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 percent pain reduction from baseline during the 13-week, placebo-controlled acute phase of the study.
The most common adverse events in the study (those occurring in more than 5 percent 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 due to adverse events during the extension phase - 13 in the placebo-treated group and five in the duloxetine-treated group.
"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 percent and 33 percent 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)
In Europe, duloxetine is approved for the treatment of diabetic peripheral neuropathic pain (DPNP), major depressive disorder (MDD), generalised anxiety disorder (GAD) and stress urinary incontinence (SUI).
Duloxetine is approved in various countries outside of Europe for the management of DPNP, for the treatment of MDD, for the treatment of GAD and for the management of fibromyalgia.
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 [â¥30 percent reduction in Brief Pain Inventory (BPI) average pain] at the end of the acute phase. If the upper bound of the 97.5 percent 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.
While 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.
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 approved only for adults 18 and over. There is a possibility of an increased risk of suicidal thoughts or behavior in children and young adults treated with antidepressants. Patients should call their doctor right away if they experience worsening depression symptoms, unusual changes in behavior or thoughts of suicide, especially at the beginning of treatment or after a change in dose.
Patients taking duloxetine may experience dizziness or fainting upon standing. The most common side effects of duloxetine include:
- For depression: Nausea, dry mouth, headache, insomnia, diarrhoea.
- For diabetic peripheral neuropathic pain: Nausea, somnolence (sleepiness), fatigue, headache, dizziness.
- For generalized anxiety disorder: Nausea, fatigue, dry mouth, drowsiness, constipation, insomnia, decreased appetite, hyperhidrosis (excessive perspiration), decreased libido, vomiting, ejaculation delay and erectile dysfunction.
- For stress urinary incontinence: Nausea, dry mouth, fatigue.
- For fibromyalgia: Constipation, dry mouth, nausea, diarrhoea, fatigue, decreased appetite, dizziness, headache, somnolence (sleepiness), insomnia.
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.
Eli Lilly and Company and Boehringer Ingelheim
In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a long-term agreement to jointly develop and commercialize duloxetine hydrochloride. This partnership covers neuroscience indications in most countries outside of the United States and Japan, with few exceptions.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers â through medicines and information - for some of the world`s most urgent medical needs.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
Duloxetine for major depressive episodes, diabetic peripheral neuropathic pain and generalized anxiety disorder is marketed by Lilly and Boehringer Ingelheim in all countries included in the partnership under the brand name Cymbalta®, except for Greece, Italy and Spain. In Greece, Italy and Spain Lilly markets the product as Cymbalta® and Boehringer Ingelheim markets the product as Xeristar®. In addition, in Germany, Lilly and Boehringer Ingelheim market duloxetine for diabetic peripheral neuropathic pain as Ariclaim®. In the United States, Cymbalta® is marketed by Lilly and Quintiles. In Japan, duloxetine is co-developed and co-marketed by Lilly and Shionogi & Co., Ltd.
Duloxetine for stress urinary incontinence is marketed by Lilly under the brand name Yentreve®.
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. "Pain Control in the Primary Care Setting." 2006:15.
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.