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Practice Uncertainties Page

Do antidepressants improve negative symptoms in schizophrenia?

BMJ 2011; 342 doi: (Published 10 June 2011) Cite this as: BMJ 2011;342:d3371
  1. Thomas R E Barnes, professor1,
  2. Carol Paton, pharmacist 1
  1. 1Centre for Mental Health, Imperial College, London W6 8RP, UK
  1. Correspondence to: T R E Barnes t.r.barnes{at}

The negative symptoms of schizophrenia comprise a range of deficits in communication, emotional responsiveness, socialisation, capacity for experiencing pleasure, and motivation. Negative symptoms occur alongside positive symptoms such as delusions and hallucinations in acute psychotic episodes, where they generally respond to treatment with antipsychotic medication, but for the 15-20% of patients for whom negative symptoms are enduring,1 2 current treatment strategies have modest benefits at best.

A critical but often difficult clinical distinction is between primary and secondary negative symptoms,3 The former constitute an enduring deficit state within schizophrenia, whereas the latter can be manifestations of depressive features or medication side effects such as bradykinesia (as part of drug induced parkinsonism), or the consequence of positive symptoms (for example, social and emotional withdrawal may be a response to persecutory delusions or reflect a patient’s avoidance of social stimulation to minimise the provocation of intrusive psychotic experiences). Irrespective of cause, persistent negative symptoms disproportionately limit recovery4 and are associated with poorer occupational and social functioning in the community, including a reduced likelihood of living independently.5 6

What is the evidence of the uncertainty?

Findings from studies that have tested drug strategies for negative symptoms in the context of acute psychotic episodes may not be generalisable to those with persistent symptoms. Few published studies have specifically recruited patients with illness characterised by persistent symptoms.

The introduction of the second generation antipsychotics, such as clozapine, risperidone, and olanzapine, was accompanied by claims of better efficacy against negative symptoms, but whether any such effect is independent of an improvement in positive symptoms or medication …

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