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Treatments of Negative Symptoms in Schizophrenia: Meta-Analysis of 168 Randomized Placebo-Controlled Trials

Research output: Contribution to journalReview article

Paolo Fusar-Poli, Evangelos Papanastasiou, Daniel Stahl, Matteo Rocchetti, William T Carpenter, Sukhwinder Shergill, Philip McGuire

Original languageEnglish
Pages (from-to)892-899
Number of pages8
JournalSchizophrenia Bulletin
Issue number4
Early online date2014
Publication statusPublished - 1 Jul 2015

King's Authors


Objectives: Existing treatments for schizophrenia can improve positive symptoms, but it is unclear if they have any impact on negative symptoms. This meta-analysis was conducted to assess the efficacy of available treatments for negative symptoms in schizophrenia. Methods: All randomized-controlled trials of interventions for negative symptoms in schizophrenia until December 2013 were retrieved; 168 unique and independent placebo-controlled trials were used. Negative symptom scores at baseline and follow-up, duration of illness, doses of medication, type of interventions, and sample demographics were extracted. Heterogeneity was addressed with the I 2 and Q statistic. Standardized mean difference in values of the Negative Symptom Rating Scale used in each study was calculated as the main outcome measure. Results: 6503 patients in the treatment arm and 5815 patients in the placebo arm were included. No evidence of publication biases found. Most treatments reduced negative symptoms at follow-up relative to placebo: second-generation antipsychotics: −0.579 (−0.755 to −0.404); antidepressants: −0.349 (−0.551 to −0.146); combinations of pharmacological agents: −0.518 (−0.757 to −0.279); glutamatergic medications: −0.289 (−0.478 to −0.1); psychological interventions: −0.396 (−0.563 to −0.229). No significant effect was found for first-generation antipsychotics: −0.531 (−1.104 to 0.041) and brain stimulation: −0.228 (−0.775 to 0.319). Effects of most treatments were not clinically meaningful as measured on Clinical Global Impression Severity Scale. Conclusions and Relevance: Although some statistically significant effects on negative symptoms were evident, none reached the threshold for clinically significant improvement.

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