Systematic Review: Antidepressants Offer Limited Pain Relief with Potential Harms in Older Adults
17 Sep, 2024 | 11:34h | UTCBackground: Chronic pain is prevalent among older adults and significantly affects their quality of life. Antidepressants are commonly prescribed for pain management in this population across various countries. While several systematic reviews have evaluated the efficacy and safety of antidepressants for pain in adults, none have specifically focused on individuals aged 65 years and older. The efficacy and safety profile of antidepressants for pain relief in older adults remains unclear.
Objective: To assess the efficacy and safety of antidepressant medications compared to all alternatives for the management of non-cancer pain in older adults aged 65 years and above.
Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Thirteen databases were searched from inception to February 1, 2024, to identify relevant studies. Trials included compared any antidepressant medication to any alternative (e.g., placebo, other medications, or non-drug therapies) for the treatment of non-cancer pain in older adults. Data extracted included study and participant characteristics, primary efficacy outcomes (pain scores converted to a 0–100 scale), and harms. Estimates for efficacy were pooled using a random-effects model and reported as mean differences with 95% confidence intervals (CIs). The quality of included trials was assessed using the Cochrane risk of bias tool.
Results: Fifteen studies encompassing 1,369 participants met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (six studies each). Pain related to knee osteoarthritis was the most commonly studied condition (six studies). For knee osteoarthritis:
- Immediate Term (0–2 weeks): Antidepressants did not provide a statistically significant reduction in pain compared to alternatives (mean difference [MD], –5.6; 95% CI, –11.5 to 0.3).
- Intermediate Term (≥6 weeks and <12 months): Duloxetine provided a statistically significant, albeit very small, reduction in pain (MD, –9.1; 95% CI, –11.8 to –6.4).
Nearly half of the studies (7 out of 15) reported increased withdrawal of participants in the antidepressant treatment group compared to the comparator group due to adverse events.
Conclusions: For most chronic painful conditions in older adults, the benefits and harms of antidepressant medications are unclear. The available evidence predominantly comes from trials with small sample sizes (less than 100 participants), disclosed industry ties, and trials classified as having unclear or high risk of bias.
Implications for Practice:
- Minimal Benefit: Antidepressants, particularly duloxetine, may offer a very small benefit for pain relief in older adults with knee osteoarthritis over the intermediate term.
- Risk of Harms: The potential harms, including increased adverse events leading to higher withdrawal rates, may outweigh these minimal benefits.
- Clinical Decision-Making: Clinicians should carefully weigh the benefits against the risks when considering prescribing antidepressants for pain in older adults.
- Alternative Strategies: Non-pharmacological interventions and alternative pain management strategies should be prioritized in this population.
Study Strengths and Limitations: Strengths include the comprehensive search strategy across multiple databases and the focus on older adults, a population often underrepresented in clinical trials. Limitations involve the generally low quality of the included trials, small sample sizes, high risk of bias, and inconsistent reporting of pain outcomes and adverse events among studies.
Future Research: Further large-scale, high-quality randomized controlled trials are needed to investigate the efficacy and safety of antidepressants for pain management in older adults. Future studies should also compare antidepressants to non-pharmacological interventions and explore long-term outcomes and optimal dosing regimens in this population.