Quetiapine-induced insulin resistance after switching from blonanserin despite a loss in both bodyweight and waist circumference

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ALTHOUGH OLANZAPINE AND clozapine can induce insulin resistance independent of bodyweight change,1 it is unknown how quetiapine causes insulin resistance. Blonanserin is a second-generation antipsychotic (SGA) that is currently only marketed in Japan and Korea, and reported to be equal to haloperidol and risperidone both in antipsychotic effect and tolerability. We report a case in which insulin resistance worsened after switching from blonanserin to quetiapine despite a loss in both bodyweight and waist circumference.

A 19-year-old woman who had been treated with 16 mg of blonanserin for 9 months was admitted to the psychiatric ward for aggravation of schizophrenia on day 0 (Brief Psychiatric Rating Scale [BPRS] score: 40). She had no history of diabetes or obesity. We performed a 75-g oral glucose tolerance test (OGTT) on day 6, and her fasting and 2-h OGTT glucose were 83 and 108 mg/dl. Her body mass index (BMI), waist circumference and the homeostasis model assessment of insulin resistance (HOMA-IR: fasting plasma insulin [µIU/mL] × fasting plasma glucose [mg/dl]/405) were 19.2 kg/m2, 74.5 cm and 0.96, respectively. On day 11, we started to switch the patient to 200 mg/d of quetiapine, and thereafter, completely stopped administering blonanserin. As a result of increasing the dosage of quetiapine from 200 mg/d to 400 mg/d (on day 21), and then 600 mg/d (on day 48), the patient's psychotic symptoms became stable (BPRS score: 20). We conducted another OGTT on day 76, and her fasting and 2-h OGTT glucose were 89 and 117 mg/dl. Her BMI, waist circumference and HOMA-IR were 19.1 kg/m2, 73.0 cm and 1.96, respectively. The patient was discharged on day 82 because her psychotic symptoms were stable.

Quetiapine can cause bodyweight gain and, as a result, induce insulin resistance.2 However, the current case showed a deterioration in HOMA-IR after a switch to quetiapine despite both bodyweight and waist circumference loss. The results of an OGTT with quetiapine treatment also showed an increase in both serum insulin secretion and plasma glucose levels compared with those during blonanserin treatment. These findings suggest a deterioration in insulin resistance induced by quetiapine. Olanzapine and clozapine can have a direct effect on pancreatic tissue or liver and skeletal muscle tissue, and several studies have indicated that these two antipsychotics can worsen insulin resistance independent of bodyweight change.1 Quetiapine may have the same mechanism of insulin resistance as these two drugs. In the current case, although blonanserin had less effect on insulin resistance than quetiapine, the mechanism of how blonanserin affects glucose-lipid metabolism remains unclear. Further studies are needed to clarify the clinical effects of blonanserin.

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