Factors Associated With Poor Response to Clozapine in Schizophrenia: A Study From Northern India

Limited numbers of studies have assessed the predictors of clozapine nonresponse. This study aimed to assess the demographic and clinical factors associated with an inadequate response to clozapine in patients with treatment-resistant schizophrenia (TRS).

Two hundred eighty-seven outpatients with TRS receiving clozapine for more than 1 year were divided into 2 groups based on the need for a second antipsychotic medication and/or electroconvulsive therapy after receiving clozapine in the maximum tolerable dose for at least 3 months.

One hundred two patients (35.4%) were considered to be clozapine nonresponders. Compared with responders, clozapine nonresponders were more often unemployed at the time of starting clozapine (P = 0.04), had a longer duration of untreated psychosis (P = 0.007), had received significantly higher number of adequate antipsychotic trials in the past (P = 0.02), had received antipsychotic polypharmacy in the past (P = 0.01), had experienced adverse effects with first- (P < 0.001) and second-generation antipsychotics (P = 0.01), and had more medical comorbidities (P = 0.03). The nonresponders more frequently had visual hallucinations (P = 0.001), and feelings/acts or impulses attributed to some external source (P = 0.03) in the lifetime, and had a significantly higher Clinical Global Impression severity score at the time of starting of clozapine (P < 0.001). While on clozapine, nonresponders received significantly higher dose of clozapine (P = 0.001) and higher proportion of them experienced constipation (P = 0.04), hypersalivation (P = 0.002), and obsessive-compulsive symptoms (P = 0.05) as adverse effects of clozapine.

The present study shows that approximately one-third of patients with TRS do not respond to clozapine. However, clozapine nonresponders, although broadly similar in sociodemographic profile to clozapine responders, differ from clozapine responders on past treatment profile.