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. 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.
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.
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.