Duloxetine for the Treatment of Chronic Low Back Pain

In late 2010, the FDA announced that it had approved duloxetine for the treatment of musculoskeletal pain, including chronic lower back pain (http://1.usa.gov/LEv7Gx). The approval was based on data from “four double-blind, placebo-controlled, randomized clinical trials” in which investigators assessed the efficacy of Cymbalta in chronic low back pain and osteoarthritis. The FDA statement announcing approval of Cymbalta for this indication noted that “at the end of the study period, patients taking Cymbalta had a significantly greater pain reduction compared with placebo.”

Although a recent overview of the available data noted that several trials have been of “short duration (12-13 weeks) and had high dropout rates” (http://bit.ly/KhxoxI), results on the efficacy of duloxetine in this patient population have generally been favorable. For example, in “Duloxetine vs. Placebo in Patients with Chronic Low Back Pain: A 12- Week, Fixed-dose, Randomized, Double-blind Trial” (http://bit.ly/KElSfV), researchers treated more than 400 adults with non-neuropathic chronic low back pain with duloxetine or placebo for 12 weeks. Participants all reported a pain intensity of 4 or greater on the Brief Pain Inventory (BPI) at baseline. After 12 weeks of treatment, patients who had received duloxetine reported a significantly greater reduction in average pain intensity scores (measured by BPI) compared to patients who received placebo. The duloxetine group also reported significantly greater improvements in Patient’s Global Impressions of Improvement measures, pain severity and interference (as measured by BPI), and 50% response rates (average BPI pain reduction of 50% or more at endpoint). Patients in the duloxetine group also reported better scores on the Roland Morris Disability Questionnaire and had improved 30% response rates. However, “significantly more patients in the duloxetine group (15.2%) than patients in the placebo group (5.4%) discontinued because of adverse events,” the most common of which were nausea and dry mouth.

Existing studies have consistently shown duloxetine to be more effective than placebo across several measures of pain intensity in this patient population.

The authors of “Duloxetine and Care Management Treatment of Older Adults with Comorbid Major Depressive Disorder and Chronic Low Back Pain” (http://1.usa.gov/JSwuSd) reported generally good results in adults age 60 years and older with major depressive disorder and comorbid chronic low back pain who were treated with up to 120 mg/day duloxetine and Depression and Pain Care Management (DPCM), which consisted of education about depression and back pain, a “careful review of symptoms of depression, low back pain, and side effects,” and management of suicide risk. Pain intensity was measured weekly using the McGill Pain Questionnaire- Short Form (MPQ-SF). More than 90% of patients experienced at least a 30% decrease in MPQ-SF scores (mean change was -6.0, from a median score of 13.0 at baseline); 60% experienced a 50% or greater decrease by week 12.

Duloxetine and concomitant acetaminophen and/or NSAID use

Patients with chronic low back pain often take acetaminophen or an NSAID in addition to other analgesic medications, which may make it difficult to determine which medication is responsible for whatever pain relief is experienced by the patient. In a clinical trial, the use of additional analgesics may be associated with “the risk of reduced assay sensitivity, and possibly a high placebo response.” To investigate whether concomitant use of acetaminophen and/or NSAIDs had an effect on the efficacy of duloxetine for chronic low back pain, the authors of “Efficacy and Safety of Duloxetine in Patients with Chronic Low Back Pain Who Used versus Did Not Use Concomitant Nonsteroidal Anti-Inflammatory Drugs or Acetaminophen” (http://1.usa.gov/LEuPiS) performed a “post hoc analysis of data pooled from two 13-week, multicenter, randomized, double-blind trials of the efficacy of duloxetine… compared with placebo on the reduction of average pain severity, improvement in physical function, and in patient global impression of improvement” in patients with chronic low back pain. Patients were characterized as duloxetine + NSAID/acetaminophen users, placebo + NSAID/acetaminophen users, duloxetine + NSAID/acetaminophen nonusers, and placebo + NSAID/acetaminophen nonusers. The authors reported that “there were no statistically significant differences in the treatment advantage of duloxetine over placebo on measures of pain reduction, improved physical function, or patient global impression of improvement observed between concomitant NSAID/APAP users and nonusers. In other words, concomitant use of an NSAID or APAP did not significantly enhance or interfere with the efficacy of duloxetine.”

Although there have been few studies comparing duloxetine to other medications in the treatment of chronic low back pain— one such study (http://bit.ly/KmKW4o) found no significant differences in safety and efficacy between escitalopram and duloxetine in the management of patients with nonradicular chronic low back pain—existing studies have consistently shown duloxetine to be more effective than placebo across several measures of pain intensity in this patient population.