title: Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder.
abstract: BACKGROUND
  We compared the prophylactic efficacy of lithium, carbamazepine, and the combination and identified possible clinical markers of response.
  
  
  METHODS
  Fifty-two outpatients who met DSM-III-R criteria for bipolar illness were randomly assigned in a double-blind design for an intended 1 year of treatment with lithium or carbamazepine, a crossover to the opposite drug in the second year, and then a third year on the combination. Patients received monthly detailed evaluations, and daily life chart ratings of the degree of functional incapacity associated with mania or depression were completed.
  
  
  RESULTS
  For evaluable patients: 13 (31.0%) of 42 failed to complete a full year of lithium therapy owing to lack of efficacy, and 2 dropped out because of side effects; 13 (37.1%) of 35 withdrew from carbamazepine within the first year owing to lack of efficacy, and 10 dropped out because of side effects (9 of the 10 had a rash); 7 (24.1%) of 29 withdrew from the combination therapy owing to lack of efficacy. The percentage of the evaluable patients who had marked or moderate improvement on the Clinical Global Impressions scale was 33.3% on lithium. 31.4% on carbamazepine, and 55.2% on the combination treatment, which was not significantly different. By a variety of measures, lithium was more effective than carbamazepine in the prophylaxis of mania. Patients with a past history of rapid cycling did poorly on monotherapy (28.0% responded to lithium; 19.0% responded to carbamazepine), but significantly better on the combination (56.3%, p < .05).
  
  
  CONCLUSIONS
  These prospective, randomized data suggest a high incidence of inadequate response to either mood stabilizer or their combination despite use of adjunctive agents as needed. Additional novel treatment regimens are needed to better decrease affective morbidity in large numbers of bipolar outpatients.
authors.affiliation: Section on Psychobiology, National Institute of Mental Health, Bethesda, Md. 20892, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Denicoff
authors.forename: E E
authors.initials: EE
authors.lastname: Smith-Jackson
authors.forename: E R
authors.initials: ER
authors.lastname: Disney
authors.forename: S O
authors.initials: SO
authors.lastname: Ali
authors.forename: G S
authors.initials: GS
authors.lastname: Leverich
authors.forename: R M
authors.initials: RM
authors.lastname: Post
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D001714:Bipolar Disorder / Q000517:prevention & control* / Q000523:psychology; D002220:Carbamazepine / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000517:prevention & control / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002220:Carbamazepine; D008094:Lithium