Harnessing this drug interaction can reduce clozapine's metabolic risks, but it needs to be done with care.
When a patient with schizophrenia does not respond to two antipsychotics, a trial of clozapine is in order. It is the only antipsychotic that can work when others have not, the only one that does not cause tardive dyskinesia, and one of few that improves negative symptoms. Only two things stand in its way, and they are big ones with clozapine: Safety and tolerability.
Two recent studies shift that risk-benefit ratio, and they are reviewed in this video. One is a randomized-controlled trial of a new dosing strategy that reduced weight gain and metabolic problems on clozapine.1 The other is a review that compared all-cause mortality with clozapine vs. other antipsychotics and arrived at a very different conclusion than clozapine’s long list of medical risks would suggest.2
1. Lu ML, Chen TT, Kuo PH, et al. Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study. Schizophr Res. 2018;193:126-133.
2. Vermeulen JM, van Rooijen G1, van de Kerkhof MPJ, et al. Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years. Schizophr Bull. 2019;45(2):315-329.