ArticleEuropean archives of psychiatry and clinical neuroscience2024
A network meta-analysis of efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia.
Article in European archives of psychiatry and clinical neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 4 of them syntheses that pooled it.
What it found
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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
30 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Guideline
- Non-Clozapine interventions in treatment-resistant schizophrenia: a systematic review and meta-analysis.Molecular psychiatry · 2026Pooled it
- Pooled it
- Evaluating Monitoring Guidelines of Clozapine-Induced Adverse Effects: a Systematic Review.CNS drugs · 2024Pooled it
- A 6-month supported online program for the treatment of persecutory delusions: Feeling Safer.Psychological medicine · 2025Trial
- Beyond Clozapine Failure: Precision Approach and Palliative Psychiatry in Ultra-Treatment-Resistant Schizophrenia.Journal of clinical medicine · 2026Review
- Clozapine-associated pneumonia: a gut-lung-brain axis perspective.European archives of psychiatry and clinical neuroscience · 2026Article
- A critical review of the early clozapine trials published in German and a discussion of the many unresolved issues left by these trials.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Glutamate change in the anterior cingulate cortex after starting clozapine: evaluating 1H-MRS pilot data.BMC psychiatry · 2026Article
- Risk of Long-Term Clozapine Medication over Decades for Cardiac Adverse Events Including Heart Failure and Its Pathophysiology: A Japan and China Retrospective Cohort Analysis.Medical sciences (Basel, Switzerland) · 2026Article
- Real-world comprehensive care of people living with schizophrenia: recommendations across different settings and clinical stages.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026Article
- Next-step treatment for schizophrenia non-responsive to antipsychotics: a systematic review and network meta-analysis.EClinicalMedicine · 2026Article
- The associations of systemic inflammation and insulin resistance-related indicators with psychopathology and BDNF in patients with chronic schizophrenia.Frontiers in psychiatry · 2026Article
- Elevated glutamine but not glutamate is associated with clozapine eligibility in an early psychosis sample.Frontiers in psychiatry · 2026Article
- Clinical response to clozapine in Black people with psychosis: A secondary analysis of an open-label clinical trial.Therapeutic advances in psychopharmacology · 2026Article
- Schizophrenia.Nature reviews. Disease primers · 2025Review
- Efficacy of low-frequency repetitive transcranial magnetic stimulation combined with risperidone in the treatment of schizophrenia patients with auditory verbal hallucinations.Pakistan journal of medical sciences · 2025Article
- The pharmacology underlying the unique antipsychotic efficacy of clozapine.Journal of psychopharmacology (Oxford, England) · 2025Review
- The sense and nonsense of antipsychotic combinations: A model for dopamine DTranslational psychiatry · 2025Article
- Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation.Schizophrenia bulletin · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectiveClozapine is considered as the standard treatment for this subgroup, but the evidence is not unequivocal. There are several potential alternatives being used because of the possible adverse effects of clozapine. We aimed to examine the efficacy and adverse events of different antipsychotics in treatment-resistant schizophrenia by performing a network meta-analysis.
methodsWe searched the Cochrane Schizophrenia Group register for randomized-controlled trials (up to March 06, 2022) and MEDLINE (up to January 20, 2023). We included blinded and open studies and participants with a broad definition of treatment resistance. The primary outcome was overall symptoms of schizophrenia; secondary outcomes were response to treatment, positive and negative symptoms of schizophrenia, discontinuation, side effects, quality of life, and functioning. The study was registered in Open Science Framework ( https://osf.io/9nf2y/ ).
resultsWe included 60 studies involving 6838 participants in the network meta-analysis. In the primary outcome, clozapine and olanzapine were more efficacious than risperidone, haloperidol, fluphenazine, sertindole, chlorpromazine, and quetiapine (range of mean SMDs, - 0.11 to - 0.48). The difference between clozapine and olanzapine was trivial and uncertain (SMD - 0.05, 95% CI, - 0.21 to 0.11). The result of other efficacy outcomes as well as subgroup and sensitivity analyses were consistent with the primary analysis. Clozapine and olanzapine were associated with more weight gain, and clozapine was associated with more sedation events compared to many other antipsychotics.
conclusionsClozapine remains the gold standard for patients with treatment-resistant schizophrenia. Olanzapine seems to be second-best and could be tried before switching to clozapine.
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Registered trials
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