Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.
BACKGROUND
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.
Baethge
Christopher
C
Department of Psychiatry, Harvard Medical School, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA. cbaethge@mclean.harvard.edu
Baldessarini
Ross J
RJ
Mathiske-Schmidt
Kirsten
K
Hennen
John
J
Berghöfer
Anne
A
Müller-Oerlinghausen
Bruno
B
Bschor
Tom
T
Adli
Mazda
M
Bauer
Michael
M
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008094:Lithium / Q000009:adverse effects / Q000627:therapeutic use*; D008134:Long-Term Care; D008297:Male; D017063:Outcome Assessment, Health Care; D010343:Patient Admission / Q000706:statistics & numerical data; D011619:Psychotropic Drugs / Q000627:therapeutic use; D055502:Secondary Prevention; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000927:Anticonvulsants; D011619:Psychotropic Drugs; D002220:Carbamazepine; D008094:Lithium