In New Study, Duloxetine Reduced Non-specific Pain and Emotional Symptoms Associated with Depression
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 remission (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:
Methodology
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, safety and tolerability.
About Duloxetine
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 and 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.
About Depression
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.
Related links:
Eli Lilly and Company
Contact:
Boehringer Ingelheim GmbH
Ute E. Schmidt
55216 Ingelheim
Germany
Phone: +49 (0)6132 7797296
Fax: +49 (0)6132 776601
E-mail
Eli Lilly and Company
David Shaffer
USA
Phone: +1, 317-651-3710
References:
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.
Posted: March 2007
