Antipsychotic induced metabolic changes & treatment response: a prospective study

Metabolic side effects of antipsychotics contribute to morbidity and non-compliance in treatment of psychosis. Multiple studies suggest that metabolic side effects correlate with response to antipsychotic treatment. However, few studies have systematically looked at this. We conducted an exploratory, naturalistic, prospective, trans-diagnostic study to examine this association.

100 patients with psychosis, initiated on antipsychotic treatment alone, were assessed on Brief Psychiatric Rating Scale (BPRS), visual analog scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and fasting serum lipid and glucose profiles at baseline, 2-4 weeks (n=71) and 8-12 weeks (n=39).

Subjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2-4 weeks) increase in appetite and triglyceride levels (R(2)=0.257; p=0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2-4 weeks) increase in triglyceride levels (R(2)=0.169; p=0.009).

Early appetite and triglyceride changes predicted antipsychotic treatment response. Involvement of dopaminergic, serotonergic and histaminergic neural pathways could explain the association between appetite and treatment response. Insulin signaling pathways have been implicated in lipid changes with antipsychotics. Study findings suggest metabolic side effects may be early predictors of antipsychotic response. These findings warrant further examination to elucidate the interaction between metabolic pathways and psychotic illnesses, and possibly mechanism of action of antipsychotics beyond dopamine blockade.