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Letter to the Editor

A Case of Successful Treatment of Comorbid Obesity and Polycystic Ovarian Disease With Add-On Metformin in Bipolar Disorder

Sri M. Agarwal, MBBS; Rishikesh V. Behere, MD; Ganesan Venkatasubramanian, MD; Naren P. Rao, MD; Shivarama Varambally, MD; and B. N. Gangadhar, MD

Published: September 22, 2011

A Case of Successful Treatment of Comorbid Obesity and Polycystic Ovarian Disease With Add-On Metformin in Bipolar Disorder

To the Editor: The association between bipolar disorder and polycystic ovarian disease has been a matter of considerable debate.1 It has been hypothesized that a genetic overlay may explain co-occurrence of both disorders.2 Treatment of bipolar disorder with valproate has also been described to be associated with increased incidence of polycystic ovarian disease.3 The co-occurrence of both disorders significantly enhances risk of associated metabolic complications, especially since bipolar disorder, by itself, has been reported to be associated with increased risk of obesity.4 In this report, we describe successful treatment of polycystic ovarian disease and obesity with add-on metformin in a female patient with DSM-IV bipolar disorder.

Case report. Ms A, a 29-year-old woman, presented to our hospital in the mid-summer of 2009 with her first manic episode with psychotic symptoms. There was no family history of psychiatric or medical illness. Personal history revealed irregular menstrual cycles occurring once in 3 or 4 months over the last year. At presentation, her weight was 83 kg and her body mass index (BMI) was 36.9 kg/m2. Further investigations showed a lipid profile, fasting blood sugar level, and renal and liver functions within normal limits; however, her thyroid-stimulating hormone levels were elevated at 11.4 mIU/L. Treatment with risperidone up to 4 mg/d and thyroxine supplementation at 100 μg/d was initiated, to which she responded favorably.

Five months later, she subsequently had a depressive episode. Her weight at this point was 88.6 kg and her BMI was 39.4 kg/m2. Oligomenorrhea and weight gain persisted despite normalization of TSH levels and a serum prolactin level (9.72 ng/mL) that was within normal limits. Polycystic ovarian disease was clinically suspected and confirmed by abdominal ultrasound, which showed polycystic ovarian changes. A diagnosis of polycystic ovarian disease was made per the Rotterdam criteria.5 She was started on carbamazepine up to 600 mg/d, quetiapine up to 300 mg/d, and metformin up to 1,500 mg/d, and lifestyle modifications were advised.

On subsequent follow-up, she had reached euthymia. Progressive loss of weight of 12.4 kg was observed over a period of 7 months. Her weight was 76.2 kg and her BMI was 33.8 kg/m2 after 7 months of metformin treatment. Her menstrual cycles had also become regular for the previous 6 months. There was no change in the patient’s food habits or physical exercise as assessed with the brief physical activity questionnaire.6

The prevalence of coexisting polycystic ovarian disease and bipolar disorder is reported variously as 11.1%7 and 28%.8 Polycystic ovarian disease is known to be associated with metabolic abnormalities and weight gain.9 Atypical antipsychotic treatment can further enhance the risk of metabolic abnormalities.10 In the case described, Ms A had a BMI in the class II obesity range (36.9 kg/m2) at baseline, possibly due to already existing polycystic ovarian disease; her BMI further increased to 39.4 kg/m2 after atypical antipsychotic treatment. Metformin treatment improved menstrual irregularities as well as reduced BMI from the class II to the class I range of obesity.

Metformin has been evaluated in the treatment of obesity and is one of the first-line agents in polycystic ovarian disease.11 Metformin has also been evaluated in a randomized controlled trial for its effectiveness in countering antipsychotic-related weight gain in schizophrenia patients.12 However, the treatment of metabolic complications in bipolar disorder13 has not been well studied. Metformin could be a useful agent in treatment of weight gain and menstrual abnormalities associated with polycystic ovarian disease and bipolar disorder and needs to be systematically examined.


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Sri M. Agarwal, MBBS

Rishikesh V. Behere, MD

Ganesan Venkatasubramanian, MD

Naren P. Rao, MD

Shivarama Varambally, MD

B. N. Gangadhar, MD

Author affiliations: The Metabolic Clinic in Psychiatry, Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, Bengaluru, Karnataka, India.

Potential conflicts of interest: None reported.

Funding/support: None reported.

Published online: September 22, 2011.

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