Summary
Clozapine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Schizophrenia would be drug repurposing rather than first-in-human development. This does not mean it is approved for Schizophrenia. ClinicalTrials.gov lists 8 registered trials linking Clozapine to Schizophrenia: 7 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT03772951). It plans or enrolled 154 participants. Registration activity spans 1998 to 2019. The literature layer holds 18 publications for this pair: 5 Cochrane reviews, 5 meta-analyses, 3 systematic reviews and 5 clinical trial publications. The dated items are from 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Schizophrenia ranks 499 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Spontaneous full remission rare (<10%); after first episode, ~80% relapse within 5 years without maintenance antipsychotic; functional disability accumulates over time; 20% achieve good long-term outcome.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 80.0 (trials 30.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 7 completed, 1 other |
| Linked publications | 18 (5 Cochrane reviews, 5 meta-analyses, 5 clinical trial publications, 3 systematic reviews) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | inhibitor |
| Data sources | DGIdb |
| Linked via biomarker / target | ADRA1B |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT03772951 | The Efficacy of Computerized Cognitive Remediation Therapy for Chronic Schizophrenia 2019 | completed | Phase 4 | 154 |
| NCT01246232 | Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia 2011 | completed | Phase 4 | 69 |
| NCT01663077 | Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients 2012 | completed | Phase 4 | 20 |
| NCT00351000 | Ziprasidone for Clozapine- or Olanzapine-Associated Diabetes Mellitus 2005 | completed | Phase 4 | 24 |
| NCT00289861 | Risperidone Augmentation in Patients With Schizophrenia 2003 | completed | Phase 4 | 24 |
| NCT00981526 | Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia 2009 | completed | Phase 4 | 66 |
| NCT00000372 | Glycine and D-Cycloserine in Schizophrenia 1998 | withdrawn | Phase 3 | — |
| NCT00179231 | Olanzapine Versus Clozapine in Treatment Refractory Schizophrenia 2000 | completed | Not applicable | 80 |
Published literature
- Clinical trial publication Empagliflozin as an Alternative to Metformin for Antipsychotic-Related Weight Gain: Double-Blind Randomized Controlled TrialDolati A, Ahmadimoghaddam D, Zamanirafe M et al. · Human psychopharmacology · 2026 · PMID 42135901
- Clinical trial publication The Immediate and Sustained Effects of Multi-Session Biparietal Transcranial Direct Current Stimulation on Insight in SchizophreniaSong J, Kim J, Carmona-Torres E et al. · Schizophrenia bulletin · 2026 · PMID 42032975
- Clinical trial publication Clozapine After 1 Failed Antipsychotic Drug Trial in First-Episode Psychosis: A Randomized Clinical TrialLi X, Lu C, Zhai Z et al. · JAMA psychiatry · 2026 · PMID 41811299
- Clinical trial publication Augmentation of clozapine with dextromethorphan in treatment-resistant schizophrenia: A randomized, group sequential adaptive design, controlled clinical trialHegde NC, Mishra BR, Mohapatra D et al. · Asian journal of psychiatry · 2026 · PMID 41780197
- Clinical trial publication Disentangling violence in schizophrenia: Interactions between symptom trajectories, conduct disorder, and pharmacotherapyKrakowski M, Czobor P · Schizophrenia research · 2026 · PMID 41638158
- Cochrane review Glucagonlike Peptide-1 (GLP-1) Receptor Agonists for Cardiometabolic Risk in Severe Mental Illness: A Narrative ReviewDomingues C, Ferreira M, Pinho R · Cureus · 2026 · PMID 42388962
- Cochrane review Effectiveness of clozapine as a transdiagnostic treatment for aggression: a systematic reviewSarpeleh S, Looi JCL, Allison S et al. · East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan · 2026 · PMID 42374952
- Cochrane review Next-step treatment for schizophrenia non-responsive to antipsychotics: a systematic review and network meta-analysisFurukawa Y, Salahuddin NH, Wei Y et al. · EClinicalMedicine · 2026 · PMID 42232685
- Cochrane review Clozapine-Induced Acute Interstitial Nephritis: A Systematic ReviewRagg J, Innes S, Bannon F et al. · Journal of clinical psychopharmacology · 2026 · PMID 42159486
- Cochrane review Underprescription of Clozapine: A Narrative Review Regarding 'Clozaphobia'Brito Castro R, Ferreira JJ, Gama-Marques J · Human psychopharmacology · 2026 · PMID 42136059
- Meta-analysis Risk factors associated with blood dyscrasia during clozapine treatment: a systematic review and meta-analysisCasetta C, Loane E, Taylor D et al. · Psychological medicine · 2026 · PMID 42112559
- Meta-analysis High-dose Olanzapine Versus Clozapine in Treatment-resistant Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled TrialsKotochinsky M, Eloa Oliveira Fonseca P, Mora L et al. · Journal of psychiatric practice · 2026 · PMID 41894186
- Meta-analysis Comparative efficacy and tolerability of antidopaminergic and muscarinic antipsychotics for acute schizophrenia: a network meta-analysis of randomised controlled trials indexed in international English and Chinese databasesSchneider-Thoma J, Zhu Y, Qin M et al. · Lancet (London, England) · 2026 · PMID 41763745
- Meta-analysis Clozapine use and COVID-19 risk: A systematic review, meta-analysis, and retrospective cohort evidenceSagués T, Ferrer A, Delgado JF et al. · Psychiatry research · 2026 · PMID 41762542
- Meta-analysis Autonomic dysfunctions in psychotic disorders, interaction with antipsychotic intervention and treatment resistance: a comprehensive systematic review and meta-analysisIannotta F, Iasevoli F, Caiazza C et al. · Journal of psychiatric research · 2026 · PMID 41475190
- Systematic review A systematic review on the effects of clozapine on B-lymphocytes and immunoglobulinsKang JT, Shields AM, Mizuno Y et al. · Schizophrenia research · 2026 · PMID 42134210
- Systematic review Immune System Alterations in Treatment-Resistant Schizophrenia: A Systematic Review of the Current Evidence and Future DirectionsKrzystanek M, Bieś R, Bąk-Sosnowska M · International journal of molecular sciences · 2026 · PMID 42123331
- Systematic review Deep brain stimulation for clozapine-resistant schizophrenia: a systematic review of target-specific outcomes and stereotactic technical considerationsArmando AR, Fahmi A, Subianto H et al. · Neurosurgical review · 2026 · PMID 42067731
Mechanism and notes
Recorded mechanism or class: inhibitor.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA1B. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Clozapine approved for Schizophrenia?
Clozapine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Schizophrenia would be drug repurposing rather than first-in-human development. This does not mean it is approved for Schizophrenia. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Clozapine in clinical trials for Schizophrenia?
ClinicalTrials.gov lists 8 registered trials linking Clozapine to Schizophrenia: 7 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT03772951). It plans or enrolled 154 participants. Registration activity spans 1998 to 2019.
What does the evidence show for Clozapine in Schizophrenia?
Clozapine has both completed registered trials and synthesis-level publications linked to Schizophrenia. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA1B. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.