Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistant depression in a 13-year nationwide cohort study

Shiau-Shian Huang,Hsi-Chung Chen,Jui Wang,Po-Hsiu Kuo,Wei J Chen,Hsi-Han Chen

doi:10.1186/s12888-020-02935-z

Abstract

BackgroundTo investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities.MethodsIn total, 31,422 depressive inpatients were followed-up from diagnostic onset for more than 10-years. Patients were diagnosed with TRD if their antidepressant treatment regimen was altered ≥two times or if they were admitted after at least two different antidepressant treatments. Multiple Cox regression model were used to determine whether physical and psychiatric comorbidities, psychosis, and prescription patterns increased the risk of TRD by controlling for relevant demographic covariates. Survival analyses were performed for important TRD-associated clinical variables.ResultsFemales with depression (21.24%) were more likely to suffer from TRD than males (14.02%). Early anxiety disorders were more commonly observed in the TRD group than in the non-TRD group (81.48 vs. 58.96%, p < 0.0001). Lifetime anxiety disorders had the highest population attributable fraction (42.87%). Seventy percent of patients with multiple psychiatric comorbidities developed TRD during follow-up. Cox regression analysis further identified that functional gastrointestinal disorders significantly increased TRD risk (aHR = 1.19). Higher doses of antidepressants and benzodiazepines and Z drugs in the early course of major depressive disorder increased TRD risk (p < 0.0001).ConclusionOur findings indicate the need to monitor early comorbidities and polypharmacy patterns in patients with depression associated with elevated TRD risk.

Highlights

To investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities
Patients were excluded if (1) Major depressive disorder (MDD) diagnosis was not made by a psychiatrist, (2) if they were diagnosed with schizophrenia (ICD-9-CM code 295) or bipolar disorder (BpD) (ICD-9CM code 296.0, 296.1, and 296.4–8) before MDD diagnosis, or (3) patients have not been admitted for diagnosis of MDD after 1999
A total of 11,078 of 31,422 (35.26%) inpatients with MDD included in the study were defined as having TRD (21.24% of female and 14.02% of male patients)

Summary

Introduction

To investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities. The proportion of patients with TRD among those with MDD varies between studies (ranging from 6 to 50% according to databased analyses vs clinical studies) due to differences in study designs and definitions of TRD [8]. Outpatient care is insufficient for a substantial proportion of patients with MDD despite advances in clinical care, treatment regimens, and drug development. 8.3% of patients with MDD are hospitalized annually [10]. These patients often exhibit worse symptoms, increased comorbidities, and higher suicide risk, and are prescribed higher doses of antidepressant [11]. MDD patients who were ever admitted to the psychiatric ward represent a prominent subgroup requiring intense care and complex treatment regimens; they are at a high risk of developing TRD

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