High Incidence of Psychopharmacologic Treatment Failure in Bipolar Disorder

Mood stabilizers and second-generation antipsychotics are associated with a high incidence of failure in bipolar disorder during the first year of treatment.

Patients with bipolar disorder experience a high incidence of first-year treatment failure, according to cohort study data published in the Journal of Affective Disorders. However, no significant difference in treatment failure likelihood was observed between mood stabilizers (MSs) and second-generation antipsychotics (SGAPs).

Investigators conducted a historical cohort study using data abstracted from the French national health insurance databases. Adult outpatients (age ≥21 years) who initiated bipolar disorder treatment with MSs, SGAPs, or a combination of MSs and SGAPs between 2011 and 2012 were selected for inclusion. Patients who did not achieve at least two consecutive months of treatment exposure were excluded from the study. Lack of response to treatment was identified based on the presence of the following indicators: treatment discontinuation, switch, or addition; psychiatric hospitalization; suicide attempt; and death. The cumulative incidence of treatment non-response was calculated for each medication type. Incidence rates were adjusted for covariates, including comorbid psychiatric and somatic conditions, co-prescription of other psychotropics, and demographic factors.

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The final cohort comprised 20,086 outpatients with bipolar disorder, of whom 8225 (40.9%) received MSs, 9342 (46.5%) received SGAPs, and 2519 (12.5%) received a combination of MSs and SGAPs. The mean patient age was 50.6±15.7 years, and 33.7% were men. The one-year adjusted cumulative incidence of treatment failure (95% CI) was 75.7% in patients using MSs, 75.3% in patients using SGAPs, and 60.5% in patients using a combination of both. The adjusted difference (95% CI) in treatment failure incidence between SGAPs and MSs was −0.40% (−1.4 to 0.6%) in the whole cohort, suggesting no significant difference (P =.4). However, the difference in incidence for SGAPs compared with MSs was −2.2% (−3.3 to −1.2%) in patients >65 years and +6.7% (4.1% to 9.1%) in patients ≤age 65 years (both P <.002). As such, differences in certain treatment non-response outcomes may exist depending on patient age. Combinations of MSs and SGAPs could not be directly compared with monotherapies in terms of failure incidence differences.

Secondary results of the study included the finding that bipolar disorder monotherapy was more frequently initiated with SGAPs than with MSs, despite the fact that SGAPs are only slightly more effective than MSs in younger patients and less effective in older patients. Also, mortality rates observed in the first year were high across ages and for all therapeutic strategies, but especially in older patients treated with SGAPs or a combination of SGAPs and MSs.

These data suggest that while no overall difference in treatment non-response was observed between MSs and SGAPs, patient age may influence the efficacy of each therapy type. Additional research is necessary to identify which patient characteristics may influence treatment success.


Tournier M, Neumann A, Pambrun E, et al. Conventional mood stabilizers and/or second-generation antipsychotic drugs in bipolar disorders: a population-based comparison of risk of treatment failure [published online July 6, 2019]. J Affect Disord. doi:10.1016/j.jad.2019.07.054