New data show patients with chronic low back pain on duloxetine hydrochloride (Cymbalta®) maintained reductions in pain for 41 weeks [1]. In patients who initially responded to duloxetine, this maintenance of pain reduction was accompanied by further reduction in pain that was statistically significant as measured by the Brief Pain Inventory (BPI) average pain rating [1]. The data was presented recently at the sixth triennial congress of the European Federation of International Association for the Study of Pain Chapters (EFIC®).

A total of 181 patients enrolled in the open-label 41-week extension phase of the study, designed to evaluate long-term maintenance of effect in patients with chronic low back pain taking duloxetine 60 mg or 120 mg once daily. Maintenance of effect was assessed in the responders – 58 duloxetine patients who had experienced at least 30% pain reduction from baseline during the 13-week, placebo-controlled acute phase of the study.

’Chronic low back pain is a painful and debilitating condition and this study is an important step in the fight against it,’ said Vladimir Skljarevski, M.D., lead study author and a neurologist and medical fellow at Lilly Research Laboratories.

Experts estimate chronic low back pain affects between 4% and 33% of the world’s population at any one time [2]. According to the International Association for the Study of Pain (IASP), the pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage [3]. Chronic pain is defined as pain that persists beyond acute pain or beyond the expected time for an injury to heal [4]. Men and women are equally affected by chronic low back pain, and it occurs most often between the ages of 30 and 50 [5].

Although duloxetine’s mechanism of action in humans is not fully known, it is believed to affect both serotonin and norepinephrine/noradrenaline-mediated nerve signaling in the brain and the spinal cord. Based on pre-clinical studies, duloxetine is a reuptake inhibitor of serotonin and norepinephrine/noradrenaline. Scientists believe its effect on mood and pain perception is due to increasing the activity of serotonin and norepinephrine in the central nervous system.

The most common adverse events in the study (those occurring in more than 5% of study participants) included headache, nausea, upper abdominal pain, excessive sweating (hyperhidrosis), back pain, diarrhoea and fatigue. Adverse events were similar to those seen in previous duloxetine studies [1]. A total of 18 patients in the study discontinued because adverse events during the extension phase – 13 in the placebo-treated group and five in the duloxetine-treated group.

Duloxetine is approved for the treatment of major depressive disorder and diabetic peripheral neuropathic pain in many countries and is also approved in some countries for the treatment of stress urinary incontinence and generalized anxiety disorder and the management of fibromyalgia. Duloxetine is contraindicated in patients who are allergic to it, who have liver disease resulting in hepatic impairment, who are taking a monoamine oxidase inhibitor (MAOI), fluvoxamine, ciprofloxacin or enoxacine, or who have severe kidney disease. The initiation of treatment with duloxetine also is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis.

Methods

Patients (N = 181) with chronic low back pain (defined as low back pain present on most days for the preceding six months or longer) entered the study’s 41-week extension phase and received duloxetine 60 mg or 120 mg once daily after completing a 13-week, placebo-controlled acute phase. Patients completing the acute phase on duloxetine remained on the same dose while those on placebo were switched to duloxetine. Maintenance of effect was assessed in 58 duloxetine patients who were responders (~30% reduction in BPI average pain) at the end of the acute phase. If the upper bound of the 97.5% Confidence Interval (CI) of the mean change from the end of the acute phase for the BPI average pain was less than the pre-specified margin of 1.5, then maintenance of effect was established.

References

1 Skljarevski V. et al. ’Maintenance of effect of duloxetine in patients with chronic low back pain.’ Poster presented at European Federation of Chapters of the International Association for the Study of Pain, September 2009
2 World Health Organization. Chronic rheumatic conditions. Available at: http://www.who.int/chp/topics/rheumatic/en. Accessed on 26 May 2009
3 International Association for the Study of Pain. ’IASP Pain Terminology‘ Available at: http://www.iasp- pain.org/AM/Template.cfm?Section=General_Resource_Links&Template=/CM/HTMLDisplay.cfm&ContentID=3058#Pain. Accessed on 26 May 2009
4 American Pain Society (2006) ’Pain Control in the Primary Care Setting.’ 15
5 National Institute of Neurological Disorders and Stroke. ’Low back pain fact sheet.’ Available at: http://www.ninds.nih.gov/disorders/backpain/detail_backpain.htm. Accessed on 26 May 2009