title: Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.
abstract: 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.
authors.affiliation: Department of Psychiatry, Harvard Medical School, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA. cbaethge@mclean.harvard.edu
authors.forename: Christopher
authors.initials: C
authors.lastname: Baethge
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: Kirsten
authors.initials: K
authors.lastname: Mathiske-Schmidt
authors.forename: John
authors.initials: J
authors.lastname: Hennen
authors.forename: Anne
authors.initials: A
authors.lastname: Berghöfer
authors.forename: Bruno
authors.initials: B
authors.lastname: Müller-Oerlinghausen
authors.forename: Tom
authors.initials: T
authors.lastname: Bschor
authors.forename: Mazda
authors.initials: M
authors.lastname: Adli
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
mesh_terms: 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
chemical_list: D000927:Anticonvulsants; D011619:Psychotropic Drugs; D002220:Carbamazepine; D008094:Lithium