Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jan;10(1):20-32.
doi: 10.4103/0973-1229.91588.

Treatment-resistant Schizophrenia: Evidence-based Strategies

Susanne Englisch  1 , Mathias Zink
Affiliations

Treatment-resistant Schizophrenia: Evidence-based Strategies

Susanne Englisch et al. Mens Sana Monogr. 2012 Jan.

Abstract

Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy.

Keywords: Add-on; Augmentation; Combination; Polypharmacy; Schizophrenia, Treatment resistance.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: S.E. has been provided with travel expenses and consultant fees from AstraZeneca, Bristol-Myers Squibb GmbH & CoKGaA, Eli-Lilly, Janssen Cilag, Lundbeck, Otsuka Pharma, Pfizer Pharma and Servier

M.Z. has received unrestricted scientific grants of German Research Foundation (DFG), ERAB (European Research Advisory Board), Pfizer Pharma GmbH, Bristol-Myers Squibb GmbH & CoKGaA, further speaker and travel support from Pfizer Pharma GmbH, Bristol-Myers Squibb GmbH & CoKGaA, Astra Zeneca, Eli-Lilly and Janssen Cilag

Figures

Figure 1
Figure 1
Flowchart of the paper
See this image and copyright information in PMC

References

    1. Aitchison KJ, Mir A, Shivakumar K, McAllister VD, O’Keane V, McCrone P. Costs and outcomes associated with an aripiprazole add-on or switching open-label study in psychosis. J Psychopharmacol. 2011;25:675–84. PMID: 20176773. - PubMed
    1. Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schwarz SF, Leucht S. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;11:CD006633. PMID: 21069690. - PMC - PubMed
    1. Assion HJ, Reinbold H, Lemanski S, Bsilowski M, Juckel G. Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial, Pharmacopsychiatry. 2008;41:24–8. PMID: 18203048. - PubMed
    1. Baandrup L, Gasse C, Jensen VD, Glenthoj BY, Nordentoft M, Lublin H, et al. Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study. J Clin Psychiatry. 2010;71:103–8. PMID: 19895781. - PubMed
    1. Barbui C, Accordini S, Nose M, Stroup S, Purgato M, Girlanda F, et al. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial. J Clin Psychopharmacol. 2011;31:266–73. PMID: 21508849. - PubMed