<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3098"
                     title="CV Events Early in Minorities With SLE (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Rheumatology/Lupus/tb/21805?impressionId=1283458814724"
                     
      &lt;p&gt;Striking racial disparities exist in the age at which patients with systemic lupus erythematosus (SLE) experience cardiovascular events, with minorities faring notably worse, a large study showed.&lt;/p&gt;
&lt;p&gt;Whereas white women with SLE were hospitalized for cardiovascular disease at a mean age of 63.5 years, black women were hospitalized at 53.9 years and Hispanics at 57.5 years (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001 for both), according to Lisabeth V. Scalzi, MD, and colleagues from the Penn State College of Medicine in Hershey, Pa.&lt;/p&gt;
&lt;p&gt;Inhospital cardiovascular mortality also occurred earlier, with black women dying at a mean age of 52.8 years compared with 67.1 years for white women (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), the researchers reported online in &lt;em&gt;Arthritis &amp;amp; Rheumatism&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Ischemic heart disease is the leading cause of death among patients with SLE. Lupus itself can be particularly severe in certain ethnic groups such as African Americans, with earlier onset, longer duration of inflammation, and greater likelihood of renal involvement.&lt;/p&gt;
&lt;p&gt;To see if this disease severity translated into earlier cardiovascular disease and death, Scalzi and her colleagues examined data from the Health Care Utilization Project National Inpatient Sample, which is the largest all-payer inpatient database in the U.S. and includes more than 1,000 hospitals.&lt;/p&gt;
&lt;p&gt;Between 2003 and 2006, there were almost 19 million hospitalizations for non-SLE causes, and 90,444 for SLE.&lt;/p&gt;
&lt;p&gt;As is typically the case, 90% of SLE patients were women.&lt;/p&gt;
&lt;p&gt;Among the SLE group, 55% were white, 28% were black, 12% were Hispanic, 2% were Asian, and 3% were &quot;other.&quot;&lt;/p&gt;
&lt;p&gt;There were 3,627 hospitalizations for cardiovascular causes among women with SLE, and patients&apos; overall mean age was 60.8 years.&lt;/p&gt;
&lt;p&gt;A total of 218 women with SLE died from cardiovascular causes during their hospitalization, at a mean age of 63.4 years.&lt;/p&gt;
&lt;p&gt;Black women with SLE died of cardiovascular disease on average 19.8 years younger than black women without SLE (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001). All the other racial groups also showed a younger cardiovascular death rate for lupus patients: &lt;ul&gt; &lt;li&gt;Asians, by 13.7 years, &lt;em&gt;P&lt;/em&gt;=0.0004&lt;/li&gt; &lt;li&gt;Hispanics, by 12.9 years, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001&lt;/li&gt; &lt;li&gt;Whites, by 12.2 years, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001&lt;/li&gt; &lt;li&gt;Other groups, by 11.9 years, &lt;em&gt;P&lt;/em&gt;=0.07&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;More than half of black women with SLE died before age 55, compared with 17% of whites, 23% of Hispanics, and 22% of Asians.&lt;/p&gt;
&lt;p&gt;Among men with SLE there were 805 admissions for cardiovascular events, at a mean age of 60.4 years.&lt;/p&gt;
&lt;p&gt;Hispanic men were the youngest, at 51.4 years, at the time of hospitalization compared with 63 years for white men (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;Mean age at hospitalization was 52.3 years for black men and 59.2 years for Asians.&lt;/p&gt;
&lt;p&gt;A total of 38 men with SLE died during their hospitalization, 33 of them white, at a mean age of 63.7 years.&lt;/p&gt;
&lt;p&gt;An adjusted logistic regression analysis that controlled for multiple variables found that the following factors were significantly associated with cardiovascular mortality: &lt;ul&gt; &lt;li&gt;Age, OR 1.044 (95% CI 1.034 to 1.055, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Congestive heart failure, OR 2.220 (95% CI 1.606 to 3.070, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001)&lt;/li&gt; &lt;li&gt;Renal failure, OR 3.024 (95% CI 2.240 to 4.083, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Overall, women with SLE were 10.5 years younger than their non-SLE counterparts at the time of hospitalization, and 14.8 years younger when they died of cardiovascular disease.&lt;/p&gt;
&lt;p&gt;And on average, men with SLE were 5.5 years younger than non-SLE men at the time of hospitalization and 11 years younger when they died.&lt;/p&gt;
&lt;p&gt;&quot;Some of the most startling results from this study include the vast age difference between SLE patients and their age-matched controls at the time of cardiovascular death,&quot; wrote Scalzi and colleagues.&lt;/p&gt;
&lt;p&gt;Because many cardiovascular risk factors are modifiable, the authors noted that&lt;strong&gt; &lt;/strong&gt;active risk management should be targeted to patients with SLE, and particularly to blacks and Hispanics.&lt;/p&gt;
&lt;p&gt;&quot;Studies are warranted in ethnically diverse lupus populations to examine the success in addressing risk factor management and what barriers may exist in optimizing risk factor management, and whether there are specific racial disparities in prescription habits, adherence to prescribed medications, optimization of risk factor management, awareness of heart attack warning signs, and appropriate management of acute cardiovascular disease events,&quot; the investigators concluded.&lt;/p&gt;
&lt;p&gt;Limitations of the study included lack of information in the database about disease severity, duration, medications prescribed, and whether or not the cardiovascular event leading to hospitalization was a first-time occurrence.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The lead author and one co-author disclosed receiving grant support from the National Institutes of Health and Pfizer.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3087"
                     title="FDA Panel Looks at CNS Depressant for Fibromyalgia"
                     score="0.006"
                     href="http://www.medpagetoday.com/Rheumatology/Fibromyalgia/tb/21792?impressionId=1283458814724"
                     
      &lt;p&gt;BETHESDA, Md.  --  A joint FDA advisory committee will meet here Friday to consider whether the narcolepsy drug sodium oxybate (Xyrem) should receive an additional indication to treat fibromyalgia.&lt;/p&gt;
&lt;p&gt;Sodium oxybate, currently approved at a 500 mg/ml dose for narcolepsy-associated cataplexy and excessive daytime sleepiness, is a central nervous system depressant and carries a boxed warning against its use in combination with other similar drugs.&lt;/p&gt;
&lt;p&gt;The label information also warns that sodium oxybate is a drug known to be abused.&lt;/p&gt;
&lt;p&gt;Members of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee will be asked if the data show that the drug is effective in treating fibromyalgia, and if it improves sleep in fibromyalgia patients.&lt;/p&gt;
&lt;p&gt;The committee also will be asked whether there are safety concerns with Jazz Pharmaceuticals&apos; marketing plan: to lower the concentration of the drug to 375 mg/ml and give it a different brand name  --  Rekinla  --  to treat fibromyalgia.&lt;/p&gt;
&lt;p&gt;In its background materials, the FDA reviewers noted that Jazz has proposed a risk evaluation and mitigation strategy (REMS) for the new indication &quot;that builds on an existing program for Xyrem,&quot; the narcolepsy drug. &quot;In order to address the risk of abuse, misuse, and overdose, the program includes enrollment of prescribers and distribution through 15 specialty pharmacy providers that would have to be certified,&quot; the reviewers wrote.&lt;/p&gt;
&lt;p&gt;To avoid confusion between the different drug names, the company has proposed different but similar programs for each indication, the FDA staff said. In its materials, Jazz Pharmaceuticals noted that no certified pharmacy will dispense the drug for both indications  --  they will either dispense for one or the other.&lt;/p&gt;
&lt;p&gt;But the reviewers added that &quot;the existence of two REMS programs for the same established name may create confusion among prescribers who treat patients for both narcolepsy and fibromyalgia. The same established product with two enrollment forms and two pharmacy dispensing mechanisms based on treatment indication may be confusing for prescribers, pharmacies, and patients and may be burdensome to the healthcare system.&quot;&lt;/p&gt;
&lt;p&gt;The agency staff also expressed concern that the 375 mg/ml dosage might be a source of potential dosing errors. &quot;The number is cumbersome for Rekinla&apos;s dose calculations and when converting the dose from milligrams to the corresponding volume in milliliters,&quot; the reviewers wrote.&lt;/p&gt;
&lt;p&gt;Although Jazz said it selected the dosage &quot;for patient dosing convenience and manufacturing efficiency&quot; and to &quot;minimize bottles and components to be dispensed each month,&quot; the company doesn&apos;t substantiate either of these reasons in its application, according to the staff reviewers.&lt;/p&gt;
&lt;p&gt;In addition, &quot;when considering this risk of dose calculation errors, we believe that the numerical value &apos;375&apos; is cumbersome when calculating the doses,&quot; they continued.&lt;/p&gt;
&lt;p&gt;&quot;Neither patients nor practitioners are likely to accurately calculate, for example, the volume of Rekinla 375 mg/mL oral solution that will deliver a 2.25 gram dose without the aid of a calculator. Even with aid of a calculator, the multistep calculation is more complex than what would be required for the 500 mg/mL concentration of sodium oxybate and therefore more prone to error.&quot;&lt;/p&gt;
&lt;p&gt;FDA staff did note that Jazz Pharmaceuticals &quot;has provided substantial evidence of effectiveness in two phase 3, adequate and well-controlled trials which demonstrated that Xyrem reduced pain in patients diagnosed with fibromyalgia.&quot;&lt;/p&gt;
&lt;p&gt;However, they added that they believed the data did not support the company&apos;s proposed claim for improved sleep.&lt;/p&gt;
&lt;p&gt;In one of the trials, involving 548 patients randomized to placebo or 4.5 g or 6 g per night of the drug, researchers reported the following improvements relative to baseline:&lt;ul&gt;&lt;li&gt;Pain visual analogue scale (VAS) score: placebo, -18 points; low drug dose, -29 points; high drug dose, -32 points (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both doses)&lt;/li&gt;&lt;li&gt;Fatigue VAS score: placebo, -17 points; low drug dose, -28 points; high drug dose, -30 points (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both doses)&lt;/li&gt;&lt;li&gt;Jenkins Sleep Scale score: placebo, -2.9 points; low drug dose, -6.1 points; high drug dose, -6.2 points (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both doses)&lt;/li&gt;&lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The results were &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAN/19635&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAN/19635&quot; target=&quot;_blank&quot;&gt;reported&lt;/a&gt; in April at the annual meeting of the American Academy of Neurology.&lt;/p&gt;
&lt;p&gt;Xyrem&apos;s safety profile for fibromyalgia, which was tested in more than 1,060 treated patients in doses up to 9 g per night, appears to be acceptable, the FDA reviewers said, noting that &quot;the adverse event profile appears acceptable across the to-be-marketed dose range and is generally consistent with that seen in the currently approved Xyrem for narcolepsy.&quot;&lt;/p&gt;
&lt;p&gt;Treatment-emergent adverse events leading to discontinuation in the efficacy studies occurred in 19% of sodium oxybate-treated patients, compared with 8% of placebo-treated patients.&lt;/p&gt;
&lt;p&gt;Nervous system disorders such as headache, dizziness, and somnolence were most common (7%), followed by psychiatric disorders (6%) and GI disorders (6%).&lt;/p&gt;
&lt;p&gt;The manufacturer noted in its materials that &quot;in the fibromyalgia clinical studies with sodium oxybate, there were no adverse events indicative of abuse, dependence, misuse, or severe withdrawal symptoms with use of sodium oxybate. There was one event of overdose in which a patient with narcolepsy took 15 times the maximum dose; the patient recovered without sequelae.&quot;&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3083"
                     title="Equivocal Message on Duloxetine for Pain from Panel"
                     score="0.005"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/21784?impressionId=1283458814724"
                     
      &lt;p&gt;BETHESDA, Md.  --  An FDA advisory committee has voted narrowly  --  8 to 6  --  to recommend that the agency expand the indication for the antidepressant duloxetine (Cymbalta) to treat chronic musculoskeletal pain.&lt;/p&gt;
&lt;p&gt;In two votes earlier in the afternoon, members of the Anesthetic and Life Support Drugs Advisory Committee telegraphed the final equivocal message when they voted  --  with equally slim margins  --  that the drug eased pain better than placebo in patients with lower back pain, but wasn&apos;t effective against arthritis pain.&lt;/p&gt;
&lt;p&gt;Drugmaker Eli Lilly is seeking an indication for treatment of chronic pain. During the meeting, FDA officials said that such a broad indication was no longer under consideration and the agency would instead consider approving the drug to treat musculoskeletal pain, because the company&apos;s trials tested the drug only as a treatment for two types of musculoskeletal pain  --  lower back pain and osteoarthritis.&lt;/p&gt;
&lt;p&gt;But &quot;musculoskeletal pain&quot; is still a broad designation and can be applied to 30 to 40 million people each year, according to the estimate of several panelists. If the FDA chooses to approve the new indication, it could significantly increase prescriptions of the drug.&lt;/p&gt;
&lt;p&gt;&quot;This will be an explosion of use in this drug seeing as most of the people sitting here my age have chronic arthritis and knee pain,&quot; said panelist Thomas Boyer, MD, of the University of Arizona.&lt;/p&gt;
&lt;p&gt;An 8 to 6 vote is considered a &quot;null&quot; vote, and provides no clear indication of what the FDA will do. The FDA is not required to follow the advice of its committees, but it often does.&lt;/p&gt;
&lt;p&gt;The panel&apos;s vote on duloxetine&apos;s efficacy in back pain was, if anything, even more equivocal than the final vote  --  8 to 5 that the drug works, with one member abstaining.&lt;/p&gt;
&lt;p&gt;To support its application, Eli Lilly had submitted three trials testing various doses of duloxetine against placebo in 1,041 chronic low-back pain patients. The primary efficacy endpoint for all the trials was the change from baseline to week 13 in pain intensity, which was measured by the 11-point Brief Pain Inventory and patient diaries.&lt;/p&gt;
&lt;p&gt;In all three back pain trials, duloxetine  --  given at between 60 mg and 120 mg  --  demonstrated greater pain reduction than placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for all).&lt;/p&gt;
&lt;p&gt;However, the benefit isn&apos;t that impressive, said panelist John Markman, MD, director of the Neuromedicine Pain Management Center at the University of Rochester Medical Center in Rochester, N.Y. He estimated that for every 10 patients treated with duloxetine, just one would experience a 30% reduction in pain.&lt;/p&gt;
&lt;p&gt;&quot;The problem we have with chronic pain is that nothing has that large of a treatment effect,&quot; said Daniel Clauw, MD, of the University of Michigan, who spoke on behalf of Eli Lilly. &quot;At least with duloxetine, you were able to see a treatment effect in all studies.&quot;&lt;/p&gt;
&lt;p&gt;However, the panel was less confident about the arthritis indication and voted 4 to 9, with one member abstaining, that the company provided convincing proof that the drug eased the pain of patients with arthritis.&lt;/p&gt;
&lt;p&gt;The drugmaker submitted two trials comparing duloxetine with placebo in 487 osteoarthritis patients. The study had the same endpoints as the back pain trials, but this time, only one of the trials showed duloxetine eases arthritis pain better than placebo.&lt;/p&gt;
&lt;p&gt;Although concerns were raised prior to the meeting about the drug&apos;s side effects  --  notably hepatoxicity  --  the panel seemed to agree the side effects, including the risk for liver damage, were acceptable. The committee voted 9 to 4 that the benefits of duloxetine outweighed the risks.&lt;/p&gt;
&lt;p&gt;&quot;The safety profile is reasonable,&quot; said panel chairman Jeffery Kirsch, MD, of the Oregon Health &amp;amp; Science University.&lt;/p&gt;
&lt;p&gt;&quot;It won&apos;t be any more toxic, and perhaps less toxic that the [medication] I currently use,&quot; said panelist Jack Rosenberg, MD, of the University of Michigan.&lt;/p&gt;
&lt;p&gt;Duloxetine use also appears to be associated with an increased risk of Stevens-Johnson syndrome, a skin disease that usually results from a drug reaction, as well as another form of the disease called toxic epidermal necrolysis.&lt;/p&gt;
&lt;p&gt;Other adverse events reported in the trials included nausea, sleep disturbances, dizziness, dry mouth, somnolence, constipation, and fatigue. Most of the events were dose-dependant.&lt;/p&gt;
&lt;p&gt;The drug also carries a boxed warning for suicidality in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders, although that issue was hardly discussed at Thursday&apos;s meeting.&lt;/p&gt;
&lt;p&gt;Duloxetine, a serotonin-norepinephrine reuptake inhibitor, was originally approved to treat depression, and its indications were subsequently extended to include &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/9830&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/9830&quot; target=&quot;_blank&quot; title=&quot;FDA&amp;#8200;Approves&amp;#8200;Duloxetine&amp;#8200;(Cymbalta)&amp;#8200;for&amp;#8200;Fibromyalgia&quot;&gt;fibromyalgia&lt;/a&gt;, anxiety, and pain associated with diabetic neuropathy.&lt;/p&gt;
&lt;p&gt;Prescriptions for the drug increased from five million in 2005 to more than 14 million in 2009, a threefold increase, according to an FDA reviewer, Rajdeep Gill, PharmD. The majority of prescriptions are for depression, but at least 14% are already for off-label use in pain treatment, she said.&lt;/p&gt;
&lt;p&gt;If approved, duloxetine would be the first non-NSAID, nonopioid analgesic broadly indicated for the treatment of chronic pain.&lt;/p&gt;
&lt;p&gt;Earlier this year, the agency took Lilly to task for making false and misleading claims in Cymbalta marketing materials, overstating drug&apos;s use against pain and minimizing its risks. During Thursday&apos;s meeting, Kirsch said he was &quot;perturbed&quot; over how the company has been marketing Cymbalta as a pain reliever for depressed patients, when the drug isn&apos;t approved for that exact indication.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3050"
                     title="FDA Panel to Consider Pain Indication for Antidepressant"
                     score="0.003"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/tb/21726?impressionId=1283458814724"
                     
      &lt;p&gt;WASHINGTON  --  An FDA advisory committee will meet later this week to review whether the antidepressant duloxetine (Cymbalta) should be used as a treatment for chronic pain despite risks that include liver damage and skin disease.&lt;/p&gt;
&lt;p&gt;Drugmaker Eli Lilly is seeking an indication for use in treatment of chronic pain, including pain related to arthritis and chronic low back pain.&lt;/p&gt;
&lt;p&gt;In briefing documents posted on Tuesday, FDA reviewers said four studies found duloxetine worked better than placebo at easing pain, but they questioned one crucial aspect of Eli Lilly&apos;s study design, and pointed to a number of major safety concerns associated with duloxetine.&lt;/p&gt;
&lt;p&gt;Earlier this year, the agency took Lilly to task for making false and misleading claims in Cymbalta marketing materials, overstating efficacy of the drug against pain and minimizing its risks.&lt;/p&gt;
&lt;p&gt;If the FDA approves Lilly&apos;s current application, it would &quot;likely result in a substantial increase in the prescribing of the product in the general population given the large number of Americans suffering from these types of chronic pain conditions,&quot; wrote &lt;span&gt;Bob &lt;span&gt;Rappaport&lt;/span&gt;, MD, director of the FDA&apos;s Division of Anesthesia and Analgesia Products in the briefing documents.&lt;/span&gt;&lt;/p&gt;
&lt;p&gt;Duloxetine, a serotonin-norepinephrine reuptake inhibitor, was originally approved to treat depression, and its indications were subsequently extended to include &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/9830&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/9830&quot; target=&quot;_blank&quot; title=&quot;FDA&amp;#8200;Approves&amp;#8200;Duloxetine&amp;#8200;(Cymbalta)&amp;#8200;for&amp;#8200;Fibromyalgia&quot;&gt;fibromyalgia&lt;/a&gt;, anxiety, and pain associated with diabetic neuropathy.&lt;/p&gt;
&lt;p&gt;Prescriptions for the drug increased from five million in 2005 to more than 14 million in 2009, a threefold increase, according to another FDA reviewer, Rajdeep Gill, PharmD. The majority of prescriptions are for depression, but at least 14% are already for off-label use in pain treatment, he said.&lt;/p&gt;
&lt;p&gt;&quot;Approving the use of Cymbalta ... for chronic pain may increase the patient exposure and physician prescribing to an area that is already not uncommon,&quot; wrote Gill.&lt;/p&gt;
&lt;p&gt;If approved, duloxetine would be the first non-NSAID, nonopioid analgesic broadly indicated for the treatment of chronic pain.&lt;/p&gt;
&lt;p&gt;&lt;span&gt;Because duloxetine is a &quot;nontraditional&quot; analgesic where the mechanism of action is not well-defined, the agency may need greater evidence to support a chronic pain indication than it would for opioids and NSAIDS, wrote &lt;/span&gt;Rappaport.&lt;/p&gt;
&lt;p&gt;The advisory committee will examine five new clinical trials from Eli Lilly: three testing various doses of duloxetine versus placebo in 1,041 chronic low-back pain patients, and two comparing duloxetine with placebo in 487 osteoarthritis patients.&lt;/p&gt;
&lt;p&gt;All five trials were multicenter, randomized, double-blind trials with a treatment duration of at least 12 weeks. The primary efficacy endpoint for all the trials was the change from baseline to week 13 in pain intensity, which was measured by the 11-point Brief Pain Inventory and patient diaries.&lt;/p&gt;
&lt;p&gt;In four of the five trials, duloxetine  --  given at between 60 mg and 120 mg  --  demonstrated greater pain reduction compared with placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for all).&lt;/p&gt;
&lt;p&gt;However, FDA reviewers criticized the trial design because it assumed that patients dropped out of the trials at random, which was likely not the case.&lt;/p&gt;
&lt;p&gt;&quot;In analgesic trials, early discontinuations should be considered treatment failures; therefore, an improvement in a subject&apos;s pain score prior to dropping out due to an adverse event should not be credited in the analysis,&quot; the FDA reviewers wrote.&lt;/p&gt;
&lt;p&gt;Patients in the duloxetine arms were more likely to discontinue treatment because of adverse events, including nausea, sleep disturbances, dizziness, dry mouth, somnolence, constipation, and fatigue. Most of the events were dose-dependant.&lt;/p&gt;
&lt;p&gt;Duloxetine use also appears to be associated with an increased risk of Stevens-Johnson syndrome, a skin disease that usually results from a drug reaction, as well as another form of the disease called toxic epidermal necrolysis. The FDA reviewers recommended that, if duloxetine is given the chronic pain indications, it should carry warning labels about the increased skin disease risks.&lt;/p&gt;
&lt;p&gt;The FDA also has concerns about duloxetine&apos;s risk of serious liver toxicity, already included in the drug&apos;s labeling.&lt;/p&gt;
&lt;p&gt;No deaths were reported during the trials.&lt;/p&gt;
&lt;p&gt;The safety findings aren&apos;t new or unexpected and are very similar to duloxetine&apos;s current safety label, the FDA reviewers said.&lt;/p&gt;
&lt;p&gt;The drug also carries a boxed warning for suicidality in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders.&lt;/p&gt;
&lt;p&gt;&quot;...duloxetine is not universally tolerated nor free of safety risks,&quot; wrote Eli Lilly staff in the company&apos;s briefing documents posted on the FDA&apos;s website. However, the safety profile is &quot;well-characterized&quot; and not any different for chronic pain patients than it is for other patients who are already using the drug.&lt;/p&gt;
&lt;p&gt;&quot;Additionally, duloxetine is a centrally acting analgesic with a mechanism of action different from that of NSAIDs and opioids,&quot; Eli Lilly reviewers wrote. &quot;As such, it constitutes a promising new modality for treatment of chronic pain.&quot;&lt;/p&gt;
&lt;p&gt;The FDA is not required to follow the advice of its advisory committees, although it often does.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3023"
                     title="Mild Mania Often Accompanies Major Depression (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/Psychiatry/BipolarDisorder/tb/21687?impressionId=1283458814724"
                     
      A high proportion of people with major depression may actually have a &quot;hidden&quot; form of bipolar disorder, according to a population-based study.&lt;br&gt;
&lt;br&gt;Interviews with a nationally-representative sample of more than 9,000 people suggest that nearly 40% of people with a history of major depressive disorder report periods of hypomania that just miss the threshold for a bipolar diagnosis, reported Kathleen R. Merikangas, PhD, of the National Institute of Mental Health in Bethesda, Md., and colleagues.&lt;br&gt;
&lt;br&gt;The group with subthreshold hypomania appeared to fall between pure depression and bipolar disorder for clinical severity, the researchers reported online in the &lt;em&gt;American Journal of Psychiatry&lt;/em&gt;.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Since such patients might benefit from the addition of a mood stabilizer after response to antidepressants, the researchers supported a proposed broadening of the criteria for bipolar disorder.&lt;/p&gt;
&lt;p&gt;Subthreshold mania hasn&apos;t made it into the current edition of the Diagnostic and Statistical Manual of Mental Diseases (DSM-IV), but changes are being debated as the psychiatric &quot;bible&quot; undergoes revision for its &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/20299&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/20299&quot; target=&quot;_blank&quot;&gt;fifth edition&lt;/a&gt;, expected in 2013.&lt;/p&gt;
&lt;p&gt;A diagnostic specifier for subthreshold bipolarity might fit well in the diagnostic category of major depression, Merikangas&apos; group suggested.&lt;/p&gt;
&lt;p&gt;&quot;Such an expansion of the bipolar concept would likely lead to important changes in the treatment of patients who are undiagnosed or misdiagnosed despite elevated morbidity and mortality rates,&quot; they wrote in the paper.&lt;/p&gt;
&lt;p&gt;Regardless, if there is such a substantial group of patients with hidden bipolarity, careful evaluation of a history of hypomanic symptoms and a family history of mania would be critical, Merikangas and colleagues noted.&lt;/p&gt;
&lt;p&gt;The group analyzed results from the nationally-representative National Comorbidity Survey Replication (NCS-R)  --  a nationally representative face-to-face household survey of the prevalence and correlates of a wide range of DSM-IV mental disorders, according to background supplied by the authors.&lt;/p&gt;
&lt;p&gt;For the current study, responses were analyzed from 9,282 people surveyed between February 2001 and April 2003.&lt;/p&gt;
&lt;p&gt;Overall, 5.4% of the NCS-R respondents met criteria for major depressive disorder alone over the prior 12 months, jumping to 10.2% for lifetime prevalence.&lt;/p&gt;
&lt;p&gt;Together, the bipolar spectrum conditions were nearly as common as major depression alone.&lt;/p&gt;
&lt;p&gt;The lifetime prevalence of major depression with subthreshold hypomania in the NCS-R respondents was 6.7% and 2.2% over the prior 12 months.&lt;/p&gt;
&lt;p&gt;Bipolar I disorder  --  major depressive disorder with mania  --  affected 0.3% of the respondents over the prior 12 months and 0.7% over their lifetime.&lt;/p&gt;
&lt;p&gt;Bipolar II disorder  --  major depressive disorder with hypomania  --  affected 0.8% of the respondents over the prior 12 months, with a 1.6% lifetime prevalence.&lt;/p&gt;
&lt;p&gt;Treatment for mood disorders was no more likely for those with subthreshold hypomania than for those with depression alone.&lt;/p&gt;
&lt;p&gt;However, the subthreshold hypomania group showed greater rates of comorbidity than the depression alone group for the following (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for all): &lt;ul&gt; &lt;li&gt;Anxiety (72.2% versus 52.6%)&lt;/li&gt; &lt;li&gt;Substance use disorders (35.3% versus 18.0%)&lt;/li&gt; &lt;li&gt;Behavioral problems (41.1% versus 19.2%)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Suicide attempts were reported by 41% of those with major depression and subthreshold hypomania, which fell between the 50% of those with bipolar II and the 31% of those with major depression alone.&lt;/p&gt;
&lt;p&gt;Age at first onset showed the same pattern as did number of episodes of depression.&lt;/p&gt;
&lt;p&gt;These differences in clinical characteristics &quot;underscore the heterogeneity of major depression and support the notion that a critical reappraisal of diagnostic criteria for mood disorders is warranted,&quot; the researchers wrote in the paper.&lt;/p&gt;
&lt;p&gt;Even more convincing, they suggested, was that family history of mania was as common for those with subthreshold hypomania as for those with mania or hypomania (76.0% versus 70.4% and 67.8%, respectively).&lt;/p&gt;
&lt;p&gt;The findings provide the first comparisons of the prevalence and clinical correlates of bipolar II disorder, major depression with subthreshold hypomania, and major depression alone in a nationally representative U.S. sample, according to Merikangas and colleagues.&lt;/p&gt;
&lt;p&gt;However, the researchers noted that the data were based on self-report in the lay-administered NCS-R survey, and precluded collection of information on the full spectrum of expression of bipolar disorder proposed in recent studies.&lt;/p&gt;
&lt;p&gt;The authors also cautioned that their definition of subthreshold bipolar disorder  --  which required a major depressive episode diagnosis and a &quot;yes&quot; answer to either of the mania screening questions that encompassed a discrete period of increased energy, activity, and euphoria or irritability not related to impairment in daily activities  --  was more restrictive than the definitions proposed by clinical researchers.&lt;/p&gt;
&lt;p&gt;Thus, they concluded, the study may have underestimated the prevalence of bipolar spectrum disorder in the population.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The National Comorbidity Survey Replication was supported by a grant from the National Institute of Mental Health with supplemental support from the National Institute of Drug Abuse; the Substance Abuse and Mental Health Services Administration; a grant from the Robert Wood Johnson Foundation; and the John W. Alden Trust.&lt;/p&gt;&lt;p&gt;Manuscript preparation was supported by the National Institute of Mental Health and the French National Center for Scientific Research.&lt;/p&gt;&lt;p&gt;Merikangas reported having no financial conflicts of interest to disclose.&lt;/p&gt;&lt;p&gt;One co-author reported having served in an advisory or consulting capacity for Eli Lilly, GlaxoSmithKline, Kaiser Permanente, Pfizer, sanofi-aventis, Shire, and Wyeth-Ayerst and having received research support for epidemiological studies from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Johnson &amp;amp; Johnson Pharmaceuticals, Ortho-McNeil, Pfizer, and sanofi-aventis. Another reported having served in advisory or speaking capacities for AstraZeneca, Eli Lilly, Janssen Cilag, and sanofi-aventis.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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