Atypical antipsychotics and diabetic ketoacidosis: a review.

Rationale: Atypical antipsychotics have been linked to weight gain and type 2 diabetes, but are also associated with diabetic ketoacidosis (DKA), which can occur more acutely and in the absence of weight gain.

Objectives: Our aim was to review current case reports of DKA in the context of atypical antipsychotic treatment to better understand (a) the scope of the problem, (b) its relationship to different atypical agents, (c) risk factors, (d) long-term outcome, and (e) putative mechanisms of action.

Method: Searches in PubMed/Medline, as well as the University of Toronto's Scholar Portal, were performed for all relevant articles/abstracts in English.

Results: Sixty reports, yielding 69 cases, affirm that DKA is a rare but serious risk with almost all atypical antipsychotics; however, liability seems to vary between agents, at least partially mirroring risk of weight gain. Mean age of onset was 36.9 years (range 12-80), with 68 % of cases occurring in males, and 41 % in individuals of African American or African Caribbean descent. Over one third of cases present with either no weight gain or weight loss, and 61 % of these require ongoing treatment for glycemic control. Death occurred in 7.25 % of cases.

Conclusion: While the underlying mechanisms are not well understood, antipsychotic-related DKA can occur soon after treatment onset and in the absence of weight gain. Although rare, clinicians must remain vigilant given its acute onset and potential lethality.