Treatment-resistant depression predicts higher mortality rate and healthcare cost

Treatment-resistant depression (TRD), defined as treatment failure following ≥2 trials of antidepressants at adequate doses, duration and adherence, is associated with a greater risk of all-cause mortality and higher healthcare costs, according to a population-based cohort study by the University of Hong Kong (HKU), Chinese University of Hong Kong, London School of Economics and Political Science and University College London.

 

“Few studies investigated the mechanism of TRD leading to the worse outcome, and economic evidence was mostly restricted to short follow-up,” wrote the researchers. “We aimed to examine the potential mediators between TRD and all-cause mortality, and estimate a long-term associated healthcare resource utilization pattern.”

 

Using territory-wide electronic medical records in Hong Kong, the researchers identified incident depression patients diagnosed in 2014 and followed them for 6 years. The TRD cohort (n=1,479; mean age, 46.6 years; female, 73.9 percent) was matched 1:4 to the non-TRD cohort (treatment-responsive depression; n=5,856; mean age, 47.1 years; female, 73.5 percent) on propensity score. [Lancet Regional Health 2022;doi:10.1016/j.lanwpc.2022.100426]

 

Results revealed that 18 percent of patients with incident depression developed TRD within 6 years. Compared with treatment-responsive patients, TRD patients had a 52 percent greater risk of all-cause mortality (hazard ratio [HR], 1.52; 95 percent confidence interval [CI], 1.14 to 2.02; p=0.004). The increased mortality was significantly mediated by post-TRD psychiatric conditions (ie, self-harm behaviours, psychosis, and schizophrenia; p=0.003).

 

“[Our analysis] reinforces the importance of ongoing monitoring for new psychiatric diagnoses after treatment resistance,” the researchers commented. “TRD serves as a marker for mortality. Early identification of potential TRD patients is essential to prevent them enduring prolonged [use of] ineffective medication.”

 

“Treatment resistance also led to higher healthcare resource use and higher economic impacts, which intensified the disease burden alongside premature mortality,” they continued.

 

TRD patients had significantly greater mean healthcare resource utilization per patient-year in outpatient visits (15.1 vs 8.2 episodes; adjusted odds ratio [OR], 1.79; p<0.001), emergency visits (1.1 vs 0.6 episodes; adjusted OR, 1.42; p<0.001) and inpatient days (8.3 vs 4.2 bed-days; adjusted OR, 1.86; p<0.001).

 

Aggregated from all settings, the unadjusted mean overall cost in TRD patients was 54 percent higher than that in treatment-responsive patients (HKD 116,731 vs HKD 75,666 per patient-year). Notably, TRD patients had 1.8-fold higher healthcare costs vs treatment-responsive patients (adjusted OR, 1.80; 95 percent CI, 1.63 to 2.00), with higher costs for both psychiatric and non-psychiatric services in all settings.

 

“Our study highlights the difficult-to-treat nature of TRD and its subsequent burden on the healthcare system, clinically and economically,” the researchers concluded. “Clinicians should be alert that identifying treatment resistance early and subsequent monitoring for post-TRD psychiatric comorbidities could be a way to prevent premature mortality.”