Keypoint: First-degree relatives of individuals with TRD are 7.47 times more likely to develop TRD than individuals without a family history.
Patients with a family history of treatment resistant depression (TRD) are at increased risk for antidepressant resistance and suicide mortality, relative to those without family history. These findings indicate that TRD treatment options beyond antidepressant monotherapy may be necessary for this patient population, according to results published in JAMA Psychiatry.
In Major Depressive Disorder (MDD), combining or altering depression treatments earlier may be beneficial, given the clinical significance of a family history of treatment-resistant depression (TRD) for antidepressant resistance and increased suicide mortality, according to study results published
Previous studies suggest that major depressive disorder (MDD) and TRD have a genetic component and may be transmitted across families. Although there is evidence that patients with TRD face increased mortality risks, relatively little is known about whether first-degree relatives are also at increased risk of mortality. The current study sought to explore the susceptibility to TRD within families and its association with treatment and mortality outcomes.
Investigators conducted a cohort study using data from the Taiwan national health insurance database between January 2003 and December 2017. The investigators identified individuals with MDD (using International Classification of Diseases [ICD] codes) and defined TRD as failure to respond to 3 different antidepressants, validated via prescription records. Once the TRD cohort was determined, the investigators identified first-degree relatives (n=34,467). Additionally, the investigators created a 1:4 comparison group (n=137,868) of first-degree relatives of individuals without TRD, matched by age, sex, and kinship.
Overall, 533,302 individuals were diagnosed with MDD and 21,046 had TRD. A total of 172,335 first-degree relatives (48.75% women) were included for analysis, of whom 34,467 were in the TRD relatives cohort and 137,868 were in the control cohort. On average, individuals were 22.9 (SD, 18.1) years of age at the beginning of follow-up. Relative to the control group, first-degree relatives of individuals with TRD had lower monthly incomes (P <.001), more physical comorbidities (P <.001), and a greater proportion lived outside of urban areas (P =.004).
In a model adjusting for sex, birth year, comorbidities, income, urbanization, and more stringent TRD inclusion criteria, the investigators found that first-degree relatives of individuals with TRD had an increased risk of all-cause mortality (adjusted risk ratio[aRR], 1.21) and suicide mortality (aRR, 2.72).
Results of the model also indicated a significantly elevated risk for developing TRD (aRR, 7.47), MDD (aRR, 3.57), bipolar disorder (aRR, 3.36), obsessive-compulsive disorder (aRR, 2.85), anxiety (aRR, 2.57), autism spectrum disorder (aRR, 2.35), attention-deficit/hyperactivity disorder (aRR, 2.22), and schizophrenia (aRR, 2.15). These mortality and psychiatric disorder risks remained robust even when excluding first-degree relatives who were themselves diagnosed with TRD.
“Family history of TRD is a clinical risk factor due to its association with increased suicide mortality and resistance to antidepressant treatment; therefore, more intensive depression treatments, such as add-on pharmacotherapy or nonpharmacotherapy might be considered earlier,” the investigators concluded.
A major study limitation is the strict definition of treatment-resistant depression, which may limit the generalizability of the study findings.
Note: This article originally appeared on Psychiatry Advisor
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