Abstract
Depression is associated with general medical conditions (GMCs), but it is not known if treatment-resistant depression (TRD) affects GMC risk and vice versa. We estimated bidirectional associations between TRD and GMCs (prior and subsequent). All individuals aged 18–69 years, born and living in Denmark, with a first-time prescription for an antidepressant between 2005 and 2012 were identified in the Danish Prescription Registry (N = 154,513). TRD was defined as at least two shifts in treatment regimes. For prior GMCs, we estimated odds ratios (ORs) using conditional logistic regression comparing TRD patients with matched non-TRD controls adjusted for other GMCs and number of other GMCs. For subsequent GMCs, we used Cox regression to calculate hazard ratios (HRs) in TRD vs. non-TRD patients adjusted for age at first prescription, calendar time, other GMCs and number of other GMCs. Patients with TRD had higher prevalence of prior GMCs related to the immune or neurological systems; musculoskeletal disorders (women aOR: 1.35, 95% CI: 1.26–1.46, men aOR: 1.30, 95% CI: 1.19–1.42) and migraine (women aOR: 1.22, 95% CI: 1.09–1.36, men aOR: 1.25, 95% CI: 1.00–1.56). Subsequent GMCs were related to a broader spectrum; cardiovascular (women aHR: 1.43, 95% CI: 1.32–1.54, men aHR: 1.31, 95% CI: 1.19–1.43), endocrine (women aHR: 1.52, 95% CI: 1.37–1.67, men aHR: 1.24, 95% CI: 1.07–1.44), and neurological disorders (women aHR: 1.24, 95% CI: 1.13–1.35, men aHR: 1.19, 95% CI: 1.07–1.34).Our study presents a broad overview of comorbid medical conditions in patients with TRD and further studies are needed to explore the associations in detail.
Highlights
Extensive evidence has shown that general medical conditions (GMCs) are associated with an increased risk for developing depression (Egede 2007; Patten 2001) and, vice versa, depression is associated with an increased risk for developing GMCs (Momen et al, 2020; Scott et al, 2016; Tegethoff et al, 2016)
A study assessing the effect of GMC comorbidity on response to next-step antidepressant treatments among treatment-resistant depression (TRD) patients showed that medical conditions were not associated with the likelihood of remission, but the sample included only 97 subjects and medical conditions were examined with a combined score (Perlis et al, 2004)
This is the first study to investigate the bidirectional associations between TRD and a broad and comprehensive range of GMCs
Summary
Extensive evidence has shown that general medical conditions (GMCs) are associated with an increased risk for developing depression (Egede 2007; Patten 2001) and, vice versa, depression is associated with an increased risk for developing GMCs (Momen et al, 2020; Scott et al, 2016; Tegethoff et al, 2016). Despite not knowing what develops first (temporality of events), the cooccurrence of depression with other medical conditions is associated with greater depression symptom severity and GMC severity, decreased treatment adherence and lower remission rates compared to individuals suffering from depression without GMCs (IsHak et al, 2018; Kronish et al, 2006; Moussavi et al, 2007; Rush et al, 2008 ) Both depression severity as well as treatment-resistant depression (TRD) influence the complexity of the bidirectional association between depression and GMCs (Amital et al, 2013; Niles et al, 2015).
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