Factors Associated With Poor Response To Clozapine In Schizophrenia: A Study From Northern India

BACKGROUND: Clozapine is considered the antipsychotic of choice for patients with Treatment-Resistant Schizophrenia (TRS). Despite its proven efficacy in TRS, around 40–70% of patients have a poor response to clozapine. Limited numbers of studies have assessed the predictors of clozapine non-response. OBJECTIVE: This study aims to assess the demographic and clinical factors associated with an inadequate response to clozapine in patients with TRS. METHODS: 287 outpatients with TRS receiving clozapine for more than one year were divided into two 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. RESULTS: One-hundred and two (35.4%) of the patients were considered to have inadequate response to clozapine. Compared to responders, clozapine non-responders were unemployed at the time of starting clozapine (p=0.04), had a higher duration of untreated psychosis (p=0.007), had received significantly higher number of adequate trials in the past (p=0.02), were treated with polypharmacy in the past (p=0.01), had experienced adverse effects of first (p<0.001) and second-generation antipsychotics (p=0.01), and had more medical comorbidities (p=0.03). The non-responders more frequently had visual hallucinations (p=0.001), and made act (p=0.04) in the lifetime, and had a significantly higher CGI score at the time of starting of clozapine (p<0.001). While on Clozapine, non-responders received significantly higher dose of clozapine (p=0.001) and experienced more constipation (p=0.04), hypersalivation (p=0.002) and obsessive compulsive symptoms (p=0.05). CONCLUSIONS: The present study shows that about one-third of the patients with TRS do not respond to clozapine. However, clozapine non-responders, though broadly similar in socio-demographic profile, differ on past treatment profile.