Meta-analysis of efficacy of mirtazapine as an adjunctive treatment of negative symptoms in schizophrenia

Carol Vidal, Carla Reese, Bernard A. Fischer, Joshua Chiapelli, Seth Himelhoch

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Context: Despite advances made in treating the positive symptoms of schizophrenia, treatment of negative symptoms remains an unmet therapeutic need. Adjunctive mirtazapine has shown promise for treatment of negative symptoms in several small clinical trials. Objective: To assess the efficacy of mirtazapine as an adjunctive treatment of negative symptoms in patients with chronic schizophrenia via meta-analysis. Data Sources: A systematic literature review of articles in English and Spanish was conducted in November 2011 by searching PubMed, the Cochrane Library, the Clinical Trial Registry of the NIH, and SIGLE (System for Grey Literature in Europe). Free text search terms for PubMed were "schizophrenia," "negative symptoms" and "mirtazapine." Publication date was not a limitation. Study Selection: Studies of people with schizophrenia/schizoaffective disorder were included in the meta-analysis if they were randomized, double-blind, and used the Positive and Negative Syndrome Scale (PANSS) as an outcome measure. Nine studies were initially identified. Five studies were included in the meta-analysis; 1 study was excluded for not using the PANSS, 3 were excluded as representing duplicate publications and open-label phases of one of the selected randomized control trials. Studies varied in the quality of their selection for participants with primary negative symptoms. Results: Three of the 5 studies showed significant improvement in negative symptoms individually. The overall analysis showed improvement in negative symptoms with an effect size of 1.00 (0.084-1.918), which was statistically significant (p=0.032). Data from the negative symptoms subscale of the PANSS from 169 subjects was used in a forest plot to illustrate the relative strength of treatment effects. The variation in standard median deviation (SMD) attributable to heterogeneity was 27.35%, indicating a high degree of heterogeneity. Conclusions: This meta-analysis supports the hypothesis that adding mirtazapine to treatment with antipsychotics can improve negative symptoms in schizophrenia. However, additional studies with more stringent negative symptom selection criteria and homogeneous use of antipsychotics are needed.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalClinical schizophrenia & related psychoses
Issue number2
StatePublished - Jun 1 2015


  • Meta-analysis
  • Mirtazapine
  • Negative symptoms
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health


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