+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Augmentation strategies for clozapine refractory schizophrenia: A systematic review and meta-analysis



Augmentation strategies for clozapine refractory schizophrenia: A systematic review and meta-analysis



Australian and New Zealand Journal of Psychiatry 52(8): 751-767



Although clozapine is the most effective medication for treatment refractory schizophrenia, only 40% of people will meet response criteria. We therefore undertook a systematic review and meta-analysis of global literature on clozapine augmentation strategies. We systematically reviewed PubMed, PsycInfo, Embase, Cochrane Database, Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database for randomised control trials of augmentation strategies for clozapine resistant schizophrenia. We undertook pairwise meta-analyses of within-class interventions and, where possible, frequentist mixed treatment comparisons to differentiate treatment effectiveness Results: We identified 46 studies of 25 interventions. On pairwise meta-analyses, the most effective augmentation agents for total psychosis symptoms were aripiprazole (standardised mean difference: 0.48; 95% confidence interval: -0.89 to -0.07) fluoxetine (standardised mean difference: 0.73; 95% confidence interval: -0.97 to -0.50) and, sodium valproate (standardised mean difference: 2.36 95% confidence interval: -3.96 to -0.75). Memantine was effective for negative symptoms (standardised mean difference: -0.56 95% confidence interval: -0.93 to -0.20). However, many of these results included poor-quality studies. Single studies of certain antipsychotics (penfluridol), antidepressants (paroxetine, duloxetine), lithium and Ginkgo biloba showed potential, while electroconvulsive therapy was highly promising. Mixed treatment comparisons were only possible for antipsychotics, and these gave similar results to the pairwise meta-analyses. On the basis of the limited data available, the best evidence is for the use of aripiprazole, fluoxetine and sodium valproate as augmentation agents for total psychosis symptoms and memantine for negative symptoms. However, these conclusions are tempered by generally short follow-up periods and poor study quality.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051554030

Download citation: RISBibTeXText

PMID: 29732913

DOI: 10.1177/0004867418772351


Related references

Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis. Schizophrenia Research 171(1-3): 215-224, 2016

Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. British Journal of Psychiatry 209(5): 385-392, 2016

Clozapine augmentation strategies - a systematic meta-review of available evidence. Treatment options for clozapine resistance. Journal of Psychopharmacology 33(4): 423-435, 2019

Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: a systematic review and meta-analysis of randomized-controlled trials. Journal of Psychiatric Research 62: 38-47, 2015

Non-glutamatergic clozapine augmentation strategies: a review and meta-analysis. Pharmacopsychiatry 47(7): 231-238, 2014

ECT augmentation of clozapine for clozapine-resistant schizophrenia: A meta-analysis of randomized controlled trials. Journal of Psychiatric Research 105: 23-32, 2018

Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica 138(4): 281-288, 2018

Clozapine and Psychosocial Function in Schizophrenia: A Systematic Review and Meta-Analysis. Cns Drugs 32(11): 1011-1023, 2018

Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry 16(1): 77-89, 2017

The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia Research 109(1-3): 10-14, 2009

Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. American Journal of Psychiatry 156(7): 990-999, 1999

Treatment Strategies for Clozapine-Induced Sialorrhea: A Systematic Review and Meta-analysis. Cns Drugs 33(3): 225-238, 2019

Antidepressant augmentation of antipsychotics in schizophrenia: a systematic review, meta-analysis and metaregression analysis. European Neuropsychopharmacology 27: S946-S947, 2017

Efficacy of adjunctive treatments added to olanzapine or clozapine for weight control in patients with schizophrenia: a systematic review and meta-analysis. Thescientificworldjournal 2015: 970730, 2015

Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years. Schizophrenia Bulletin 45(2): 315-329, 2019