Association between antipsychotic-induced metabolic side-effects and clinical improvement: a review on the Evidence for "metabolic threshold".

Over the last two decades, several studies have reported an intriguing association between clinical improvement with antipsychotics and metabolic side effects. In this review, we attempt a critical evaluation of fifteen such studies. The following are the summary observation from these studies: weight gain over a period of few weeks to more than a year, has been consistently found to be associated with clinical improvement. In addition, serum triglyceride changes have also been found to demonstrate this association. This relationship was not affected by socio-demographic factors, duration of illness or baseline body mass index. Findings from these studies depict changes mainly in schizophrenia patients on treatment with clozapine or olanzapine. Other drugs and diagnoses are poorly represented. Moreover, appetite, physical activity, other metabolic parameters have not been adequately examined. This review raises an important question - "Is there a metabolic threshold for antipsychotics?" i.e. is response to antipsychotics contingent upon the production of metabolic side effects. Current research proposes the involvement of insulin, leptin and phospholipid pathways in pathogenesis as well as therapeutics of psychosis. Though knowledge in this area is preliminary, it clearly warrants further systematic evaluation.