Longitudinal changes in clozapine dose in patients with treatment-resistant schizophrenia: a 5-year retrospective cohort study

Abstract

This retrospective cohort study aimed to investigate the longitudinal changes in clozapine dose over a 5-year period in patients with treatment-resistant schizophrenia (TRS). Patients with TRS who were administered clozapine at a hospital between April 2012 and December 2016 and continued treatment with clozapine for at least 1 year were included. Clozapine doses were compared at the dose-fixation point, defined as when the same regimen of clozapine had been continued for 8 weeks or longer, and the post-dose-fixation phase, at 12, 36 and 60 months after clozapine initiation. We included 103 patients and found no significant differences in clozapine dose between the dose-fixation point and post-dose-fixation phase. Approximately half of the patients were categorized into an unchanged group at 12 months after clozapine initiation, whereas approximately 40% of patients were categorized into either the decreased or increased group at 60 months. Multivariable regression analysis revealed that the change in clozapine dose between the dose-fixation point and 60 months after clozapine initiation was negatively associated with clozapine dose at the dose-fixation point. On average, the clozapine dose was unchanged during long-term treatment in patients with TRS, although the dose was decreased or increased in approximately 40% of the patients.

Response to the letter to the Editor from Araujo and colleagues on the research article entitled, “Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment‐resistant schizophrenia receiving clozapine: A 1‐year retrospective cohort study”

“…We appreciate the interest and comments on our retrospective cohort study 1 expressed by Araujo and colleagues in their letter to the Editor. 2 In this response letter, we expand on our previously reported findings and address concerns regarding: (1) a lack of or inadequate information; (2) sex-related differences in the effects of smoking habits and concomitant valproic acid (VPA) use;…”

Restarting smoking after discharge from clozapine inpatient initiation: Elevated rehospitalization rates smoking & clozapine rehospitalization

“…We also plotted Kaplan-Meier curves for each subgroup. This was a secondary analysis of our previous study 8 complying with the Declaration of Helsinki. The institutional review board of the OPMC approved the protocol.…”

The challenge of managing difficult to treat psychiatric conditions

“…However, little is known about the maintenance dose of clozapine, and drug plasma levels can be affected by several factors, for example, infections (Zhang et al , 2021). The article by Tsukahara et al (2022) in this issue investigates longitudinal changes in clozapine oral dose, using a long naturalistic follow-up to 60 months after clozapine initiation in Asian patients. The study suggests that the maintenance of an effective clozapine plasma level may be relevant, because many dose adjustments were naturalistically made by clinicians during follow-up, in order to optimize clinical benefits.…”