Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan

Psychother Psychosom. 2024;93(1):36-45. doi: 10.1159/000535777. Epub 2024 Jan 9.

Abstract

Introduction: This study aimed to estimate all-cause mortality in patients after a first-episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality.

Methods: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs).

Results: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI: 2.31-2.45) and suicide death (10.80, 5.88-19.84) than controls. Lithium (0.62, 0.55-0.70), divalproex (0.89, 0.83-0.95), and aripiprazole (0.81, 0.66-1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89-1.01), risperidone (0.92, 0.82-1.02), and paliperidone (1.24, 0.88-1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65-0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1).

Conclusion: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality.

Keywords: Bipolar disorder; Depression; Lithium; Mania; Mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents* / adverse effects
  • Aripiprazole
  • Bipolar Disorder* / drug therapy
  • Humans
  • Lithium / therapeutic use
  • Mania / chemically induced
  • Mania / drug therapy
  • Paliperidone Palmitate / therapeutic use
  • Quetiapine Fumarate / therapeutic use
  • Retrospective Studies
  • Risperidone / adverse effects
  • Taiwan / epidemiology
  • Valproic Acid / adverse effects

Substances

  • Lithium
  • Valproic Acid
  • Quetiapine Fumarate
  • Aripiprazole
  • Risperidone
  • Paliperidone Palmitate
  • Antipsychotic Agents

Grants and funding

This study is supported by grants from the National Science and Technology Council, Taiwan (NSTC 109-2314-B-182A-009-MY2, 111-2314-B-182A-027-, and 112-2314-B-182A-036-MY3), and the funding sources had no role in the design of the study. M.B. is supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator Grant (1156072 and 2017131).