Antidepressants may relieve pain in knee osteoarthritis, but with "CAUTION", research suggests

Australia: A review published in the Cochrane Database of Systematic Reviews has concluded that antidepressant use in knee osteoarthritis is related to improved pain and function (non‐clinically). The researchers also mentioned a 50% or greater "important improvement" in a small number of people.

It is already known that Osteoarthritis is a painful disease of the joints characterized by deformity and disability. In this joint condition, there is reduced cartilage and narrowing of the space between the joints.

Pain is common in Osteoarthritis, and most patients fail to achieve adequate pain relief. There are many investigations of medications affecting pain processing due to increasing acknowledgement of contribution in pain sensitization.

Antidepressants may play a role in managing pain in Osteoarthritis. These act by modulating nerve pathways that affect pain in the central nervous system.

Considering this, a review was done by a team of researchers led by Dr Leaney from the Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. The team evaluated the benefits and harm of antidepressants for knee and hip osteoarthritis pain.

The critical points of the review are:

• The search method used was the standard, extensive Cochrane search method.

• January 2021 was the latest search.

• The review included randomized controlled trials of adults with a history of Osteoarthritis.

• The use of antidepressants was compared to a placebo or alternative comparator.

• Pain, responder rate, physical function, life quality, and withdrawal due to an adverse event was the major outcome.

• The minor outcomes measured in the study were the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and dropper proportion of participants.

• The certainty of the evidence was assessed using GRADE.

• The review included nine clinical trials of trial size 36 to 388 participants, seven for knee osteoarthritis and two for hip osteoarthritis.

• The mean age of study participants was 54.5 to 65.9 years, primarily females.

• The duration of the trial was 8 to 16 weeks.

• Duloxetine was examined in six trials.

• The antidepressants resulted in a small benefit as compared to the placebo.

• The pain reduction in the placebo group was 1.73 points.

• The pain reduction in the antidepressant group was 2.32 points.

• The mean improvement in function was 10.51 points with placebo and 16.16 points with antidepressants (clinically unimportant).

• There was more risk of stopping treatment, 2.15 more in the antidepressant group than placebo.

• In placebo, life quality improved by 0.07 points per the EuroQol 5‐Dimension scale.

• The life quality improved by 0.11 points with antidepressants.

• Total adverse events were more in the antidepressant group (64%) than in the placebo group (49%), with an RR of 1.27.

• 11% of participants on antidepressants withdrew from trials compared to 5% on placebo with RR, 2.15 and NNTH, 17.

The researchers said the cause of pain osteoarthritis is due to various causes that vary with different individuals. It may be due to this reason that only a small number of people respond to the therapy.

• As recorded, 28.65% and 45.2 % of people on placebo and antidepressants had a clinical response respectively.

• Physical function improved 6% more with antidepressants than with placebo.

• The improvement in function in the placebo and antidepressant groups was 10.51 and 16.16 points.

Quality of life improved by 4%, with 0.07 points in placebo and 0.11 points in antidepressants.

The researcher wrote the following in conclusion,

We conclude that 1 in 6 patients with painful hip or knee osteoarthritis achieved a 50% or more significant reduction in pain when treated with antidepressants than placebo.

We recorded little difference in serious side effects between antidepressants and placebo. Nearly 5.1 % in the placebo and 10.9 % in the antidepressant group withdrew due to side effects. Antidepressants have more side effects than placebo, so they are likely to be stopped, 64.1 % in antidepressants and 49.3 % in placebo.

The serious side effects in the antidepressant and placebo group were 1.6 % and 1.7 %, they mentioned.

Mentioning the total side effect, they wrote the risk of any side effects is 1.27 more in the antidepressant than in the placebo group. In the antidepressant group, 14.8 % had side effects equivalent to 1 in every 7patient having a side effect.

Further reading:

Leaney AA, Lyttle JR, Segan J, Urquhart DM, Cicuttini FM, Chou L, Wluka AE. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022 Oct 21;10(10)