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Medical comorbidity in bipolar disorder: relationship between illnesses of the endocrine/metabolic system and treatment outcome


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Corresponding author:
David E. Kemp, M.D.
Case Western Reserve University
10524 Euclid Avenue, 12th Floor
Cleveland, OH 44106, USA
Fax: 216-844-2875


Kemp DE, Gao K, Chan PK, Ganocy SJ, Findling RL, Calabrese JR. Medical comorbidity in bipolar disorder: relationship between illnesses of the endocrine/metabolic system and treatment outcome.
Bipolar Disord 2010: 12: 404–413. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  The present study examined the relationship between medical burden in bipolar disorder and several indicators of illness severity and outcome. It was hypothesized that illnesses of the endocrine/metabolic system would be associated with greater psychiatric symptom burden and would impact the response to treatment with lithium and valproate.

Methods:  Data were analyzed from two studies evaluating lithium and valproate for rapid-cycling presentations of bipolar I and II disorder. General medical comorbidity was assessed by the Cumulative Illness Rating Scale (CIRS). Descriptive statistics and logistic regression analyses were conducted to explore the relationships between medical burden, body mass index (BMI), substance use disorder status, and depressive symptom severity.

Results:  Of 225 patients enrolled, 41.8% had a recent substance use disorder, 50.7% were male, and 69.8% had bipolar I disorder. The mean age of the sample was 36.8 (SD = 10.8) years old. The mean number of comorbid medical disorders per patient was 2.5 (SD = 2.5), and the mean CIRS total score was 4.3 (SD = 3.1). A significant positive correlation was observed between baseline depression severity and the number of organ systems affected by medical illness (p = 0.04). Illnesses of the endocrine/metabolic system were inversely correlated with remission from depressive symptoms (p = 0.02), and obesity was specifically associated with poorer treatment outcome. For every 1-unit increase in BMI, the likelihood of response decreased by 7.5% [odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.87– 0.99; p = 0.02] and the likelihood of remission decreased by 7.3% (OR = 0.93, 95% CI: 0.87–0.99; p = 0.03). The effect of comorbid substance use on the likelihood of response differed significantly according to baseline BMI. The presence of a comorbid substance use disorder resulted in lower odds of response, but only among patients with a BMI ≥ 23 (p = 0.02).

Conclusion:  Among patients with rapid-cycling bipolar disorder receiving lithium and valproate, endocrine/metabolic illnesses, including overweight and obesity, appear to be associated with greater depressive symptom severity and poorer treatment outcomes.