The atypical antipsychotics currently available in Singapore are clozapine (Clozaril®, Novartis), risperidone (Risperdal®, Janssen-Cilag), quetiapine (Seroquel®, AstraZeneca), olanzapine (Zyprexa®, Eli Lilly) and ziprasidone (Zeldox®, Pfizer).
In recent years, based on postmarketing studies, there have been increasing reports on the increased risks of hyperglycaemia and diabetes in patients treated with this group of drugs. Two large-scale studies led by Francesca Cunningham1 (n = 12,235) and Michael Sernyak2 (n = 38,632) reported the increased prevalence of diabetes mellitus associated with patients taking atypical antipsychotics compared to those treated with conventional antipsychotics.
Cunningham et al demonstrated that the risk of diabetes appears to be significantly increased with the use of olanzapine (hazard ratio 1.27; 95% CI 1.04 – 1.56), quetiapine (3.34; 2.51 – 4.45) and risperidone (1.49; 1.22 – 1.81) but not clozapine (1.48; 0.65 – 3.37). The conventional antipsychotics used in the study included haloperidol, thioridazine, perphenazine, chlorpromazine, fluphenazine, thiothixene, trifluoperazine, loxapine, mesoridazine and molindone.
In the study reported by Sernyak et al, a total of 22,648 (58.6%) patients were treated with atypical antipsychotics. When the effects of age were controlled (patients age range from < 40 to > 70 years old), patients who received atypical antipsychotics were 9% (95% CI 1.03 – 1.15) more likely to develop diabetes than those who were treated with the conventional drugs. The odds of having a diagnosis of diabetes mellitus were significantly greater for all patients receiving clozapine (odds ratio 1.25; 95% CI 1.07 – 1.46), olanzapine (1.11; 1.04 – 1.18) and quetiapine (1.31; 1.11 – 1.55) but not risperidone (1.05; 0.98 – 1.12). However, in younger patients (< 40 years old), the use of all four types of atypical antipsychotics was associated with a significant increased prevalence of diabetes mellitus (odds ratio 1.63; 95% CI 1.23 – 2.16).
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Regulatory decisions
The US Food and Drug Administration (FDA) has recently requested the manufacturers of all atypical antipsychotics to include warnings of potential increased risk of hyperglycaemia and diabetes in the package inserts. While FDA acknowledges that the relationship between atypical antipsychotics and diabetes mellitus adverse events has not been completely described, it believes that the safe use of these drugs can be enhanced by informing prescribers and patients about these events.
HSA's advisory
HSA will be reviewing the package inserts of the atypical antipsychotics. In the meantime, we advise that patients treated with these drugs be monitored for symptoms of hyperglycaemia including polydipsia, polyuria, polyphagia and weakness.
Healthcare professionals are encouraged to report any serious suspected adverse drug reactions to this class of drugs.
References
- Cunningham F et al. Pharmacoepidemiology and Drug Safety, 2003, 12, S154-5
- Sernyak MJ et al. Am J Psychiatry, 2002; 159(4):561-6
