<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_450"
                     title="SSRI and Tamoxifen Increase Mortality Risk (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18376?impressionId=1265749929969"
                     
      Overlapping use of tamoxifen and the antidepressant paroxetine (Paxil) significantly increases the risk of breast cancer mortality, data from a large cohort of breast cancer patients showed.&lt;br&gt;
&lt;br&gt;The excess breast-cancer mortality risk ranged as high as 91%, depending on the duration of simultaneous use, researchers reported online in &lt;em&gt;BMJ.&lt;/em&gt;&lt;br&gt;
&lt;br&gt;Women taking other antidepressants with tamoxifen, including other selective serotonin reuptake inhibitors (SSRIs), did not have an increased risk of breast cancer death.&lt;br&gt;
&lt;br&gt;&quot;We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 patients so treated; the risk with more extensive overlap would be greater,&quot; David Juurlink, MD, PhD, of Sunnybrook Health Sciences Center in Toronto, and colleagues concluded.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The findings add to an accumulation of evidence suggesting that inhibition of the cytochrome P450 2D6 isozyme (CYP2D6) may adversely affect outcomes in breast cancer patients taking tamoxifen. CYP2D6 is the principle catalyst for converting tamoxifen into endoxifen, a metabolite with 100-fold greater affinity for the estrogen receptor.&lt;/p&gt;
&lt;p&gt;Multiple studies have shown that women who have a poor-metabolizer phenotype have lower levels of endoxifen, as do women treated with drugs that inhibit CYP2D6.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, in patients who receive tamoxifen in addition to a CYP2D6 inhibitor, endoxifen concentrations vary inversely with the degree of CYP2D6 inhibition,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Paroxetine is used to treat depression and vasomotor symptoms in breast cancer patients treated with tamoxifen. Paroxetine is not the only SSRI antidepressant used by breast cancer patients, but it is the only SSRI that irreversibly inhibits CYP2D6.&lt;/p&gt;
&lt;p&gt;Whether the metabolic effects of CYP2D6 inhibition translated into adverse breast cancer outcomes had not been determined.&lt;/p&gt;
&lt;p&gt;To examine the issue, Juurlink and colleagues compared prescribing data with clinical records of 24,430 breast cancer patients, ages 66 and older, who initiated tamoxifen therapy from 1993 to 2005. Of those, 7,500 also received an antidepressant.&lt;/p&gt;
&lt;p&gt;Ultimately, the investigators narrowed the study population to 2,430 women who took a single SSRI during tamoxifen therapy. The most commonly prescribed SSRI was paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15%), fluoxetine (10.4%), and fluvoxamine (7.2%).&lt;/p&gt;
&lt;p&gt;During a mean follow-up of 2.38 years, 1,074 patients died, including 374 breast cancer deaths.&lt;/p&gt;
&lt;p&gt;The analysis showed an increased risk of breast cancer death only among women taking paroxetine.&lt;/p&gt;
&lt;p&gt;The breast cancer mortality risk increased with the duration of concomitant use of paroxetine and tamoxifen. As the duration of therapeutic overlap increased from 25%, to 50%, to 75% of time on tamoxifen, the excess risk of breast cancer death increased from 24%, to 54%, to 91%.&lt;/p&gt;
&lt;p&gt;Investigators repeated the analysis, using death from any cause. Overlapping treatment with tamoxifen and paroxetine led to an increased mortality risk of 13%, 28%, and 46% as the duration of overlap increased from 25% to 75%.&lt;/p&gt;
&lt;p&gt;The results suggest clear implications for use of SSRIs in breast cancer patients on tamoxifen, Frank Andersohn, MD, and Stefan Willich, MD, of Charite University in Berlin, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;&quot;The straightforward answer is to avoid prescribing strong CYP2D6-inhibiting SSRIs (such as paroxetine or fluoxetine) for women with breast cancer who are prescribed tamoxifen, and to consider instead drugs with low potential to inhibit CYP2D6 (such as citalopram or venlafaxine),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;For women who are already taking a potent inhibitor of CYP2D6, doctors should consider switching to a drug that does not inhibit the enzyme, they added. However, any switch should be accomplished gradually, as abrupt discontinuation of an antidepressant confers risk, as well, they noted.&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;Co-author Kathleen Pritchard disclosed relationships with sanofi-aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Novartis, Abraxis, Amgen, GlaxoSmithKline, Bristol Myers Squibb, and Roche&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_427"
                     title="AAPM: Botox May Relieve Postherpetic Neuralgia (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18345?impressionId=1265749929969"
                     
      &lt;p&gt;SAN ANTONIO  --  Subcutaneous injection of botulinum toxin A (Botox) significantly reduced postherpetic neuralgia compared with lidocaine and saline placebo in a small randomized clinical study, researchers reported here.&lt;/p&gt;
&lt;p&gt;Patients randomized to receive botulinum toxin also had significant improvement in sleep and a significant reduction in opioid requirements compared with the lidocaine and saline groups. The differences emerged within one week and persisted to 90 days.&lt;/p&gt;
&lt;p&gt;&quot;Our preliminary data suggest that Botox may be useful for the treatment of refractory postherpetic neuralgia,&quot; Lizu Xiao, MD, of Nanshan Hospital in Shenzhen, China, said at the American Academy of Pain Medicine meeting. &quot;Patients were assessed for side effects at each visit, and none were observed, suggesting this is a simple, safe technique with essentially no adverse effects.&lt;/p&gt;
&lt;p&gt;&quot;Its use is particularly appropriate in older individuals who cannot tolerate antineuropathic medications.&quot;&lt;/p&gt;
&lt;p&gt;The analgesic mechanisms of botulinum toxin remains unclear. The neurotoxin inhibits the release of acetylcholine at the synapse and blocks the release of several other neurotransmitters involved in pain perception, said Xiao.&lt;/p&gt;
&lt;p&gt;Botulinum toxin has produced favorable results in limited clinical experience involving neuromuscular and myofascial conditions, such as strabismus and tension-type headache.&lt;/p&gt;
&lt;p&gt;Botulinum toxin also has provided pain relief in patients with neuropathic conditions, such as diabetic neuropathy and complex regional pain syndrome. The positive findings provided the impetus for the randomized controlled clinical trial of botulinum toxin in postherpetic neuralgia.&lt;/p&gt;
&lt;p&gt;The study involved 60 patients with diagnosed postherpetic neuralgia. They were randomized to subcutaneous injections of botulinum toxin, lidocaine, or saline, administered at a dosage of 1 mL/cm of affected area.&lt;/p&gt;
&lt;p&gt;The primary outcomes were improvement in pain assessed by visual analog scale (VAS), improvement in sleep on day one and day seven, and change in opioid use at day seven and three months.&lt;/p&gt;
&lt;p&gt;The patients&apos; mean age was 65 to 70. The baseline pain score was about 8 on a 10-point scale, and the duration of postherpetic pain averaged about one year.&lt;/p&gt;
&lt;p&gt;Patients randomized to lidocaine had the greatest improvement in pain on day one, a decrease to a VAS score of about 5, compared with a mean of 6 to 7 for the botulinum toxin and saline groups. The average pain score declined significantly in the lidocaine group compared with baseline and compared with the other two groups (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;By day seven, the average pain score had declined to about 3 compared with about 5 in the other two groups (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01). At the three-month follow-up, the mean VAS score remained at 5 in the lidocaine and saline groups (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 versus baseline), while the mean in the botulinum toxin group was less than 4 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 versus baseline and the other two groups).&lt;/p&gt;
&lt;p&gt;Baseline sleep time averaged three hours in all three groups and increased to five hours in the lidocaine group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) by day one and to four hours in the other two groups.&lt;/p&gt;
&lt;p&gt;By day seven, average sleep time in the botulinum toxin group had increased to six hours (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 versus baseline) compared with about four hours in the other two groups (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 versus botulinum toxin).&lt;/p&gt;
&lt;p&gt;At 90 days the mean sleep time exceeded six hours in the botulinum toxin group, which remained significantly better than the other two groups, whose sleep time had increased to about five hours (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;Opioid requirements in the botulinum toxin group had declined to 20% of baseline by day seven, compared with about 50% in the lidocaine group and more than 60% in the saline group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;At the three-month follow-up, opioid use had declined to 30% to 40% of baseline in the lidocaine and saline groups, whereas opioid use remained at 20% of baseline in the botulinum toxin group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&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 study was funded by the Chinese government.&lt;/p&gt;&lt;p&gt;Xiao had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_426"
                     title="AAPM: Spine Stimulation Leads to Durable Pain Relief (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18344?impressionId=1265749929969"
                     
      &lt;p&gt;SAN ANTONIO  --  Spinal cord stimulation provided durable pain relief for patients with complex regional pain syndrome (CRPS) but did not halt progression, a retrospective analysis of a small clinical series showed.&lt;/p&gt;
&lt;p&gt;During follow-up for as long as 20 years, patients continued to rate their pain as significantly below baseline levels. Improvements in depression, medication use, and quality of life also proved durable.&lt;/p&gt;
&lt;p&gt;However, the pain syndrome progressed to other areas in all patients.&lt;/p&gt;
&lt;p&gt;&quot;All patients in this series experienced a gradual enlargement in the area affected over time,&quot; Krishna Kumar, MB, BS, of Regina Qu&apos;appelle Health Region in Regina, Saskatchewan, said at the American Academy of Pain Medicine meeting. &quot;Stimulation does not appear to retard disease spread.&quot;&lt;/p&gt;
&lt;p&gt;Nonetheless, 22 of the 25 patients in the series said they were satisfied with their pain relief and would have the procedure again.&lt;/p&gt;
&lt;p&gt;In a separate presentation at the meeting, Kumar reported that spinal cord stimulation led to significantly better outcomes than medical management in patients with failed back surgery syndrome.&lt;/p&gt;
&lt;p&gt;CRPS has an undetermined etiology, and there&apos;s no cure. The condition responds poorly to conventional medical therapy and to interventions such as transcutaneous electrical nerve stimulation, chemical blocks, sympathectomy, and physical therapy, said Kumar.&lt;/p&gt;
&lt;p&gt;Several studies and meta-analyses have shown that spinal cord stimulation relieves pain and other symptoms of CRPS during short- and mid-term follow-up. Whether the benefits persisted over the long term was unclear, Kumar continued.&lt;/p&gt;
&lt;p&gt;To assess long-term outcomes after spinal cord stimulation, Kumar and colleagues examined records of 196 patients who underwent spinal cord stimulation procedures. They identified 25 patients who met International Association for the Study of Pain criteria for CRPS and who agreed to participate.&lt;/p&gt;
&lt;p&gt;The cohort had a median follow-up of 63 months, a mean of 88 months, and a range of 18 to 235 months. The group comprised 13 men and 12 women whose mean age was 51 and whose ages ranged from 32 to 91. Ten of the 25 had upper-extremity pain and 15 had lower-extremity pain. In all cases the pain had not responded to conventional medical therapy.&lt;/p&gt;
&lt;p&gt;Assessment of each patient included pain rating by a visual analog scale (VAS), an index of physical functioning, a depression scale, a general health status survey, and a quality-of-life survey. Patients were assessed at implantation, three months and one year after implantation, and at last follow-up.&lt;/p&gt;
&lt;p&gt;All categories of medication use remained below baseline levels at last follow-up, including antidepressants, anticonvulsants, anti-inflammatory drugs, and narcotic drugs.&lt;/p&gt;
&lt;p&gt;Average scores on all of the survey instruments improved significantly from implantation to three months (&lt;em&gt;P&lt;/em&gt;=0.002 to &lt;em&gt;P&lt;/em&gt;=0.000). One-year results showed some reversal of the improvement, but scores for all outcomes remained below baseline levels.&lt;/p&gt;
&lt;p&gt;At last follow-up, mean scores remained significantly improved over baseline values (&lt;em&gt;P&lt;/em&gt;=0.003 to &lt;em&gt;P&lt;/em&gt;=0.001).&lt;/p&gt;
&lt;p&gt;The greatest improvement in health status and pain scores occurred in patients who were 40 or younger, who had stage I CRPS, and who underwent spinal cord stimulation within a year of diagnosis, said Kumar.&lt;/p&gt;
&lt;p&gt;&quot;Spinal cord stimulation is equally effective for men and women and for upper- and lower-limb CRPS,&quot; he said. &quot;Early institution is necessary to secure optimal patient outcomes, as delay exceeding one year appears to limit the effectiveness of the intervention.&quot;&lt;/p&gt;
&lt;p&gt;&quot;On the basis of these results, we conclude that spinal cord stimulation is an effective long-term management modality for CRPS and should be considered earlier in the treatment continuum, preferably within the first year of symptom onset,&quot; Kumar added.&lt;/p&gt;
&lt;p&gt;In a separate poster presentation, Kumar reported findings from a study of 100 patients with failed back surgery syndrome who were treated at 12 centers worldwide. Half the patients received conventional medical management and half had medical management plus spinal cord stimulation. The primary outcome was pain at six and 24 months after treatment.&lt;/p&gt;
&lt;p&gt;At six months, 48% of patients with spinal cord stimulation had at least 50% improvement in leg pain, compared with 9% of patients who received only medical treatment. Additionally, 38% of the spinal stimulation-group reported at least 30% improvement in back pain at six months versus 14% of the medically managed patients.&lt;/p&gt;
&lt;p&gt;Patients who were dissatisfied with their assigned treatment after six months were allowed to switch to the opposite therapy. Kumar reported that 30 of 50 patients in the medical group opted for spinal cord stimulation, compared with four of 50 in the spinal stimulation group who opted for continued treatment with medication alone.&lt;/p&gt;
&lt;p&gt;At 24 months, 42 of the original 50 patients remained in the spinal stimulation group, compared with 11 of 50 in the medical group. Differences observed at six months were maintained, including leg pain (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), physical functioning (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0002), and quality of life (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&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;Kumar disclosed relationships with Medtronic and Boston Scientific.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_415"
                     title="AAPM: Drug for Fibromyalgia Boosts Multiple Outcomes (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18327?impressionId=1265749929969"
                     
      &lt;p&gt;SAN ANTONIO  --  The fibromyalgia drug milnacipran (Savella) achieved clinically meaningful reductions in pain throughout almost four months of randomized therapy, a post-hoc analysis of daily pain control showed.&lt;/p&gt;
&lt;p&gt;Half of patients treated with the serotonin/norepinephrine reuptake inhibitor had at least a 30% improvement in pain scores at 15 weeks, and 35% to 40% had at least a 50% improvement, according to analyses reported here at the American Academy of Pain Medicine meeting.&lt;/p&gt;
&lt;p&gt;Two different doses of milnacipran led to at least 30% improvement in pain on almost half of the days during the randomized trial. Patients treated with milnacipran had at least 50% improvement during 30% of the days.&lt;/p&gt;
&lt;p&gt;&quot;A 30% improvement in pain is clinically significant, and half the patients treated with milnacipran attained that level of pain relief,&quot; Aroon Datta, MD, of Forest Laboratories in Jersey City, N.J., said in an interview. &quot;Even when the more stringent criteria of 50% improvement were applied, significantly more patients in the milnacipran groups achieved that threshold compared with placebo.&quot;&lt;/p&gt;
&lt;p&gt;&quot;By any measure, it is fair to say that patients treated with milnacipran had significantly better pain control,&quot; he added.&lt;/p&gt;
&lt;p&gt;Milnacipran is chemically similar to the antidepressant venlafaxine (Effexor). However, milnacipran has three times the power to inhibit norepinephrine reuptake. The drug was approved in 2009 for treatment of fibromyalgia.&lt;/p&gt;
&lt;p&gt;Datta reported results of a post-hoc analysis of data from two randomized, placebo-controlled clinical trials. One lasted 27 weeks, and the other had a 15-week follow-up.&lt;/p&gt;
&lt;p&gt;In the 27-week trial, approximately 900 patients were randomized 1:1:2 to placebo, milnacipran 100 mg/d (50 mg BID), or milnacipran 200 mg/d (100 mg BID). In the 15-week trial, 1,200 patients were randomized in equal proportion to placebo and the two doses of milnacipran.&lt;/p&gt;
&lt;p&gt;Patients recorded their pain level several times a day by means of an electronic diary. They rated their pain according to a visual analog scale (VAS) with a range of 0 to 100.&lt;/p&gt;
&lt;p&gt;The post-hoc analysis centered on outcomes at 15 weeks in both trials. The primary outcomes were change from baseline in weekly 24-hour VAS pain score, the proportion of patients who achieved &amp;#8805;30% and &amp;#8805;50% improvement in the VAS pain score, and the proportion of days with &amp;#8805;30% and &amp;#8805;50% improvement in pain.&lt;/p&gt;
&lt;p&gt;In the longer trial, the change in the weekly average of 24-hour recall of VAS scores differed significantly in both milnacipran groups within two weeks, and the difference was maintained through 15 weeks (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Significant differences emerged within the first week in the second trial and persisted through week 15 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;In both trials, 52% of patients assigned to 100 mg of milnacipran and 56% of those assigned to 200 mg had &amp;#8805;30% improvement in pain scores, compared with 40% to 42% of placebo-treated patients (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;When the more stringent criterion of &amp;#8805;50% improvement was used, 31% to 35% of the 100-mg milnacipran patients achieved that goal, as did 36% to 37% of patients treated with 200 mg.&lt;/p&gt;
&lt;p&gt;About 25% of placebo patients had &amp;#8805;50% improvement. Only the 200-mg dose differed significantly from placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;A similar pattern emerged in evaluation of the proportion of days with threshold pain reductions. Milnacipran-treated patients had &amp;#8805;30% improvement on 44% to 47% of days in the trial and &amp;#8805;50% improvement on 25% to 30% of days.&lt;/p&gt;
&lt;p&gt;For both thresholds, milnacipran was significantly better than placebo, whose patients had &amp;#8805;30% pain improvement on about a third of days and &amp;#8805;50% improvement on fewer than 20% of days (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Datta also reported findings from a randomized, placebo-controlled clinical trial evaluating the pain relief afforded by the 100-mg daily dose of milnacipran. The study involved 1,025 patients with fibromyalgia randomized to placebo or active therapy.&lt;/p&gt;
&lt;p&gt;The trial had two principal 12-week efficacy outcomes: the composite of &amp;#8805;30% improvement in pain and the Patient Global Impression of Change (PGIC), and the composite of the same two outcomes plus improvement &amp;#8805;6 points on the physical function component of the SF-36 health assessment survey.&lt;/p&gt;
&lt;p&gt;The principal efficacy analysis used baseline observation carried forward (BOCF) for patients with missing data. By that statistical method, 29% of milnacipran patients were responders compared with 18% of the placebo group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;An analysis that employed last observation carried forward (LOCF) showed response rates of 33% with milnacipran and 19&lt;strong&gt;%&lt;/strong&gt; with placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;An analysis of observed cases resulted in response rates of 42% versus 26% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Similar results emerged from analyses of the three-measure outcome. Milnacipran led to significantly higher (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) response rates by BOCF (20% versus 11%), by LOCF (28% versus 12%), and by observed cases (30% versus 16%).&lt;/p&gt;
&lt;p&gt;Milnacipran therapy also led to significantly higher (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) response rates for each component of the composite outcomes: &amp;#8805;30% improvement in pain (45% versus 31%), PGIC (42% versus 26%), and &amp;#8805;6-point improvement in physical function (40% versus 31%).&lt;/p&gt;
&lt;p&gt;The results indicate that milnacipran 100 mg (50 mg BID) could offer an alternative for patients who cannot tolerate the FDA-approved 200-mg dose, said Datta. If physicians choose to start patients on 100 mg and then titrate up to the approved dose, that also would appear feasible, he said.&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 studies were supported by Forest Laboratories and Cypress Bioscience.&lt;/p&gt;&lt;p&gt;All but two of the authors are employees of the study sponsors.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_358"
                     title="Poststroke Antidepressant Boosts Mental Agility (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Cardiology/Strokes/tb/18240?impressionId=1265749929969"
                     
      &lt;p&gt;Antidepressants in the first months after a stroke may aid cognitive recovery for patients without depression, according to a randomized trial analysis.&lt;/p&gt;
&lt;p&gt;Global cognitive function scores improved significantly more with escitalopram (Lexapro) than with problem-solving therapy or placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), according to Ricardo E. Jorge, MD, of the University of Iowa in Iowa City, and colleagues.&lt;/p&gt;
&lt;p&gt;Memory scores rose significantly higher with the antidepressant as well (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), with both effects independent of those on depression, they reported in the February &lt;em&gt;Archives of General Psychiatry&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Adjunctive restorative therapies administered during the first few months after stroke, the period with the greatest degree of spontaneous recovery, reduce the number of stroke patients with significant disability,&quot; the researchers concluded.&lt;/p&gt;
&lt;p&gt;The &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Strokes/9621&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Strokes/9621&quot; target=&quot;_blank&quot;&gt;primary analysis&lt;/a&gt; of the trial, reported in the &lt;em&gt;Journal of the American Medical Association on&lt;/em&gt; May 28, 2008, showed that prophylactic escitalopram treatment would prevent poststroke depression in one patient for every 7.2 treated &lt;em&gt;(P&lt;/em&gt;&amp;lt;0.001 compared with placebo). That article ultimately raised a controversy over an undisclosed conflict of interest.&lt;/p&gt;
&lt;p&gt;Escitalopram is a selective serotonin reuptake inhibitor (SSRI). Since serotonin plays a role in neuroplastic changes in the developing brain as well as in depression, Jorge&apos;s group analyzed whether there might be such an effect after a stroke.&lt;/p&gt;
&lt;p&gt;The study randomized patients to double-blind treatment with escitalopram (10 mg/d under age 65 or 5 mg/day age 65 and older) or placebo or unblinded problem-solving therapy (12 sessions of going through steps to arrive at a course of action for a patient-selected problem).&lt;/p&gt;
&lt;p&gt;The intent-to-treat analysis included 129 patients treated starting within the first three months after their mild to moderate severity stroke and who did not meet criteria for major or minor depression.&lt;/p&gt;
&lt;p&gt;Overall, global cognitive functioning was significantly changed between groups as measured on the Repeatable Battery for the Assessment of Neuropsychological Status (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;After controlling for change in depression score and type of stroke, escitalopram was associated with the best cognitive recovery, an adjusted mean change of 9.9 points compared with 1.9 for problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) and 4.0 for placebo (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;Similarly, for delayed memory scores on the same test battery, escitalopram came out on top (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;After adjustment for depression score change and stroke mechanism, the antidepressant was associated with an 11.2 point improvement in delayed memory, compared with a change of -0.7 with problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 3.9 with placebo (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;On test of immediate memory, escitalopram again yielded the best recovery.&lt;/p&gt;
&lt;p&gt;The researchers found mean improvement of 13.4 points with the antidepressant compared with 2.0 with problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 7.2 with placebo (&lt;em&gt;P&lt;/em&gt;=0.04), after adjustment for time between stroke and treatment, depression score change, and stroke type.&lt;/p&gt;
&lt;p&gt;These mental benefits appeared to have an impact on functional status as well.&lt;/p&gt;
&lt;p&gt;Cognitive domain scores on the Functional Independence Measure were better for escitalopram-treated patients than those who didn&apos;t get the drug (&lt;em&gt;P&lt;/em&gt;=0.05), as were memory domain scores on the same measure (&lt;em&gt;P&lt;/em&gt;=0.03).&lt;/p&gt;
&lt;p&gt;At baseline, the global cognitive functioning and delayed and immediate memory scores were nonsignificantly lower in the antidepressant group than in the other two groups, which could have biased the results.&lt;/p&gt;
&lt;p&gt;However, the treatment effects appeared to be real, Jorge explained in an interview.&lt;/p&gt;
&lt;p&gt;In an unpublished regression analysis, the baseline scores were not a significant covariate. &quot;If [the results were] related only to the difference in baseline, this would be significant but it wasn&apos;t,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Moreover, with an initially lower score it might have been expected that the escitalopram-treated group would have had a lower score at the end of the study than the other groups, added co-author Robert G. Robinson, MD, also of the University of Iowa.&lt;/p&gt;
&lt;p&gt;But that wasn&apos;t the case, he said in an interview. With regard to delayed memory, for example, &quot;the escitalopram-treated group went from the most impaired to the best performing.&quot;&lt;/p&gt;
&lt;p&gt;The researchers didn&apos;t compare end scores for the escitalopram, problem solving therapy, and placebo groups, but they were: &lt;ul&gt; &lt;li&gt;For global cognitive functioning 89.8, 89.1, and 91.0 points, respectively&lt;/li&gt; &lt;li&gt;For delayed memory, 96.6, 89.1, and 94.2, respectively&lt;/li&gt; &lt;li&gt;For immediate memory, 95.1, 94.9, and 98.5, respectively&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The treatment showed no effect on other individual cognitive measurements, including those for attention, language, and IQ. Nor were there significant differences in changes in occupational or living conditions.&lt;/p&gt;
&lt;p&gt;Although SSRIs such as escitalopram have been associated with hospitalization for GI bleeding and falls in prior studies, these complications did not occur in Jorge&apos;s study.&lt;/p&gt;
&lt;p&gt;&quot;Long-term administration of SSRIs appears to be an effective and safe treatment option to improve cognitive outcomes among patients with cerebrovascular disease,&quot; they concluded in the &lt;em&gt;Archives&lt;/em&gt; paper.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that the study was limited by lack of CT or MRI scans and the younger age of escitalopram-treated patients, compared with other groups. That may have been a source of bias, although age did not appear to be a significant factor in the trial results.&lt;/p&gt;
&lt;p&gt;In this analysis, the researchers emphasized that the trial was not financially supported in any way by any drug company  --  a declaration hinting at the controversy that brewed last year over failure of one of the authors of the original &lt;em&gt;JAMA&lt;/em&gt; article to &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/13391&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/13391&quot; target=&quot;_blank&quot;&gt;properly disclose ties&lt;/a&gt; to Forest Pharmaceuticals, which makes escitalopram.&lt;/p&gt;
&lt;p&gt;Another scientist who discovered that omission published the information in a competing journal, inducing &lt;em&gt;JAMA&lt;/em&gt; to issue a gag rule on reporting of undisclosed conflicts of interest. That policy encourages those who discover such conflicts to report them to &lt;em&gt;JAMA&apos;s&lt;/em&gt; editors but prohibits them from disclosing the conflicts publicly pending an investigation by the journal.&lt;/p&gt;
&lt;p&gt;In the current analysis, the disclosure statement indicated that co-author Robertson, had received honoraria and speakers&apos; bureau fees from Forest, with the caveat that &quot;none of the design, analysis, or expenses (including the cost of medications) of this study were supported by monies, materials, or any intellectual input from Forest Laboratories.&quot;&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 study was supported solely by a grant from the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Jorge reported having received travel awards to participate in national meetings from the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company.&lt;/p&gt;&lt;p&gt;Co-authors reported financial conflicts of interest with Merck, NMT Medical, Eli Lilly, Centocor, Sanofi-Bristol-Meyers-Squibb, Boerhringer-Ingelheim, Schering-Plough, AstraZeneca, and GlaxoSmithKline, the former Hamilton Pharmaceutical Company, Avanir Pharmaceutical Company, Lubeck, Forest Laboratories, and Pfizer.&lt;/p&gt;&lt;p&gt;No pharmaceutical company donated medications for or had any financial interest in the study.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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