ArticleWorld psychiatry : official journal of the World Psychiatric Association (WPA)2017
Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis.
Article in World psychiatry : official journal of the World Psychiatric Association (WPA), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 6 of them syntheses that pooled it.
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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.
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Who cites it
94 citing papers in PubMed, 6 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- Interventions for negative symptoms in schizophrenia: efficacy and clinical interpretability in a meta-analysis of 451 randomized controlled trials.Molecular psychiatry · 2026Pooled it
- Cariprazine and clozapine: a systematic review of a promising antipsychotic combination for treatment-resistant schizophrenia.The international journal of neuropsychopharmacology · 2025Pooled it
- Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia - a systematic review.Journal of psychopharmacology (Oxford, England) · 2025Pooled it
- Early Non-Response to Antipsychotic Treatment in Schizophrenia: A Systematic Review and Meta-Analysis of Evidence-Based Management Options.CNS drugs · 2023Pooled it
- Antipsychotic polypharmacy reduction versus polypharmacy continuation for people with schizophrenia.The Cochrane database of systematic reviews · 2022Pooled it
- Schizophrenia.Deutsches Arzteblatt international · 2020Pooled it
- 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
- Combining Three Long-acting Injectable Antipsychotics: A Case Series.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Trends in Antipsychotic Polypharmacy and Potential Overtreatment with Antipsychotics: A Naturalistic Cohort Study of People in Long-term Care.Schizophrenia bulletin · 2026Article
- Health-Related Quality of Life Among Patients with Treatment-Resistant Schizophrenia Receiving Clozapine-Based Therapy in South Kalimantan, Indonesia.Patient preference and adherence · 2026Article
- Clinical practice guidelines for management of schizophrenia in India: A comprehensive overview.Indian journal of psychiatry · 2026Article
- Adjunctive treatment with evenamide, a glutamate modulator, is associated with clinically meaningful benefits in patients with treatment-resistant schizophrenia and inadequate response to antipsychotics: recent clinical findings from randomized trials.Therapeutic advances in psychopharmacology · 2026Article
- The influence of social capital and evidence-based orientation on psychiatrists' attitudes toward antipsychotic polypharmacy in schizophrenia.Scientific reports · 2025Article
- Antipsychotic load during olanzapine mono- versus polytherapy and in relation to age.European journal of clinical pharmacology · 2025Article
- The Use of Long-Acting Injectables for People with Schizophrenia: Consensus Panel Recommendations for Overcoming Barriers and Implementing Treatment.Neurology and therapy · 2025Article
- Schizophrenia.Nature reviews. Disease primers · 2025Review
- The sense and nonsense of antipsychotic combinations: A model for dopamine DTranslational psychiatry · 2025Article
- Strategic and tactic use of antipsychotic medications in schizophrenia: a perspective on current prescription practice.Discover mental health · 2025Review
- Schizophrenia treatment preferences of psychiatrists versus guidelines: A European perspective.European psychiatry : the journal of the Association of European Psychiatrists · 2025Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 11 institutions in 8 countries.
Funding
Abstract
Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta-analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co-primary outcomes were total symptom reduction and study-defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=-0.53, 95% CI: -0.87 to -0.19, p=0.002). However, superiority was only apparent in open-label and low-quality trials (both p<0.001), but not in double-blind and high-quality ones (p=0.120 and 0.226, respectively). Study-defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non-significant in double-blind and high-quality studies (both p=0.990). Findings were replicated in clozapine and non-clozapine augmentation studies. No differences emerged regarding all-cause/specific-cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=-0.38, 95% CI: -0.63 to -0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=-0.41, 95% CI: -0.79 to -0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double-blind/high-quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation.
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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.