Predictors of non-stabilization during the combination therapy of lithium and divalproex in rapid cycling bipolar disorder: A post-hoc analysis of two studies

Keming Gao, David E. Kemp, Zuowei Wang, Stephen J. Ganocy, Carla Conroy, Marry Beth Serrano, Martha Sajatovic, Robert L. Findling, Joseph R. Calabrese

Research output: Contribution to journalArticlepeer-review

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). Method: 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% versus 19% (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.

Original languageEnglish (US)
Pages (from-to)23-38
Number of pages16
JournalPsychopharmacology bulletin
Volume43
Issue number1
StatePublished - Feb 15 2010

Keywords

  • Anxiety disorder
  • Bipolar disorder
  • Mood stabilizer
  • Non-stabilization
  • Substance use disorder

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

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