Clinical outcomes after clozapine discontinuation in responders versus nonresponders: a retrospective chart review

Abstract

No studies have compared clinical outcomes after discontinuation of clozapine between patients who responded to clozapine and those who did not. Therefore, we examined 1-year clinical outcomes after clozapine discontinuation in responders and nonresponders. We reviewed data on patients who discontinued clozapine and retrospectively followed them for 1 year. Clinical information was collected from medical records starting at the initiation of clozapine administration, at discontinuation and at 1 year after discontinuation. In addition, clinical status was assessed using the Clinical Global Impression -Severity (CGI-S) and Clinical Global Impression -Improvement (CGI-I) scales. We classified the patients into clozapine responder and nonresponder groups according to the CGI-I score. Thirty-nine patients were enrolled in this study. Olanzapine was the most common antipsychotic prescribed after clozapine discontinuation in both the responder and nonresponder groups. The mean CGI-S score significantly increased 1 year after clozapine discontinuation in the responder group and significantly decreased in the nonresponder group; there was a significant difference in changes in the CGI-S scores between the groups. The difference remained significant after controlling for clozapine dose and duration of treatment. The findings suggest that clinicians may consider continuing and discontinuing clozapine treatment for patients who responded to clozapine and those who did not, respectively.

Clinical Outcomes after Clozapine Discontinuation in Patients with Schizophrenia: A Systematic Review

“…A total of 28 clinical studies from 27 articles 11 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 37 were identified and included in this systematic review ( Fig. 1 ); these were three randomized controlled trials (RCTs) 13 28 37 , 10 single-arm trials 11 15 21 21 23 32 33 35 35 37 , six retrospective cohort studies 17 20 24 25 31 34 , two mirror-image studies 26 27 , and seven retrospective studies 12 14 16 18 19 29 30 ( Table 1 ). The included studies were published between 1988–2021.…”

“…Regarding the length of follow-up period after clozapine discontinuation, there was considerable variation from weeks to years. Among the 17 studies 11 11 11 12 13 14 15 17 19 20 22 23 28 31 31 33 35 36 that described the type of non-clozapine antipsychotics used after clozapine discontinuation, olanzapine was the most frequently used, and six studies 13 19 23 32 33 35 exclusively used olanzapine ( Table 1 ). In one large-scale retrospective cohort study 17 , antipsychotic polypharmacy was most frequently used after clozapine discontinuation, followed by olanzapine monotherapy.…”

“…Although psychiatric symptoms generally worsened following the discontinuation of clozapine, the current systematic review identified only one study that reported clinical outcomes after clozapine discontinuation based on response to clozapine 16 . This study reported clinical outcomes separately for clozapine responders, who reported worsened outcomes, and clozapine non-responders (i. e., CRS), who reported improved outcomes after clozapine discontinuation.…”

“…Additionally, clozapine rechallenge, antipsychotic polypharmacy, quetiapine, and olanzapine had lower mortality rates than no anti psychotic medication after clozapine discontinuation. In one retrospective study [16], clinical outcomes worsened after clozapine discontinuation in clozapine responders and improved in clozapine non-responders. In one mirror-image study [26], early and late clozapine discontinuation were compared and were found to be associated with prolongation and shortening of bed days, respectively, albeit not significantly.…”

“…Among the 12 studies [11,13,14,16,18,20,30,32,33,[35][36][37] that described the mean ± SD dose of clozapine before discontinuation, the doses ranged from 200 ± 0 mg/day to 565 ± 156 mg/day and relatively low doses ( < 400 mg/day) of clozapine were used in nine studies [13,14,16,18,20,30,33,35,37] (▶ Table 1…”