title: Predictors of non-stabilization during the combination therapy of lithium and divalproex in rapid cycling bipolar disorder: a post-hoc analysis of two studies.
abstract: OBJECTIVE
  To study predictors of non-stabilization (i.e., not bimodally stabilized for randomization or not randomized due to premature discontinuation) during open-label treatment with lithium and divalproex in patients with rapid-cycling bipolar disorder (RCBD) with or without comorbid recent substance use disorders (SUDs).
  
  
  METHODS
  Data from the open-label phase of two maintenance studies were used. The reasons for non-stabilization were compared between patients with a recent SUD and those without. Predictors for non-stabilization were explored with logistic regression analyses.
  
  
  RESULTS
  Of 149 patients with recent SUD and 254 without recent SUD enrolled into the open-label acute stabilization phase, 21% and 24% were stabilized and randomized, respectively. Compared to those without recent SUD, patients with recent SUD were more likely to discontinue the study due to non-adherence to the protocol, 53% versus 37% (OR = 1.92) or refractory mania/hypomania, 15% versus 9% (OR = 1.87), but less likely due to refractory depression 16% versus 25% (OR = 0.58) or adverse events, 10% versus19% (OR = 0.44). A history of recent SUDs, early life verbal abuse, female gender, and late onset of first depressive episode were associated with increased risk for non-stabilization with ORs of 1.85, 1.74, 1.10, and 1.04, respectively.
  
  
  CONCLUSIONS
  During open treatment with lithium and divalproex in patients with RCBD, a recent SUD, a lifetime history of verbal abuse, female gender, and late onset of first depression independently predicted nonstabilization. The non-stabilization for patients with SUD was related to non-adherence and refractory mania/hypomania.
authors.affiliation: Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA. keming.gao@uhhospitals.org
authors.forename: Keming
authors.initials: K
authors.lastname: Gao
authors.forename: David E
authors.initials: DE
authors.lastname: Kemp
authors.forename: Zuowei
authors.initials: Z
authors.lastname: Wang
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ganocy
authors.forename: Carla
authors.initials: C
authors.lastname: Conroy
authors.forename: Marry Beth
authors.initials: MB
authors.lastname: Serrano
authors.forename: Martha
authors.initials: M
authors.lastname: Sajatovic
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D016009:Chi-Square Distribution; D015897:Comorbidity; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000453:epidemiology; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D014635:Valproic Acid