SynthesisCNS drugs2019
Treatment Strategies for Clozapine-Induced Sialorrhea: A Systematic Review and Meta-analysis.
Synthesis in CNS drugs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 6 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
19 citing papers in PubMed, 6 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Pharmacological and Somatic Treatments for First-Episode Psychosis and Schizophrenia: Synopsis of the US Department of Veterans Affairs and US Department of Defense Clinical Practice Guidelines.Schizophrenia bulletin · 2025Guideline
- Guidelines for Parkinson's disease management part II: consensus from the movement disorders scientific department of the Brazilian Academy of Neurology - non-motor symptoms.Arquivos de neuro-psiquiatria · 2025Guideline
- Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.Molecular psychiatry · 2023Pooled it
- Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.Schizophrenia bulletin · 2023Guideline
- A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia.CNS drugs · 2022Guideline
- A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions.Psychopharmacology · 2021Pooled it
- The effect of sublingual atropine sulfate on clozapine-induced hypersalivation: a multicentre, randomised placebo-controlled trial.Psychopharmacology · 2020Trial
- Silent Inflammation: A Critical Narrative Review of the Relationship Between Periodontal Disease and Psychosis-The Role of Oxidative Stress and Iatrogenic Comorbidities.Antioxidants (Basel, Switzerland) · 2026Review
- Long-Term Safety and Efficacy of Repeated Cycles of RimabotulinumtoxinB in the Treatment of Chronic Sialorrhea: Results of the OPTIMYST Trial.Neurology and therapy · 2025Article
- Clozapine Efficacy and Adverse Drug Reactions Among a Nationwide Study of 1021 Australians Prescribed Clozapine: The ClozaGene Study.Schizophrenia bulletin · 2025Article
- Guideline for pharmacological treatment of schizophrenia 2022.Neuropsychopharmacology reports · 2025Article
- The effects of clinical and pharmacological factors on the ratio of clozapine to norclozapine in psychiatric patients.Frontiers in pharmacology · 2024Article
- [Safety aspects during treatment with clozapine: : Adverse effects, titration, and therapeutic drug monitoring - a narrative review].Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater · 2023Review
- Efficacy of sofpironium bromide gel on clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia: double-blind, controlled crossover study.BJPsych open · 2023Article
- Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia.Therapeutic advances in psychopharmacology · 2023Review
- A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH).BMC psychiatry · 2022Observational
- Efficacy and safety of clozapine in psychotic disorders-a systematic quantitative meta-review.Translational psychiatry · 2021Review
- Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation.Clinical pharmacokinetics · 2021Article
- Management of clozapine treatment during the COVID-19 pandemic.Therapeutic advances in psychopharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea.
methodsWe systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm.
results19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1).
conclusionClozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.
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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.