SynthesisSchizophrenia bulletin2012
Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review.
Synthesis in Schizophrenia bulletin, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02533232 (Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia), which is not on this map. Cited by 36 papers, 5 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.
Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial
Who cites it
36 citing papers in PubMed, 5 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Maximizing response to first-line antipsychotics in schizophrenia: a review focused on finding from meta-analysis.Psychopharmacology · 2019Pooled it
- Antipsychotic combinations for schizophrenia.The Cochrane database of systematic reviews · 2017Pooled it
- Valproate for schizophrenia.The Cochrane database of systematic reviews · 2016Pooled it
- Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2015Pooled it
- Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia.Schizophrenia research · 2015Pooled it
- Cognitive behavioural therapy in clozapine-resistant schizophrenia (FOCUS): an assessor-blinded, randomised controlled trial.The lancet. Psychiatry · 2018Trial
- Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms.Journal of clinical psychopharmacology · 2015Trial
- Adjuvant Mood Stabilisers for Long-Term Management of Treatment-Resistant Schizophrenia: A Case Report.Cureus · 2026Article
- Long-Acting Injectable Second-Generation Antipsychotics in Seriously Ill Patients with Schizophrenia: Doses, Plasma Levels, and Treatment Outcomes.Biomedicines · 2024Article
- Plasmatic Levels and Response to Variable Doses of Monthly Aripiprazole and Three-Month Paliperidone in Patients with Severe Schizophrenia. Treatment Adherence, Effectiveness, Tolerability, and Safety.Neuropsychiatric disease and treatment · 2023Article
- The Use of Second-Generation Antipsychotics in Patients with Severe Schizophrenia in the Real World: The Role of the Route of Administration and Dosage-A 5-Year Follow-Up.Biomedicines · 2022Article
- Machine Learning Algorithm-Based Prediction Model for the Augmented Use of Clozapine with Electroconvulsive Therapy in Patients with Schizophrenia.Journal of personalized medicine · 2022Article
- Prescribing patterns of long-acting injectable antipsychotics in a community setting in South Africa.The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa · 2022Article
- Japanese Society of Neuropsychopharmacology: "Guideline for Pharmacological Therapy of Schizophrenia".Neuropsychopharmacology reports · 2021Article
- Clozapine resistant schizophrenia: Newer avenues of management.World journal of psychiatry · 2021Review
- A Review of Multimodal Hallucinations: Categorization, Assessment, Theoretical Perspectives, and Clinical Recommendations.Schizophrenia bulletin · 2021Review
- Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives.Neurobiology of disease · 2019Review
- Clozapine augmentation strategies.The mental health clinician · 2019Article
- Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia.JAMA psychiatry · 2019Article
- Clinical Course, Neurobiology and Therapeutic Approaches to Treatment Resistant Schizophrenia. Toward an Integrated View.Frontiers in psychiatry · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhen schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder.
methodsOnly double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated from individual studies and combined to standardized mean differences (Hedges's g).
resultsTwenty-nine studies reporting on 15 different augmentations were included. Significant better efficacy than placebo on total symptom severity was observed for lamotrigine, citalopram, sulpiride, and CX516 (a glutamatergic agonist). The positive effect of lamotrigine disappeared after outlier removal. The other positive findings were based on single studies. Significantly better efficacy on positive symptom severity was observed for topiramate and sulpiride. The effect of topiramate disappeared after outlier removal. Results for sulpiride were based on a single randomized controlled trial. Citalopram, sulpiride, and CX516 showed better efficacy for negative symptoms than placebo, all based on single studies.
conclusionsEvidence for efficacy of clozapine augmentation is currently scarce. Efficacy of lamotrigine and topiramate were both dependent on single studies with deviating findings. The effect of citalopram, sulpiride, and CX516 were based on single studies. Thus, despite their popularity, pharmacological augmentations of clozapine are not (yet) demonstrated to be superior to placebo.
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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.