The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis

Abstract

Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40–75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no difference between duloxetine and placebo (P>0.05) was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine (P=0.029) compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain.

Reduced anterior cingulate grey matter volume in painful hand osteoarthritis

“…The full clinical trial results are published [10, 11]. Of the 39 patients who underwent a baseline MRI, 30 patients agreed to have a post-treatment MRI scan.…”

“…The clinical endpoints of this study, in addition to the full trial protocols, have been reported elsewhere [10, 11]. All trial protocols were approved by the study sponsor and the MHRA (Medicines and Healthcare products Regulatory Agency), UK.…”

“…Before the treatment, all groups were homogeneous for pain reporting measures, concomitant medication use and duration of diagnosis, as previously published [10]. All three treatments were administered using a dose escalation/de-escalation protocol over a period of 12 weeks: week 1: pregabalin, 150 mg once nightly (ON), vs. duloxetine, 30 mg ON, vs. placebo, 1 capsule ON; weeks 2–11: pregabalin, 300 mg ON, vs. duloxetine, 60 mg ON, vs. placebo, 2 capsules ON; week 12: pregabalin, 150 mg ON, vs. duloxetine, 30 mg ON, vs. placebo, 1 capsule ON; followed by cessation of therapy.…”

Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta‐analysis of randomised controlled trials

“…Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor and was first approved by the US Food and Drug Administration for the treatment of severe depression in 2004 . Subsequent studies have demonstrated that it can reduce chronic pain by enhancing serotonergic and noradrenergic activity in the central nervous system and has the potential to become a new clinical treatment option for chronic musculoskeletal pain including knee OA . In 2015, a meta‐analysis of three randomised controlled trials (RCT) reported before 2012 supported the efficacy of duloxetine for knee OA with acceptable AE; however, the efficacy and tolerability of duloxetine remain controversial due to the limited number of published trials.…”

“…14 Subsequent studies have demonstrated that it can reduce chronic pain by enhancing serotonergic and noradrenergic activity in the central nervous system and has the potential to become a new clinical treatment option for chronic musculoskeletal pain including knee OA. 15,16 In 2015, a meta-analysis of three randomised controlled trials (RCT) reported before 2012 supported the efficacy of duloxetine for knee OA with acceptable AE; 17 however, the efficacy and tolerability of duloxetine remain controversial due to the limited number of published trials. In addition, several new RCT have since been reported, which were not included in previous analyses.…”