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

Hélène Verdoux, Clélia Quiles, Jose de Leon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalSchizophrenia Research
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.


  • Adverse drug reaction
  • Clozapine
  • Drug-drug interaction
  • Neutropenia
  • lithium

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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