Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder

Anastasiya Nestsiarovich; Berit Kerner; Aurélien J Mazurie; Daniel C Cannon; Nathaniel G Hurwitz; Yiliang Zhu; Stuart J Nelson; Tudor I Oprea; Annette S Crisanti; Mauricio Tohen; Douglas J Perkins; Christophe G Lambert

doi:10.1016/j.psyneuen.2019.104511

Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder

Psychoneuroendocrinology. 2020 Feb:112:104511. doi: 10.1016/j.psyneuen.2019.104511. Epub 2019 Nov 9.

Affiliations

¹ Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
² Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
³ TwoFoldChange Consulting, Bozeman, MT, USA.
⁴ Iterative Consulting, Albuquerque, NM, USA.
⁵ New Mexico Behavioral Health Institute, Las Vegas, NM, USA.
⁶ Division of Epidemiology, Biostatistics, and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
⁷ University of New Mexico Health Sciences Library and Informatics Center, Albuquerque, NM, USA; Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
⁸ Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
⁹ Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
¹⁰ Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: cglambert@unm.edu.

PMID: 31744781
DOI: 10.1016/j.psyneuen.2019.104511

Abstract

Objective: To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM).

Methods: The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug".

Results: The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed.

Conclusions: There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.

Trial registration: ClinicalTrials.gov NCT02893371.

Keywords: Bipolar; Diabetes; Drug; Glucose; Polypharmacy; Treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Anticonvulsants / adverse effects*
Antidepressive Agents / adverse effects*
Antimanic Agents / adverse effects*
Antipsychotic Agents / adverse effects*
Bipolar Disorder / drug therapy*
Bipolar Disorder / epidemiology
Databases, Factual
Diabetes Mellitus / chemically induced*
Diabetes Mellitus / epidemiology*
Drug Therapy, Combination / adverse effects*
Female
Humans
Incidence
Lithium Compounds / adverse effects*
Male
Middle Aged
Polypharmacy
Retrospective Studies
Risk
United States / epidemiology
Young Adult

Substances

Anticonvulsants
Antidepressive Agents
Antimanic Agents
Antipsychotic Agents
Lithium Compounds

Associated data

ClinicalTrials.gov/NCT02893371