Posted by jrbecker on October 24, 2005, at 11:49:16
A recent press release regarding Valdoxan's effcicacy is posted below. Also, an update of research studies that were presented at this week's 18th Annual Congress of European College of Neuropsychopharmacology (ECNP)is pasted below.
Valdoxan is currently being reviewed in Europe and is predicted to be approved there in early to mid- 2006. Currently, Valdoxan has not been submitted for approval in the US.
For more drug development updates, see ...
http://neurotransmitter.net/newdrugs.htmlNews Release
Monday 24 October 2005, 14:45 GMT Monday 24 October 2005
HEALTH
Servier
New Melatonergic Antidepressant Combines Efficacy With Very Favourable Side-Effect Profile
AMSTERDAM, The Netherlands, October 24 /PRNewswire/ --- Valdoxan(R) (agomelatine) Provides Antidepressant Efficacy With the Additional Clinical Benefit of Sleep Improvement With no Effect on Daytime Vigilance
The first melatonergic antidepressant, Valdoxan(R) (agomelatine), offers an innovative new approach to the treatment of depression. Valdoxan combines antidepressant efficacy, even in severely depressed patients, with an extremely favourable side-effect profile and has the additional benefit of sleep regulation in depressive patients, according to new data presented at the 18th Congress of the European College of Neuropsychopharmacology (ECNP) today. The ability of Valdoxan to relieve depressive patients' sleep disruption without affecting daytime vigilance is a key advantage for an antidepressant medicine as sleep complaints are a very common and disabling feature of depression.
Antidepressant efficacy and additional clinical benefits
Valdoxan was shown to be an effective antidepressant, by reducing the initial HAMD score to a similar extent to that of the selective serotonin reuptake inhibitor (SSRI) paroxetine and significantly greater than placebo (1). Results from two other clinical trials presented in Amsterdam show that Valdoxan also has a similar efficacy to the serotonin noradrenergic reuptake inhibitor (SNRI) venlafaxine, but not the often observed side-effects associated with the SNRI. Preliminary results of a specific study comparing Valdoxan (25 - 50 mg / day) with venlafaxine (75 - 150 mg / day) in depressed patients showed that Valdoxan had a similar antidepressant effect. However, Valdoxan treatment resulted in significantly better and earlier improvement in initiating sleep (p<0.001). In addition, a polysomnography study in depressed patients showed that Valdoxan 25 mg had a beneficial effect on sleep architecture.
"In addition to its effective antidepressant properties, Valdoxan is the only antidepressant to have a specific action on circadian rhythms", says Dr Raymond Lam from the Department of Psychiatry, University of British Columbia, Canada. "It can relieve sleep complaints in depressed patients without residual impairment and thus appears to be an innovative, new pharmacological treatment for depression."
Further studies versus placebo and comparators have confirmed the antidepressant efficacy of Valdoxan in adults of all ages, including elderly depressed patients.(1, 2) In addition, Valdoxan has shown particularly interesting results in severely depressed patients; its antidepressant efficacy increased as the severity of the depression increased, including in patients with a HAMD>30, therefore providing clear patient benefits.
Excellent side-effect profile
Valdoxan has an innovative pharmacological profile; it is the first melatonergic antidepressant acting as a MT1 and MT2 receptor agonist with additional 5-HT2C receptor antagonist properties. Due to this unique mode of action, it does not show the typical side effects found with SSRIs and SNRIs, in particular sexual dysfunction and drug discontinuation symptoms(i), two common side-effects that patients find particularly troubling.
A trial comparing Valdoxan with venlafaxine showed comparable antidepressant efficacy of both treatments, but significantly less sexual dysfunction with Valdoxan. In addition, a placebo-controlled, double-blind study comparing Valdoxan with paroxetine showed that, after one week of treatment discontinuation, no signs of discontinuation symptoms were seen in the Valdoxan group compared to significant discontinuation symptoms in the paroxetine group.(3)
A new and effective approach to depression treatment
Patient acceptability of antidepressants is a major concern and is still one of the unmet needs in treating depression. Special emphasis has been given to the acceptability of Valdoxan throughout its clinical development programme, in particular its effect on sexual dysfunction and drug discontinuation symptoms.
Valdoxan was discovered and developed by Servier. The drug is currently in Phase III trials and a registration dossier for an indication in major depressive disorder (MDD) was submitted to the European Regulatory Agency (EMEA) in 2005.
(i) Discontinuation symptoms occur when treatment with certain antidepressants (mainly SSRIs and SNRIs) is stopped. They can include nausea, headache, dizziness, sleep disturbances, anxiety and irritability.
References
1. Lôo H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17:239-247
2. Emsley, CINP 2004; Int.J.Neuropsychopharm. 2004; Vol 7; suppl 1: P02.174
3. Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I. Int Clin Psychopharmacol. 2004; 19 :271-280
Distributed by PR Newswire on behalf of Servier
--------------------------------------------------------------------------------
PR Newswire Europe Ltd.209 - 215 Blackfriars Road, London, SE1 8NL
Tel : +44 (0)20 7490 8111
Fax : +44 (0)20 7490 1255
E-mail : info@prnewswire.co.ukCopyright © 2005 PR Newswire Europe Limited. All rights reserved.
A United Business Media Company.
Terms and conditions of use apply.
___________________________________
Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S416
Confirmed clinical efficacy of agomelatine (25-50mg) in major depression: two randomized, double blind, placebo-controlled studies
J.P. Olié1, R. Emsley21Sainte-Anne Hospital, University Department of Psychiatry, Paris cedex 14, France
2Faculty of Medicine, Psychiatry, South Africa
Aim of the studies: Agomelatine, the first melatonin receptor agonist antidepressant, has proven its efficacy in major depressive disorder (MDD) in a pivotal 8-week study with 711 patients[1]. In this dose ranging study, agomelatine 25 mg/day demonstrated a significant antidepressant efficacy versus placebo with a good tolerability. The two presented 6-week studies were aimed to confirm the efficacy and safety of agomelatine in the treatment of MDD, starting at 25 mg/day with the possibility of increasing at 50 mg/day after two weeks of treatment in case of insufficient improvement.
Methods: Patients (212 in the first study and 238 in the second one) fulfilling DMS-IV criteria for MDD were randomised to agomelatine 25 mg or placebo. In the first study, 107 patients received agomelatine and 105 placebo, with respective mean baseline scores of 26.5 and 26.7 on the Hamilton Depression scale (HAM-D). In the second study, 118 patients received agomelatine and 120 placebo, with respective baseline scores of 27.4 and 27.2. Insufficient improvement was based on the HAM-D and the Clinical Global Impression (CGI) scales and were blind for both the clinician and the patient. The primary outcome measure was the HAM-D final score using the last observation carried forward (LOCF). Secondary outcome measures were Clinical Global Impression Scale, response to treatment (decrease from baseline of HAM-D score equal to or superior than 50%) and time to first response.
Results: In both studies, agomelatine was significantly better than placebo on the mean HAM-D final score (delta = 2.30, p = 0.026 and delta = 3.44, p < 0.001 for the first and second study respectively). Similar results were observed in the agomelatine 25–50 mg arms in comparison to ``placebo increased'' arms (p < 0.05).Likewise significant results were observed on the CGI severity and/or improvement scales in comparison with placebo. In both studies, the analysis of rate of responders were also significantly (p < 0.05) in favour to agomelatine as well as the survival analysis of time to first response. The tolerability of both doses of agomelatine was good and similar to placebo as reflected in the low number of emergent adverse events.
Conclusion: In conclusion, agomelatine has confirmed its efficacy in MDD with a favourable tolerability profile. This results validate agomelatine as a new and efficient approach in the treatment of depression.References:
Lôo, H. et al., 2002. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol 17:239–247.Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S417
Agomelatine, the first melatonergic receptor agonist antidepressant, shows confirmed efficacy in severely depressed patients
S.A. Montgomery1, S. Kasper21Imperial College, University of London, London, United Kingdom
2University of Vienna Medical School, Department of Clinical Psychiatry, Austria
Statement of the study: The search for new drugs with efficacy in severe depression accompanied by a good tolerability profile has become a major goal since it is an important unmet need in depression treatment. Agomelatine, the first melatonergic receptor agonist antidepressant, has been shown to have efficacy in major depression in the overall population in three pivotal trials at the standard dose of 25 mg with the possibility of a dose increase to 50 mg if needed [1,2]. The primary outcome for efficacy was the Hamilton Depression Scale (HAM-D). The tolerability was good and similar to placebo, while paroxetine, the active comparator, showed significantly (P < 0.001) more gastrointestinal adverse events than placebo [1]. The aim of the present analysis is to investigate whether agomelatine also has antidepressant efficacy in severely depressed populations and a good tolerability profile.
Methods: The efficacy of agomelatine was analysed in the severely depressed patient population from these three positive pivotal trials. Two criteria of severity were defined: a HAM-D score equal to or superior than 25 and the stringent criterion of a HAM-D score equal to or superior than 25 combined with a Clinical Global Impression Severity Scale (CGI-s) score equal to or superior than 5. According to this, 238, 202, and 151 patients fulfilled the first criterion and 168, 165 and 121 fulfilled the second criterion. A meta-analysis of the three studies was also performed.
Results: The three pivotal studies all showed the antidepressant efficacy of agomelatine in the severely depressed patients defined according to the above severity criteria. The meta-analysis of these studies also shows that agomelatine 25–50 mg per day provides antidepressant efficacy in severe populations with a level of significance of P < 0.001. The number of responders and remitters also showed a significant (P < 0.001 and P < 0.01, respectively) advantage for agomelatine. Agomelatine was also found to be effective in a subpopulation with severe depression in an elderly population (over 60 years old) in a specific placebo-controlled study. Tolerability in all studies was as good in the severely depressed population as in the overall population.
Conclusion: These results show that agomelatine, an antidepressant drug with a new pharmacological profile, is also effective in severe depression in both adult and elderly populations as judged by both response and remission and has a good tolerability profile.References:
Loo, H. et al., 2002, Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol 17: 239–247.
Emsley, R, 2004, Efficacy and safety of agomelatine (25 mg/50 mg), a melatonergic and specific serotonergic antidepressant, in the treatment of major depressive disorder: a randomised, double-blind placebo-controlled study. Int J Neuropsychopharmacol 7: S350.
Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S419
Efficacy of agomelatine versus venlafaxine on subjective sleep of patients with major depressive disorder
C. GuilleminaultSleep Disorder Clinic, Sleep Disorder, Stanford, USA
Sleep disorders constitute one of the main complaints of patients suffering from major depressive disorder (MDD). Forty (40) to 60% of outpatients with MDD report difficulties initiating and maintaining sleep as well as early awakening; some of them also experience daytime sleepiness [1]. As improvement of sleep problems appears as essential in the course of antidepressant therapy, some antidepressive medications have deleterious effects on sleep by causing insomnia, daytime sleepiness or sedation. Agomelatine (Valdoxan) is the first melatonergic antidepressant with an innovative pharmacological profile: melatonin receptors agonist with 5-HT2C antagonist properties. Agomelatine 25 mg/day [2] has been shown to be effective in MDD without being sedative or associated with daytime drowsiness. The purpose of this study was to demonstrate that agomelatine improves subjective sleep (onset and quality) faster than venlafaxine in patients suffering from MDD.
Methods: This double-blind randomised multicentre trial involved out-patients aged between 18 and 60 years (inclusive) who met the criteria for MDD (DSM-IV), single or recurrent episodes, and presenting a baseline HAM-D score superior than or equal to 20. At their entry in the study, patients were randomised either to agomelatine 25 mg/day or venlafaxine 75 mg/day from W0 to W2. According to the improvement of patients' depressive symptoms, the dosage of treatments was increased to 50 mg daily dose of agomelatine or venlafaxine 150 mg, from W2 to W6. Patients were assessed with HAM-D at W0, W2, W4 and W6. The subjective sleep onset and sleep quality were evaluated based on the ``ease of getting to sleep (GTS)'' and ``Quality of Sleep (QOS)'' items of the Leeds Sleep Evaluation Questionnaire (LSEQ). This questionnaire was filled at W1, W2, W3, W4 and W6. Another objective of the study was to explore agomelatine's impact on daytime condition using visual analogue scales (VAS). The VAS assessed ``daytime sleepiness'' and ``feeling good'' dimensions.
Results: 332 patients were included in the study (agomelatine, n = 165, and venlafaxine, n = 167). In the Full Analysis Set last HAM-D scores were respectively 9.9±6.6 and 11.0±7.4 in the agomelatine and venlafaxine groups (95%-CI [-0.45;2.45]). A significantly better improvement on LSEQ ``getting to sleep'' (p = 0.007) and also on ``quality of sleep'' items (p = 0.015) was shown as early as the end of the 1st week of treatment with agomelatine compared to venlafaxine. This effect lasted till the end of treatment phase (p = 0.001 on GTS and p = 0.021 on QOS). Earlier improvement with significant differences for ``daytime sleepiness'' and ``feeling good'' VAS items (p inferior than or equal to 0.001 at W1) were also noted indicating earlier subjective daytime improvement. (All results will be presented during the session).
Conclusion: agomelatine and venlafaxine showed a comparable antidepressant efficacy. But beside its antidepressant properties, agomelatine is able to relieve sleep complaints of depressed patients with a favourable impact on daytime alertness and as such is a clear innovative treatment of depression.References:
Fava M. Daytime Sleepiness and Insomnia as correlates of depression. J Clin Psychiatry 2004; 65 suppl 16: 27–32.
Lôo H, Hale A, D'haenen H. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol. 2002; 17: 239–247.
Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S435
Effect of agomelatine on the sleep EEG in patients with major depressive disorder (MMD)
M.-A. Quera-Salva1, B. Vanier1, F. Chapotot1, M. Bohic1, C. Moulin1, F. Lofaso1, C. Guilleminault21Hôpital Raymond Poincaré, Unité du Sommeil, Garches, France
2Stanford Sleep Disorders Centre, Sleep Disorder, USA
Agomelatine is the first melatonergic antidepressant presenting an innovative pharmacological profile: melatonin receptors agonist with 5-HT2C antagonist properties. Agomelatine 25 mg per day1 has been shown to be effective in Major Depressive Disorder (MDD) without being sedative or associated with daytime drowsiness. The purpose of the study was to assess if agomelatine 25 mg induces specific effects on sleep architecture in outpatients suffering from MMD.
Methods: This unicenter open study involved out-patients with a new major depression episode (DSM-IV), aged between 20 and 56 years, with a baseline HAM-D score superior than or equal to 20. Patients received agomelatine 25 mg p.o. a day for 42 days. Polysomnography and subjective evaluations were performed at D-1 (adaptation night), D0, D7, D41 (adaptation night) and D42. Recordings were performed with Pamela computerized sleep system (MEDATEC, Belgium) with a 100 Hz sampling rate per channel, and included the following variables: EEGs (C3-A2, C4-A1 and C3-O2), 2 EOGs and one EMG. Wake and sleep staging were analysed by international criteria (Rechtschaffen and Kales) and quantitative EEG analysis was performed with the PRANA software (PhiTools, Strasbourg). EEG power spectral analysis was performed on successive 2-sec windows using a FFT algorithm with previous artefact rejection. Artefacts were detected by combining digital filtering and signal-dependent amplitude thresholds and were subsequently reviewed by an expert. The delta ratio was calculated as following: delta power first sleep cycle / delta power second sleep cycle. The Leeds Subjective Scale was used to measure patient's subjective sleep perception. Results are expressed as median.
Results: 15 patients (8 women), mean age 36 years (SD:11.3), were included in the study. Patients had 2.3 previous MDD episodes as a mean (SD:1.1). The HAM-D 17 item score was 21.8 (SD:1.5). After 42 days of treatment the HAM-D 17 item score decreased to a mean score of 9.2 (SD:5.5). The sleep efficiency (TTS/TSP * 100) increased by 4% (95% CI: 0.03–8.69), and the wake after sleep onset decreased from 42 to 19 minutes. Slow wave sleep (stages 3 and 4) increased by 16 minutes (95% CI: 1.79–26.06) with an increase of 4% of the total sleep period (95% CI: 0.69–6.28). Median time of sleep onset advanced from 00 h 03 to 23 h 37, and median time of minimum heart rate advanced from 05 h 10 to 04 h 34 (95% CI: -2:42–5:14). Delta ratio presented a trend to increase (from 0.93 to 1.3; 95% CI -0.06–0.62). Subjectively, ``sleep quality'' and ``easiness falling asleep'' improved on Leeds Subjective Scale from day 7 on. No effect was seen in different REM sleep indices.
Conclusion: This pilot study shows that agomelatine 25 mg at night time improved sleep continuity and quality in depressed patients. It normalized the distribution of SWS throughout the night. After only seven days of treatment, an effect on sleep quality was perceived by patients. Furthermore, agomelatine advanced the time of sleep onset, and the time of minimum heart rate suggesting a circadian effect.References:
Lôo H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17: 239–247.
Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S440
Sexual function in remitted depressed patients following agomelatine and venlafaxine XR treatment
S.H. KennedyUniversity Health Network, Department of Psychiatry, Toronto, Canada
Background and objectives: Current antidepressant medications have comparable effectiveness, the most recent ones offering better safety profile. However sexual dysfunction is recognised as a potential side-effect across all classes of antidepressants (MAOIs, TCAs, SSRIs, SNRIs and newer antidepressants [1,2]). Agomelatine (Valdoxan) is the first melatonergic antidepressant. Its innovative pharmacological profile combines melatonin receptor agonist and 5-HT2C antagonist properties. Agomelatine 25 mg/day3 has been shown to be effective in MDD with a good safety and tolerability profile. In the course of development, agomelatine did not appear to be associated with sexual dysfunction. The purpose of this study was to assess the sexual acceptability of agomelatine 50 mg in comparison with venlafaxine 150 mg, in remitted depressed patients.
Methods: This double-blind randomised multicentre trial involved out-patients aged between 18 and 60 (inclusive) who met the criteria for MDD (DSM-IV-TR), single or recurrent episode, and had a baseline MADRS score > = 20. At entry into the study, patients were randomised either to agomelatine 50 mg/day or venlafaxine 75 mg/day from W0 to W2, then venlafaxine 150 mg/day from W2 to W12. They were assessed with MADRS at W0, W2, W6, W10 and W12. Stable remitted patients were defined as being responders (having a 50% reduction from baseline MADRS score) at W12 and having a MADRS score < = 12 at W12. Sexual function was evaluated using the Sex Effects (SEX-FX) scale and was assessed at W0, W2, W6, W10 and W12.
Results: 277 patients were included in the study. 78 of 137 (57%) agomelatine and 83 of 140 (59%) venlafaxine treated patients achieved remission. In the Full Analysis Set the rate of responders was 82.5% in the agomelatine group and 79.9% in the venlafaxine group. Last MADRS scores were respectively 10.1±7.8 and 9.8±7.9 in the agomelatine and venlafaxine groups (95% CI [-2.16;1.55]). Among sexually active patients (n = 111) at the end of the trial, 41.2% of venlafaxine-treated patients experienced sexual dysfunction on desire-arousal factor in comparison with 20% in agomelatine group only (p = 0.015, Chi-squared test). On the orgasm factor 47.0% of venlafaxine-treated patients experienced sexual dysfunction versus 20% in agomelatine group (p < 0.002, Chi-squared test).
Conclusion: Both groups showed comparable antidepressant efficacy, whereas agomelatine offered a better profile of sexual function.References:
Montgomery, S.A., Baldwin, D.S., Riley, A. 2002. Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. Journal of Affective Disorders 69: 119–140.
Clayton, A.H., Zajecka, J., Ferguson, J.M., Filipiak-Reisner, J.K., Brown, M.T., Schwartz, G.E. 2003. Lack of sexual dysfunction with the selective noradrenaline reuptake inhibitor reboxetine during treatment for major depressive disorder. International Clinical Psychopharmacology 18: 151–156.
Loo, H., Hale, A., Dhaenen, H. 2002. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. International Clinical Psychopharmacology 17: 239–247.
Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S660
Clinical efficacy of agomelatine in depression: the evidence
J. Den Boer, F. Bosker, Y. MeestersGroningen University Medical, Department of Psychiatry, Groningen, The Netherlands
Agomelatine is the first melatonergic antidepressant being a potent agonist of melatonin receptors (MT1 and MT2) with 5-HT2C antagonist properties. In the course of development, agomelatine's efficacy in treating major depressive disorder (MDD) has been demonstrated in several placebo-controlled studies, at the dose of 25 mg/day. In clinical trials performed versus selective serotonin reuptake inhibitors (SSRIs)1 and serotonin noradrenergic reuptake inhibitors (SNRIs), agomelatine showed a treatment effect in line with these antidepressants; the results will be presented during the symposium. Agomelatine's efficacy was also studied in subgroups of severely depressed patients defined as having a HAMD baseline score ≥25 (or MADRS score ≥30) or a HAMD baseline score ≥25 (or MADRS score ≥30) and CGI severity ≥5 at baseline. Agomelatine was clearly shown to be more effective than placebo in the severely depressed patients (P < 0.05). Similar results were observed in the subgroup of patients aged 60 and over (elderly patients). Moreover, analysis of scores on the Hamilton Anxiety Rating Scale (HAMA) and HAMD anxiety items obtained in MDD studies showed a significant effect of agomelatine compared with placebo on anxiety symptoms within depression. Similar results were observed in patients with a high level of anxiety (score ≥5 on HAMD anxiety items) at their entry to the studies (P < 0.001). In view of the available data on agomelatine, this new antidepressant appears as an effective and innovative treatment for patients with MDD, including severely depressed patients.References:
Lôo H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17: 239–247.Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S660
The benefits of agomelatine beyond antidepressant efficacy: impact on sleep
R. LamMood Disorders Centre, Univ. of British Columbia, Dept. of Psychiatry, Vancouver, Canada
Sleep disturbances are common disabling symptoms in depression. Agomelatine is the first melatonergic antidepressant being a potent agonist of melatonin receptors (MT1 and MT2) with 5-HT2C antagonist properties. Agomelatine was shown to be effective in treating major depressive disorder at the dose of 25 mg per day [1]. Analysis of the HAMD sleep items of efficacy studies showed agomelatine to be superior to placebo in improving all 3 types of insomnia: initial insomnia (P < 0.001), middle insomnia (P = 0.015), and early wakening (P = 0.006), with a similar treatment effect size. Furthermore, results from the Leeds Sleep Evaluation Questionnaire (LSEQ) showed that agomelatine significantly improved the ability to initiate sleep (P < 0.001) and improved sleep quality (P = 0.002) compared with placebo, whereas SSRIs did not. Agomelatine's superiority over placebo was seen as early as week 2 of treatment. In a study comparing agomelatine (25–50 mg/day) with venlafaxine (75–150 mg/day) in depressed patients, both groups showed comparable efficacy whereas agomelatine resulted in a significantly better and earlier improvement in the ``getting to sleep'' and ``quality of sleep'' LSEQ items (P = 0.007 and P = 0.015, respectively) as early as week 1, simultaneously improving daytime alertness. A polysomnography study was conducted to examine the effects of agomelatine 25 mg on sleep architecture in depressed patients. Results will also be discussed during the presentation. Thus, beside its antidepressant properties, agomelatine is able to relieve sleep complaints in depressed patients while improving daytime alertness, and appears to be an innovative pharmacological treatment for depression.References:
Lôo H et al. Int Clin Psychopharmacol. 2002; 17: 239–247.Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S660
Efficacy/tolerance profile of agomelatine and practical use in depressed patients
F. RouillonHopital André Chenevier, Department of Psychiatry, Créteil, France
Agomelatine, a new antidepressant with a unique pharmacological profile, is the first melatonergic (MT1 and MT2 receptor agonist) antidepressant. Its efficacy has been demonstrated in the treatment of major depressive disorder (MDD) at a dose of 25 mg per day, including in severely depressed patients [1]. As the acceptability of a new antidepressant is a major concern, special emphasis has been placed on that property of agomelatine. Compared with placebo, agomelatine did not show in the course of development the typical side effects found with SSRIs. Since sexual dysfunction is a significant side effect with current antidepressants, a placebo-controlled trial in MDD comparing the impact of agomelatine and venlafaxine on sexual function was undertaken. The results, indicating agomelatine's very favorable profile, will be discussed. Given concerns about drug discontinuation syndromes associated with SSRIs and other antidepressants, a double-blind, placebo-controlled trial versus paroxetine with abrupt discontinuation of treatments was conducted. The study revealed no discontinuation symptoms with agomelatine, in contrast to paroxetine. Since sleep complaints are a major presenting feature of depression, it is important for an antidepressant to relieve them without sedative effects. Agomelatine has been shown to significantly improve all phases of disturbed sleep and overall sleep quality in depressed patients. Thus, agomelatine offers a novel approach to depression treatment combining efficacy, including in severely depressed patients, with an extremely favorable side-effect profile and sleep regulation. These properties confer on agomelatine a definite clinical advantage in the treatment of depression.References:
Lôo H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17: 239–247.
Citation: European Neuropsychopharmacology; The Journal of the European College of Neuropsychopharmacology, Volume 15 (2005), Supplement 3, Page S659
Pharmacology of a new antidepressant: benefit of the implication of the melatonergic system
E. FuchsDPZ Deutsches Primatenzentrum, Division of Neurobiology, Göttingen, Germany
Since depression is associated with internal rhythm desynchronization, resetting normal circadian rhythms could have antidepressant potential. Initial attempts to demonstrate this with melatonin were unsuccessful. However, experiments using agomelatine, a novel melatonergic agonist antidepressant with 5-HT2C receptor antagonist properties, revealed clear antidepressant-like effects in animal models. In rats subjected to chronic mild stress, agomelatine overcame anhedonic behavior quicker than imipramine or fluoxetine. Agomelatine exerts its antidepressant effects mainly when administered at the end of the daily activity period. In vitro binding studies revealed that agomelatine is a high-affinity agonist at both the melatonin MT1 and MT2 receptors. Moreover, agomelatine-unlike melatonin-blocks with high affinity 5-HT2C receptors. This combination contributes to agomelatine's rapid onset and efficacy at least in animal models. To validate this further, we investigated nocturnal sleep of psychosocially stressed male tree shrews – a valid animal model of depression – and agomelatine's effect on sleep quantity and quality during chronic stress. One control week was followed by 7 days' psychosocial stress before daily oral agomelatine administration (40 mg/kg), with stress continued throughout 28 days' treatment. During the first stress week, total REM sleep increased substantially whereas the average length of each REM period fell, and the sleep pattern became fragmented. In this model of depression, agomelatine reduced total REM sleep and created less fragmented sleep suggesting that sleep disturbances within depression might be successfully treated by agomelatine.
poster:jrbecker
thread:571357
URL: http://www.dr-bob.org/babble/20051024/msgs/571357.html