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Hypoglycaemia induced by second generation antipsychotic agents in schizophrenic non-diabetic patients

BMJ 2009; 338 doi: (Published 26 May 2009) Cite this as: BMJ 2009;338:a1792
  1. Yutaro Suzuki, psychiatrist and medical researcher1,
  2. Junzo Watanabe, psychiatrist and medical researcher1,
  3. Naoki Fukui, psychiatrist and medical researcher1,
  4. Vural Ozdemir, clinical pharmacologist and bioethics/science policy researcher2,
  5. Toshiyuki Someya, psychiatrist and medical researcher1
  1. 1Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  2. 2Département de Médecine Sociale et Préventive, Programmes de Bioéthique, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
  1. Correspondence to: T Someya psy{at}

    We report three cases of hypoglycaemia in non-diabetic non-obese Japanese inpatients who had schizophrenia and were being treated with a second generation antipsychotic. The clinical findings of hypoglycaemia emerged typically 2-3 hours after meals in all patients during escalation of the dose of second generation antipsychotic. No other antipsychotic or concomitant drug with a metabolic effect was coadministered.

    Case 1—A 27 year old woman who took 400 mg of quetiapine a day complained of dizziness, tremor, and palpitations on day 112 of her inpatient stay. These symptoms worsened with a 600 mg daily dose of quetiapine (day 132). At this point, her blood glucose three hours after lunch was 3.2 mmol/l. Her symptoms (tremor, irritability) resolved after oral sugar intake. An oral glucose tolerance test during quetiapine treatment (600 mg a day, day 154), found further evidence of hypoglycaemia (table). We replaced quetiapine with perospirone (day 167), and her hypoglycaemia symptoms resolved clinically but asymptomatic hypoglycaemia was still present upon repeat oral glucose tolerance test.

    Results of the 75 g oral glucose tolerance test in three Japanese patients with schizophrenia

    View this table:

    Case 2—A 53 year old man received an oral glucose tolerance test on two successive risperidone doses at 6 mg a day (day 43 of admission) and 8 mg a day (day 86). His plasma glucose was markedly low (2.5 mmol/l) two hours after the test, with 8 mg daily risperidone (table). Although he complained of tremor and palpitations after meals while taking 8 mg of risperidone a day, these symptoms were absent with 6 mg a day, and no biochemical evidence showed hypoglycaemia after an oral glucose tolerance test. Hypoglycaemic symptoms and abnormal oral glucose tolerance test results resolved after risperidone was reduced to 3 mg a day and coprescription of 18 mg of aripiprazole a day.

    Case 3—A 32 year old woman received an oral glucose tolerance test while taking two successive doses of olanzapine—10 mg a day (day 74 of admission) and 20 mg a day (day 115). With 10 mg a day she did not have clinical symptoms of hypoglycaemia or low plasma glucose during oral glucose tolerance testing. Taking 20 mg a day she exhibited irritability after meals, marked hypoglycaemia during testing, and a higher peak insulin response with an unstable time course (table). This is consistent with increased insulin release by olanzapine in vitro and in vivo.1 2

    Hypoglycaemia is a serious medical condition and can cause seizures, permanent neurological damage, or death. Although the risk of hyperglycaemia induced by second generation antipsychotics is known, this case series shows hypoglycaemia associated with use of second generation antipsychotics after verification with oral glucose tolerance testing. Because hypoglycaemia generates symptoms of adrenergic stimulation, such as irritability and anxiety, recognition of the possible link between second generation antipsychotics and hypoglycaemia can prevent missed cases in the future and improve differential diagnosis of exacerbation of schizophrenia.


    Cite this as: BMJ 2008;337:a1792


    • Funding: Health and Labour Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health, H17-kokoro-002); grant in aid for scientific research (KAKENHI) from the Japan Society for the Promotion of Research (#17591199); intramural grant from the Niigata University to TS. VO is recipient of an operating grant for ethics and science policy research on personalised medicine from the Canadian Institutes of Health Research.

    • Competing interests: None declared.

    • Patient consent obtained.

    • Provenance and peer review: Not commissioned; externally peer reviewed.


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