Antidepressants for pain management in rheumatoid arthritis

Pain management is a high priority for patients with rheumatoid arthritis (RA). Antidepressants are sometimes used as adjuvant agents to enhance pain relief, help with sleep and reduce depression. Such antidepressants include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin noradrenaline reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). However, the prescription of antidepressants in this population remains controversial because of conflicting scientific evidence.

The aim of this review was to determine the efficacy and safety of antidepressants in pain management in patients with RA.

We performed a computer assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter); MEDLINE (1950 to November Week 1, 2010); EMBASE (2010 Week 44); and PsycINFO (1806 to November Week 2, 2010). We also searched the 2008-2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of articles.

We included randomised controlled trials (RCTs) which compared an antidepressant therapy to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA who had at least one clinically relevant outcome measure. Outcomes of interest were pain, adverse effects, function, sleep, depression and quality of life.

Two blinded review authors independently extracted data and assessed the risk of bias in the trials. We conducted meta-analyses to examine the efficacy of antidepressants on pain, depression and function, as well as their safety.

We included eight RCTs (652 participants) in this review. All trials evaluated TCAs and two trials evaluated a SSRI as a comparator. Seven of the eight trials had high risk of bias. There was insufficient data for a number needed to treat for an additional beneficial outcome (NNTB) to be calculated for the primary outcome measure of pain. The qualitative analyses found no evidence of an effect of antidepressants on pain intensity or depression in the short-term (less than one week), and conflicting evidence of a medium- (one to six weeks) or long-term (more than six weeks) benefit. There were significantly more minor adverse events in patients receiving TCAs compared with those receiving a placebo (risk ratio (RR) 2.27, 95% confidence interval (CI) 1.17 to 4.42), but there was no significant increase in withdrawals due to an adverse event (RR 1.09, 95% CI 0.49 to 2.42).

There is currently insufficient evidence to support the routine prescription of antidepressants as analgesics in patients with RA as no reliable conclusions about their efficacy can be drawn from eight placebo RCTs. The use of these agents may be associated with adverse events which are generally mild and do not lead to cessation of treatment. More high quality trials are needed in this area.