Treatment-resistant depression (TRD) has great clinical importance because it has the highest disability burden of all depressive conditions. We investigated the prevalence of TRD and identified the risk and protective factors associated with antidepressant resistance among adult patients with major depressive disorder (MDD). A total of 176 132 adult patients with MDD were selected from the Taiwan National Health Insurance Research Database between 2001 and 2010 and followed for 1 year. TRD was defined as nonresponse to at least two antidepressants, and treatment-resistant tendency was defined as nonresponse to at least the first antidepressant. General physical condition measured by the Charlson Comorbidity Index (CCI), psychiatric comorbidities, and economic status were assessed. Only 2.6% ( n = 4608) of the adults with MDD met the TRD criteria, but 26.4% ( n = 46 491) were classified as having treatment-resistant tendency. The following psychiatric comorbidities were related to TRD: anxiety disorders [odds ratio (OR): 1.88], substance use disorders (OR: 1.73), alcohol use disorders (OR: 1.27), and personality disorders (OR: 2.12). In addition, a more severe physical condition (higher CCI) increased the likelihood of TRD (OR: 1.12). Psychiatric comorbidities and poor general physical condition may increase the likelihood of antidepressant treatment failure.
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