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Meta-Analysis
. 2024 Dec;90(12):3097-3118.
doi: 10.1111/bcp.16234. Epub 2024 Sep 12.

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis

Sujita W Narayan  1   2 , Vasi Naganathan  3   4 , Lisa Vizza  1   2 , Martin Underwood  5   6 , Rowena Ivers  7 , Andrew J McLachlan  8 , Linyi Zhou  1 , Ramnik Singh  1 , Shunyu Tao  1 , Xiao Xi  1 , Christina Abdel Shaheed  1   2
Affiliations
Meta-Analysis

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis

Sujita W Narayan et al. Br J Clin Pharmacol. 2024 Dec.

Abstract

Aims: In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years).

Methods: Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool.

Results: Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2 weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6 weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). 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.

Conclusions: For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

Keywords: antidepressive agents; knee; osteoarthritis; pain; serotonin and noradrenaline reuptake inhibitors; systematic review; tricyclic antidepressants.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/. S.W.N., L.V., L.Z., R.S., S.T. and X.X. have nothing to declare. M.U. received grants/contracts from the National Institute for Health and Care Research, Norwegian Medical Research Council, Australian National Health and Medical Research Council, has royalties/licences from the University of Warwick, participates on a Data Safety Monitoring Board or Advisory Board of the National Institute of Health and Care Research and has received supply of clinical materials for three randomized controlled trials funded by National Institute for Health and Care Research from Stryker PLC. R.I. is a Chief Investigator on the COMFORT trial funded by the Australian National Health and Medical Research Council. C.A.S. has received funding from the Australian National Health and Medical Research Council (Investigator Grant ID: APP202603 and Clinical Trials and Cohort Studies Grant ID: APP2000989).

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart.
FIGURE 2
FIGURE 2
Antidepressants (duloxetine and escitalopram) vs. placebo for pain related to knee osteoarthritis in the immediate term. We adopted the standard deviation value for the Lunn et al. 2015 trial from the Koh et al. 2019 trial for data extraction and analysis purposes.
FIGURE 3
FIGURE 3
Duloxetine vs. placebo for pain related to knee osteoarthritis in the intermediate term.
See this image and copyright information in PMC

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