EPA guidance on treatment of negative symptoms in schizophrenia

EPA · 2021 · Europe

Source and licence

Authors: S Galderisi, S Kaiser, I Bitter et al.
Title: EPA guidance on treatment of negative symptoms in schizophrenia
Journal: European Psychiatry, 2021
DOI: 10.1192/j.eurpsy.2021.13
Licence: CC BY 4.0
Changes: Verbatim excerpts; formatting adapted

Full text retrieved 2026-10-27 from Europe PMC · PMC8057437

Licence statement of the original publication

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

This page reproduces excerpts of the original publication; the original is authoritative. It has not been reviewed by a physician, does not state a recommendation of Medelix and does not replace medical advice. The guideline may have been updated since.

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Recommendations

Verbatim, with grade of recommendation or strength of consensus where given.

General principles

Depression, positive symptoms, and side effects should be treated in patients presenting with negative symptoms. The treatment of these problems should follow available guidelines for their treatment as there is no evidence for a specific approach in patients presenting with negative symptoms.Grade: B

Negative symptoms secondary to depression

In a patient presenting with negative symptoms and comorbid depression, a switch to an antipsychotic with antidepressant properties should be considered.Grade: B
In a patient presenting with negative symptoms and comorbid depression, add-on antidepressant treatment should be considered.Grade: B
If the trial with an add-on antidepressant is not associated with an improvement of negative symptoms and/or depression, the antidepressant should be discontinued to avoid polypharmacy.Grade: B
In a patient presenting with negative symptoms and comorbid depression, cognitive behavior therapy should be considered.Grade: B

Negative symptoms secondary to positive symptoms

In a patient presenting with negative symptoms that are considered to be secondary to positive symptoms, antipsychotic treatment can be optimized by following existing recommendations regarding dose range and switching of medications.Grade: C
In a patient presenting with negative symptoms that are considered to be secondary to treatment-resistant positive symptoms, a trial with clozapine should be considered.Grade: B
In patients with negative symptoms considered to be secondary to positive symptoms, CBT can be considered.Grade: C

Negative symptoms secondary to side effects

If a patient with negative symptoms shows extrapyramidal and/or sedative side effects, a reduction of the antipsychotic dose or a switch to an antipsychotic with lower risk for extrapyramidal and/or sedative side effects can be considered.Grade: C

Recommendations concerning antipsychotic treatment for negative symptoms

For patients with negative symptoms who are treated with a first-generation antipsychotic, a switch to a second-generation antipsychotic should be considered.Grade: B

Antidepressants

If negative symptoms do not improve after optimization of antipsychotic treatment, a trial with an add-on antidepressant should be considered for patients with negative symptoms after careful evaluation of risks and benefits.This recommendation concerns also patients who do not show depressive symptoms. However, no specific recommendations for patients with primary negative symptoms can be given.SSRIs are the most studied agents, but the currently available evidence does not allow a recommendation for a particular drug class or individual drug.Grade: B

Social skills training

Social skills training should be offered to patients with negative symptoms, but no specific recommendation for patients with primary negative symptoms can be given. Furthermore, the available evidence does not allow recommending one specific program for social skills training.Grade: B

Cognitive remediation

Cognitive remediation can be considered for patients with negative symptoms, in particular for those who also show cognitive impairment.No specific recommendation for cognitive remediation in the treatment of primary or predominant negative symptoms can be given.Grade: C

Exercise

Exercise can be considered for persons suffering from negative symptoms as part of an integrated treatment plan also aiming at improving physical health.Grade: C

Access to treatment and psychosocial rehabilitation

The access to care for patients with negative symptoms should have a low-threshold and should be facilitated by assertive community interventions.Grade: B
Patients with negative symptoms should have access to rehabilitation interventions such as supported employment and supported housing.Grade: B

First-episode psychosis

Early intervention services should be provided for patients with a first episode of psychosis. There is evidence that the use of these services can improve negative symptoms.However, no specific recommendation can be formulated with regard to the type of intervention program and the target population with primary and persistent negative symptoms.Grade: B

Abstract

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.

However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.

Contents of the original publication

The section headings of the original.

Introduction
Methodology
Systematic literature search
Inclusion criteria
Exclusion criteria
Treatment of Secondary Negative Symptoms
General principles
Negative symptoms secondary to depression
Negative symptoms secondary to positive symptoms
Negative symptoms secondary to side effects
Biological Treatments
Antipsychotics
Add-on treatment
Brain stimulation
Psychosocial Treatments
Psychotherapy
Training interventions
Exercise
Access to treatment and psychosocial rehabilitation
General comment on psychosocial interventions
Specific Treatments Depending on Illness-Stage
At-risk mental-state
First-episode psychosis
Discussion
Conclusions
Financial Support

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