symptomatic outpatients with bipolar disorder type I or II were randomized to receive lithium plus “optimal personalized treatment (OPT)”, or OPT alone. Participants were assessed using structured diagnostic interviews, clinician-rated blinded assessments, and questionnaires. We employ linear mixed effects models to test the effect of treatment overall and adjunct lithium specifically on quality of life or functioning. Similar models are used to examine the association of baseline demographics and clinical features with quality of life and life functioning. Results Quality of life and impaired functioning at baseline were associated with lower income, higher depressive severity, and more psychiatric comorbid conditions. Over 6 months, patients in both treatment groups improved in quality of life and life functioning (p-Values<0.0001); without a statistically significant difference between the two treatment groups (p-Values>0.05). Within the lithium group, improvement in quality of life and functioning was not associated with concurrent lithium levels at week 12 or week 24 (p-Values>0.05). Lower baseline depressive severity and younger age of onset predicted less improvement in functioning over 6 months. Conclusions Optimized care for bipolar disorder improves overall quality of life and life functioning, with no additional benefit from adjunct moderate doses of lithium. Illness burden and psychosocial stressors were associated with worse quality of life and lower functioning in individuals with bipolar disorder.
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    • "Carbamazepine has been reported to be effective in some patients with rapid cycling bipolar disorder (Post et al 1986; Joyce 1988; Tondo et al 2003), especially when used in combination with lithium (Baethge et al 2005). However, this combination caused a rash in the patient presented here and was subsequently discontinued; this is in agreement with studies showing an increase in adverse events with combined carbamazapine/lithium therapy (Baethge et al 2005). A small number of reports have demonstrated effectiveness of lamotrigine in rapid-cycling, especially when combined with valproate (da Rocha et al 2007). "
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