Data Suggest Cymbalta(R) Reduced Severity of Night Pain in Patients with Diabetic Nerve Pain
May 03 2007 - 9:05AM
PR Newswire (US)
New Analysis Examines Impact of Pain on Sleep Interference
INDIANAPOLIS, May 3 /PRNewswire-FirstCall/ -- Data from a pooled
analysis of three studies suggest that in patients with pain caused
by diabetic nerve damage, or diabetic peripheral neuropathy, who
are treated with Cymbalta (duloxetine HCl), improvements in both
average daily pain and night pain severity were associated with
less pain-related sleep interference than in those patients taking
sugar pill. Results from the analysis of more than 1,000 patients
were presented today at the annual meeting of the American Pain
Society in Washington D.C. The average daily night pain severity
and sleep interference correlation assessments were secondary
analyses of data from trials in which the primary efficacy endpoint
was to measure the reduction in average weekly pain. For these
assessments, a subset of nonsomnolent patients was created by
removing those who experienced treatment-related somnolence (such
as daytime sleepiness, drowsiness, grogginess or difficulty
awakening) or who were on other sedating medications. At the end of
the 12-week analysis, this subset of patients treated with 60 mg of
Cymbalta once- and twice-daily experienced significantly more
improvement in 24-hour average pain scores than those taking sugar
pill (47 percent, 50 percent and 29 percent respectively), as
measured by reduction of scores on the self-reported, 11-point
Likert scale. In analyses of the effect of Cymbalta on night pain
and pain-related sleep interference, nonsomnolent/nonsedating drug
patients treated with 60 mg of Cymbalta once- and twice-daily
experienced significantly more improvement in nighttime pain than
those taking sugar pill after one week of treatment (22 percent, 21
percent and 10 percent, respectively) and at the end of the 12
weeks (47 percent, 51 percent compared with 34 percent). Both doses
of Cymbalta reduced pain-related sleep interference at the end of
the 12 weeks significantly more than sugar pill (55 percent, 57
percent and 45 percent respectively), as measured by the Brief Pain
Inventory (BPI). No significant difference was seen between the 60
mg and 120 mg doses of Cymbalta. Of greatest interest is the fact
that for the first time, a clear correlation between reduction in
average daily pain and average night pain and reduction in pain
sleep interference was demonstrated in a population that was not
depressed, did not experience treatment-emergent somnolence and was
not on medications commonly associated with sedation. Other
published studies of the relationship between pain and sleep
interference have been confounded by at least one of those
conditions. "Patients with diabetic nerve pain often complain of
being awoken, or having difficulty falling asleep because of pain,
and it is difficult for physicians to know whether sleep problems
are the cause or effect of pain," said David Fishbain, M.D.,
distinguished professor of psychiatry, adjunct professor of
neurological surgery and anesthesiology at the University of Miami,
and lead study author. "This new analysis is important because it
suggests that interference with sleep generally improves if
nighttime pain improves." In this analysis, the most common adverse
events experienced in the entire patient population as a whole were
nausea, somnolence, dizziness, constipation, hyperhidrosis, dry
mouth and decreased appetite. The median duration of nausea,
somnolence and dizziness in Cymbalta-treated patients was six days,
14 days and five days, respectively, with the majority of patients
who experienced these adverse events rating them as mild to
moderate in severity. The overall discontinuation rate for patients
on Cymbalta was 14 percent, while the overall discontinuation rate
for patients on placebo was 7 percent. The most common adverse
event cited as a reason for discontinuation was nausea (4 percent),
followed by somnolence (2 percent), dizziness (2 percent), fatigue
(1 percent) and vomiting (1 percent). Methods: Data were pooled
from three double-blind, randomized, placebo-controlled, 12-week
studies, to investigate associations between pain and sleep. In the
first study, patients were treated with Cymbalta 20 mg once daily,
60 mg once daily, 60 mg twice daily and sugar pill. The second and
third studies compared Cymbalta 60 mg once daily and 60 mg twice
daily with sugar pill. A subset of nonsomnolent patients was
created by removing patients reporting treatment-emergent
somnolence or who were on sedating concomitant medications (No
patients in any of the trials reported baseline somnolence.). In
the pooled data, the primary efficacy measure was the reduction in
the weekly mean of the 24-hour average pain scores, calculated from
daily patient diary entries and measured by an 11-point Likert
scale. Secondary measures included average daily night pain
severity measured by an 11-point Likert scale and the BPI sleep
interference item. Patients with diabetic nerve pain who also had
major depressive disorder (MDD) were excluded from this study,
since depression could have had an effect on sleep interference,
and improvements in depression could have improved sleep
interference in these patients.(1,2,3) Data on treatment-emergent
adverse events, including reports of somnolence, were collected by
spontaneous report, and while spontaneous reporting is the standard
practice for evaluating treatments, solicited scales specifically
designed for particular adverse events would have been preferable
for the investigation. About Diabetic Peripheral Neuropathy
According to the National Institute of Diabetes & Digestive
& Kidney Diseases, approximately half of those with diabetes
have some form of nerve damage, or neuropathy, but not all will
develop symptoms. While nerve problems can occur at any time, the
highest rates are among those who have had diabetes for at least 25
years. People who have had problems controlling their blood sugar
levels, have high blood pressure, are overweight, have high levels
of blood fat or are over the age of 40, may also have a greater
risk of developing diabetic peripheral neuropathy. Symptoms can
include numbness, tingling or pain and weakness in the toes, feet,
legs, hands, arms and fingers. These symptoms are often worse at
night.(4) About Cymbalta Serotonin and norepinephrine in the brain
and spinal cord are believed to both help regulate the perception
of pain and mediate core mood symptoms. Based on pre-clinical
studies, duloxetine is a balanced and potent reuptake inhibitor of
serotonin and norepinephrine that is believed to potentiate the
activity of these chemicals in the central nervous system (brain
and spinal cord). While the mechanism of action of duloxetine is
not fully known, scientists believe its effect on pain perception,
as well as its effects on depression and anxiety symptoms, may be
due to increasing the activity of serotonin and norepinephrine in
the central nervous system. Cymbalta is approved in the United
States for the treatment of major depressive disorder, the
management of diabetic peripheral neuropathic pain and the
treatment of generalized anxiety disorder, all in adults. Cymbalta
is not approved for use in pediatric patients. Important Safety
Information Cymbalta is approved to treat major depressive
disorder, diabetic peripheral neuropathic pain and generalized
anxiety disorder. 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. Cymbalta is approved only for adults 18 and over. Cymbalta
is not for everyone. Patients should not take Cymbalta if they have
recently taken a type of antidepressant called a monoamine oxidase
inhibitor (MAOI), are taking Mellaril(R) (thioridazine) or have
uncontrolled glaucoma. Patients should speak with their doctor
about all medicines they are taking, including those for migraine,
to avoid a potentially life- threatening condition. Patients should
tell their doctor about their alcohol consumption, if they have
liver disease and about all of their medical conditions. Patients
taking Cymbalta may experience dizziness or fainting upon standing.
The most common side effects of Cymbalta include: -- For MDD:
nausea, dry mouth and constipation -- For DPNP: nausea, sleepiness
and dizziness -- For GAD: nausea, fatigue and dry mouth. This is
not a complete list of side effects. For full patient information,
visit http://www.cymbalta.com/. For full prescribing information,
including boxed warning, visit http://www.cymbalta.com/. About Eli
Lilly and Company Lilly, a leading innovation-driven corporation,
is developing a growing portfolio of first-in-class and
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. Additional information about Lilly is available at
http://www.lilly.com/. P-LLY This press release contains
forward-looking statements about the potential of Cymbalta for the
treatment of diabetic peripheral neuropathic pain and reflects
Lilly's current beliefs. However, as with any pharmaceutical
product, there are substantial risks and uncertainties in the
process of development and commercialization. There is no guarantee
that the product will continue to be commercially successful. For
further discussion of these and other risks and uncertainties, see
Lilly's filings with the United States Securities and Exchange
Commission. Lilly undertakes no duty to update forward-looking
statements. (1) Goldstein DJ, et al. Duloxetine vs. placebo in
patients with painful diabetic neuropathy. Pain. 2005;116:109-118.
(2) Raskin J, et al. A Double-Blind, Randomized Multicenter Trial
Comparing Duloxetine with Placebo in the Management of Diabetic
Peripheral Neuropathic Pain. Pain Med. 2005;6(5):346-356. (3)
Wernicke JF, Pritchett YL, D'Souza DN, Waninger A, Tran P, Iyengar
S, Raskin J. A randomized controlled trial of duloxetine in
diabetic peripheral neuropathic pain. Neurology.
2006;67(8):1411-1420. (4) National Diabetes Information
Clearinghouse. Diabetic Neuropathies: The Nerve Damage of Diabetes.
National Institute of Diabetes and Digestive and Kidney Diseases.
http://www.diabetes.niddk.nih.gov/dm/pubs/neuropathies/, August
2004. (Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Charles McAtee (US),
+1-317-277-1566, mobile: +1-317-997-1627, or David Shaffer (OUS),
+1-317-651-3710, mobile: +1-317-614-5106, both of Eli Lilly and
Company
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