Non-Glutamatergic Clozapine Augmentation Strategies: A Review and Meta-Analysis

Abstract Persistent negative symptoms and cognitive impairment are major clinical problems in the treatment of schizophrenia. There is no convincing evidence regarding the efficacy of augmentation of clozapine with a second antipsychotic, ethyl eicosapentaenoic acid (E-EPA), an antidepressant, a mood stabilizer or extract of Ginkgo biloba in clozapine-resistant schizophrenia. We present an overview of studies in which the potential clinical utility of the addition of non-glutamatergic agents to clozapine is assessed. We performed a meta-analysis on the efficacy of both risperidone and aripiprazole compared to placebo. We compared the effects of the addition of a second antipsychotic or an antidepressant to clozapine on positive, negative, overall and affective symptoms of schizophrenia in double-blind placebo-controlled trials.

[1]  L. Hedges.  DISTRIBUTION THEORY FOR GLASS'S ESTIMATOR OF , 2016 .

[2]  D. Goff,et al.  Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia , 2013, Acta psychiatrica Scandinavica.

[3]  H. Gunduz-Bruce,et al.  Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia , 2013, Schizophrenia Research.

[4]  S. Leucht,et al.  Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. , 2012, Schizophrenia bulletin.

[5]  George A Kelley,et al.  Statistical models for meta-analysis: A brief tutorial. , 2012, World journal of methodology.

[6]  A. Serretti,et al.  Clozapine resistance: Augmentation strategies , 2012, European Neuropsychopharmacology.

[7]  E. Spina,et al.  Duloxetine as adjunctive treatment to clozapine in patients with schizophrenia: a randomized, placebo-controlled trial , 2011, International clinical psychopharmacology.

[8]  E. Spina,et al.  Effect of aripiprazole augmentation of clozapine in schizophrenia: A double-blind, placebo-controlled study , 2011, Schizophrenia Research.

[9]  R. Conley,et al.  Adjunctive Risperidone for Partially Responsive People with Schizophrenia Treated with Clozapine , 2010, Neuropsychopharmacology.

[10]  P. Falkai,et al.  Combination Therapy in the Treatment of Schizophrenia , 2010, Pharmacopsychiatry.

[11]  Jijun Wang,et al.  Sulpiride augmentation for schizophrenia. , 2010, Schizophrenia bulletin.

[12]  David Taylor,et al.  Augmentation of clozapine with a second antipsychotic – a meta‐analysis of randomized, placebo‐controlled studies , 2009, Acta psychiatrica Scandinavica.

[13]  M. Berk,et al.  Mirtazapine add‐on therapy in the treatment of schizophrenia with atypical antipsychotics: a double‐blind, randomised, placebo‐controlled clinical trial , 2009, Human psychopharmacology.

[14]  S. Englisch,et al.  Combined antipsychotic treatment involving clozapine and aripiprazole , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[15]  A. Doruk,et al.  A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia , 2008, International clinical psychopharmacology.

[16]  J. Chang,et al.  Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. , 2008, The Journal of clinical psychiatry.

[17]  G. Juckel,et al.  Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial. , 2008, Pharmacopsychiatry.

[18]  D. Goff,et al.  Risperidone augmentation for schizophrenia partially responsive to clozapine: A double-blind, placebo-controlled trial , 2007, Schizophrenia Research.

[19]  J. Sacher,et al.  P.3.c.037 Haloperidol in combination with clozapine in treatment-refractory patients with schizophrenia , 2006, European Neuropsychopharmacology.

[20]  G. L’italien,et al.  Naturalistic Impact of Second-Generation Antipsychotics on Weight Gain , 2006, The Annals of pharmacotherapy.

[21]  Peter Falkai,et al.  Clozapine alone versus clozapine and risperidone with refractory schizophrenia. , 2006, The New England journal of medicine.

[22]  L. Guang.  A Randomized, Placebo - controlled Clinical Trial of Combined Citalopram and Clozapine in the Treatment of Negative Symptoms of Schizophrenia , 2006 .

[23]  V. Kontaxakis,et al.  Randomized controlled augmentation trials in clozapine-resistant schizophrenic patients: a critical review , 2005, European Psychiatry.

[24]  E. Kohegyi,et al.  Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial. , 2005, The American journal of psychiatry.

[25]  J. Newcomer.  Second-Generation (Atypical) Antipsychotics and Metabolic Effects , 2005, CNS drugs.

[26]  A. E. Rosa,et al.  The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study , 2004, International clinical psychopharmacology.

[27]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[28]  R. Emsley,et al.  Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. , 2002, The American journal of psychiatry.

[29]  D. Horrobin,et al.  A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. , 2002, Journal of psychiatric research.

[30]  Abraham Weizman,et al.  Sulpiride augmentation in people with schizophrenia partially responsive to clozapine , 1997, British Journal of Psychiatry.

[31]  R. Buchanan,et al.  Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. , 1996, The American journal of psychiatry.