Guest guest Posted January 26, 2011 Report Share Posted January 26, 2011 iam thinking about to try Agomelatine... > > > In Europe they've released a new antidepressant. Apparentely as well as inhibiting 5H2C and raising NE and DA it also has an effect on melatonin levels regulating the sleep cycle. No mention of sexual side effects and has outperformed Prozac in depression trials. > > Im desperately needing some help with depression/sleep and if this thing is truly sex neutral Id be very tempted to give it a try > > Any of the science guys on here fancy doing some research on this > > It is produced by Servier which is quite a well renowned company > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 27, 2011 Report Share Posted January 27, 2011 I've been taking Valdoxan for a week now, and i actually feel a bit more depressed/pessimistic than usual, and I think there are mild sexual side effects in the form of libido loss. I was taking the drug for the dopamine and noradrenaline boost, but I have yet to feel anything positive from the it. I plan on continuing for another week or two to see what it does. I don't feel anything related to sleep benefits either. The side effects don't seem as severe as an SSRI, though. I'll let you know how I feel in a week or two. I had better results on Servier's older anti-depressant, Stablon, which I took for 6 months. I believe it helped in my recovery from PSSD. > > > > > > In Europe they've released a new antidepressant. Apparentely as well as inhibiting 5H2C and raising NE and DA it also has an effect on melatonin levels regulating the sleep cycle. No mention of sexual side effects and has outperformed Prozac in depression trials. > > > > Im desperately needing some help with depression/sleep and if this thing is truly sex neutral Id be very tempted to give it a try > > > > Any of the science guys on here fancy doing some research on this > > > > It is produced by Servier which is quite a well renowned company > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 27, 2011 Report Share Posted January 27, 2011 Are you saying that you actually recovered from PSSD after using Stablon? Or was it that you had sexual dysfunction while on SSRIs and you took Stablon simultaneously to help with the symptoms? Subject: Re: AgomelatineTo: SSRIsex Date: Thursday, January 27, 2011, 4:18 PM I've been taking Valdoxan for a week now, and i actually feel a bit more depressed/pessimistic than usual, and I think there are mild sexual side effects in the form of libido loss. I was taking the drug for the dopamine and noradrenaline boost, but I have yet to feel anything positive from the it. I plan on continuing for another week or two to see what it does. I don't feel anything related to sleep benefits either. The side effects don't seem as severe as an SSRI, though. I'll let you know how I feel in a week or two. I had better results on Servier's older anti-depressant, Stablon, which I took for 6 months. I believe it helped in my recovery from PSSD. > > > > > > In Europe they've released a new antidepressant. Apparentely as well as inhibiting 5H2C and raising NE and DA it also has an effect on melatonin levels regulating the sleep cycle. No mention of sexual side effects and has outperformed Prozac in depression trials. > > > > Im desperately needing some help with depression/sleep and if this thing is truly sex neutral Id be very tempted to give it a try > > > > Any of the science guys on here fancy doing some research on this > > > > It is produced by Servier which is quite a well renowned company > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 28, 2011 Report Share Posted January 28, 2011 Stablon seemed to take my recovery to the next level, yes. I stopped using Lexapro in January, 2007, and within 2 weeks had full blown PSSD and a host of other symptoms that made me suicidal. My libido, previously enormous, literally disappeared overnight. I woke up one morning in January and it was gone and I felt like I woke up a different person. Everything in life was meaningless. This was most of 2007. I got by with taking Buspar, which probably prevented me from killing myself and used it on and off through 2008. Recovery has been slow, although, it has progressed. I started Stablon in June of 2010. It seemed to correct some of the following sexual issues: retrograde (or non existent) ejaculation, weak (or almost no) orgasms. I may consider going back on Stablon as Valdoxan is totally messing with my emotional state. I'm a wreck on it. I feel like I should give it another week just to make sure, though. The prospect of increased dopamine and noradrenaline without the use of an agonist or reuptake inhibitor, seem, in theory, to be a goal I want to accomplish. But the reality is that I am not experiencing any perceivable benefit in this area. I am just experiencing increased anxiety, depression, and possibly, reverse progress of my recovery from PSSD. For the record, I would say my recovery is somewhere between 30-50%. And I started at zero-nothing; the absolute bottom. Sometimes I feel encouraged that I've come as far as I have, and then often I'm frustrated that it hasn't progressed further. I took the recommended 3 pill per day dose of Stablon. I tapered off of it slowly for about the last 5 weeks I took it. I ended my use of Stablon on December 31st, 2010. There were no withdrawal effects. > > > > > > > > > > > > In Europe they've released a new antidepressant. Apparentely as well as inhibiting 5H2C and raising NE and DA it also has an effect on melatonin levels regulating the sleep cycle. No mention of sexual side effects and has outperformed Prozac in depression trials. > > > > > > > > Im desperately needing some help with depression/sleep and if this thing is truly sex neutral Id be very tempted to give it a try > > > > > > > > Any of the science guys on here fancy doing some research on this > > > > > > > > It is produced by Servier which is quite a well renowned company > > > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 4, 2011 Report Share Posted May 4, 2011 How is the agomelatine going? > > > > After trying all kinds of antidepressants and experiencing the sexual side effects that all we know, I'm now on agomelatine. This is my third week and I feel better. On one hand, agomelatine works with my depression. On the other hand, my sexual performance has improved. I can reach orgasm easily and my libido is a little stronger. Nevertheless, my orgasm pleasure isn't still as intense as I'd like. > > > > Any more experiences with agomelatine? > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 5, 2011 Report Share Posted May 5, 2011 Ssri down regulation and agomelatine upregulation? Is this correct? Help me out boys > > > > > > After trying all kinds of antidepressants and experiencing the sexual side effects that all we know, I'm now on agomelatine. This is my third week and I feel better. On one hand, agomelatine works with my depression. On the other hand, my sexual performance has improved. I can reach orgasm easily and my libido is a little stronger. Nevertheless, my orgasm pleasure isn't still as intense as I'd like. > > > > > > Any more experiences with agomelatine? > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 10, 2011 Report Share Posted May 10, 2011 Hi All Agomelatine is available in Canada--FDA approval next year 2012 Link to Agomelatine approval Info in Europe. http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/landing/epar_search\ ..jsp & murl=menus/medicines/medicines.jsp & mid=WC0b01ac058001d125 & source=homeMe dSearch Agomelatine Info from studies / c-trials. Improvement in subjective sleep in major depressive disorder with a novel antidepressant, agomelatine: randomized, double-blind comparison with venlafaxine. Lemoine P, Guilleminault C, Alvarez E. Clinique Lyon-Lumière, Lyon Bron, France. patrick.lemoine99@... Abstract OBJECTIVE: Patients with major depressive disorder (MDD) experience sleep disturbances that may be worsened by some antidepressant drugs early in treatment. The aim of this study was to assess the subjective quality of sleep of patients receiving agomelatine, a new antidepressant with melatonergic MT(1) and MT(2) receptor agonist and 5-HT(2C) antagonist properties, compared with that of patients receiving venlafaxine, a serotonin-norepinephrine reuptake inhibitor. METHOD: This double-blind, randomized study involved 332 patients with MDD (DSM-IV criteria), lasted 6 weeks, and compared the effects of agomelatine 25-50 mg/day and venlafaxine 75-150 mg/day, with a possible dose adjustment at 2 weeks. Subjective sleep was assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ), and the main efficacy criterion was the " getting to sleep " score. Antidepressant efficacy was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) global improvement scale. The study was performed between November 2002 and June 2004. RESULTS: After 6 weeks, the antidepressant efficacy of agomelatine was similar to that of venlafaxine. The LSEQ " getting to sleep " score was significantly better with agomelatine (70.5 +/- 16.8 mm) than with venlafaxine (64.1 +/- 18.2 mm); the between-treatment difference at the last visit was 6.36 mm (p = .001), and the difference was already significant at week 1. Secondary sleep items, including LSEQ quality of sleep (p = .021), sleep awakenings (p = .040), integrity of behavior (p = .024), and sum of HAM-D items 4, 5, and 6 (insomnia score) (p = .044), were also significantly improved compared to venlafaxine, as was the CGI global improvement score (p = .016). Incidence of adverse events was 52.1% with agomelatine and 57.1% with venlafaxine, and withdrawals due to adverse events were more common with venlafaxine than with agomelatine (13.2% vs. 4.2%). CONCLUSION: Agomelatine showed similar antidepressant efficacy with earlier and greater efficacy in improving su CNS Drugs. 2009;23 Suppl 2:41-7. doi: 10.2165/11318660-000000000-00000. Agomelatine: efficacy at each phase of antidepressant treatment. Kennedy SH. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. sidney.kennedy@... Abstract Antidepressant pharmacotherapy forms the basis of management of major depressive disorder (MDD). In principle, the management of MDD should first elicit rapid relief of symptoms and then restore normal functioning and prevent relapse. It is recommended that treatment should continue for at least one year to minimize the risk of recurrence. Currently, most antidepressants fail to fulfill these goals, and rates of remission and long-term compliance are usually unsatisfactory. These shortcomings may be linked to tolerability and residual symptoms. Agomelatine is a novel antidepressant with an innovative mode of action characterized by agonism at the melatonergic MT(1)/MT(2) receptors and antagonism at the 5-HT(2C) receptors. As early as one week into treatment, depressive symptoms evaluated by the Clinical Global Impression Scale - Improvement (CGI-I) showed a significant improvement with agomelatine compared with venlafaxine (p < 0.0001). This rapid antidepressant efficacy was also seen at 2 weeks on the Hamilton Rating Scale for Depression (HAM-D), on which the mean total scores for agomelatine were lower than those for placebo (p < 0.05). At 6-8 weeks, evaluation on HAM-D, CGI-I and the CGI - Severity of illness (CGI-S) showed significant improvements with agomelatine versus placebo (p < 0.05). Patients treated with agomelatine also experienced greater relief of symptoms on CGI-I at 6 weeks compared with venlafaxine (p < 0.05). The antidepressant efficacy of agomelatine is maintained over the long term; almost 80% of patients remain free from relapse after 10 months of treatment. Agomelatine also significantly improves disturbed sleep and anxiety within depression, and this broad efficacy minimizes the risk of residual symptoms. The recent registration of agomelatine by the European Medicines Agency now offers the potential of fulfilling many currently unmet clinical needs throughout the time course of management of MDD. PMID: 19708725 [PubMed - indexed for MEDLINE] Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Olié JP, Kasper S. Sainte Anne Hospital, University Department of Psychiatry, Paris, France. jp.olie@... Comment in: * Int J Neuropsychopharmacol. 2007 Oct;10(5):575-8. Abstract Current antidepressants used in major depressive disorder (MDD) are still not efficacious enough for many patients due to high levels of treatment resistance and bothersome side-effects. Using a novel blinding method (interactive voice response system), this flexible-dosing study examined the effects of therapeutic doses of agomelatine, a new approach to depressive therapy offering potent melatonergic MT1/MT2 receptor agonism with 5-HT2C receptor antagonist properties, in patients with moderate-to-severe MDD. This 6-wk, double-blind, parallel-group study randomized 238 patients to 25 mg/d agomelatine (with dose adjustment at 2 wk to 50 mg/d in patients with insufficient improvement) or placebo. Depression severity was assessed using the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression (CGI) scale. Agomelatine was significantly more efficacious than placebo, with an agomelatine-placebo difference of 3.44 (p<0.001) using the HAMD final total score. Compared with placebo, agomelatine also had a significant positive impact on CGI - Improvement (treatment difference=0.45) and CGI - Severity (treatment difference=0.50) (both p=0.006), response rate (54.3% vs. 35.5% with placebo, p<0.05) and time to first response (p=0.008). Similar results were seen in patients with the most severe MDD. Depressed mood and sleep items of the HAMD were also significantly improved with agomelatine, which was well tolerated with a safety profile similar to placebo at both doses. This study confirms that agomelatine is effective in treating major depression, including the most severely depressed patients, with a good safety and tolerability profile, therefore providing physicians with an effective pha CNS Drugs. 2010 Jun 1;24(6):479-99. doi: 10.2165/11534420-000000000-00000. Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. Kennedy SH, Rizvi SJ. Department of Psychiatry, University Health Network, Toronto, Ontario, Canada. Abstract To demonstrate the clinical effectiveness of an antidepressant drug requires evidence beyond short- and long-term efficacy, including a favourable adverse-effect profile and sustained treatment adherence. Under these conditions, patients should experience enhanced social and functional outcomes. The novel antidepressant agomelatine, a melatonergic MT(1)/MT(2) receptor agonist with serotonin 5-HT(2C) receptor antagonist activity, displays antidepressant efficacy with a favourable adverse-effect profile that is associated with good patient adherence. Specifically, agomelatine has demonstrated significant short-term (6-8 weeks) and sustained (6 months) antidepressant efficacy relative to placebo, as well as evidence of relapse prevention (up to 10 months). In head-to-head comparative studies with venlafaxine and sertraline, there was evidence of early (at 1-2 weeks) and sustained (at 6 months) advantages for agomelatine. In addition to evidence of early efficacy, agomelatine also restored disturbed sleep-wake patterns early in treatment. There was no evidence of antidepressant-induced sexual dysfunction, weight gain or discontinuation-emergent symptoms. Agomelatine has demonstrated a range of properties that suggest it could offer advantages over current treatments for major depressive disorder, although further comparative trials are still required, as is evidence from real-world clinical practice. World J Biol Psychiatry. 2009;10(2):117-26. Beyond the monoaminergic hypothesis: agomelatine, a new antidepressant with an innovative mechanism of action. Kasper S, Hamon M. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. sci-biolpsy@... Abstract There are many potentials for the development of more effective, better tolerated, and more rapidly acting antidepressants. As there is large prevalence of circadian dysfunction in various affective disorders, including depression, one of the approaches is the development of antidepressant drugs with melatonergic agonist properties. Agomelatine, with its melatonergic agonistic (at both MT(1) an MT(2) receptors) and 5-HT(2C) antagonistic properties, represents a new concept for the treatment of depression. The antidepressant action of agomelatine has been initially demonstrated in animal models of depression, such as the forced swim - the learned helplessness - and the chronic mild stress paradigms. Subsequent studies demonstrated that the antidepressant activity of agomelatine does not solely depend on its agonistic action at melatonergic receptors, but also on its antagonistic activity at 5-HT(2C) receptors. Agomelatine also exhibits anxiolytic properties that bear a striking resemblance to those of selective 5-HT(2C) receptor antagonists. In patients with major depressive disorder, agomelatine had efficacy at least comparable to that seen with available antidepressants. Interestingly, agomelatine demonstrated antidepressant efficacy not only in patients with a moderate depressive episode but also in a more severe depressed subpopulation of patients. The treatment effect increased with the severity of the disease. Agomelatine also rapidly regulates the sleep-wake cycle without causing sedation and improves daytime condition. Agomelatine has an excellent safety profile, is weight neutral, does not affect sexual functioning and does not cause discontinuation syndrome. Collectively, its efficacy, together with its excellent tolerability, makes agomelatine an especially promising antidepressant for the near future. CNS Drugs. 2009;23 Suppl 2:27-34. doi: 10.2165/11318640-000000000-00000. Agomelatine: innovative pharmacological approach in depression. Popoli M. Center of Neuropharmacology, Department of Pharmacological Sciences, University of Milan, Milan, Italy. maurizio.popoli@... Abstract Currently available antidepressant agents such as tricyclic antidepressants (TCAs) act primarily through monoaminergic systems in the brain, and have proved to be suboptimal for the management of major depressive disorder (MDD). Such agents are also active at non-target receptor sites, contributing to the development of often serious adverse events. Even the newer selective serotonin reuptake inhibitors (SSRIs), which also act through monoaminergic systems, have suboptimal antidepressant efficacy, and the adverse events that do occur often negatively influence adherence. Although the pathophysiology of depression is not completely understood, it is increasingly recognized that monoamine deficiency/disruption is not the only pathway involved. Recognition that circadian rhythm desynchronization also plays a key role in mood disorders has led to the development of agomelatine, which is endowed with a novel mechanism of action distinct from that of currently available antidepressants. Agomelatine is an agonist of the melatonergic MT(1) and MT(2) receptors, as well as a 5-HT(2C) receptor antagonist. The antidepressant activity of agomelatine is proposed to stem from the synergy between these sets of receptors, which are key components of the circadian timing system. Agomelatine has shown antidepressant-like activity in a number of animal models of depression, such as the learned helplessness model, the chronic mild stress model, the forced swim test and the chronic psychosocial stress test. Moreover, agomelatine has been found to restore normal circadian rhythms in animal models of a disrupted circadian system, and has proved beneficial in an animal model of delayed sleep phase syndrome. Likewise, it has been shown to improve disturbed sleep-wake rhythms in depressed patients. Moreover, current pharmacological and clinical data strongly support the use of agomelatine in the management of MDD. CNS Drugs. 2009;23 Suppl 2:41-7. doi: 10.2165/11318660-000000000-00000. Agomelatine: efficacy at each phase of antidepressant treatment. Kennedy SH. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. sidney.kennedy@... Abstract Antidepressant pharmacotherapy forms the basis of management of major depressive disorder (MDD). In principle, the management of MDD should first elicit rapid relief of symptoms and then restore normal functioning and prevent relapse. It is recommended that treatment should continue for at least one year to minimize the risk of recurrence. Currently, most antidepressants fail to fulfill these goals, and rates of remission and long-term compliance are usually unsatisfactory. These shortcomings may be linked to tolerability and residual symptoms. Agomelatine is a novel antidepressant with an innovative mode of action characterized by agonism at the melatonergic MT(1)/MT(2) receptors and antagonism at the 5-HT(2C) receptors. As early as one week into treatment, depressive symptoms evaluated by the Clinical Global Impression Scale - Improvement (CGI-I) showed a significant improvement with agomelatine compared with venlafaxine (p < 0.0001). This rapid antidepressant efficacy was also seen at 2 weeks on the Hamilton Rating Scale for Depression (HAM-D), on which the mean total scores for agomelatine were lower than those for placebo (p < 0.05). At 6-8 weeks, evaluation on HAM-D, CGI-I and the CGI - Severity of illness (CGI-S) showed significant improvements with agomelatine versus placebo (p < 0.05). Patients treated with agomelatine also experienced greater relief of symptoms on CGI-I at 6 weeks compared with venlafaxine (p < 0.05). The antidepressant efficacy of agomelatine is maintained over the long term; almost 80% of patients remain free from relapse after 10 months of treatment. Agomelatine also significantly improves disturbed sleep and anxiety within depression, and this broad efficacy minimizes the risk of residual symptoms. The recent registration of agomelatine by the European Medicines Agency now offers the potential of fulfilling many currently unmet clinical needs throughout the time course of management of MDD. J Psychopharmacol. 2008 Sep;22(7 Suppl):19-23. Treating each and every depressed patient. Kennedy SH. University Health Network, University of Toronto, Toronto, Ontario, Canada. sidney.kennedy@... Abstract Major depressive disorder (MDD) is a prevalent condition with substantial heterogeneity in terms of clinical symptom profiles, overlapping syndromes and degree of severity. The challenge for any new antidepressant is to demonstrate efficacy across the spectrum of patient subpopulations with a diagnosis of MDD. The anxious depressed patient historically has a lower rate of response to traditional antidepressants and high pretreatment anxiety symptoms have also been shown to increase the risk of recurrence. In addition, severity based on standard antidepressant rating scale scores influences treatment outcomes. Some antidepressants display greater placebo separation at higher levels of severity while others fail to separate from placebo in more severe populations. Gender differences in antidepressant response have also been reported in several studies. In particular, women appear to experience a greater side-effect burden with current antidepressants. This is also important in treating late-life depression, where elderly patients are more prone to experiencing side effects and drug interactions. Despite the improved tolerability with SSRIs and other novel antidepressants, restoration of healthy sleep patterns has frequently been lacking. Finally, antidepressant efficacy must include demonstrated relapse prevention during placebo-controlled drug discontinuation trials. As a novel antidepressant with melatonin receptor agonist and 5HT(2C) antagonist properties, agomelatine has demonstrated efficacy in randomized placebo-controlled trials. Additional analyses support the benefits of agomelatine in anxious depression, increasing efficacy with greater baseline severity, including severe late-life depression. Agomelatine has also demonstrated favourable tolerability and efficacy in separate analyses of women and men and displays successful relapse prevention at doses 25 and 50 mg. Both subjective and polysomnographic measures of sleep support increased sleep efficiency and decreased awakenings during agomelatine treatment. Combining these efficacy data with favourable effects on sexual function, CNS and GI systems, there are grounds to endorse the view that agomelatine is a well-tolerated and efficacious antidepressant for a diverse range of depressed populations. Quote Link to comment Share on other sites More sharing options...
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