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Treatment of depression in schizophrenia: Systematic review and meta-analysis

  • Angharad Gregory (a1), Pavan Mallikarjun (a2) and Rachel Upthegrove (a2)

Depression in schizophrenia predicts poor outcomes, including suicide, yet the effectiveness of antidepressants for its treatment remains uncertain.


To synthesise the evidence of the effectiveness of antidepressants for the treatment of depression in schizophrenia.


Multiple databases Were searched and inclusion Criteria included participants aged over 18 years with schizophrenia or related psychosis with a depressive episode. Papers were quality assessed used the Cochrane risk bias tool. Meta-analyses were performed for risk difference and standardised mean difference of all antidepressants, antidepressant class and individual antidepressant where sufficient studies allowed.


A total of 26 moderate- to low-quality trials met inclusion criteria. In meta-analysis a significant risk difference was found in favour of antidepressant treatment, with a number needed to treat of 5 (95% CI 4–9). Studies using tools specifically designed to assess depression in schizophrenia showed a larger effect size. However, after sensitivity analysis standardised mean difference of all antidepressants did not show a statistically significant improvement in depression score at end-point, neither did any individual antidepressant class.


Antidepressants may be effective for the treatment of depression in schizophrenia, however, the evidence is mixed and conclusions must be qualified by the small number of low- or moderate-quality studies. Further sufficiently powered, high-quality studies are needed.

Corresponding author
Rachel Upthegrove, The Barberry, University of Birmingham, 25 Vincent Drive Edgbaston Birmingham B152FG, UK. Email:
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Treatment of depression in schizophrenia: Systematic review and meta-analysis

  • Angharad Gregory (a1), Pavan Mallikarjun (a2) and Rachel Upthegrove (a2)
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