Risks and benefits of clozapine and lithium co-prescribing: A systematic review and expert recommendations

Hélène Verdoux; Clélia Quiles; Jose de Leon

doi:10.1016/j.schres.2023.03.032

Risks and benefits of clozapine and lithium co-prescribing: A systematic review and expert recommendations

Schizophr Res. 2023 Mar 29:S0920-9964(23)00126-3. doi: 10.1016/j.schres.2023.03.032. Online ahead of print.

Authors

Hélène Verdoux¹, Clélia Quiles², Jose de Leon³

Affiliations

¹ Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, team pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France. Electronic address: helene.verdoux@u-bordeaux.fr.
² Centre Hospitalier Charles Perrens, F-33000 Bordeaux, France.
³ Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA; Institute of Neurosciences, University of Granada, Granada, Spain; Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain; Psychiatry and Neurosciences Research Group (CTS-549), USA.

PMID: 37002013
DOI: 10.1016/j.schres.2023.03.032

Abstract

Objectives: To identify the risks and benefits of clozapine‑lithium co-prescription.

Methods: Articles published in English or French were identified with a MEDLINE, Web of Sciences and PsycINFO search, from inception through January 2023, using the term 'clozapine' in combination with 'lithium'. Data were synthesized narratively.

Results: Of the 67 articles included in the review, more than half (n = 38, 56.7 %) were focused on clozapine-related blood dyscrasia. A body of evidence drawn from case reports and retrospective chart studies highlights the potential benefits of lithium prescription for clozapine-related neutropenia, since this strategy may avoid clozapine discontinuation or allow its rechallenge. The most documented adverse drug reactions (ADRs) associated with clozapine‑lithium co-prescription are neurotoxic events, which may be prevented or detected early by clinical, electroencephalographic and therapeutic drug monitoring. Causality assessment cannot be established for other reported ADRs occurring during clozapine‑lithium co-prescription. The benefits of the combined prescription on psychotic and/or mood symptoms are poorly documented.

Conclusion: The risks and benefits of clozapine‑lithium co-prescription require further exploration as the combination might significantly contribute to reducing underprescription or premature discontinuation of clozapine.

Keywords: Adverse drug reaction; Clozapine; Drug-drug interaction; Neutropenia; lithium.