Treatment-Resistant Depression Linked to Increased Mortality

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality compared to non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals (median age at diagnosis, 40 years; 63% women) diagnosed with MDD and treated with an antidepressant were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25), due to higher mortality to external causes.
• Mortalities due to suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11 in the Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine. Detailed disclosures are given in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.