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Eplivanserin Beats Flurazepam on Next-Day Cognitive Effects

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Eplivanserin Beats Flurazepam on Next-Day Cognitive Effects JANUARY 2010 • WWW.CLINICALPSYCHIATRYNEWS.COM PSYCHOSOMATIC MEDICINE 45 CVD May Be Linked to Depression in Lupus BY MITCHEL L. ZOLER generally occurs and remits over time. Dr. Julian and her associates analyzed a variety of de- P HILADELPHIA — Patients with lupus have a high mographic and clinical variables to see which factors EWS prevalence of depression, which may be linked to the N were linked with new-onset depression during the 5 cardiovascular disease that’s also highly prevalent in lu- years of follow-up. A multivariate analysis identified pus patients. EDICAL three measures that had a significant association: a so- Cardiovascular disease and cardiovascular risk “may M cioeconomic status below the poverty level, which precipitate development of depression in patients with linked with a greater than threefold risk for incident de- LOBAL lupus,” Laura Julian, Ph.D., said at the annual meeting G pression; a history of myocardial infarction or stroke, of the American College of Rheumatology. It’s also pos- linked with a twofold greater rate of new depression; sible that depression in patients with systemic lupus ery- LSEVIER and greater SLE disease activity, linked with a 12% high- thematosus (SLE) exacerbates cardiovascular disease by /E er rate of new depression. making patients poorly compliant with treatment. “The OLER Analyzing the data a different way, the researchers relationship between cardiovascular disease and depres- L. Z found that through the 5 years of follow-up, 25% of the sion [in lupus patients] may be bidirectional,”she said. SLE patients without a history of cardiovascular disease ITCHEL Because of this apparent interrelationship, physi- M or poverty had an episode of new depression. Among cians who care for SLE patients should regularly screen Laura Julian, Ph.D., says vascular disease in specific those with either cardiovascular disease or poverty, the them for depression and treat it when diagnosed. Physi- white-matter regions may cause the depression. rate for a new depression episode was about 40%. And cians should also be diligent about screening for and in patients with a history of both cardiovascular disease treating cardiovascular disease risks in lupus patients, ed data from 725 lupus patients who were followed for and poverty, 80% had an episode of incident depression said Dr. Julian, a neuropsychologist at the University of more than 5 years. More than 90% of the patients were during the study. California, San Francisco. women, and average age at entry to the study was 51. The CES-D could also be used to diagnose depression “Our working hypothesis is that accumulation of vas- At entry and regularly during follow-up, the patients in a routine-practice setting, and it would be reasonable cular disease in specific white-matter regions of the were assessed for depression by having them complete for physicians to screen patients with SLE for depression brain might precipitate development of depression. In lu- the CES-D (Center for Epidemiology Studies–Depres- every few months, Dr. Julian said. So far, there is no ev- pus patients there is a very high risk of cardiovascular out- sion) scale, a commonly used, self-report, 20-question idence proving that conventional behavioral and medical comes, so we think this is reasonable,” she said in an in- survey. People who scored 23 or higher on the CES-D treatments for depression are effective in SLE patients, terview. This etiology has been called vascular depression. were considered to have probable depression. In the se- but until this is evaluated in a study, it is reasonable to Evidence supporting the occurrence of vascular de- ries, 23% met this set of criteria at baseline. use these treatments on depressed SLE patients, she said. pression in SLE patients came from following patients During follow-up, about 12% of the SLE patients de- Dr. Julian said that she had no financial disclosures. ■ who were enrolled in the Lupus Outcomes Study, which veloped depression each year, but another 10% who had enrolled patients with SLE at the University of Califor- been previously identified with depression remitted. Dr. Watch a video interview with Dr. Julian at nia, San Francisco. Dr. Julian and her associates collect- Julian said this pattern is typical for depression, which http://www. youtube.com/watch?v= jm4KZ6KFoMM. Eplivanserin Beats Flurazepam Early Pain Reduction Flags On Next-Day Cognitive Effects Greater Duloxetine Efficacy BY BRUCE JANCIN subjects were switched to the other treat- BY BRUCE JANCIN line (VAS score of greater than 30 out ment arm and testing was repeated. of a possible 100). During the 6-month I STANBUL, TURKEY — The novel The morning after taking flurazepam, I STANBUL, TURKEY — Early study, 26.5% of subjects dropped out. sleep aid eplivanserin proved to be well participants displayed significantly worse marked reduction in pain in response to The mean VAS pain score in the over- tolerated, with no effects on next-day cognitive performance, significantly duloxetine proved to be the strongest all study population improved from 55 at cognitive or psychomotor performance, more sedation, and—somewhat surpris- predictor of significant long-term im- baseline to 31 at 6 months. Forty-eight whether given alone or in combination ingly—significantly better psychomotor provement in depressive symptoms in percent of patients reported at least a with zolpidem in a randomized, double- performance than after placebo. depressed subjects in the German 50% reduction in pain on the VAS after blind, placebo- and benzodiazepine-con- In the second phase of the study, sub- PADRE study. 4 weeks of treatment, a clinically signif- trolled crossover trial. jects took 5 mg of eplivanserin or place- A 50% or greater improvement in icant improvement. Nearly two-thirds of Eplivanserin (Ciltyri) is an investiga- bo at bedtime on 21 consecutive nights, self-gauged overall pain symptoms on these early pain responders experienced tional agent, the furthest along in terms then took the six psychometric tests on a visual analog scale (VAS) after 4 weeks remission of their depression by 6 of development in a new drug class the morning of day 22. That night they on the selective norepinephrine reup- months as defined by an Inventory for called the antagonists of serotonin two- took 10 mg of immediate-release zolpi- take inhibitor was associated with a IDS score of 12 or less; this remission A receptors, or ASTARs. Eplivanserin dem (Ambien) with their eplivanserin or threefold greater likelihood of achiev- rate was twice that of patients who did increases EEG slow-wave sleep, Dr. placebo, then once again underwent psy- ing at least a 50% decrease on the clin- not achieve at least a 50% decrease in Christine Roy explained at the annual chometric testing the following morn- ician-rated Inventory for Depressive pain at 4 weeks, noted Dr. Linden of congress of the European College of ing. Then the eplivanserin and placebo Symptomatology (IDS) scale at 6 Charité University Hospital, Berlin. Neuropsychopharmacology. groups were crossed over, and the se- months, the primary study end point, The secondary end point was the As an ASTAR, eplivanserin would be quence was repeated. Dr. Michael Linden said at the annual change over 6 months in the KUSTA, a expected to avoid impairment of next- After 21 nights of eplivanserin, the congress of the European College of 100-point German-language depression day functioning, unlike benzodiazepines, test results for next-day cognitive and Neuropsychopharmacology. scale encompassing mood, activity, which exert their hypnotic effect by bind- psychomotor performance and sedation PADRE was a prospective observa- sleep, and tension/relaxation. The ing to GABA receptors, added Dr. Roy of weren’t significantly different from the tional study in which 4,517 adult out- mean KUSTA improved from a baseline Sanofi Aventis in Chilly-Mazarin, France. following 21 nights of placebo. The same patients with a depressive episode re- of 25 to 58 points at 6 months in those She presented a study in which epli- was true after taking eplivanserin plus ceived treatment with duloxetine who did not show a significant pain re- vanserin’s effects upon cognitive and psy- zolpidem, compared with placebo plus (Cymbalta) at 693 centers in Germany. sponse by 4 weeks, and by an additional chomotor performance were compared zolpidem, Dr. Roy reported. Lilly Deutschland and Boehringer In- 13.3 points in those who did. to those of flurazepam and placebo in 24 In September, the Food and Drug Ad- gelheim sponsored the study. The mean Seventeen percent of PADRE partic- healthy subjects. In the first portion of ministration responded to Sanofi Aventis’ age of participants was 52 years, and ipants reported one or more treatment- the study, participants were randomized application for marketing approval for 72% were women. emergent adverse events, most com- to a single bedtime 30-mg dose of flu- eplivanserin with a request for additional The mean baseline score on the clin- monly mild nausea and other GI side razepam or placebo. The next morning data on the drug’s risk/benefit ratio. ician-rated IDS was 40 on the 0-84 scale. effects, hyperhidrosis, vertigo, and they had to complete six psychometric Dr. Roy’s randomized trial was spon- Eighty percent of subjects had moder- headache. There was no weight gain tests. After a 21-day washout period, sored by Sanofi Aventis. ■ ate to severe painful symptoms at base- during the 6 months of therapy. ■.
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