Antidepressants for people with both schizophrenia and depression

Abstract

Background: 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.

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

Search strategy: 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.

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).

Reviewer's 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.

1.1. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 1 No important clinical response (Global Psychiatric Status, CGI, or significant reduction in HAM‐D).

1.2. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 2 Mental state: 1a. Depressive symptoms (HAM‐D total endpoint, high = poor).

1.3. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 3 Mental state: 1b. Depressive symptoms (HAM‐D total change, decline = good).

1.4. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 4 Mental state: 2a. General (BPRS total endpoint, high = poor).

1.5. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 5 Mental state: 2b. General (BPRS total change, decline = good).

1.6. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 6 Adverse effects: 1. Any side effects.

1.7. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 7 Adverse effects: 2. Extrapyramidal effects ‐ clinically significant severity.

1.8. Analysis

Comparison 1 ANY ANTIDEPRESSANT + ANTIPSYCHOTIC vs PLACEBO + ANTIPSYCHOTIC, Outcome 8 Leaving the study early.