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Involuntary Clozapine Treatment: A Systematic Review.

Hélène Verdoux1,2, Alexis Lepetit1,3, Peter F J Schulte4,5

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Acta Psychiatrica Scandinavica
|February 12, 2026
PubMed
Summary
This summary is machine-generated.

Involuntary clozapine treatment, particularly intramuscular (IM) or nasogastric routes, serves as a last resort for severe psychotic disorders. While evidence is limited, it shows potential for life-saving recovery when other treatments fail.

Keywords:
barriersclozapineintramuscularinvoluntary treatmentnasogastric

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Area of Science:

  • Psychiatry and Clinical Pharmacology
  • Neuroscience and Behavioral Science

Background:

  • Involuntary clozapine treatment is a critical option for severe psychotic disorders.
  • Clinical practice guidelines for this treatment are synthesized.
  • PROSPERO registration CRD420251234475.

Purpose of the Study:

  • To synthesize information relevant to clinical practice regarding involuntary clozapine treatment.
  • To review evidence on different administration routes (oral, intramuscular, nasogastric).

Main Methods:

  • Comprehensive literature search of MEDLINE, Web of Sciences, and PsycINFO.
  • Inclusion of all articles on involuntary clozapine treatment.
  • Narrative synthesis of data from identified studies.

Main Results:

  • Most studies were case reports/series (18/29) involving 236 patients.
  • Intramuscular (IM) or nasogastric routes were last-resort options for severe, risky psychotic disorders.
  • Oral route acceptance occurred in nearly half of cases post-decision for IM/nasogastric.
  • Pain at injection site was the most common adverse event for IM administration.
  • Transition to IM/nasogastric routes often led to rapid symptom reduction and decreased coercion.
  • Clozapine was maintained orally post-acute phase in most cases.

Conclusions:

  • Involuntary clozapine treatment, though evidence-based on limited studies, can be life-saving and promote recovery for treatment-refractory patients.
  • Restricted access to IM clozapine in many countries presents a significant barrier.
  • Further discussion is needed on overcoming access barriers for severely ill patients with impaired decision-making capacity.