Researchers conducted a meta-analysis and systematic review to determine the efficacy of using antidepressants to treat older adults for knee osteoarthritis pain.
After completing a meta-analysis aiming to define the best treatment option for knee osteoarthritis (OA) pain in adults 65 and over, researchers were unable to recommend antidepressants as an effective treatment for pain, despite its use in other countries and trials. With chronic pain being most prominent in studies regarding knee OA, the authors suggested future research to include larger sample sizes to get a further understanding of the overall efficacy of antidepressant medications for treating pain.
“Population studies have shown that the proportion of older adults taking antidepressants is high (17%-73%) and increases with age. In many countries, pain is the most common indication for use of antidepressants in older adults. Several systematic reviews have explored the efficacy, tolerability, and safety of antidepressants for pain in adults; however, none have specifically looked at this question in older adults,” wrote authors of a study published in the British Journal of Clinical Pharmacology.1
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In a previous study published in the Cochrane Database of Systematic Reviews, researchers looked at specific antidepressants for adults with chronic pain on a larger scale. They found that at a standard dose, duloxetine was the only effective antidepressant for the use of chronic pain, despite finding “promising evidence” for the drug milnacipran.2
However, in Nayran et al’s review of literature exploring antidepressants specifically in adults 65 and older, the focus on knee OA was necessary because of its significance among various studies included in the meta-analysis.
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The researchers’ systematic review consisted of 15 studies with a total of 1369 participants included. Similar to Birkinshaw et al’s previous study, which found duloxetine as a viable option for treating chronic pain, the most commonly studied antidepressants were duloxetine and amitriptyline observed in 6 of 15 studies. They also found knee OA pain to be the most studied type of chronic pain, also identified in 6 of 15 studies.1
Among the trials explored in the analysis, the 15 that were included were published up until February 1, 2024, and were retrieved from 13 databases. Two reviewers were tasked with stratifying data from the trials and assessing primary efficacy, which was calculated on a scale determining pain scores from 0-100, and harms of antidepressant medications.
“For knee [OA], antidepressants did not provide a statistically significant effect for the immediate term (0-2 weeks), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term (≥6 weeks and <12 months). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events,” they continued.1
While the key findings of antidepressant use for older adults with chronic pain showed minimal improvements, authors of the study mentioned that the adverse effects identified throughout the trials may outweigh findings regarding antidepressant efficacy.
Further discussing both the efficacy and harms of using duloxetine to treat chronic pain, the frequency of adverse events in duloxetine trial arms was much more significant than placebo groups across a significant number of trials. Taking away from the strength of study results, the main reaction that participants exhibited was discontinuation of trials.
However, aligning with the authors’ suggestion for further research on the topic, study results regarding adverse effects of antidepressants are scattered throughout the years. A previous study that took a closer look at adverse effects of antidepressants for chronic pain stated that “the most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high.”3
While the primary outcome of antidepressant efficacy for adults’ chronic knee OA pain was not met, the authors concluded their study by noting how the uncertainties of the harm these drugs have on older adults may have skewed results of the analysis, leading them to suggest further research on the topic.
“The evidence to support [antidepressant] use is guided by high quality of evidence for knee OA pain only and is challenged by inconsistencies among the trials included in our review. The uncertainties in reporting of associated adverse events further challenges the use of antidepressants in older adults. Any future trials should focus on increasing the sample sizes to enhance the generalizability of their results, and adequate reporting of safety data is encouraged to produce clinically meaningful findings,” they concluded.1
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