Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side...

Full description

Bibliographic Details
Main Authors: Mishal Qubad, Robert A. Bittner
Format: Article
Language:English
Published: SAGE Publishing 2023-03-01
Series:Therapeutic Advances in Psychopharmacology
Online Access:https://doi.org/10.1177/20451253231158152
_version_ 1797860194766553088
author Mishal Qubad
Robert A. Bittner
author_facet Mishal Qubad
Robert A. Bittner
author_sort Mishal Qubad
collection DOAJ
description Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.
first_indexed 2024-04-09T21:42:24Z
format Article
id doaj.art-03856194e61e4e5fbf1595fa8fe64ff5
institution Directory Open Access Journal
issn 2045-1261
language English
last_indexed 2024-04-09T21:42:24Z
publishDate 2023-03-01
publisher SAGE Publishing
record_format Article
series Therapeutic Advances in Psychopharmacology
spelling doaj.art-03856194e61e4e5fbf1595fa8fe64ff52023-03-26T05:03:22ZengSAGE PublishingTherapeutic Advances in Psychopharmacology2045-12612023-03-011310.1177/20451253231158152Second to none: rationale, timing, and clinical management of clozapine use in schizophreniaMishal QubadRobert A. BittnerDespite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.https://doi.org/10.1177/20451253231158152
spellingShingle Mishal Qubad
Robert A. Bittner
Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia
Therapeutic Advances in Psychopharmacology
title Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia
title_full Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia
title_fullStr Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia
title_full_unstemmed Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia
title_short Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia
title_sort second to none rationale timing and clinical management of clozapine use in schizophrenia
url https://doi.org/10.1177/20451253231158152
work_keys_str_mv AT mishalqubad secondtononerationaletimingandclinicalmanagementofclozapineuseinschizophrenia
AT robertabittner secondtononerationaletimingandclinicalmanagementofclozapineuseinschizophrenia