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


Eighteen eligible studies including 6140 stabilized SZ outpatients (Birchwood et al;[52] Bressan et al;[7] Sim et al;[53] Maggini and Raballo;[47] Conley et al;[45] Gaha;[54] Karadayı et al;[55] Martín-Reyes et al;[46] Ekinci et al;[56] Majadas et al;[57] Schennach et al;[43] Jeyagurunathan et al;[8] Rossi et al;[44] Chiang et al;[58] Faugere et al;[59] Fond et al [2018, 2019]; Arraras et al[60]) were included in the quantitative analysis (flowchart shown in Figure 1; study characteristics shown in Table 1). The percentage of men was 64.1% in the studies in which the sex ratio was reported. One study with a small sample (n = 40) was excluded because of probable selection bias based on voluntary participation in a study targeting the link between cognitive ruminations and depressive symptoms.[61]

Figure 1.

Flow chart.

Only one study each was carried out in Africa (Tunisia), South America (Brazil), and Latin America (Cuba). The assessment of study quality is presented in Supplementary Tables S2 and 3. Only one study had very poor quality (quality score = 13) and 7 studies had high quality (quality score ≥25). None of the included studies were sponsored by the pharmaceutical industry.

Prevalence Estimates

The pooled estimate of the prevalence of SZ-MDD was 32.6% (95% CI: 27.9–37.6, Figure 2). There was a significant amount of heterogeneity between studies (I 2 = 92.587, p < .001). The prevalence ranged from 16.3% to 69.0%, with the 2 highest prevalences being reported in a study including a homeless population in France (50.5%) and the only study using the PHQ questionnaire (69.0%; Table 1).

Figure 2.

Pooled prevalence of major depressive disorder in stabilized outpatients with schizophrenia in observational studies.

The funnel plot is shown in Figure 3 and suggests evidence of small-study effects, but this finding was not supported by Egger's test (p = .122). The results of the leave-1-out sensitivity analyses indicate that no single study had a disproportionate effect on the pooled estimate of the prevalence of SZ-MDD.

Figure 3.

Funnel plot.

Subgroup Analyses (Table 2)

The results of the subgroup analyses are presented in Table 2. The prevalence of SZ-MDD was found to be significantly higher in studies published in or after 2015 (39% vs 27.3%, p = .031). The prevalence was lower in studies with nonselected patients (28.6% vs 39.2%, p = .019). The prevalence was higher in studies using self-reported questionnaires (46.9% [3 studies]) than in studies using clinician rated-questionnaires (CDSS 30.1% [10 studies], MADRS (33.8% [2 studies]), and studies using structured clinical interviews (16.4% [2 studies], p < .001) after removing the only study including homeless patients, which had a high prevalence (50.5%).[62] The prevalence was also higher in studies including patients with substance use disorders (38.2% vs 27.5%, p = .020) and patients with chronic somatic illnesses (40.8% vs 26.6%, p < .001). No significant association was found with the other variables (all p > .05).

Meta-regression Analyses (Table 3)

The results of the meta-regression analyses are presented in Table 3, and the figures for significant results are presented in Supplementary Figure S1. A higher prevalence of SZ-MDD was associated with older age (b = 0.064, 95% CI = 0.016–0.112, p = .009), a lower percentage of patients with high education levels (b = −0.051, 95% CI = −0.070 to −0.031, p < .001), a higher number of lifetime hospitalizations (b = 0.307, 95% CI = 0.038–0.576, p = .025), and a higher percentage of patients treated with antidepressants (b = 0.047, 95% CI = 0.020–0.074, p < .001). No significant association was found with the other variables (all p > .05).