A Cochrane review [Abstract] 1 included 5 short-term studies with a total of 190 subjects. Antidepressants used in the studies were amitriptyline, mianserin, paroxetine, fluvoxamine and fluoxetine. In studies comparing antipsychotic plus antidepressant combination versus antipsychotic and placebo, no significant difference for 'leaving the study early for any reason' (n=90, 3 RCTs, RR 3.0 CI 0.35 to 26.04), leaving early due to adverse events (n=64, 2 RCTs, RR 5.0 CI 0.26 to 97.0) and leaving the study early due to inefficacy (n=34, 1 RCT, RR 3.0 CI 0.13 to 68.84) was found. The antipsychotic plus antidepressant group showed a greater improvement in clinical response (n=30, 1 RCT, WMD -1.0 CI -1.61 to -0.39) and lower severity at endpoint (n=30, 1 RCT, WMD -0.9 CI -1.55 to -0.25) on the Clinical Global Impression Scale. More people allocated to combination therapy had improvement in negative symptoms (n=60, 2 RCTs, RR 0.56 CI 0.32 to 0.97, NNT 3 CI 3 to 34). The combination therapy was better in different aspects of negative symptoms: 'affective flattening' (n=30, 1 RCT, WMD -7.0 CI -10.37 to -3.63), 'alogia' (n=26, 1 RCT, WMD -3.00 CI -5.14 to -0.86) and 'avolition' (n=30, 1 RCT, WMD -3.0 CI -5.04 to -0.96). No difference was found between treatment groups in the outcome 'at least one adverse event' (n=84, 2 RCTs, RR 1.80 CI 0.66 to 4.90), in movement disorders and in other adverse effects.
Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison) and by limitations in study quality (inadequate follow up; omission of important outcomes). There are no data on outcomes such as compliance, cost, social and cognitive functioning, relapse, recurrence of negative symptoms, rehospitalisation or quality of life. There are no medium or long term data.
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