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Longest controlled duloxetine trial to-date showed significant advantages over placebo
Indianapolis/ IN/USA, and Ingelheim/Germany, 10th December 2008 – Duloxetine hydrochloride (Cymbalta®/Xeristar®), administered at 60 to 120 mg once daily, delayed the onset of a new episode of depression in patients with recurrent depressive disorder, compared with placebo (p<.001), according to new data from an international study presented at a meeting of a major scientific society. Up to 85 percent of patients with depression experienced epressive recurrences.1
Duloxetine is currently approved in Europe for the treatment of major depressive episodes.
Results from the longest controlled duloxetine study to-date showed that, during the trial’s 52-week placebo-controlled maintenance phase, duloxetine-treated patients (n=288) had a longer time to a depressive recurrence, and were less likely to experience a new episode of depression than the patients (n=226) who received placebo (recurrencerates were 14.4 percent vs. 33.1 percent, respectively).
A depressive episode is defined when a patient experiences at least five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning including depressive mood, markedly diminished interest in activities most of the day, significant weight loss, insomnia and increased tiredness in accordance with the DSM-IV criteria for major depressive disorder (MDD).2 The purpose of the study was to understand whether the long-term use of duloxetine would prevent the onset of new depressive episodes in patients with MDD who are at a high risk of experiencing a depressive recurrence. Patients had to have experienced at least 3 episodes of depression over the previous 5 years in order to be eligible for the study.
Previous research has shown that many patients with depression will suffer from multiple depressive episodes.3 The number of episodes,4 their duration5 and the presence of lingering depressive symptoms increase the risk of recurrence, or future episodes of depression.6 For those who experience depression multiple times in their life, studies have shown that the illness may cause structural changes in the brain, making it more difficult to treat over time.7
“Recurrent depressive episodes are detrimental to long-term health and well being of patients,” said Dr. Giuseppe Maina, University of Turin, Italy, an investigator and an author on the study.
In the maintenance phase, which followed up to 34 weeks of open-label treatment, the most common adverse events (those occurring in at least 5 percent of patients in any treatment group) were headache, insomnia,dizziness, fatigue, back pain, common cold and flu. The results of the study were similar between duloxetine and placebo-treated patients in the incidence of any individual adverse event.
In addition to being approved for the treatment of major depressive episodes, duloxetine is approved in Europe for the treatment of generalised anxiety disorder (GAD) diabetic peripheral neuropathic pain(DPNP) and stress urinary incontinence (SUI).
Notes to Editors:
Additional Study Findings
The proportion of duloxetine-treated patients who discontinued the study due to adverse events during the acute, continuation and maintenance phases was 6.6 percent, 6.1 percent and 4.1 percent, respectively. Following are the most common adverse events:
The 52-week maintenance phase was preceded by up to 34-weeks of open-label treatment with duloxetine 60-120 mg once daily. Of the 514 patients initially entered into the study, 288 patients met responsecriteria at the end of up to 34 weeks treatment and entered the 52-week, double-blind, maintenance phase of the study. Patients were randomly assigned to receive either duloxetine at the dose to which they had previously responded or placebo during the maintenance phase.
The primary endpoint of the study was time to recurrence of a major depressive episode during 52 weeks of maintenance treatment, asassessed by any of the following recurrence criteria: a CGI-S score ≥4and meeting DSM-IV criteria for MDD; three consecutive visits meeting re-emergence criteria or 10 total re-emergence visits; or study discontinuation due to lack of efficacy. Secondary measures included the HAMD17 total score and subscales, CGI-S and PGI-I scales, SQ-SS and VAS forpain. Safety and tolerability were assessed via analysis of treatment-emergent adverse events, vital signs, weight, ASEX for sexual functioning, and laboratory measures. The primary study manuscript has already been submitted for review with a view to publication in apeer-reviewed medical journal.
About Major Depressive Disorder
Major Depressive Disorder (MDD) affects approximately 121 million people worldwide.8 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.8 It can happen to anyone of any age, race or ethnicity; however, women are nearly twice as likely to experience depression as men.9 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.10
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 are uptake inhibitor of serotonin and no repinephrine/noradrenaline. Scientists believe its effect on mood and pain perception is due to increasing the activity of serotonin and norepinephrine in the centralnervous 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. Duloxetine is approvedonly for adults 18 and over. There is a possibility of an increase drisk 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 duloxetineinclude:
This is not a complete list of side effects.
Duloxetine is contrain dicated in patients who are allergic to it, who have liver disease resulting in hepatic impairment, who are taking amonoamine oxidase inhibitor (MAOI), fluvoxamine, ciprofloxacin orenoxacine 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 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 135 affiliates in 47 countries and almost 38,900 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 2007, Boehringer Ingelheim posted net sales of 10.9 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 Mueller TI, Leon AC, Keller MB, et al. Recurrence after recovery from major depressive disorder during 15 years of observational follow-up.” Am J Psychiatry 1999;156:1000-1006.
2 First Ml B. et al. DSM-IV-TR® Handbook of Differential Diagnosis. American Psychiatric Publishing, Inc. 2002; 1-6
3 Kessing LV. Recurrence in affective disorder: II. Effect of age and gender. Br J Psychiatry 1998;172:29-34.
4 Solomon DA, Keller MB, Leon AC, et al. Multiple recurrences of major depressive disorder. Am J Psychiatry 2000;157:229-233
5 Melartin TK, Rytsala HJ, Leskela US, et al. Severity and comorbidity predict episode duration and recurrence of DSM-IV major depressive disorder. J Clin Psychiatry 2004;65:810-819.
6 Judd LL, Akiskal HS, Maser JD, et al. Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. J Affect Disord 1998;50:97-108
7 Maletic, V., et al. Neurobiology of depression: an integrated view of key findings. Int J Clin Pract 2007 Dec;61(12):2030-40.
8 World Health Organization. Factsheet - Depression, 2008. WHO. Available at: http://www.who.int/mental_health/management/depression/definition/en/. Accessed on 21 November 2008
9 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision. Washington DC: American Psychiatric Association; 2000:345-428.
10 Paykel ES, Scott J, Teasdale JD, et al. Prevention of relapse in residual depression an important outcome in depression. Psychol Med. 1995;25:1171- 1180.