Major depressive disorder severity and the frequency of painful physical symptoms: a pooled analysis of observational studies

Objective: This retrospective post-hoc analysis of observational studies assesses the frequency of painful physical symptoms (PPS) in patients with major depressive disorder (MDD) of varied severity as may be seen in clinical practice. Methods: Observational studies of MDD that collected a clinician-reported measure of depression severity and included assessment of PPS were screened for this individual patient-level analysis. Six observational studies were included that enrolled outpatients with a diagnosis of MDD (assessed using the 17-item Hamilton depression scale, Hospital Anxiety and Depression Scale-Depression, or Inventory of Depressive Symptomatology). Measures of PPS were based on the original study assessment (modified Somatic Symptom Inventory [SSI] and Visual Analogue Scale [VAS]). Patients were divided into analysis cohorts based on the presence or absence of PPS. To model PPS status, odds ratios were calculated from logistic regression for cross-sectional analysis (main analysis) and generalized linear mixed models for longitudinal models (exploratory longitudinal analysis). Results: For the main analysis, four studies (N = 2943, 71.6% female, mean age 45.3 years) were identified. Of 2901 eligible patients, 61.7% were classified as having painful physical symptoms (PPS+). At study entry, 73.1% (957/1309) of patients in the severe category of depression, 56.8% (537/945) of those with moderate depression, and 45.6% (295/647) of those with mild depression were PPS+. The exploratory longitudinal analysis was performed using a subset (N = 2430) from the studies used in the main analysis plus two others (an additional 7984 patients, 6742 of which were modeled). The likelihood of patients that were PPS- at baseline later developing PPS was 5% to 13% greater for patients with increased depression severity (P<0.001) and the likelihood of PPS+ patients later not having PPS was 9% to 17% less for patients with increased depression severity (P<0.0001). Conclusions: Since this is a retrospective aggregate analysis of several observational studies, and due to missing data, care should be taken in the interpretation of these results. Despite the use of adjustment techniques, selection bias and unmeasured confounding may still be an issue for comparative analysis as not all variables were collected for all studies. For patients treated in typical care settings, PPS were associated with depression severity. However, patients with mild and moderate depression also exhibited PPS. Clinicians should be aware that PPS are present, and may warrant treatment, across depression severities.