MADRID, Spain, 19 march 2007 - The antidepressant duloxetine, at a once-daily dose of 60 mg, significantly reduced non-specific pain and emotional symptoms associated with depression in a new, eight-week, placebo-controlled study of 327 adult patients with at least moderate pain and major depression. The results were presented today at the 15th European Congress of Psychiatry (AEP) in Madrid, Spain.
Duloxetine, a member of a class of drugs commonly referred to as serotonin and norepinephrine reuptake inhibitors (SNRIs), is approved in more than 70 countries for the treatment of major depression.
“Whereas traditionally, the focus has been on treating only emotional symptoms of depression, we now know that the presence of physical symptoms, specifically pain, can obscure the diagnosis and complicate the management of patients,” said Professor Koen Demyttenaere, Department of Psychiatry at University Hospital Gasthuisberg in Belgium and lead study investigator. “In this study of depressed patients with at least moderate pain, duloxetine helped by significantly reducing both painful and emotional symptoms of depression, and in decreasing the interference of pain with functioning.”
In the study:
Average pain scores, the primary outcome measured, decreased significantly among patients treated with duloxetine by 45 percent (on an 11-point Likert scale from 5.7 at baseline to 3.13 at the final visit in Week 8) compared with a decrease of 29 percent (from 5.7 to 4.06) among those taking placebo (p< 0.001).
Duloxetine significantly reduced core emotional symptoms, as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), by 56 percent (from an average score of 29.6 at baseline to 12.91 at Week 8), compared with a 39-percent reduction (from 29.6 to 18.29) in patients taking placebo (p<0.0001).
53 percent of duloxetine-treated patients reached remis sion (MADRS <12) by the end of the study, compared with 29 percent of placebo-treated patients (p< 0.0001).
Compared with placebo, duloxetine-treated patients also experienced a significantly better outcome in response to pain (>30% reduction from baseline in average pain severity) and improved daily functioning not limited by pain (BPI interference subscale).
10.5 percent of study patients treated with duloxetine and 5.5 percent of patients treated with placebo discontinued treatment because of adverse events. The most commonly reported adverse events among those taking duloxetine were nausea (24.7 percent for duloxetine-treated patients, vs. 7.9 percent for those taking placebo), excessive sweating (11.7 percent vs. 2.4 percent), dry mouth (10.5 percent vs. 3.6 percent), headache (7.4 percent vs. 9.1 percent), fatigue (8.0 percent vs. 1.8 percent), dizziness (5.6 percent vs. 3.6 percent), and constipation (5.6 percent vs. 1.2 percent).
Notes to Editors:
This double-blind, eight week study included 327 patients
randomized to placebo (n=165) or duloxetine 60mg (n=162) and was
conducted in Belgium, Finland, France, Germany and Slovakia.
Trial participants were outpatients aged 18 or older presenting with:
Major depressive disorder (MDD), as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS, with a score of >20) and the Clinical Global Impression of Severity scale (CGI-S, with a score of >4).
At least moderate pain not attributable to a diagnosed pain syndrome, as assessed by the Brief Pain Inventory (BPI, with a score of >3), a validated scale used to assess the severity of pain and the impact of pain on daily functions.
The primary outcome measure was the brief pain inventory average pain score at endpoint, and the change from baseline, using the mixed-model-repeated-measures (MMRM) method.
Secondary measures included MADRS total score, CGI-S, SCL-90-R, response and remission, s afety and tolerability.
Duloxetine is believed to impact both serotonin and norepinephrine/noradrenaline mediated nerve signalling in the brain and the spinal cord. Based on pre-clinical studies, duloxetine is a balanced and potent reuptake inhibitor of serotonin and norepinephrine/noradrenaline. While the mechanism of action of duloxetine in humans is not fully known, scientists believe its effect on pain perception is due to increasing the activity of serotonin and noradrenaline in the central nervous system.
Duloxetine is approved for the treatment of depression and diabetic peripheral neuropathic pain in many countries and is approved in some countries for the treatment of stress urinary incontinence. Duloxetine also is approved in the United States and Mexico for the treatment of generalised anxiety disorder. Duloxetine is approved only for adults 18 and over. In children and teens, antidepressants can increase the risk of suicidal thoughts or actions. 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.
The most commonly reported adverse reactions in patients with depression treated with duloxetine in clinical trials were nausea, dry mouth, headache and diarrhea. However, the majority of common adverse reactions were mild to moderate, they usually started early in therapy and most tended to subside even as therapy was continued. The most commonly observed adverse reactions in patients with diabetic neuropathic pain treated with duloxetine were: nausea; somnolence; dizziness; and headache. The most common adverse reactions in patients with generalised anxiety disorder treated with duloxetine in clinical trials were nausea, fatigue, dry mouth, drowsiness, constipation, insomnia, decreased appetite, hyperhidrosis, decreased libido, vomiting, ejaculation delay an d erectile dysfunction.
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.
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide.1 The World Health Organization estimates depression will be among the highest-ranking causes of disability in developed countries by 2020, second only to ischemic heart disease worldwide.2 It can happen to anyone of any age, race or ethnicity; however, women are nearly twice as likely to experience depression as men.3 Although it is one of the most frequently seen psychiatric disorders in the primary care setting, it often goes undiagnosed or is under-treated.4 This may be because depressed people often present physical symptoms rather than emotional complaints; pain is present in approximately 45 to 95 percent of patients with MDD, and can include headache, back, shoulder and abdominal pain.5
Complete elimination of symptoms, or remission, is the primary goal of depression treatment. Treating the full spectrum of emotional and physical symptoms to remission decreases a patient’s risk of relapse.6
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 best-in-class 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 – 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 143 affiliates in 47 countries and almost 37,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. In 2005, Boehringer Ingelheim posted net sales of 9.5 billion euro while spending almost one fifth of net sales in its largest business segment Prescription Medicines on research and development.
Duloxetine for major depressive episodes will be 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 will market the product as Cymbalta and Boehringer Ingelheim will market the product as Xeristar®. In the United States, Cymbalta is marketed by Lilly and Quintiles. In Japan, duloxetine will be co-developed and co-marketed by Lilly and Shionogi & Co., Ltd.
Duloxetine for stress urinary incontinence will be marketed by Lilly under the brand name Yentreve.®
Please be advised
This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for all international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.
Eli Lilly and Company
Boehringer Ingelheim GmbH
Ute E. Schmidt
Phone: +49 (0)6132 7797296
Fax: +49 (0)6132 776601
Eli Lilly and Company
Phone: +1, 317-651-3710
1 World Health Organization. Factsheet - Depression, 2005. http://www.who.int/mental_health/management/depression/definition/en/
2 Murray CJL, Lopez AD, eds. The Global Burden of Disease; 1996.
3 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision. Washington DC: American Psychiatric Association; 2000:345-428.
4 Kroenke K, et al. Am J Med. 1997; 103(5):339-347.
5 Simon GE et al. New Engl J Med. 1999;341:1329-35.
6 Paykel ES, et al. Psychol Med. 1995;25(6):1171-1180.