SynthesisActa psychiatrica Scandinavica2018
Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis.
Synthesis in Acta psychiatrica Scandinavica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Clozapine once- versus multiple-daily dosing: a two-center cross-sectional study, systematic review and meta-analysis.European archives of psychiatry and clinical neuroscience · 2023Pooled it
- Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.Schizophrenia bulletin · 2023Guideline
- Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis.Acta psychiatrica Scandinavica · 2018Pooled it
- Randomised controlled trial of clozapine in resistant schizophrenia and schizoaffective disorder.Journal of psychopharmacology (Oxford, England) · 2025Trial
- Underprescription of Clozapine: A Narrative Review Regarding 'Clozaphobia'.Human psychopharmacology · 2026Review
- Mental health nurses' knowledge and attitudes toward clozapine management protocols challenges and implications for clinical practice: A narrative review.AIMS public health · 2026Review
- A Call to Action for Starting Clozapine: Increasing Clozapine Use and Safety in a Post-REMS Era.Focus (American Psychiatric Publishing) · 2025Review
- Lights and shadows of clozapine on the immune system in schizophrenia: a narrative literature review.Metabolic brain disease · 2025Review
- Comparative effectiveness of antipsychotic treatment strategies for relapse prevention in first-episode schizophrenia in Finland: a population-based cohort study.The lancet. Psychiatry · 2025Article
- Declines and pronounced state-level variation in clozapine use among Medicare patients.PloS one · 2025Article
- Longitudinal changes in DNA methylation associated with clozapine use in treatment-resistant schizophrenia from two international cohorts.Translational psychiatry · 2024Article
- [Management of treatment resistance-Treatment-resistant schizophrenia].Der Nervenarzt · 2024Review
- Clozapine-Related Functional Bowel Obstruction: A Rare Adverse Effect Unmasking Quetiapine and Benztropine Interaction Raising Need for Bowel Surveillance.ACG case reports journal · 2024Article
- Impact of COVID-19 quarantines on clozapine-induced constipation: Experience of utilizing a clozapine-induced constipation protocol at a state forensic psychiatric facility.The mental health clinician · 2024Article
- Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug.Brain sciences · 2024Review
- Clozapine and Sweet's syndrome: case report.BJPsych open · 2023Article
- Effects of Early Clozapine Treatment on Remission Rates in Acute Schizophrenia (The EARLY Trial): Protocol of a Randomized-Controlled Multicentric Trial.Pharmacopsychiatry · 2023Article
- Clozapine but not lithium reverses aberrant tyrosine uptake in patients with bipolar disorder.Psychopharmacology · 2023Article
- Enhanced L-β-Aminoisobutyric Acid Is Involved in the Pathophysiology of Effectiveness for Treatment-Resistant Schizophrenia and Adverse Reactions of Clozapine.Biomolecules · 2023Article
- The dilemma of polypharmacy in psychosis: is it worth combining partial and full dopamine modulation?International clinical psychopharmacology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveNo consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta-analysis therefore focus on the use of clozapine as first-line or second-line treatment in non-treatment-resistant patients.
methodsArticles were eligible if they investigated clozapine compared to another antipsychotic as a first- or second-line treatment in non-treatment-resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random-effects meta-analyses.
resultsFifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta-analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges' g = 0.220, P = 0.026, 95% CI = 0.026-0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges' g = 0.274, P = 0.030, 95% CI = 0.027-0.521).
conclusionThe few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first- or second-line treatment. Only large clinical trials may comprehensively probe disease stage-dependent superiority of clozapine and investigate overall tolerability.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.