Individuals with a family history of treatment-resistant depression (TRD) have an increased risk of experiencing antidepressant resistance themselves, a study published yesterday in JAMA Psychiatry found. Further, individuals with a family history of TRD have a greater risk of other psychiatric illnesses and dying by suicide.
“In recent years, an increasing number of genetic studies have attempted to understand the genetic architecture of antidepressant response or TRD phenotype,” wrote Chih-Ming Cheng, M.D., of the Taipei Veterans General Hospital in Taiwan and colleagues. “Although the efforts to understand the genetic mechanism behind antidepressant response are promising, these positive results require more replication and must overcome methodological concerns, such as relatively small sample size and diverse definitions of TRD.”
Cheng and colleagues used data from the Taiwan National Health Insurance program, which covers nearly the entire population of Taiwan and includes diagnoses of psychiatric disorders. The authors used all medical records from 2003 to 2017, which were linked to records from the Database of National Mortality Registry to determine date and cause of death. Patients who were diagnosed with major depressive disorder and received at least three adequate antidepressant trials (exceeding 56 daily doses in an eight-week period) within two years were defined as having TRD. In total, 21,046 individuals met these criteria. The authors then identified 34,467 first-degree relatives of those with TRD and matched them by birth year, sex, and kinship with 137,868 first-degree relatives of individuals without TRD.
Relatives of those with TRD had nine times the risk of developing TRD compared with those in the control group. They were also significantly more likely to develop other psychiatric illnesses, including schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, major depressive disorder, autism spectrum disorder, anxiety, and obsessive-compulsive disorder. These findings persisted even after controlling for factors such as birth year, sex, income, and comorbid conditions. Relatives of those with TRD also had a higher risk of all-cause and suicide mortality, and this risk remained even after excluding relatives who developed TRD from the analysis.
“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, as opposed to antidepressants alone, for treating the symptoms of individuals with TRD,” the authors concluded.
For related information, see the Psychiatric News article “To Address Treatment-Resistant Depression, First You Have to Define It.”
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