Psychiatric ward admission, recurrent depression, cohabitation, and migraine are some of the risk factors strongly associated with treatment-resistant depression, according to a recent study published in the Journal of Affective Disorders

The study investigators conducted a population-based large cohort study examining the independent influence of multiple treatment-resistant depression risk factors. The study population was a country-wide sample of Denmark citizens registered between January 1, 1996, and December 31, 2014, with first-time depression (N=244,653). Exclusion criteria included prior diagnosis with a comorbid manic disorder, bipolar disorder, persistent mood disorder, and schizophrenia. Study investigators determined treatment-resistant depression within 12 months of depressive registration at the second shift in treatment and after reviewing numerous sociodemographic and clinical factors that might lead to treatment-resistance (eg, gender, age, education level, cohabitation, family history, employment status, obesity, physical disease, and alcohol or drug abuse).  

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Of the 194,074 patients enrolled in the study who were at risk of developing treatment-resistant depression within the 12-month follow up, 30,595 (15.8%) developed the condition. Study investigators observed higher rates of treatment-resistant depression in patients who were women (n=19,797; adjusted hazard ratio [aHR] 1.13; 95% CI, 1.10-1.16), aged 65 to 84 years (n=7562), continuously cohabiting (n=14,441; aHR 1.27; 95% CI, 1.23-1.30), and being unemployed (n=3659; aHR 1.12; 95% CI, 1.08-1.16); the likelihood of developing treatment resistance was higher in patients with moderate and severe depression, those admitted to or diagnosed at a psychiatric ward, and those with recurrent depression. 

Study authors observed lower rates of treatment-resistant depression in patients diagnosed with cardiovascular disease, epilepsy, infectious disease, and alcohol or drug abuse. However, diagnoses of anxiety (n=716; aHR 1.18; 95% CI, 1.10-1.27), insomnia (n=121; aHR 1.27; 95% CI, 1.06-1.51), or migraine (n=96; aHR 1.42; 95% CI, 1.16-1.73) were associated with higher rates of treatment-resistant depression. Patients with prescriptions for benzodiazepines showed markedly high rates of developing the condition (n=17,227; aHR 1.79; 95% CI, 1.75-1.84) compared with those taking other medications (eg, beta blockers, statins, carbamazepine, valproate, and nonsteroidal anti-inflammatory drugs). 


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Study limitations included not having access to information on drug use during hospitalization, and not having a more precise assessment of severity (the investigators relied on information from registers and shifts in antidepressant treatment). 

The study authors concluded that “besides indicators of disease severity, other important risk factors of [treatment-resistant depression] were those related [to] cohabiting with a partner and lost labor market affiliation as well as anxiety, insomnia, migraine, and the use of psychotropic drugs.” 

Reference

Gronemann FH, Jorgensen MB, Nordentoft M, Andersen PK, Osler M. Socio-demographic and clinical risk factors of treatment-resistant depression: a Danish population-based cohort study. J Affect Disord. 2019;261:221-229