Back pain and osteoarthritis are a major cause of disability in people all around the world. In fact, it is believed that low back pain and neck pain affect 7.3% and 5.0% of the global population, respectively. Furthermore, osteoarthritis-related hip and knee symptoms are thought to affect 12% of people, worldwide.
While the number of people affected by these conditions and symptoms is vast, treatment options remain limited and, in some cases, ineffective. The prescription of antidepressants to treat back pain and osteoarthritis has been on the rise in recent years.
Antidepressants to Treat Pain
Antidepressants are the most prescribed medicines in the UK and the use of antidepressants to treat pain is increasingly common. In the USA, antidepressants are the fourth most prescribed medicines for the treatment of back pain. Furthermore, most clinical practice guidelines (75%) recommend the use of antidepressants for lower back pain.
Despite these recommendations and the common use of antidepressants for these ailments, clinical evidence of their efficacy remains uncertain. A recent review aimed to assess both the safety and efficacy of this treatment option for back pain and osteoarthritis.
What methods were used in the review?
The review included randomised controlled trials that compared any antidepressant drug with placebo in patients with back pain or hip or knee osteoarthritis. These trials were located from peer-reviewed journals as well as unpublished data posted on trial registry platforms.
The primary outcomes of this review were pain intensity and disability, and adverse events/side effects were also recorded as secondary outcomes to determine the efficacy and safety of antidepressants.
Of 131 potentially relevant studies, 33 trials, enrolling a total of 5318 participants, were included in the review.
The Findings of the Review
The majority of the trials (32) reported data from participants with chronic pain and only five trials restricted inclusion to participants with depression. The median duration of trial drug regimen was eight weeks, with six antidepressant drug classes being evaluated overall.
Efficacy of Antidepressants for Back Pain
A total of 19 trials included in the review aimed to determine the efficacy of antidepressants for back pain – 16 trials focused on low back pain, one trial focused on neck pain, and two reported data for low back and neck pain.
Moderate certainty evidence collected from these trials showed that serotonin and norepinephrine reuptake inhibitors (SRNIs) may reduce pain at two weeks or less and between 3-13 weeks. SNRIs were also found to reduce disability at 3-13 weeks. However, this effect was small and found to be below the predetermined threshold of clinical importance for this review.
Evidence ranging to low to very low certainty suggests that tricyclic antidepressants (TCAs) did not reduce pain at two weeks or less. Furthermore, low to very low certainty evidence also showed no benefits for pain and disability of a range of antidepressant classes including serotonin reuptake inhibitors (SSRIs), tetracyclic antidepressants, noradrenaline-dopamine reuptake inhibitors (NDRIs), and serotonin antagonist and reuptake inhibitors (SARIs), across follow-ups of up to two weeks, 3-13 weeks, and 3-12 months.
Efficacy of Antidepressants for Osteoarthritis
Eight trials (1941 participants) evaluated the efficacy of antidepressants in patients with osteoarthritis (100% focused on knee osteoarthritis). All eight of the trials assessed the efficacy of SNRIs.
Moderate certainty evidence showed that SNRIs may reduce pain at two weeks or less, and low certainty evidence shows that pain was reduced at 3-13 weeks. In addition, low certainty evidence showed that SNRIs reduced disability at up to two weeks and 3-13 weeks of follow-up.
The reported effect of SNRIs was small and was determined to be below the predetermined threshold of this review. However, researchers did report clinically important effects for pain, but not for disability.
Efficacy of Antidepressants for Sciatica
Six trials assessed the efficacy of antidepressants for sciatica. The results presented very low certainty evidence that SNRIs reduce pain at two weeks or less but not at 3-13 weeks. In addition, low to very low certainty evidence suggests that TCAs does not reduce pain at two weeks or less but did at 3-13 weeks and at 3-12 months follow-ups.
Furthermore, tricyclic antidepressants were found to reduce disability at 3-12 months but not at two weeks or less.
Safety of Antidepressants for Back Pain and Osteoarthritis (Adverse Events)
Twenty-one trials included in the review aimed to determine the safety of antidepressants for back pain and osteoarthritis. A total of 4107 patients participated in these trials. The type and reporting of adverse events/side effects varied significantly across these trials.
Nausea was the most reported adverse event in eight of the trial. Low certainty evidence showed that SNRIs increase the risk of any adverse event, but not serious adverse events. Collectively, participants receiving SNRIs were also more likely to drop out of the study due to adverse events.
In comparison, other classes of antidepressants, including TCAs, SSRIs and Tetracyclic antidepressants did not seem to increase the risk of adverse events or drop-outs related to adverse events. However, the researchers note that the limited number of trials and large uncertainty around the risk estimates limited the ability to determine the safety of antidepressants for back pain, sciatica, and osteoarthritis.
The researchers conclude that while SNRIs were found to reduce both pain and disability in patients with back pain up to three months, these results were not likely to be clinically important. However, a clinically important effect cannot be excluded for antidepressants for osteoarthritis.
The UK and US guidelines for back pain provide conflicting recommendations on the use of SNRIs. This review finds that while SNRIs may have some effect, patients are unlikely to find these clinically important. Furthermore, around two-thirds of patients using SNRIs experience adverse events.
The authors of this review encourage that these findings be made clear to patients, enabling them to make an informed decision on the use od SNRIs. The researchers also stress that more trials are needed – free of industry ties – to further evaluate the efficacy of antidepressants (all but one of the trials included in this study with sample sizes of more than 100 were sponsored by industry). Moreover, the long-term effects of antidepressants when used to treat chronic pain remain unclear.