Cardiometabolic risk markers during mood-stabilizing treatment: Correlation with drug-specific effects, depressive symptoms and treatment response

Maya Kuperberg; Ole Köhler-Forsberg; Alec P Shannon; Nevita George; Sophie Greenebaum; Charles L Bowden; Joseph R Calabrese; Michael Thase; Richard C Shelton; Melvin McInnis; Thilo Deckersbach; Mauricio Tohen; James H Kocsis; Terence A Ketter; Edward S Friedman; Dan V Iosifescu; Michael J Ostacher; Louisa G Sylvia; Susan L McElroy; Andrew A Nierenberg

doi:10.1016/j.jad.2021.12.047

Cardiometabolic risk markers during mood-stabilizing treatment: Correlation with drug-specific effects, depressive symptoms and treatment response

J Affect Disord. 2022 Mar 1:300:41-49. doi: 10.1016/j.jad.2021.12.047. Epub 2021 Dec 21.

Authors

Maya Kuperberg¹, Ole Köhler-Forsberg², Alec P Shannon³, Nevita George³, Sophie Greenebaum³, Charles L Bowden⁴, Joseph R Calabrese⁵, Michael Thase⁶, Richard C Shelton⁷, Melvin McInnis⁸, Thilo Deckersbach³, Mauricio Tohen⁹, James H Kocsis¹⁰, Terence A Ketter¹¹, Edward S Friedman¹², Dan V Iosifescu¹³, Michael J Ostacher¹³, Louisa G Sylvia³, Susan L McElroy¹⁴, Andrew A Nierenberg³

Affiliations

¹ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: Mayakuperberg@moh.health.gov.il.
² Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁴ Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA.
⁵ Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
⁶ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA.
⁸ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁹ Department of Psychiatry, University of New Mexico Health Science Center, Albuquerque, NM, USA.
¹⁰ Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
¹¹ Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
¹² Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹³ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁴ Department of Psychiatry and Behavioral Neuroscience, OH and Lindner Center of HOPE, University of Cincinnati College of Medicine, Cincinnati, Mason, OH, USA.

PMID: 34952123
DOI: 10.1016/j.jad.2021.12.047

Abstract

Background: Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response.

Methods: We analyzed data from two similar 24-weeks comparative effectiveness trials, with a combined sample of 770 participants randomized to two different lithium doses, quetiapine (300 mg/day), or standard treatment without lithium. Glucose, lipids and vital signs were measured before and after 24 weeks of treatment. We calculated several cardiovascular risk scores, assessed baseline correlations and compared the four treatment arms via multiple linear regression models.

Results: Higher cholesterol and LDL levels were associated with greater depression severity, showing differential correlations to specific symptoms, particularly agitation, low energy and suicidality. Those randomized to quetiapine showed a significant worsening of cardiometabolic markers during the 24-week trial. Neither baseline nor change in lipid levels correlated with differential treatment response.

Limitations: Study duration was short from the perspective of cardiometabolic risk markers, and all treatment arms included patients taking adjunct antipsychotics. The trials compared quetiapine to lithium, but not to other medications known to affect similar risk factors.

Conclusions: Treatment with 300 mg/day quetiapine for 24 weeks, representing a short and common dose course, resulted in increased cardiometabolic risk markers, emphasizing the importance of monitoring during mood-stabilizing treatment. The symptom-specific associations are in line with previous studies in unipolar depression, suggesting a cardiometabolic-depression link that needs to be further studied in bipolar depression.

Keywords: Bipolar disorder; Cardiometabolic risk; Cardiovascular disease; Lithium; Metabolic syndrome; Quetiapine.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Antipsychotic Agents* / adverse effects
Bipolar Disorder* / diagnosis
Cardiovascular Diseases* / chemically induced
Cardiovascular Diseases* / epidemiology
Depression / drug therapy
Humans
Quetiapine Fumarate / adverse effects

Substances

Antipsychotic Agents
Quetiapine Fumarate

Abstract

Publication types

MeSH terms

Substances

Grants and funding