Get access

Antidepressants for people with both schizophrenia and depression

  • Review
  • Intervention




Depressive symptoms, often of substantial severity, are found in 50% of newly diagnosed suffers of schizophrenia and 33% of people with chronic schizophrenia who have relapsed. Depression is associated with dysphoria, disability, reduction of motivation to accomplish tasks and the activities of daily living, an increased duration of illness and more frequent relapses.


To determine the clinical effects of antidepressant medication for the treatment of depression in people who also suffer with schizophrenia.

Search methods

We undertook electronic searches of the Cochrane Schizophrenia Group's Register (October 2000), ClinPsych (1988-2000), The Cochrane Library (Issue 3, 2000), EMBASE (1980-2000) and MEDLINE (1966-2000). This was supplemented by citation searching, personal contact with authors and pharmaceutical companies.

We updated this search January 2013 and added 71 new trials to the awaiting assessment section.

Selection criteria

All randomised clinical trials that compared antidepressant medication with placebo for people with schizophrenia or schizoaffective disorder who were also suffering from depression.

Data collection and analysis

Data were independently selected and extracted. For homogeneous dichotomous data the fixed effects risk difference (RD), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. Statistical tests for heterogeneity were also undertaken.

Main results

Eleven studies met the inclusion criteria. All were small, and randomised fewer than 30 people to each group. Most included people after the most acute phase of psychosis and investigated a wide range of antidepressants. The quality of reporting varied a great deal. For the outcome of 'no important clinical response' antidepressants were significantly better than placebo (n=209, 5 RCTs, summary risk difference fixed effects -0.26, 95% CI -0.39 to -0.13, NNT 4 95% CI 3 to 8). The depression score at the end of the trial, as assessed by the Hamilton Rating Scale (HAM-D), seemed to suggest that using antidepressants was beneficial, but this was only statistically significant when a fixed effects model was used (n=261, 6 RCTs, WMD fixed effects -2.2 95% CI -3.8 to -0.6; WMD random effects -2.1 95% CI -5.04 to 0.84). There was no evidence that antidepressant treatment led to a deterioration of psychotic symptoms in the included trials. Heterogeneous data on 'any adverse effect' are equivocal (n=110, 2 RCTs, RD fixed 0.11 CI -0.03 to 0.25, Chi square 7.5, df=1, p=0.0062). In one small study extrapyramidal adverse effects were reported less often by those allocated to antidepressant (n=52, 1 RCT, RD fixed -0.28 CI -0.5 to -0.04). Only about 10% of people left these studies by 12 weeks. There was no apparent difference between those allocated placebo and those given an antidepressant (n=426, 10 RCTs, RD fixed 0.04 CI -0.02 to 0.1).

Authors' conclusions

Overall, the literature was of poor quality, and only a small number of trials made useful contributions. Though our results provide some evidence to indicate that antidepressants may be beneficial for people with depression and schizophrenia, the results, at best, are likely to overestimate the treatment effect, and, at worst, could merely reflect selective reporting of statistically significant results and publication bias.

At present, there is no convincing evidence to support or refute the use of antidepressants in treating depression in people with schizophrenia. We need further well-designed, conducted and reported research to determine the best approach towards treating depression in people with schizophrenia.

Note: the 71 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.

Plain language summary

Antidepressants for people with both schizophrenia and depression

Depression is common in people with schizophrenia and is associated with substantial problems including an increased risk of suicide. Many clinicians use antidepressant drugs in addition to anti-psychotics in order to treat depression. This review identified eleven randomised controlled trials that compared antidepressants with a placebo in people with schizophrenia who also had depression. There was some evidence that antidepressants did lead to an improvement in global outcome, but the small number of studies providing usable data and their poor quality, suggest that this evidence should be interpreted with caution. At present, there is no convincing evidence either to support or refute the use of antidepressants in treating depression in people with schizophrenia. Further well-designed, conducted and reported research is needed in this area.

Laienverständliche Zusammenfassung

Antidepressiva für Patienten mit Schizophrenie und Depression

Bei Menschen mit Schizophrenie findet sich häufig eine Depression; dies ist mit erheblichen Problemen, einschließlich eines erhöhten Selbstmordrisikos verbunden. Viele Ärzte verwenden Antidepressiva zusätzlich zu Antipsychotika, um die Depressionen zu behandeln. Diese Übersichtsarbeit identifizierte elf randomisierte kontrollierte Studien, die Antidepressiva mit einem Placebo bei Patienten mit Schizophrenie und Depression verglichen. Es gab Hinweise darauf, dass Antidepressiva zu einer Verbesserung des Gesamtergebnisses führten, aber die geringe Anzahl an Studien, die brauchbare Daten lieferten, und deren schlechte Qualität, legen nahe, dass diese Hinweise mit Vorsicht interpretiert werden sollten. Derzeit gibt es keine überzeugende Evidenz, die den Einsatz von Antidepressiva in der Behandlung von Depression bei Menschen mit Schizophrenie unterstützt oder widerlegt. Weitere gut gestaltete, durchgeführte und berichtete Forschung ist in diesem Bereich erforderlich.

Anmerkungen zur Übersetzung

J. Meerpohl, Koordination durch Cochrane Schweiz

Get access to the full text of this article