Family History of Depression May Impact Resistance to Antidepressants

A family history of treatment-resistant depression (TRD) may be an important risk factor for resistance to antidepressants, according to a population-based cohort study published in JAMA Psychiatry.

The researchers utilized data from Taiwan’s National Health Insurance Research Database from January 2003 and December 2017. TRD was defined as having experienced at least 3 antidepressant treatments during the current episode, with each treatment having adequate dose and duration. Researchers then identified first-degree relatives of individuals with TRD.

In total, 172,335 participants were included in the analysis. Compared with matched controls, first-degree relatives of individuals with TRD were at an increased risk of developing TRD (adjusted relative risk [aRR], 9.16; 95% CI, 7.21-11.63) and other psychiatric disorders.

The aRRs of developing other psychiatric disorders for first-degree relatives of individuals with TRD were:

• Schizophrenia: 2.36 (95% CI, 2.10-2.65)
• Bipolar disorder: 3.74 (95% CI, 3.39-4.13)
• Major depressive disorder: 3.65 (95% CI, 3.44-3.87)
• Attention-deficit/hyperactivity disorder: 2.38 (95% CI, 2.20-2.58)
• Autism spectrum disorder: 2.26 (95% CI, 1.86-2.74)
• Anxiety disorder: 2.71 (95% CI, 2.59-2.84)
• Obsessive-compulsive disorder: 3.14 (95% CI, 2.70-3.66)

First-degree relatives of individuals with TRD also tended to have lower incomes, more physical comorbidities, and higher suicide mortality. These findings were validated via sensitivity and subgroup analyses.

The authors noted that their study is “the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders.” Based on their findings, they suggested earlier consideration of more intensive treatments for depressive symptoms for patients with relatives with TRD as opposed to antidepressant monotherapy.