Comorbid Major Depressive Disorder in Schizophrenia

A Systematic Review and Meta-Analysis

Damien Etchecopar-Etchart; Theo Korchia; Anderson Loundou; Pierre-Michel Llorca; Pascal Auquier; Christophe Lançon; Laurent Boyer; Guillaume Fond


Schizophr Bull. 2021;47(2):298-308. 

In This Article


Literature Search Strategy

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines.[35] Systematic bibliographic searches were carried out according to the Cochrane methodology. This project was registered in PROSPERO (reference number CRD420181116475).

The search paradigm was based on the PubMed interface (Medline database) and adapted for 4 databases: Cochrane, ScienceDirect, PsycINFO, and Google Scholar. We only search for studies published in the last 3 decades (1990–2020) until January 18, 2020. The search paradigm was based on the following combination (depressive disorder, major[MeSH Terms]) AND (schizophrenia[MeSH Terms]). To ensure exhaustivity, the term "schizophrenia" was also combined with each identified depression assessment scale, namely, the CDSS,[15] Montgomery and Åsberg Depression Rating Scale (MADRS),[17] Hamilton Rating Scale for Depression,[36] Beck Depression Inventory,[16] Center for Epidemiologic Studies-Depression Scale,[37] Hospital Anxiety and Depression Scale,[38] Patient Health Questionnaire (PHQ),[19] Major Depression Inventory,[39] Maryland Trait and State Depression,[40] Zung Self-rating Depression Scale,[41] and Geriatric Depression Scale.[42] The full name and the abbreviation of each scale were used in the search paradigm to avoid overlooking any articles. In case of missing data, authors were contacted by email if possible.

The corresponding authors were asked to provide additional data that were not included in the original publications, and they were asked to provide any unpublished results.[43–47] The last search was carried out on January 18, 2020. The reference lists and bibliographies of relevant reviews and articles retrieved from the database searches were manually searched for additional eligible articles.


The inclusion criteria were as follows: (1) any language and date of publication; (2) original research papers; (3) observational studies (cohort studies or cross-sectional studies); (4) participants with a diagnosis of SZ or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, any version, or the International Statistical Classification of Diseases and Related Health Problems; and (5) diagnosis of MDD based on a validated scale or structured interview.

The exclusion criteria were as follows: studies using a nonvalidated scale, studies using a scale without cutoff value (eg, Positive And Negative Syndrome Scale [PANSS] depressive subscore), and studies using a nonstructured interview for the diagnosis of MDD. The titles and abstracts were screened by 2 researchers (D.E.E. and G.F.). The full texts of manuscripts were then reviewed to determine whether a study would be included (D.E.E. and G.F.).

Data Extraction

The 82 extracted variables are presented in Supplementary Table S1. Two researchers (D.E.E. and G.F.) extracted data from the included studies in a systematic manner using a predesigned extraction form, which was based on the Joanna Briggs Institute Data Extraction Form for Prevalence and Incidence Studies.[48] Additional items relevant to the current study were also added. Each discrepancy in data extraction was examined by the first and last authors (D.E.E. and G.F.) to reach consensus.

Statistical Analyses

A random effects model was used to calculate the pooled estimate of the prevalence of SZ-MDD and its 95% CI. Heterogeneity between studies was quantified with the I2 statistic.[49] Sensitivity analyses were conducted using the leave-1-out method. Publication bias was assessed graphically with a funnel plot and statistically with Egger's test.[50] Finally, subgroup analyses for 9 binary and 1 categorial variable and univariate meta-regressions for 17 quantitative variables were used to evaluate factors that moderated the individual study estimates of the prevalence of SZ-MDD (Supplementary Table S1). Multivariate meta-regression was not performed due to an inadequate number of studies.[51] The other variables (51 variables) were not explored due to insufficient data (reported in <4 studies). All analyses were carried out using Comprehensive Meta-Analysis software (version 3).

Role of the Funding Source

No drug manufacturing company was involved in the study design, the data collection, the data analysis, the data interpretation, the writing of the report, or the decision to submit the report for publication.