We thank Jindal and Keshavan (1) for their contribution explaining the results of our study (2), which stated that in a cross-sectional design (n = 200), no differences in the prevalence of diabetes or hyperglycemia between typical- or atypical-treated patients were found. We would like to make two comments on this statement. First, although the muscarinic M3 receptor affinity fits well with the diabetogenic properties of antipsychotic drugs, so does H1-histaminergic (but not muscarinic M3) receptor affinity with short-term weight gain, a factor that is often, but not always, present in antipsychotic-related diabetes (3,4). Second, it has been suggested (5) that risk factors of diabetes exert less predictive power in schizophrenia than in the general population. This hypothesis was tested (6) by examining the effect of the two major risk factors for diabetes: age and weight. In 200 patients with schizophrenia, typical (but not atypical) antipsychotic drugs modified the effect of these risk factors, confirming a less straightforward relationship between diabetes risk factors in schizophrenia than in the general population.
The statement by Jindal and Keshavan (1), that no cases of diabetes have been reported with haloperidol, may be interpreted as stressing the same point. Taken literally, it is simply untrue, as the following cases (7) have been reported: 10 of new-onset diabetes, 2 of worsening of existing diabetes, and 1 with an unknown preexisting status (on haloperidol monotherapy) with 4, 2, and 1 cases on haloperidol-risperidone combination therapy, respectively. More broadly speaking, Jindal and Keshavan (1) justly criticize the typical-atypical classification of antipsychotics as a scientifically unproductive dichotomy. This was shown (8) in cell culture, for instance, where haloperidol’s inhibiting effect on cell proliferation was comparable with the atypical clozapine but not to the typicals chlorpromazine and fluphenazine. In this very complex matter, the ability to take any stance on explanatory pathways is currently precluded by the fact that research into the diabetogenic properties of antipsychotic medication and its pathways is just beginning.
