Up to half of individuals on clozapine receive another antipsychotic agent because of non response.Various typical and atypical agents are tried with varying response.Pimozide is a strong antagonist at the postsynaptic D2 receptors ( unlike clozapine) and it makes pharmacological sense to try this with Clozapine. One open label trial found it effective, but an RCT among in patients found no benefit (Friedman et al 1997 & 2011).
Handan Gunduz-Bruce and team wanted to know whether pimozide augmentation can help in outpatients with Schizophrenia who are on clozapine. This was a 12 week, randomized, double-blind, placebo controlled augmentation trial with 32 patients. Patients were on a stable dose of clozapine with a blood level of at least 350 ng/ml for at least 2 weeks prior to randomisation.Pimozide can increase the QTc interval and hence those with baseline QTc values greater than 450 ms were excluded.
Findings: BPRS scores at weeks 8 and 12 were significantly lower than the scores at baseline, indicating significant placebo response. Both groups improved over time. There was no significant difference between groups.
Conclusions: Adding a potent D2 blocking agent to clozapine do not have any advantage.
Comment: Two patients in this study had their QTc prolonged. Those on combination antipsychotics should be monitored carefully.Adding pimozide ( or similar agent) is not an effective strategy. Search for effective combinations in clozapine resistant patients continues.
Summary of the article:
Gunduz-Bruce H, Oliver S, Gueorguieva R, Forselius-Bielen K, D’Souza DC, Zimolo Z, Tek C, Kaliora S, Ray S, Petrides G.Schizophr Res. 2013 Feb;143(2-3):344-7.