Treatment of depression in schizophrenia: a systematic review and meta-analysis

Background: Depression in schizophrenia predicts poor outcomes, including suicide, yet the effectiveness of antidepressants for its treatment remains uncertain. The aim of this study was to synthesise the evidence of the effectiveness of antidepressants for the treatment of depression in schizophrenia.

Methods: Following Prisma guidelines, multiple databases were searched for trials investigating the effectiveness of antidepressant treatment for people with schizophrenia and depression. 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. Data was extracted with meta-analyses performed for risk difference and standardised mean difference of all antidepressants, antidepressant class and individual antidepressant where sufficient studies allowed.

Results: 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.

Conclusion: 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.