FDA OKs duloxetine hydrochloride to treat chronic musculoskeletal pain

In patients with chronic knee pain due to osteoarthritis, 60 mg to 120 mg of duloxetine hydrochloride, a serotonin-norepinephrine reuptake inhibitor (SNRI), administered daily, was found to provide both significant pain control and improve physical functioning.

These were the findings of a new, multicenter, randomized, double-blind, parallel group, placebo-controlled trial published on-line ahead of print in the journal Pain Practice.

In this trial, researchers randomly assigned [stratified by nonsteroidal anti-inflammatory (NSAID) use] 256 patients whom met the American College of Rheumatology (ACR) clinical and radiographic criteria for osteoarthritis of the knee to receive either duloxetine once daily (n=128) or matching placebo (n=128). To be included in the trial, patients also had to report experiencing pain for >14 days per month during the previous 3 consecutive months and a pain severity of ≥4 on the 24-hour average pain severity scale (ranging from 0 to 10). Patients assigned to duloxetine were started on a  30-mg once-daily dose for 1 week before being titrated up to duloxetine 60 mg once daily. At week 7, patients reporting a <30% reduction in pain from baseline using the Brief Pain Inventory (BPI) 24-hour average pain rating (and no tolerability issues) were further titrated up to a dose of 120 mg of duloxetine once daily, where they remained until the end of the treatment phase (week 13).

The researchers found that patients treated with duloxetine had significantly (P≤.001) greater improvement at all time points on BPI average pain scale, as well as significantly greater improvement on BPI pain severity ratings (P≤.05), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index total (P=.044) and physical functioning scores (P=.016), and the Clinical Global Impressions of Severity (CGI-S) scale (P=.009). Subgroup analyses did not suggest differing efficacy in patients based upon age, gender, and origin, nor in patients with differing durations and severities of osteoarthritic pain.

In their paper the researchers suggested, ”These findings provide significant evidence for the efficacy of duloxetine to improve pain in patients with osteoarthritis of the knee.” They also stressed, “These findings are consistent with and confirm the findings of the recently published first study of duloxetine treatment of patients with chronic pain due to osteoarthritis of the knee.”

The frequency of nausea, constipation, and hyperhidrosis were found to be significantly higher in the duloxetine group (P≤.05) compared to placebo. As a result of these adverse effects, significantly more duloxetine-treated patients dropped out of the trial (P=.002).

Duloxetine is currently FDA indicated for the management of diabetic peripheral neuropathic pain and fibromyalgia, in addition to the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Duloxetine is not currently FDA approved for the management of osteoarthritis pain.

This trial was sponsored by Eli Lilly and Co, manufacturer of Cymbalta.