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Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review

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Abstract

Negative symptoms (such as amotivation and diminished expression) associated with schizophrenia are a major health concern. Adequate treatment would mean important progress with respect to quality of life and participation in society. Distinguishing primary from secondary negative symptoms may inform treatment options. Primary negative symptoms are part of schizophrenia. Well-known sources of secondary negative symptoms are psychotic symptoms, disorganisation, anxiety, depression, chronic abuse of illicit drugs and alcohol, an overly high dosage of antipsychotic medication, social deprivation, lack of stimulation and hospitalisation. We present an overview of reviews and meta-analyses of double-blind, controlled randomised trials, in which the efficacy of pharmacological and non-pharmacological interventions for negative symptoms was assessed. Unfortunately, there have been very few clinical trials focusing on primary negative symptoms and selecting chronically ill patients with predominant persistent negative symptoms. An important limitation in many of these studies is the failure to adequately control for potential sources of secondary negative symptoms. At present, there is no convincing evidence regarding efficacy for any treatment of predominant persistent primary negative symptoms. However, for several interventions there is short-term evidence of efficacy for negative symptoms. This evidence has mainly been obtained from studies in chronically ill patients with residual symptoms and studies with a heterogeneous study population of patients in both the acute and chronic phase. Unfortunately, reliable information regarding the distinction between primary and secondary negative symptoms is lacking. Currently, early treatment of psychosis, add-on therapy with aripiprazole, antidepressants or topiramate, music therapy and exercise have been found to be useful for unspecified negative symptoms. These interventions can be considered carefully in a shared decision-making process with patients, and are promising enough to be examined in large, well-designed long-term studies focusing on primary negative symptoms. Future research should be aimed at potential therapeutic interventions for primary negative symptoms since there is a lack of research in this field.

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Authors and Affiliations

  1. Mental Health Service Noord-Holland Noord, Community Mental Health Division, Flexible Assertive Community Treatment, Oude Hoeverweg 10, 1816 BT, Alkmaar, The Netherlands

    Selene R. T. Veerman

  2. Mental Health Service Noord-Holland Noord, Specialised Treatment Division, Treatment Centre for Bipolar Disorders, Alkmaar, The Netherlands

    Peter F. J. Schulte

  3. Academic Medical Center, University of Amsterdam, Academic Psychiatric Centre, Early Psychosis Department, Arkin, Amsterdam, The Netherlands

    Lieuwe de Haan

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  1. Selene R. T. Veerman
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  3. Lieuwe de Haan
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Correspondence to Selene R. T. Veerman.

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S.R.T. Veerman reports no financial relationships with commercial interests. Dr. P.F.J. Schulte reports personal fees from H. Lundbeck A/S, outside the submitted work, and is a board member of the Dutch Clozapine Collaboration Group. Dr. L. de Haan has received investigator-led research grants or remuneration for presenting his research from Eli Lilly, Bristol-Myers Squibb, Janssen-Cilag and AstraZeneca, all more than 36 months ago.

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Veerman, S.R.T., Schulte, P.F.J. & de Haan, L. Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review. Drugs 77, 1423–1459 (2017). https://doi.org/10.1007/s40265-017-0789-y

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