Metformin-induced first-episode psychosis in patient with polycystic ovary syndrome using drospirenone.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5–15% of reproductive-aged women. The oral contraceptive pill (drospirenone) for improving menstrual cycle regularity and metformin for lowering body mass index are two common medications for treatment of PCOS. Here we detail a case of first-episode psychosis after taking drospirenone and metformin in a woman with PCOS and further discuss the possible mechanism. A 21-year-old female college student was brought to the emergency room due to suddenly becoming violent towards her roommate. She had insomnia first, followed by persecutory delusion, delusion of reference, and bizarre behavior for a week. One year previously (September 2017), she had been diagnosed with PCOS due to irregular menstrual cycle, dysmenorrhea, and menorrhagia, and her gynecologist had suggested she take metformin, but she discontinued the medication. Before this first episode of psychosis, she had taken drospirenone 3 mg/day and metformin 250 mg/day again for 1 month. As drospirenone or metformin may have induced the psychotic symptoms, both were discontinued and antipsychotics (paliperidone) were used. Psychotic symptoms were controlled within 1 week and the patient was discharged after 7 days’ admission. This patient had had no psychotic experiences previously, only some mood changes after using drospirenone, but her hypomanic-like symptoms had been eliminated after discontinuation of the drug. Meta-analysis studies have reported PCOS as being comorbid with bulimia, schizophrenia, bipolar disorder, depression, anxiety disorders, and personality disorders.1, 2 Hypothalamic–pituitary–adrenocortical dysfunction after the increased adrenal androgen production of PCOS might be the reason for such an association. Indeed, this woman had some mood changes previously but had never visited a psychiatrist for mental disorder diagnosis. Metformin is a widely used antidiabetic drug and is frequently used in patients with PCOS for symptoms of hyperlipidemia. It has, however, been reported to worsen psychotic symptoms in patients with schizophrenia as it can reduce the level of insulin-like growth factor 1, which may contribute to the pathophysiology of schizophrenia.3 Metformin may play a role in the formation of psychotic symptoms. Here we provide the first report of metformin-induced psychosis in a PCOS patient whose symptoms were relieved after discontinuation of metformin and drospirenone. In conclusion, in a patient in a neuroendocrinologically vulnerable condition, using metformin may reduce the level of insulin-like growth factor 1 in the brain, which may contribute to the pathophysiology of schizophrenia. Therefore, we recommend watching out for psychotic symptoms in patients with PCOS using the oral contraceptive pill and metformin simultaneously. Authors Han-Yun Cheng, Kai Ting Ko, and Ruu-Fen Tzang designed the study and wrote the protocol. All authors contributed to and have approved the final manuscript. The authors declare no conflicts of interest.