Evidence Lacking for TRD Treatment Effectiveness in Older Adults, Review Finds
A systematic review published in BMJ Mental Health found weak quality evidence to support the effectiveness of several commonly prescribed pharmacological and non-pharmacological interventions for treatment-resistant depression (TRD) in older adults.
“Most evidence underpinning TRD therapeutic guidelines derives from research with younger adults, but optimal treatment of depression in older and younger populations may differ,” wrote lead author Alice Jane Larsen, Wolfson Institute of Population Health, Queen Mary University of London, London, UK, and study co-authors.
The review analyzed 14 research studies from 2010 through 2023 that investigated the efficacy of common TRD interventions, including ketamine therapy, transcranial magnetic stimulation (TMS), augmentation with aripiprazole, neuroplasticity-based computerized cognitive remediation (NCCR), and pharmacogenetic testing-guided prescribing (PGP), in adults aged 55 or older. The researchers assessed the studies for bias using the Cochrane Risk of Bias (RoB) 2 tool, evaluated the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, and meta-analyzed the interventions’ remission rates.
While the review found that several of the assessed interventions increased remission rates, the quality of the analyzed corresponding research studies was “weak” or “very weak.” For example, the meta-analysis found that the overall odds of remission for participants in the ketamine therapy trials was 2.91 (n=3; 95% CI=1.11; 7.65), favoring the intervention over control groups. However, based on RoB and GRADE criteria, the researchers determined that the quality of the research supporting ketamine therapy’s effectiveness in TRD treatment for older adults was weak.
Researchers similarly found weak quality evidence that aripiprazole augmentation increased remission, and very weak quality evidence that TMS, NCCR, and PGP increased remission.
The researchers noted that a lack of evidence of efficacy does not prove that these treatments are ineffective for older adults. “Over a third of older adults with TRD responded to experimental treatments in included studies, suggesting that a significant proportion of TRD in older populations could be alleviated by greater implementation of evidence-based treatment,” the researchers wrote.
The authors acknowledged that the review was limited by the small evidence base selected and the heterogeneity of populations across the assessed studies. The researchers further emphasized the need for future studies investigating the efficacy of TRD intervention in older populations.
“Lack of evidence regarding routinely prescribed treatments is problematic, requiring clinicians to extend evidence from younger populations. Studies to enhance the evidence base for commonly prescribed treatments in this population have the potential to improve the lives of the many older adults with TRD,” the authors concluded.
