| Suicidal tendencies a possible problem when using anti-seizure drugs.
FDA informed healthcare professionals that the Agency has analyzed reports
of suicidality (suicidal behavior or ideation) from
placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as
psychiatric disorders, and other conditions. In
the FDA's analysis, patients receiving antiepileptic drugs had approximately twice the
risk of suicidal behavior or ideation (0.43%)
compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior
and suicidal ideation was observed as early as one
week after starting the antiepileptic drug and continued through 24 weeks. The results
were generally consistent among the eleven drugs.
The relative risk for suicidality was higher in patients with epilepsy compared to
patients who were given one of the drugs in the
class for psychiatric or other conditions.
Healthcare professionals should closely monitor all patients currently taking or starting
any antiepileptic drug for notable
changes in behavior that could indicate the emergence or worsening of suicidal thoughts or
behavior or depression.
The drugs included in the analyses include (some of these drugs are also available in
generic form):
Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)
Although the 11 drugs listed above were the ones included in the analysis, FDA expects
that the increased risk of suicidality is
shared by all antiepileptic drugs and anticipates that the class labeling changes will be
applied broadly.
Read the complete 2008 MedWatch Safety Summary including a link to the Healthcare
Professional Sheet regarding this issue at:
http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antiepileptic
Return to Index
FDA Approves Second
Drug to Treat Fibromyalgia June, 2008
The U.S. Food and Drug Administration (FDA) approved Cymbalta
(duloxetine) on June 16 for treating fibromyalgia. Cymbalta is the first
serotonin-norepinephrine reuptake inhibitor (SNRI) that has been proven to reduce pain in
fibromyalgia patients. This is the second FDA-approved medication to treat the disease,
while the first was Lyrica (pregabalin) in June 2007.
The Fibromyalgia Network has been reporting on the progress of
Cymbalta through clinical trials since the spring of 2004.
SNRI drugs, such as Cymbalta, are thought to relieve pain by
increasing the availability of serotonin and norepinephrine (NE) in the central nervous
system. These two neurotransmitters help filter out pain signals in the spinal cord so
that fewer make it up to the brain. When serotonin and NE are released at the nerve
endings, SNRIs latch onto these two neurotransmitters and carry them back across the nerve
junction so that both can be reused to fight pain. In a way, SNRIs "recycle" the
two neurotransmitters that are low in many patients with fibromyalgia.
In the most recent double-blind, randomized, phase III clinical
trial of 520 men and women with fibromyalgia, researchers compared Cymbalta at 20 mg, 60
mg, and 120 mg doses taken once daily for six months versus placebo. People taking the two
higher doses (but not 20 mg/day) reported pain reduction after the first week. After three
and six months, patients taking either 60 or 120 mg daily reported a significant reduction
in pain compared to patients taking the placebo. Aside from measures of pain, the two
higher doses of Cymbalta also reduced mental fatigue, which might possibly relate to
improvements in mental clarity.
Cymbalta was shown to be equally effective in men and women with
and without mood disorders. Even people over 65 years of age reaped similar improvements
in pain as those in the younger age groups.
Nausea, dry mouth, constipation, and sleepiness were the most
common side effects of the medication. The side effects increased at the higher dose.
Weight gain or blood pressure elevations may occur in a subgroup of patients taking
Cymbalta.
Details on overcoming side effects, monitoring blood pressure and
making adjustments for daytime sleepiness were reported in the January 2008 issue of the
Fibromyalgia Network Journal. "The key message is to not give up too soon: try
different doses and try taking it at different times during the day. Patients usually find
the right approach for them," said Lesley Arnold, M.D. of the University of
Cincinnati College of Medicine, in Ohio, and lead investigator for the clinical trials on
Cymbalta.
Cymbalta has already been FDA-approved to treat diabetic peripheral
neuropathic pain (DPNP), major depressive disorder, and generalized anxiety disorder, all
in adults older than 18 years of age.
The FDA also added important warnings and precautions to the Cymbalta prescription information
including who should not take this medication.
Return to Index
17
Apr 2008
Pfizer's Lyrica reduced pain of fibromyalgia in patients regardless of whether they
experienced symptoms of anxiety or depression at the beginning of the study, according to
a pooled analysis presented today at the American Academy of Neurology annual meeting. The
analysis, which looked at data pooled from previous clinical trials, also showed that
patients' self-reported improvements were more closely associated with improvements in
pain and sleep than fatigue or symptoms of anxiety or depression.
Fibromyalgia is the most common, chronic widespread pain condition in the United States
and is thought to result from neurological changes in how patients perceive pain.
Fibromyalgia is usually accompanied by poor sleep, stiffness and fatigue.
"The data showed that Lyrica reduced fibromyalgia pain, and alleviating that pain was
associated with patients' overall feeling of well-being," said Dr. Lesley Arnold, one
of the study's authors and associate professor in the department of psychiatry at the
University of Cincinnati Medical Center. "Understandably, many patients with a
chronic pain condition such as fibromyalgia also experience depression and anxiety, and
importantly we found that Lyrica helped reduce pain in patients regardless of the presence
of symptoms of these co-morbid conditions."
About the Analysis
The results are from a retrospective, pooled analysis of data from three
placebo-controlled clinical trials (8 weeks, 13 weeks and 14 weeks long) of Lyrica in over
2,000 fibromyalgia patients. These studies randomized patients to receive Lyrica 150 mg,
300 mg, 450 mg or 600 mg or placebo dosed twice daily. Patients were asked to measure
their pain on a scale of zero to 10; the baseline score for study participants was 6.9
(150 mg, 450 mg, 600 mg) or 7.0 (300 mg). A score of 4.0 to 6.9 is considered moderate
pain and a score of greater than 7.0 is considered moderate to severe pain on this 10-
point scale.
In the studies, 38 percent of fibromyalgia patients had moderate to severe anxiety
symptoms, while 27 percent had moderate to severe depressive symptoms, as assessed using
the Hospital Anxiety and Depression Scales (HADS-A or HADS-D). Patients with severe
depression or unstable psychiatric conditions were excluded from the studies.
The new analysis confirmed that Lyrica was significantly more effective than placebo in
reducing pain in patients with fibromyalgia. Patients receiving 600 mg a day of Lyrica had
a pain reduction of 2.08 on the pain scale; 450 mg a day had a reduction of 2.01; 300 mg a
day had a reduction of 1.76; 150 mg a day had a reduction of 1.37, and placebo had a
reduction of 1.25.
Additionally, Lyrica was found to reduce pain in patients regardless of whether they had
symptoms of anxiety or depression.
The analysis also examined the relationship between improvements in pain, sleep, fatigue,
anxiety and depressive symptoms with patients reporting feeling "much improved"
or "very much improved" as measured by the Patient Global Impression of Change
(PGIC). The PGIC is a standardized, self-reported tool that measures the change in a
patient's overall status ranging from "very much improved" to "very much
worse."
Pain reduction was found to have the greatest association on patients reporting
improvement as measured by PGIC. The relationships between feeling much or very much
improved were strongest for pain and sleep, and less pronounced for fatigue and symptoms
of anxiety or depression, but statistically significant for all variables.
The most common side effects in the pooled analysis versus placebo of these three studies
were dizziness and somnolence, followed by weight gain, blurred vision and dry mouth.
About Lyrica
In the United States, Lyrica® (pregabalin) capsules, CV, is approved for the management
of fibromyalgia. Lyrica is also indicated for the management of neuropathic pain
associated with diabetic peripheral neuropathy, postherpetic neuralgia (pain after
shingles), and as adjunctive therapy for adults with partial onset seizures. The 600
mg/day is not an approved dosage for Lyrica in the management of fibromyalgia.
Return to Index
Opioids and Fibromyalgia
Jane
Kohler. FMS Community.org 2007
If
you suffer with fibromyalgia pain, chances are that you have already tried a variety of
medications and therapies. For many who suffer with Fibro pain the mainstream therapies
can change their life, treatments like antidepressants, muscle relaxers, stretching, water
exercise, anti-seizure drugs or heat and massage may lessen the pain and allow you to work
and take care of your family.
There
is a subset of Fibro sufferers who do not respond to these types of treatments, and others
who may have overlapping conditions such as Diabetes, CMP, TMJ, Arthritis, Degenerative
Disc Disease and other conditions, for them the only answer may be Opiods.
This
is where controversy enters your life as the use of opioids to treat chronic pain is a
subject of great debate. Many of the physicians in the U.S. are reluctant to prescribe
opioids as they were trained to fear addiction. They were taught that anyone who was
prescribed opiods for pain relief would develop a tolerance for the drug or become
addicted to the drug. All this keeps you from pain relief despite the studies that prove
that chronic pain patients do not feel high, or euphoric when taking opiods. They do not
exhibit the usual benefits that someone who takes a drug for fun will experience; they
simply experience less pain and are able to function within society.
This
brings up the dependency issue, if you are not addicted, but dependent on a drug it is
just as bad. Wrong again! You can be dependent on your glasses, you are not addicted to
them, but you sure lead a better life when you can see where you are going. Is a diabetic
addicted to insulin? No, but they are dependent on it, they need it to survive and have a
quality life. You can depend on a drug to insure a better quality of life; this does not
mean you are addicted.
Why
are doctors reluctant to prescribe? Let’s toss our government into the mix; their
stand on the issue has caused the majority of care providers to back away from the issue.
Many doctors have been under investigation, or arrested for prescribing opioids to pain
patients. As a result fibromyalgia patients and others who suffer with chronic pain will
be left without appropriate pain relief.
If
you are interested in using opioids for pain relief, do the research so you can understand
the controversy and present your case to your care provider in an educated manner.
What
are Opioids?
Opioids are more commonly known as narcotics. They stem from opium, a
natural element that is found in the opium plant. Natural opium has been in use for
hundreds of years, and synthetic opium is now available. Opioids are most widely
prescribed for acute pain, such as having surgery, or having a tooth removed. They can be
used to treat chronic pain if prescribed, and used carefully.
The
most common forms of prescribed opiods:
- oxycodone
- morphine
- fentanyl
Why the Controversy?
There is much debate about both the usefulness and safety over the use
of opioids to treat fibromyalgia pain. The main reason most care providers will not
prescribe opioids is the lack of documented research to show that opioids actually provide
pain relief for fibro patients. Others cite concerns about tolerance and addiction issues
associated with long-term opioid use. Antidotal evidence from fibromyalgia patients show
that opioids can be highly-effective in treating widespread pain and muscle stiffness.
Thanks to the lack of scientific study and the fear of legal repercussions the majority of
doctors shy away from prescribing opiods and fibromyalgia sufferers find it difficult to
get help.
Do Opioids Relieve Fibromyalgia Pain?
The effectiveness of opioids in fibromyalgia pain relief is one of the
key components to the controversy, many patients claim that opioids have given them
significant pain relief, some doctors disagree. However, there is research that shows that
opioids are effective in relieving fibromyalgia pain. A recent study showed that
fibromyalgia sufferers experienced pain relief and a better quality of life from the use
of opioids. It was reported that 38% of the subjects a noticeable reduction in pain, the
subjects also reported less anxiety and depression, less sleep disturbance, increased
mobility and an over all better quality of life.
Do Opioids Cause Addiction?
If we tackle this issue with facts, less than 0.5% of people who are
given opioids for pain become addicted. Is there a risk? Of course some people will become
addicted; it is a sad fact that there are drug users in the world who seek these drugs to
get high, feel good, and to avoid dealing with life’s stressors. Heredity and mental
health issues also play a part in addiction, in these cases opioids help them to feel
high, get away from life. Chronic pain patients will not feel the “high”, they
will only feel a lessening of symptoms and they will be able to work, care for their
family and themselves. We may become dependent on the drug to keep moving, but we will not
become addicted.
How do you ask for Opioids?
Asking your doctor for pain relief can be stressful, you feel like some kind of
trash asking for drugs thanks to media hype, but you can do it in a calm and professional
way.
It is important to provide your doctor with as much information as possible about
your symptoms and their severity. Provide a list of things you have already tried to get
rid of the symptoms, list drugs and therapies tried such as massage, stretching or water
aerobics. Keep a daily log, journal or chart that records your symptoms and their
severity, rate the pain level for each day from 1 to 10, with 10 being the most severe
pain. If you go shopping and carry the bags into the house and then are unable to put the
items away, say so. If taking a shower and washing your hair leaves you in so much pain
you can not go to work, tell them. Make sure they are aware of overlapping conditions you
may be dealing with such as disc disease, diabetic pain, arthritis etc.
Always include a paragraph about your life before the disease infiltrated your
life. If you worked full time, played tennis and rode bikes, say so. Let them know the
pain is keeping you from making a living or leading a decent quality of life with your
family.
My Doctor will not Prescribe Opioids.
Some doctors will not prescribe opioids unless it is an end of life circumstance,
nothing you say will change their mind. The best thing you can do is change care providers
if your insurance allows. You may have used the same doctor for years, you trust and
respect them, but you may have to cut them loose to find a caring doctor who will help, if
your insurance allows. Your quality of life must come first.
Return to Index
Pain Patients Should Not be Punished for Opioid Medication Abuse or
Addiction
Practitioners prescribing opioids for pain should be prepared to
deal with patients' problems in using the medicines, according to a
special report from Pain-Topics.org. Patients should not be discharged from treatment if
opioid abuse or addiction occurs. Report
explains how opioids can be continued while medication-misuse problems are addressed.
Newswise - "Any practitioner prescribing opioids for chronic use should be
accountable for having a strategy in place if medication
abuse or addiction occurs," says Peggy Compton, RN, PhD. "Providing daily opioid
pain relievers without suitable addiction expertise or
support in place puts both the pain-management practitioner and patient at risk for poor
outcomes."
Unfortunately, the common practice of discharging patients from opioid therapy when there
are concerns about substance abuse or
addiction can do significant harm; not just to patients, but also affecting their
families, the healthcare system, and society at
large. Such practice should be avoided, Compton urges.
Compton is an Associate Professor of Nursing at the UCLA School of Nursing, Los Angeles.
Her report, exclusively for Pain Treatment
Topics and published at the Pain-Topics.org website - "Should Opioid Abusers Be
Discharged From Opioid-Analgesic Therapy?" - can be
accessed atS http://pain-topics.org/clinical_concepts/comments.php#Compton
In her report, Compton stresses that instead of denying patients their pain-relieving
opioids, working partnerships between addiction
and pain specialists should be developed, with the pain practitioner continuing treatment
for pain while also playing a role in addiction
treatment. This does not require the pain-management practitioner to become an addiction
specialist; however, pain practitioners should be
involved in, rather than draw away from, addiction treatment for their patients with
chronic pain who have need for such services.
Important suggestions in the report include:
# It is very difficult to identify true addiction in patients with chronic pain.
# Patients taking opioids every day should be monitored for signs of drug abuse or
addiction.
# If opioid-use problems arise, and are accurately assessed, substance-abuse treatment
strategies should become part of the pain
treatment plan.
# Pain practitioners should stay involved, since there is a lack of special services for
treating patients with both pain and addiction.
# Pain practitioners can support a patient's addiction recovery by encouraging attendance
at 12-step programs, limiting the patient's
access to opioid medicines, and monitoring the patient's mental health status.
Such participation by pain practitioners not only enhances therapy for chronic pain but
provides them a unique opportunity to help stem
the significant public health problem of opioid abuse and addiction. In this report,
Compton outlines specific steps for any healthcare
provider to follow.
Pain Treatment Topics and the associated Pain-Topics.org website provide open and free
access to noncommercial, evidence-based
clinical news, information, research, and education on the causes and effective treatment
of the many types of pain conditions. It is
independently produced and currently supported by an unrestricted educational grant from
Covidien/Mallinckrodt Inc., St. Louis, MO, a
leading manufacturer of generic opioid analgesic products.
© 2008 Newswise. All Rights Reserved.
Return to Index
Cymbalta (Duloxetine) shows efficacy in fibromyalgia with or without concurrent
major depression
By Janis Kelly
Cymbalta
is a drug that inhibits both norepinephrine and serotinin reuptake. It is currently
marketed for depression and has showns a significant improvement in fibromyalgia symtpoms.
This effect was independent of whether or not the patient had major depression.
This
was a double-blind, placebo-controlled trial involving 207 patients, and it was sponsored
by the manufacturer.
I
would say the weight of the evidence shows that duloxetine leads to sustained relief of
pain, especially in the female subjects, who improved on all pain outcomes," said
principal investigator Dr Lesley M Arnold (University of Cincinnati College of Medicine,
OH) .
"Are
we on the brink of a new era of fibromyalgia syndrome management?" According to Dr.
Geoffrey Littlejohn "The future does seem positive in regard to significant
improvement in FMS symptoms with these new potential therapies. However, it is wise to
continue to reflect on the FMS process and to recognize that social and psychological
factors, even everyday life stressors, can dramatically affect FMS neurobiology."
The
duloxetine study is part of an effort to improve on results with tricyclic
antidepressants, which are widely used in FM in doses lower than those typically used in
mood disorders, Arnold et al explain. The tricyclics produce some improvement in
FM-related fatigue and in sleep, overall well-being, and pain severity but have less
effect on tenderness. These drugs reduce both NE and 5-HT reuptake but also have varied
effects on choloinergic and histamine activities and on other mechanisms that modulate
pain.
Separating
out the effect on reuptake inhibition has not been useful. Targeted inhibition of NE
reuptake with venlafaxine (Efexor, Wyeth) and selective inhibition of 5-HT reuptake with
fluoxetine (Prozac, Eli & Lilly Co) have both been relatively ineffective in FM
The duloxetine study combines both approaches by using a combination reuptake inhibitor to
elevate levels of both NE and 5-HT, but without the other effects of the tricyclics.
The
multicenter study enrolled 207 subjects meeting the American College of Rheumatology (ACR)
criteria for primary fibromyalgia. Patients were randomized to placebo (n=103, including
92 women) or to duloxetine 60 mg bid (n=104, including 92 women). In the placebo group,
42/103 patients had major depressive disorder. In the duloxetine group, 37/104 patients
had major depressive disorder.
The
double-blind treatment phase continued for 12 weeks and included weekly visits for the
first 2 weeks, then visits every 2 weeks.
Significant
improvement on most FM symptoms
I
would say the weight of the evidence shows that duloxetine leads to sustained relief of
pain, especially in the female subjects, who improved on all pain outcomes.
The
2 primary outcome measures were pain severity as measured by the Fibromyalgia Impact
Questionnaire (FIQ) pain item and the FIQ total score, reflecting the overall impact of
FM. Secondary end points included the FIQ items for fatigue, morning tiredness, and
stiffness, and tender point assessment.
Other
secondary end points were the Clinical Global Impressions of Severity scale, the Patient
Global Impression of Improvement scale, the Brief Pain Inventory (short form), the Beck
Depression Inventory, the Beck Anxiety Inventory, the Medical Outcomes Study Short Form 36
(SF-36), the Quality of Life in Depression Scale, and the Sheehan Disability Scale. All of
them were assessed on an intention-to-treat analysis.
"The
FIQ score was improved at week 12. Only the FIQ pain score was not significantly improved
at week 12, although it was improved at week 4. Another pain score, the Brief Pain
Inventory, was significantly improved at week 12, as was the SF-36 bodily pain score.
Furthermore, the female subjects improved on all pain outcomes (including the FIQ pain
score) at week 12," Arnold tells rheumawire.
There
was a striking improvement in the FIQ total score for the entire duloxetine group, which
became significant at week 4 and continued through week 12 (p=0.027). The group difference
in the other primary end point, the FIQ pain score, became significant at week 4 but was
not significant at week 12 (p=0.130). Response rates, defined as a <50% decrease in FIQ
pain score, were 27.7% for duloxetine vs 16.7% for placebo at week 12 (p=0.06).
Arnold
points out that the improvement in tender point measures was particularly important, since
previous studies using tricyclic antidepressants found little improvement in tender
points.
The
duloxetine-treated patients also had significant improvements in general activity, mood,
walking ability, normal work, sleep, and enjoyment of life, as measured on the Brief Pain
Inventory.
Equally
effective in patients without depression
Duloxetine
was equally effective in patients with or without major depressive disorder, Arnold notes.
"I was not surprised that the improvement in fibromyalgia symptoms with duloxetine
was independent of the presence or absence of depression. Duloxetine may have an effect on
the descending pain pathways that involve serotonin and norepinephrine that is independent
of its effect on mood."
Although
the numbers are small, the data also suggest that there may be a sex difference in
response to duloxetine for FM. The investigators found that duloxetine-treated women
improved significantly more than placebo-treated women on both the primary and secondary
end points, while male subjects treated with duloxetine did not have significantly better
responses than the placebo-treated men on either primary or secondary efficacy measures.
"I
was surprised by the lack of effect in men. I think the power was not great enough to show
an effect in men. We need to study a larger group of men before coming to any firm
conclusion about duloxetine in the treatment of men with fibromyalgia," Arnold says.
Return to Index
Merck to Enter a Venture for Pain Drugs
By
ANDREW POLLACK
Merck & Company, stung by the withdrawal of Vioxx from the market, will enter a
collaboration to develop new painkilling drugs with Neuromed
Pharmaceuticals, a privately held biotechnology company.
In a deal that is expected to be announced today, Merck will pay an initial $25 million to
gain the exclusive rights to Neuromed's family of drugs for
chronic pain. The most advanced of the drugs, NMED-160, has entered midstage clinical
trials. Merck would pay Neuromed an additional $202 million if NMED-160 wins approval
worldwide. If NMED-160 is approved for a second use, and another drug is approved for two
uses, payments would reach $450 million. Janet Skidmore, a spokeswoman for Merck, said the
deal was not an attempt to replace Vioxx, which was withdrawn from the market after it was
found to raise the risk of heart attacks.
Rather, she said, Merck has identified pain as one of the nine medical treatment areas in
which it is focusing. The company already has two other
pain drugs in Phase 2 trials, and one in Phase 1. Neuromed's drugs are made to interfere
with the transmission of pain signals by blocking the influx of calcium ions into nerve
cells. "We think these have the potential to become very powerful agents for chronic
pain, on the level of morphine,"
Christopher Gallen, the chief executive of Neuromed, said in an interview.
The first drug that works by that mechanism, Prialt from the Elan Corporation, won Food
and Drug Administration approval in December 2004 for
use by patients who do not get relief from other analgesics. But because Prialt can cause
severe side effects including heart problems and
hallucinations, it must be delivered directly into the fluid surrounding the spinal cord
by a catheter and implanted pump. Sales in 2005 were only $6.3
million.
NMED-160, by contrast, is taken orally. Dr. Gallen said animal studies suggested the drug
did not share Prialt's problems and could have fewer side
effects than morphine. But more extensive testing is required, so the drug is not likely
to reach the market until early next decade, he said. Neuromed has offices in Vancouver,
British Columbia, and Conshohocken, Pa.
Copyright 2006 The New York Times Company
Return to Index
Sodium Oxybate May Reduce Fibromyalgia Pain New
SAN
DIEGO, CA -- February 24, 2006 -- The sleep aid sodium oxybate (Zyrem) may also help
reduce pain, tenderness, and chronic fatigue
from fibromyalgia, according to a preliminary study presented here February 23rd at the
22nd Annual Meeting of the American Academy of
Pain Management (AAPM). No drugs are currently approved by the U.S. FDA for the treatment
of fibromyalgia.
"Fibromyalgia is notoriously refractory to treatment," said lead investigator
Patrick B. Wood, MD, assistant professor of family
medicine at the Louisiana State University Health Sciences Center in Shreveport,
Louisiana.
The researchers hypothesized that sodium oxybate would regulate neurotransmitter levels
required for normal sleep cycles, which are
frequently disrupted during stage III and IV sleep in people with fibromyalgia.
"This study demonstrates a pretty novel application of this drug," said Dr.
Wood, but he acknowledged that some clinicians have used the
drug off label for fibromyalgia.
In the double-blind, multicenter study, 150 fibromyalgia patients were randomized to
receive 4.5 g or 6 g of sodium oxybate or placebo.
They filled out a daily electronic diary reporting pain and fatigue visual analog scale
scores as well as rescue medication use. Other
measures of sleepiness, function, and global impression were recorded at office visits
throughout the 27-day study.
Both doses of the drug resulted in significant reductions in pain, fibromyalgia impact
scores, and patient-reported change in global
impression scores compared to placebo.
There was a strong trend toward significant reductions in tender point count and tender
point index. The sodium oxybate group reported
1.5 fewer tender points on average and about a 3-point reduction in tender point index
score compared with the placebo group. Sleep
scores were about 2 points lower on average for the active treatment arm.
There was a dose-dependent increase in nausea, vomiting, headache, and dizziness for
patients receiving
sodium oxybate compared with those who received placebo.
The authors cautioned that this is preliminary, proof-of-concept data. They are currently
designing further studies to determine
sodium oxybate's efficacy in treating fibromyalgia.
Orphan Medical, a subsidiary of Jazz Pharmaceuticals, sponsored this study.
[Presentation title: A Randomized, Double-Blind, Placebo-Controlled,
Parallel-Group, Multi-Center Trial Comparing the Effects of Orally
Administered Xyrem (Sodium Oxybate) With Placebo for the Treatment of
Fibromyalgia.
Return to Index
Duloxetine Reduces Fibromyalgia Pain: Presented at AAPM
By
Crystal Phend SAN DIEGO, CA -- February 27, 2006 -- The antidepressant duloxetine
(Cymbalta) appears effective in treating
pain and improving quality of life compared to placebo in women with fibromyalgia,
researchers said here February 23rd at the 22nd Annual
Meeting of the American Academy of Pain Management (AAPM).
"There are no approved drugs for fibromyalgia," said presenting author Michael
J. Detke, MD, PhD, medical director for Cymbalta at
Lilly Research Laboratories, Indianapolis, Indiana. "It's a significant medical
problem."
Although the same serotonin and norepinephrine systems responsible for depression are
dysfunctional in patients with fibromyalgia, Dr.
Detke said duloxetine's pain-relieving effect appears independent from its effect on mood.
The researchers presented two randomized, placebo-controlled, double-blind studies of
women with fibromyalgia according to the
American College of Rheumatology criteria and significant pain (an intensity of at least 4
on the Fibromyalgia Impact Questionnaire or
Brief Pain Inventory). Twenty-five to 40% of the patients had a current major depressive
disorder and all baseline characteristics
were similar between treatment arms.
In the first study, 92 women received 60 mg of duloxetine twice daily while another 92
received placebo. In the second study, 118 were
randomized to 60 mg of duloxetine once daily, 116 to a dose of 60 mg twice daily, and
another 120 to placebo.
Average pain scores were significantly lower by about 1 point in both studies for the
duloxetine groups compared with placebo, but there
was no difference between once and twice daily dosing groups in the second study. Both
studies showed significantly greater percentages
of patients achieving a 50% reduction in pain on duloxetine versus placebo, which Dr.
Detke called a "pretty robust" finding.
Fatigue and rest scores showed similar significant reductions in the second study for
duloxetine versus placebo. The reductions were not
significant in the first study.
Patients with and without major depressive disorder experienced the same significant
reduction in pain compared to placebo. No
significant interaction between pain alleviation and depression was found in either study.
The authors concluded that duloxetine was safe and effective in treating fibromyalgia
pain.
[Presentation title: Duloxetine in the Treatment of Fibromyalgia in
Women -- Results from Two Clinical Trials.
Return to Index
Cough Drug May Help Fibromyalgia Pain
Findings
Could Affect Other Chronic Pain Conditions By Salynn Boyles WebMD
Medical News Reviewed By Brunilda
Nazario, MD on Monday, May 23, 2005
May
23, 2005 -- An ingredient found in over-the-counter cough medicines may help ease the pain
of fibromyalgia, according to new research from the University of Florida.
Fibromyalgia
patients who took dextromethorphan experienced temporary reductions in the intensity of
pain associated with minor repetitive physical contact -- a common characteristic of the
poorly understood disease.
Researchers
say the findings may have broader implications for the treatment of a host of chronic pain
conditions. But they added that patients should definitely not self-medicate with
over-the-counter drugs containing dextromethorphan.
"We
are not telling people to try cough medicine to relieve their fibromyalgia pain,"
researcher Roland Staud, MD, tells WebMD.
Staud
characterized the pain-relieving impact of the drug as "moderate." But he added
that dextromethorphan or similarly acting medications may prove to be important additions
to current treatments for fibromyalgia and other conditions involving heightened pain
sensitivity.
Constant,
Chronic Pain
It
is estimated that as many as 10 million Americans have fibromyalgia -- a baffling disease
that strikes mostly women and is characterized by pervasive pain, stiffness, fatigue, and
muscle tenderness.
While
the cause of fibromyalgia remains unknown, it is now thought that a mechanism known as
central sensitization plays a major role in the disease. The theory is that the brain and
spinal cord magnify pain signals to abnormally high levels.
Fibromyalgia
patients often experience pain to stimuli that are not normally perceived as painful, such
as a pat on the back. The pain can get worse with repeated contact.
Dextromethorphan
has been shown to block the action of chemicals that relay pain to the spinal cord. It
works by blocking a receptor known as N-methyl-D-aspartate or NMDA, which responds to
these pain-transmitting chemicals. For this reason, Staud and colleagues evaluated the
drug for pain control in fibromyalgia.
They
found that people with fibromyalgia treated with dextromethorphan experienced moderate
improvement in pain associated with repeated physical contact compared with those who got
placebo treatments.
Better
Drugs Needed
Staud
tells WebMD that pharmaceutical researchers are working to develop more effective drugs
that target the NMDA receptor with fewer side effects than the medications that are now
available.
He
estimates that these drugs could be commercially available within three to five years and
could eventually be major players in pain control.
NMDA-receptor
blockers like dextromethorphan have already been shown to improve pain control when given
with morphine and other widely used opium-based medications. The hope is that combining
the two drugs will allow a lower dose of the opioids to be used to control pain.
Fibromyalgia
expert Laurence Bradley, PhD, agrees that more research is needed before doctors or their
patients turn to dextromethorphan for pain control.
"It
would be a disservice to start to recommend that either patients or physicians begin
experimenting right away with dextromethorphan, because I think there are some important
questions about how to minimize the side effects [of the drug]," he says.
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There is finally a generic version of the fentanyl Pain patch. Just approved.
LOS ANGELES (Reuters) - U.S. regulators approved the first generic rival to Johnson &
Johnson's Duragesic pain relief skin patch, the U.S. Food and Drug Administration said on
Friday.
Mylan Laboratories Inc. said it will produce several different strengths of the patch,
known generically as the fentanyl transdermal system, and launch the product immediately.
Johnson & Johnson's annual sales of the patch total about $1.63 billion. Mylan, the
biggest U.S. maker of generic drugs, had hoped to launch its copycat version last year,
but the FDA (news
- web
sites) granted J&J an additional six months of market exclusivity in return for
testing the drug's safety and effectiveness in children. Shares of Mylan, which fell 4
cents to close at $16.60 on the New York Stock Exchange (news
- web
sites), were higher at $17 after hours. Shares of J&J, which rose 40 cents to
close at $64.62, were little changed after hours. (Additional reporting by Deena Beasley
in Los Angeles)
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Oxygenol on Chronic Fatigue and Fibromyalgia
RENO,
Nev., May 12, 2005 (PRIMEZONE) -- Martin Nutraceuticals Inc.'s (Pink Sheets:MTNU) Director
of Research and Development, Dr. A. W. Martin, is pleased to announce results of recent
clinical trials of Oxygenol(tm) in the aid of Chronic Fatigue Syndrome and Fibromyalgia.
Oxygenol(tm)
is a proprietary blend of antioxidants with many health benefits. In the study,
Oxygenol(tm) was given to patients suffering from Chronic Fatigue Syndrome and
Fibromyalgia. These two conditions are characterized by extreme fatigue and cognitive
symptoms which include sleep disorder, short term memory loss, concentration difficulties,
widespread musculoskeletal aches, pain and stiffness and soft tissue tenderness.
Dr.
Martin states, "Fibromyalgia is a symptom of the greater complex of Chronic Fatigue
Syndrome -- one that perhaps should be considered a sister ailment."
The
test patients were given 200 mg daily of Oxygenol(tm) in a 6-week period. In this amount
of time, over 3/4 of the patients showed that 85% of all cognitive symptoms were decreased
and remarkably 1/4 of these cases showed over 95% improvement of all cognitive symptoms
with the use of Martin Nutraceuticals Oxygenol(tm). The tests that were used included
Short Term Memory Testing using recall and concentration, as well as Cognitive Testing.
Dr.
Martin attributes these findings to Oxygenol's ability to cross the blood brain barrier
and increase micro circulation to the brain. "Oxygenol's efficacy is what makes it a
fantastic product, one that we anticipate will prosper in a market that does more than $1
billion in annual sales," concurs Dr. Martin.
Dr.
Martin is a Canadian nutritional researcher and author of several books including
"Chronic Fatigue Syndrome: the Modern Women's Curse."
Martin
Nutraceuticals' Oxygenol(tm) will be available in exclusive retail outlets by the third
quarter of this year.
Forward-Looking
Statements
The
management of the company, who take full responsibility for its content, prepared this
press release. Statements in this news release concerning the company's business outlook
or future economic performance, anticipated profitability, revenues, expenses, or other
financial items, and statements concerning assumptions made or expectations as to any
future events, conditions, performance or other matters, are "forward-looking
statements" as that term is defined under the Federal Securities Laws.
Forward-looking statements are subject to risks, uncertainties and other factors which
could cause actual results to differ materially from those contained in such statements.
Such risks, uncertainties and factors include, but are not limited to, future capital
needs, changes and delays in product development plans and schedules, customer acceptance
of new products, changes in pricing or other actions by competitors, and general economic
conditions.
CONTACT:
Martin Nutraceuticals Inc.
Harvey Panesar, President
(780) 707-0587
www.martinnutra.com
Return to Index
Atypical antipsychotics in the treatment of fibromyalgia: a case series with
olanzapine
Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):161-4.Rico-Villademoros F,
Hidalgo J, Dominguez I, Garcia-Leiva JM, Calandre EP.
Biometrica, Departamento Medico, Eloy Gonzalo 27, 28010 Madrid, Spain.
Fibromyalgia is a common and disabling chronic pain syndrome. Although a wide array of
symptomatic pharmacological treatments has been used to treat this condition, only modest
results have been obtained. Olanzapine has been proven effective in some chronic pain
conditions. The authors present a case series of patients suffering from fibromyalgia who
received olanzapine as add-on therapy during a 3-month period. Olanzapine (2.5-20.0
mg/day) was administered to 25 consecutive patients (24 females, 1 male) meeting the
American College of Rheumatology diagnostic criteria for fibromyalgia, and who were
receiving nonsteroidal anti-inflammatory drugs (NSAIDs; 68%), benzodiazepines/zolpidem
(48%), antidepressants (32%), and cyclobenzaprine (4%), either alone or in combination.
Overall, 6 of the 14 patients (43%) who completed the 12-week trial reported to be much or
very much improved ('responders'), according to the Clinical Global Impression (CGI) scale
and 7 of them (50%) reported a good or very good sense of well-being. Olanzapine's modal
dose among responders was
10.0 mg/day. It was discontinued in 11 patients (44%) due to adverse reactions, most
commonly weight gain (n=5, 20%). Our preliminary findings suggest a possible role for
olanzapine in treating fibromyalgia. Unfortunately, the beneficial
outcome of olanzapine was largely obscured by its poor tolerability, which could be
explained by the greater propensity of patients with fibromyalgia toadverse drug
reactions, and the greater risk of antipsychotic-induced weight gain among women. Whether
other atypical antipsychotics will provide similar symptomatic relief, while showing a
better tolerability profile than olanzapine in patients with fibromyalgia, should be
further investigated.
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A fatal drug interaction between oxycodone and clonazepam.
Burrows
DL, Hagardorn AN, Harlan GC, Wallen ED, Ferslew KE.
Section
of Toxicology, Department of Pharmacology, James H. Quillen College of Medicine, East
Tennessee State University, Johnson City,TN 37614, USA. toxdoc2b@yahoo.com
A
case is presented of a fatal drug interaction caused by ingestion of oxycodone (Oxycontin)
and clonazepam (Klonapin). Oxycodone is an
opium alkaloid used in long-term pain management therapy. Clonazepam is a benzodiazepine
used for the treatment of seizures and panic
disorders. The Drug Abuse Warning Network (DAWN) has reported an increase of 108% in the
last two years of emergency department
episodes related to Oxycontin. Six billion prescriptions were written for Oxycontin in the
year 2000, an 18-fold increase from
four years previous (1). Oxycontin has recently gained enormous notoriety at the local and
national levels; however, there are very
few previously documented cases of lethal drug interactions between oxycodone and
clonazepam. Synergistic effects between these two
drugs are postulated to arise from different agonistic mechanisms producing similar
physiological changes. It is also theorized that
clonazepam may inhibit the metabolism of oxycodone. A 38-year-old white female was found
dead in Jefferson County, Tennessee in March
of 2001. The deceased had physical evidence of previous drug abuse and positive
serological findings of hepatitis B and C. Prescription
pill bottles filled under the name of the deceased, as well as another name, were found
with the body. Serum, urine and gastric
contents from the deceased were screened for numerous drugs and metabolites using a
combination of thin layer chromatography and
immunoassay techniques (EMIT and FPIA).
Analysis
of biological specimens from the deceased revealed the presence of: benzodiazepines,
opiates (oxycodone), and trazodone metabolites in
the serum; cannabinoids, benzodiazepines, opiates (oxycodone), trazodone, trazodone
metabolites, nicotine, and nicotine metabolite
in the urine; and benzodiazepines, opiates (oxycodone), nicotine, and nicotine metabolite
in the gastric contents. Quantitative
analyses for clonazepam was performed by high performance liquid chromatography (HPLC) and
revealed a plasma concentration of 1.41
microg/mL. Plasma oxycodone and urine 11-nor-carboxy-delta-9-tetrahydrocannabinol
concentrations were
determined by gas chromatography/mass spectrometry and revealed concentrations of 0.60
microg/mL and 27.9 ng/mL, respectively. The
deceased had pathologies consistent with severe central nervous system (CNS) and
respiratory depression produced by high
concentrations of clonazepam and oxycodone including collapsed lungs, aspirated mucus, and
heart failure. The pathologies were
sufficient to cause death, which was officially attributed to a drug overdose; however,
the manner of death was unknown.
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Painkiller Users: Heartburn Pill a Day Keeps Ulcers Away
ANN
ARBOR, MI - For those who take certain painkiller drugs regularly to help ease arthritis
pain or other chronic aches, the relief comes with a tradeoff: a quadrupled chance of
developing painful ulcers over the long
term, as their digestive systems brim with acid that erodes the lining of their stomachs
and upper intestinal tract.
But
a new study may offer a promising way to prevent this unwelcome effect.
In
an international, multicenter, randomized, placebo-controlled study, a prescription
heartburn drug called esomeprazole effectively prevented ulcers among 573 long-term
painkiller users. And, it produced few side effects.
“This
is a very encouraging result, especially since the participants represented the ‘real
world’ population that faces this ulcer risk,” says James Scheiman, M.D., a University of Michigan Health System
gastroenterologist who will present the results Tuesday in Baltimore at the 68th Annual
Scientific Meeting of the American
College of Gastroenterology. “The effect was strong in participants taking
over-the-counter painkillers, as well as in those taking prescription Cox-II inhibitor
drugs.”
Esomeprazole,
which is marketed as Nexium® (esomeprazole magnesium) by Astra Zeneca Pharmaceuticals LP, is a member of the
class of acid-reducing drugs known as proton pump inhibitors. It blocks the production and
secretion of gastric acid.
Astra
Zeneca funded the study, and Scheiman is a paid member of the panel that advised the
company on the study, as well as presenter of the ACG presentation. Scheiman is also a
paid consultant to Astra Zeneca on other research, on which he serves as principal
investigator.
The
study results show that ulcers and other effects can be prevented by countering the acid
that increases the injury to the gastrointestinal tract that can be caused by use of
non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen, naproxen, and
Cox II inhibitors, all commonly used to treat chronic pain.
The
study participants were three-quarters women, and more than 80 percent were taking NSAIDs
for some form of arthritis. Although all had screened negative at the study’s outset
for the bacteria Helicobacter pylori that causes ulcers, they were all at an increased
risk of developing ulcers because of their regular painkiller use combined with a history
of previous ulcers (about 26 percent), an age over 60 years (about 64 percent), or both
(about 10 percent).
The
study was done in this group of patients to represent more accurately the “real
world” mix of drugs, medical histories and risk factors seen in millions of patients
worldwide, says Scheiman, a professor of internal medicine in the U-M Medical School.
All
of the participants were taking NSAIDs at least five days a week, either one drug alone or
in combination. Around 15 percent were taking Cox II inhibitors (such as celecoxib,
marketed as Celebrex, or rofecoxib, marketed as Vioxx). Some were also taking aspirin at
doses designed to protect their cardiovascular systems.
Previous
studies have shown that about 10 percent to 30 percent of such patients might develop
ulcers in a given year. And in fact, among those in the study who received a placebo
instead of esomeprazole, 12.3 percent developed either a gastric ulcer or duodenal ulcer
in the six months of the study.
But
the ulcer rate was 5.2 and 4.4 percent, respectively, for non-Cox II inhibitor NSAID users
who received either 20 milligrams or 40 milligrams of esomeprazole daily.
In
the small subgroup of patients who were using Cox II inhibitors, 17 percent taking placebo
pills developed ulcers. And although the group was not large enough to achieve statistical
significance, none of those patients on either dose of esomeprazole developed ulcers
during the study.
This
last result intrigues Scheiman, who notes that clinicians may want to take note even
before further studies are conducted to evaluate whether a Cox II inhibitor-proton pump
inhibitor combination might be the best option for such patients.
In
addition to being effective at preventing ulcers and other effects, esomeprazole was safe
and well-tolerated. Only 6 percent of patients receiving it stopped taking the drug during
the study because of any adverse event, compared with 13 percent of placebo patients.
In
all, Scheiman notes, the results should give hope to any patient who needs to take
painkillers regularly. “With these data, and results from other studies, we can say
that we have a way to prevent ulcers and other gastrointestinal effects, in long-term
NSAID users,” he says. “There doesn’t have to be a tradeoff between one
kind of pain and another.”
The
study’s main authors include Neville Yeomans of the University of Melbourne,
Australia; Christopher J. Hawkey of the University of Nottingham, United Kingdom; Nicholas
Talley of the Mayo Clinic, Rochester, Minnesota; Joseph Sung of the Chinese University of
Hong Kong; Roger Jones, London, and Lena Gothe and Jorgen Naesdal, Astra Zeneca, Molndal,
Sweden. Written by: Kara Gavin
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The trilateral
opioid contract. Bridging the pain clinic and the primary care physician through the
opioid contract.
Fishman SM, Mahajan G, Jung SW, Wilsey
BL. Department of Anesthesiology and Pain Medicine, University of California, Davis, CA,
USA
We have extended the traditional use of opioid contracts to involve the primary care
physician (PCP). The PCP was asked to collaborate with the
pain specialist's decision to use opioids by cosigning an opioid contract. Explicit in the
agreement was the understanding that the
primary care physician would assume prescribing the refills for these medications once the
opioid regimen had become stabilized. The present
study was a retrospective chart review of the first 81 patients with non-malignant chronic
pain who received an opioid agreement requiring
the participation of the primary care physician. Sixty-nine of the 81 patients (85%)
agreed to the terms of the contract
initially, but only 50 of these 69 individuals (72%) successfully obtained their PCP's
written agreement for the prescribing of opioids
for chronic pain management.
Despite expecting reluctance on the part
of the PCP to enter into this agreement, the low compliance rate was due to
lack of commitment on the part of the patient, who either refused to sign the contract
outright or, after initially agreeing to sign the
contract, did not have it signed by the PCP. If the PCP did not agree to sign the opioid
contract, the patient was tapered off the medication. If
the contract was approved and signed by the PCP, there were no subsequent reversals by
this physician in terms of agreeing to continue
to prescribe opioids. In all cases in which a contract was completed, the patient was
successfully stabilized on an appropriate opioid regimen
and then discharged back to the care of the PCP for long-term opioid treatment. The opioid
contract may be an effective tool for networking
specialty and primary care services in the delivery of chronic opioid therapy.
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Off-label
applications for SSRIs.
Am Fam Physician. 2003 Aug 1;68(3):498-504. Stone KJ, Viera AJ, Parman CL. Naval Hospital
Jacksonville, Florida 32214, USA. PMID: 12924832
Selective serotonin reuptake inhibitors (SSRIs) are widely used because of their safety,
tolerability, and demonstrated efficacy across a broad range of clinical conditions.
Medical literature supports the use of SSRIs for the treatment of many conditions outside
of the indications approved by theU.S. Food and Drug Administration.
SSRIs offer a reasonable alternative to traditional therapy for generalized anxiety
disorder. A side effect of SSRIs coincidentally provides therapy
for premature ejaculation. SSRIs may reduce the frequency and severity of migraine
headaches and are possibly effective in reducing the pain of
diabetic neuropathy.
When taken in combination with tricyclic antidepressants, SSRis offer more potent therapy
for fibromyalgia than either agent alone. SSRIs appear to be effective in some patients
with neurocardiogenic syncope that is refractory to standard therapies.
Clinical experience supported by ongoing research continues to expand on the broad array
of therapeutic applications for this class of medication.
[The full text of this article can be found at
http://www.aafp.org/afp/20030801/498.html
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United Kingdom Expands Approval
For Provigil (Modafinil) To Include Sleep Apnea/ Hypopnea Syndrome, Narcolepsy
WEST CHESTER, Pa., Dec. 3 /PRNewswire-FirstCall/ --
Cephalon, Inc. (Nasdaq: CEPH) today announced that it has received marketing approval from
the Medicines Control Agency (MCA) in the United Kingdom to expand the label of Provigil®
(modafinil) to treat excessive daytime sleepiness in patients with obstructive sleep
apnea/hypopnea syndrome. The 200 mg tablet of Provigil was also approved, in addition to
the 100 mg dosage currently available in this territory. Cephalon UK Limited will
officially launch the new indication at a symposium during the British Thoracic Society
meeting being held December 4-6 in London.
"We are pleased that the data used to support this label expansion was accepted by
the UK regulatory authority," said Paul Blake, MB, FRCP, Senior Vice President of
Clinical Research and Regulatory Affairs at Cephalon. "Achievement of this milestone
will enable us to grow the market for modafinil in the United Kingdom and sets the stage
for regulatory submissions in other European countries over the next year."
The UK approval is the first of two regulatory milestones that Cephalon expects to achieve
this year for Provigil. Cephalon intends to file an application with the U.S. Food and
Drug Administration at year-end seeking to expand the label of Provigil to include
treatment of excessive sleepiness associated with sleep disorders beyond narcolepsy.
Provigil
Modafinil is the first in a new class of wake-promoting agents and is currently approved
in more than 20 countries for the treatment of excessive daytime sleepiness associated
with narcolepsy. Provigil was initially launched in the UK in 1998 for the treatment of
narcolepsy.
In controlled clinical trials, Provigil has been found to be generally well tolerated with
a low incidence of adverse events relative to placebo. The most commonly observed adverse
events associated with the use of Provigil were headache, infection, nausea, nervousness,
anxiety and insomnia.
Obstructive Sleep Apnea Hypopnea Syndrome
Obstructive sleep apnea/hypopnea syndrome is a serious and potentially life-threatening
sleep disorder affecting four percent of middle-aged men and two percent of middle-aged
women. Individuals with obstructive sleep apnea hypopnea syndrome experience frequent
awakenings throughout the night as a result of blockage of the airway during sleep. This
disruption of sleep leads to excessive daytime sleepiness causing many people to doze off
repeatedly throughout the day -- at their jobs and at home.
The most commonly used standard treatment is continuous positive airway pressure (CPAP). A
nasal CPAP device can prevent airway closure while in use, but despite this treatment many
patients continue to experience residual excessive sleepiness.
Cephalon, Inc.
Founded in 1987, Cephalon, Inc., is an international biopharmaceutical company dedicated
to the discovery, development and marketing of innovative products to treat sleep and
neurological disorders, cancer and pain. Cephalon employs 1,200 people in the United
States and Europe. The company markets three proprietary products in the United States and
22 products internationally. Full prescribing information on Cephalon's US products is
available by calling 1-800-896-5855.
Cephalon's biotechnology pipeline is focused on the identification of novel molecules that
affect cell survival and death. Additional information about Cephalon and its subsidiaries
can be obtained by visiting the company's Website at http://www.cephalon.com
.
Cephalon UK Limited has headquarters in Guildford and markets drugs to treat a number of
central nervous system disorders. In collaboration with Novartis, Cephalon UK markets
Tegretol® (carbamazepine), Ritalin® (methylphenidate), Anafranil® (clomipramine) and
Lioresal® (baclofen). Also included in this collaboration is Provigil (modafinil) for the
UK. In addition, Cephalon UK also markets Gabitril® (tiagabine monohydrate) and Actiq ®
(fentanyl -- as citrate) in the UK and Ireland.
In addition to historical facts or statements of current condition, this press release may
contain forward-looking statements. Forward-looking statements provide Cephalon's current
expectations or forecasts of future events. These may include statements regarding
anticipated scientific progress on its research programs, development of potential
pharmaceutical products, interpretation of clinical results, prospects for regulatory
approval, manufacturing development and capabilities, market prospects for its products,
sales and earnings projections, and other statements regarding matters that are not
historical facts. You may identify some of these forward-looking statements by the use of
words in the statements such as "anticipate," "estimate,"
"expect," "project," "intend," "plan,"
"believe" or other words and terms of similar meaning. Cephalon's performance
and financial results could differ materially from those reflected in these
forward-looking statements due to general financial, economic, regulatory and political
conditions affecting the biotechnology and pharmaceutical industries as well as more
specific risks and uncertainties such as those set forth below and in its reports on Form
8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these
risks and uncertainties, any or all of these forward-looking statements may prove to be
incorrect. Therefore, you should not rely on any such factors or forward-looking
statements. Furthermore, Cephalon does not intend to update publicly any forward-looking
statement, except as required by law. The Private Securities Litigation Reform Act of 1995
permits this discussion.
SOURCE: Cephalon, Inc.
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Gabapentin for the treatment of pain in guillain-barre syndrome: a
double-blinded, placebo-controlled, crossover study.
Pandey CK, Bose N, Garg G, Singh N, Baronia A, Agarwal A, Singh PK, Singh U.
Departments of Anaesthesiology and Critical Care Medicine and Bio-statistics, Sanjay
Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Pain syndromes of Guillain-Barre are neuropathic as well as nociceptive in origin. We
aimed to evaluate the therapeutic efficacy of gabapentin in relieving the bimodal nature
of pain in Guillain-Barre syndrome in a randomized, double-blinded, placebo-controlled,
crossover study in 18 patients admitted to the intensive care unit for ventilatory
support. Patients were assigned to receive either gabapentin (15 mg. kg(-1). d(-1) in 3
divided doses) or matching placebo as initial medication for 7 days. After a 2-day washout
period, those who previously received gabapentin received placebo, and those previously
receiving placebo received gabapentin as in the initial phase. Fentanyl 2 micro g/kg was
used as a rescue analgesic on patient demand or when the pain score was >5 on a numeric
rating scale of 0-10. The numeric rating score, sedation score, consumption of fentanyl,
and adverse effects were noted, and these observed variables were compared. The numeric
pain score decreased from 7.22 +/- 0.83 to 2.33 +/- 1.67 on the second day after
initiation of gabapentin therapy and remained low during the period of gabapentin therapy
(2.06 +/- 0.63) (P < 0.001). There was a significant decrease in the need for fentanyl
from Day 1 to Day 7 during the gabapentin therapy period (211.11 +/- 21.39 to 65.53 +/-
16.17 [ micro g]) in comparison to the placebo therapy period (319.44 +/- 25.08 to 316.67
+/- 24.25 [ micro g]) (P < 0.001). IMPLICATIONS: Gabapentin, an antiepileptic drug, has
been used effectively for different types of pain management. This study demonstrates that
gabapentin has minimal side effects and is an alternative to opioids and nonsteroidal
antiinflammatory drugs for management of the bimodal nature of pain of Guillain-Barre
Syndrome patients.
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EFFICACY OF TRAMADOL IN TREATMENT
OF PAIN IN FIBROMYALGIA.
I. Jon Russell, Marc Kamin, Robert Bennett, Thomas Schnitzer, Jerry Green, Warren Katz.
An outpatient, randomized, double-blind, placebo-controlled clinical trial was conducted
to evaluate the efficacy and safety of tramadol in the treatment of the pain of
fibromyalgia syndrome.
One hundred patients with fibromyalgia syndrome, (1990 American College
of Rheumatology criteria) were enrolled into an open-label phase and treated with tramadol
50-400 mg/day.
Patients who tolerated tramadol and perceived benefit were randomized to
treatment with tramadol or placebo in the double-blind phase. The primary efficacy outcome
measurement was the time (days) to exit from the double-blind phase because of inadequate
pain relief, which was reported as the cumulative probability of discontinuing treatment
because of inadequate pain relief.
One hundred patients entered the open-label phase; 69% tolerated and achieved
benefit with tramadol. These patients were then randomized to continue tramadol (n=35) or
convert to a placebo (n=34) during a 6-week, double-blind treatment period.
The Kaplan-Meier estimate of cumulative probability of discontinuing
the double blind period because of inadequate pain relief was significantly lower in the
tramadol group compared with the placebo (p=0.0001). Twenty (57.1%) patients in the
tramadol group successfully completed the entire double-blind phase compared with nine
(27%) in the placebo group (p=0.15).
These results support the efficacy of tramadol over a period of 6-weeks in a
double blind study for
the treatment of pain of fibromyalgia in a group of patients who had been determined to
tolerate it and perceive benefit. Reference: Journal of Clinical Rheumatology
2000;6:250-257
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OPIOID ANALGESICS IN
FIBROMYALGIA-FOLLOW-UP STUDY OF THERAPY SELECTION,
EFFICACY AND PREDICTORS OF OUTCOMES.
Kip L. Kemple, Northwest Rehabilitation Network; Gregory T. Smith, Progressive
Rehabilitation Association; Julia Wong-Ngan, Oregon Health Sciences University.
Theme: Arthritis and Rheumatic Pain While opioid analgesics have gained acceptance in the
management of non-cancer pain, indications for their use in Fibromyalgia (FM) have not
been defined. We have completed baseline and 12-24 month follow-up
evaluations of 43 patients with FM enrolled in an opioid treatment protocol. Our goal was
to study therapy selection patterns, efficacy and to evaluate whether specific pain or
psychological profiles predict outcome.
Methods: All patients met ACR criteria for FM. Most patients were on low (#22) or moderate
(#13) dose opioids at enrollment. They were allowed to adjust Rx according to pain
severity, balanced with review of risks.
Evaluations included: pain scores (VAS), FIQ, MMPI, Beck or Zung Depression Index, McGill
Pain Questionnaire, SF-36 and diagnostic interview including review of abuse history.
Results: Initial FM morbidity levels were high (SF-36 scores low and FIQs high). Opioid
doses increased in 31 patients, decreased in 3 and were unchanged in 9. Mean dose at FU
was 52 mg Morphine equiv/24 hr with mean increase of 26 mg Meq/24. Benefit was rated as
"good" by 26 patients; "fair" by 16; and "poor" by 1.
Measures of pain, fatigue, function and depression all improved modestly but changes were
not significant. Since outcome changes were small, correlations with other predictive
measures were difficult to assess. MMPI profiles did not correlate with pain or function,
but improvement in function (FIQ) was significant (p<.05) in patients with abuse
history. Affective and sensory pain descriptors (McGill) correlated with greater pain
severity, higher FIQs, higher opioid doses and with less benefit (p<.05).
Conclusion: Pain in FM is complex. Response to opioids is variable. Evaluation of
affective and sensory pain domains may help predict outcome. Disclosure: This project was
supported in part by Purdue Pharma.
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Addiction?
Tolerance? Dependency? New stance on using pain drugs.
Three major medical societies, The American Academy of Pain Medicine (AAPM), the American
Pain Society (APS), and the American Society of
Addiction Medicine (ASAM) have issued a joint consensus paper which clearly defines the
frequently misunderstood terms addiction, tolerance,and physical dependence, and discusses
their definitions in the context of opioid use in the treatment of pain.
"The addiction community was concerned because of inaccurate diagnosis. The pain
community was concerned about over-diagnosis of addiction when it didn't exist, and how
this misdiagnosis interfered with treatment with opioids," said Edward Covington, MD,
Director of the Chronic Pain
Rehabilitation Program at the Cleveland Clinic and past president of AAPM, who was one of
the paper's authors. "Also we needed agreement about what is and what is not an
addictive disorder."
Dr. Covington noted that addiction a primary, chronic, neurobiologicdisease can be
identified by the three "Cs" Craving or Compulsive use,loss of Control, and
use despite adverse Consequences.
Other behaviors that signal addiction include "drug seeking" behavior, taking
multiple doses of medications, and an inability to take them on
schedule, "doctor shopping," frequent reports of lost or stolen prescriptions,
isolation from friends and family members, and taking pain
medications for sedation, increased energy, or to get "high."
Physical dependence and tolerance are often confused with addiction.
According to the consensus paper definitions, both of these are normalresponses to regular
use of some prescribed medications, including opioids,and are not in themselves evidence
of an addictive disorder.
"Unlike tolerance and physical dependence, addiction is not a predictable effect of
[taking] a drug but an adverse reaction in biologically and psychosocially vulnerable
individuals."
It is also important for healthcare professionals to recognize the difference between true
addiction and "pseudoaddiction," notes Albert Ray, MD, President of AAPM.
With pseudoaddiction, patients whose pain is undertreated appear to behave "like
addicts" to get the pain relief they need. They may focus on getting more medication,
for example, and appear to be engaging in drug-seeking behavior. But unlike a person with
a true addictive disorder, however, once their pain is properly managed, these behaviors
stop immediately." (The Pain Connection. Spring 2001; 1-4.)
Return to Index
New Data Suggest Cymbalta® Reduced Pain In Fibromyalgia Patients With
And Without Depression
New
data suggest that patients with fibromyalgia treated with 60mg or 120mg of Cymbalta®
(duloxetine HCl) experienced greater reduction in pain severity beginning one week after
starting duloxetine than those taking placebo (sugar pill), as measured by the Brief Pain
Inventory Average Pain Score (BPI). The study, which included patients with and without
depression, also showed greater improvements in patients taking duloxetine than in those
taking placebo in scores on the Patient's Global Impression of Improvement questionnaire
(PGI I), which measures how the patient has felt overall since beginning to take the
medication. The data were presented today at the 2007 Congress of the International
MYOPAIN Society in Washington, D.C.
At three months, patients treated with 60mg per day or 120mg per day of duloxetine showed
significantly greater reduction in pain and improvement in PGI-I scores compared with
patients taking placebo. At three months, more patients treated with either 60mg or 120mg
of duloxetine showed significantly greater reduction in pain as measured by a 30 percent
improvement in baseline BPI scores (50.7 percent and 52.1 percent, respectively) compared
with patients taking placebo (36 percent).
"Fibromyalgia is a chronic illness, characterized by widespread pain, tenderness and
fatigue. It can also affect the patient's overall emotional health and well-being,"
said I. Jon Russell, M.D., Ph.D., associate professor of medicine at the University of
Texas Health Science Center in San Antonio. "Between 34 percent(1) and 62 percent(2)
of those living with fibromyalgia will experience depression at some point in their lives.
In this study, which included patients with and without depression, duloxetine reduced the
pain associated with fibromyalgia."
Fibromyalgia is estimated to affect 2 percent to 4 percent of the U.S. population(3), the
majority being women. In addition to chronic pain, fibromyalgia patients often have
complaints about cloudy thinking, morning stiffness and overall inability to function in
their everyday lives.
Additional Study Highlights
-- At six months, patients taking duloxetine 60mg or 120mg maintained reduced BPI scores
and patients taking 120mg had improved PGI-I scores compared with those taking placebo.
-- At the end of the six-month trial, more patients treated with both 60mg or 120mg of
duloxetine showed a response to treatment, defined as a 50 percent reduction of baseline
BPI scores (32.6 percent and 35.9 percent of patients, respectively), compared with
patients taking placebo (21.6 percent).
-- Discontinuation rates over six months were similar among the groups (45.3 percent and
46.3 percent for duloxetine 60mg and 120mg patients, compared with 50 percent for
placebo).
Adverse event-related discontinuation was significantly higher in patients taking 120mg
(26.5 percent) but not in the 60mg (15.3 percent) group as compared with placebo (13.2
percent). Discontinuations due to lack of efficacy were not statistically different among
treatment groups.
Adverse events were similar to those seen in prior duloxetine studies. In this study, the
most common adverse events (occurred at a rate of greater than or equal to 5 percent and
at least twice the rate of placebo) included nausea, dry mouth, constipation, somnolence
(sleepiness), fatigue, insomnia, decreased appetite, hyperhydrosis, cough, tremor, rash
and weight increase.
Fibromyalgia sNDA Submitted to FDA
Eli Lilly and Company (NYSE: LLY) also announced today that it recently submitted a
supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA)
for Cymbalta for the management of fibromyalgia. The sNDA submission is based on data from
approximately 1,400 patients in five clinical trials.
"Lack of awareness of fibromyalgia can lead to frustration as patients often see
multiple physicians over a number of years before receiving a formal diagnosis," said
Alan Breier, M.D., vice president for medical and chief medical officer, Eli Lilly and
Company. "This research may help increase recognition of fibromyalgia and offer hope
to those living with this debilitating condition."
About Cymbalta
Serotonin and norepinephrine in the brain and spinal cord are believed to both mediate
core mood symptoms and help regulate the perception of pain. 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 effects on depression and anxiety
symptoms, as well as its effect on pain perception, 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
(MDD), the management of diabetic peripheral neuropathic pain (DPNP) and the treatment of
generalized anxiety disorder (GAD), all in adults (age 18+). Cymbalta is not approved for
use in pediatric patients.
Important Safety Information
Cymbalta is approved to treat major depressive disorder and generalized anxiety disorder
and manage diabetic peripheral neuropathic pain. Antidepressants can increase suicidal
thoughts and behaviors in children, adolescents and young adults. Patients should call
their doctor right away if they experience worsening depression symptoms, unusual changes
in behavior or thoughts of suicide. Be especially observant within the first few months 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® (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, somnolence (sleepiness), dizziness and constipation
-- For GAD: Nausea, fatigue, dry mouth, somnolence (sleepiness) and constipation
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 fibromyalgia, 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.
References
(1) Ahles TA, et al. "Psychiatric status of patients with primary fibromyalgia,
patients with rheumatoid arthritis, and subjects without pain: a blind comparison of
DSM-III diagnoses." American Journal of Psychiatry 1991; 148:1721-1726.
(2) Arnold LM, et al. "Comorbidity of fibromyalgia and psychiatric disorders."
Journal of Clinical Psychiatry 2006; 67:1219-1225.
(3) American College of Rheumatology Web site - http://www.rheumatology.org/public/factsheets/fibromya_new.asp;
visited Aug. 3, 2007.
Article URL: http://www.medicalnewstoday.com/articles/80629.php
Return to Index
Just give me something for the pain
While physicians with experience in prescribing opioids for chronic pain are sometimes
outspoken about their efficacy, many physicians continue to
approach this class of analgesics with trepidation due to concerns that opioids
"inevitably cause addiction or intolerable side effects." Still
others, who do see the benefits of opioids, avoid prescribing them based on fears of
regulatory scrutiny. Within the swirl of this controversy, remains the question of
how effective opioids may be in treating some types of chronic pain. The one
certainty among the questions and opinions is that 40 million Americans each year visit a
doctor for chronic pain due to nonmalignant conditions ranging from back trouble and
arthritis to headaches and fibromyalgia. Moreover, a recent survey revealed that
more than 40% of people with chronic pain are not receiving adequate pain relief.
As a result, specialists in pain medicine and their professional associations are working
to clarify misconceptions and to educate both
colleagues and patients on the benefits of opioid therapy for treating chronic, noncancer
pain.
Russell Portenoy, M.D., Chairman of Pain Medicine and Palliative Care at Beth Israel
Medical Center in New York and James Campell, M.D., Director of the Johns Hopkins
Blaustein Pain Treatment Center, are among the leading pain specialists working to promote
the use of opioids for chronic,
noncancer pain. They are working against a significant history of negative attitudes
and long-held beliefs regarding both the therapeutic and side
effects of opioids. Twenty years ago, recalls Campbell, many physicians opposed
using opioids even in patients with terminal illness. In general,
concerns focused on opioids causing depression, social withdrawal, and impaired thinking
as well as tolerance and unmanageable side effects.
In the 1970s, when oncologists found morphine offered effective pain relief for their
cancer patients and experienced little or no apparent evidence of addiction, sentiments
about opioids for treating pain began to shift. Pharmaceutical companies soon began
marketing timed-release morphine
preparations that delivered the drug slowly rather than in the short bursts of relief
provided by short-acting drugs. The effects of the latter would
wear off in three to four hours and leave patients "counting minutes until the next
dose."
Campbell and Portenoy focus significant attention on educating referring physicians,
particularly primary care physicians. An important topic is the
difference between addiction and physical dependence. Addiction is a psychological
phenomenon manifested as a compulsion to use a drug, despite
adverse and even dangerous consequences. Studies show that, in the absence of a
history of substance abuse, very few pain patients become addicted to their opioid pain
relievers. Physical dependence is the physiological response of the body to
long-term use of a drug. People treated with opioids do become dependent and will
experience withdrawal symptoms if they stop taking the drug abruptly. While
uncomfortable, the symptoms are not life-threatening.
Tolerance - the need for increasingly larger doses of medication to achieve the same level
of pain relief - is a physiological phenomenon that is well
understood. A joint consensus statement issued by the American Pain Society
and the American Academy of Pain Medicine states that "Tolerance .
has not proven to be a prevalent limitation to long-term opioid use." In cancer
patients, it is often found that what appears at first to be
tolerance is actually progression of the underlying disease. Tolerance to some
opioid side effects can be expected. Side effects can largely be
minimized by titrating opioids carefully, starting with a low dose and increasing the
amount gradually until pain relief is achieved and side
effects are tolerable.
The thought leaders in pain medicine are careful to point out that opioids may not be
perfect for every patient with chronic pain. Nathan Rudin,
another Hopkins specialist, from the Division of Physical Medicine and Rehabilitation,
believes that opioids "can be useful tools if you carefully
pick your patients." He adds that criteria for that selection process is still
a matter for discussion. It is also the opinion of pain specialists
that the most effective pain management is a multidisciplinary effort and does not rely on
a single modality or form of treatment. Often pain
medication is combined with physical therapy, psychological counseling, perhaps even nerve
blocks or surgery. The net effect of an
interdisciplinary approach should be to "steer patients back into the normal flow of
life, in addition to reducing their pain."
But despite professional reticence, there are signs of change. Growing numbers of
state medical boards and professional organizations are issuing
guidelines and policies that clarify the use of opioids and reassure physicians that they
can prescribe opioids for pain relief without fearing
sanctions. (Hendricks M. Johns Hopkins Magazine. June, 1999. Available
at Johns Hopkins Magazine website, http://www.jhu.edu/%7Ejhumag/
0699web/pain.html. Accessed on May 19, 2000.)
Return to Index
Pharmacologic Management of Acute and Chronic Pain: Focus on Drug
Interactions and Patient-Specific Pharmacotherapeutic Selection
[South Med J 94(8):756-812, 2001. © 2001 Southern Medical Association]
Robert L. Barkin, MBA, PharmD, Diana Barkin, Departments of Anesthesiology, Family
Medicine, Pharmacology, and Psychiatry, Rush Medical College and The Rush Pain Center at
Rush Presbyterian St. Luke's Medical Center, Chicago, Ill; and The Pain Center of Rush
North Shore, Skokie, Ill
Introduction
Pain is among the most common reasons patients seek medical care. Acute and chronic pain
is debilitating. Recovery is slow, interference with daily
activities occurs, and pain manifests as a decremental change in the patient's quality of
life. This is compounded by societal costs.[1-5]
Acute pain is often associated with an identifiable injury or trauma as a known
antecedent, responds to therapeutic options, and resolves in less than 1 to 3 months.
Chronic pain is more of a treatment challenge because the pathogenesis may be unclear,
with less opportunity to predict the course of recovery. For patients already under great
psychologic and financial stress, such an ambiguous prognosis is devastating. The goal of
the clinician is to provide an opportunity for patients to regain some sense of control
over their lives by providing the most effective pain treatment regimen possible.[1-5]
Pain usually defined as chronic lasts longer than 1 to 3 months or exceeds the typical
recovery time for an initial injury. Chronic pain may be
continuous or episodic or a combination of both. Overall, chronic pain is commonly
accompanied by emotional stress, increased irritability,
depression, social withdrawal, financial distress, loss of libido, disturbed sleep
patterns, diminished appetite, and/or weight loss. Chronic pa |