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C.09.03 The benefits of agomelatine beyond antidepressant efficacy: impact on sleep
P8 Other topics
$660
pressant 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 MT 1 and MT2 receptors. Moreover, agomelatineunlike 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.
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Clinical efficacy of agomelatine in depression: the evidence
J. Den Boer*, F. Bosker, Y. Meesters. Groningen 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 [l] L6o H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17: 239 247.
~ T h e
benefits of agomelatine beyond antidepressant efficacy: impact on sleep
R. Lam*. Mood Disorders Centre, Univ. of British Columbia, Dept. of Psychiatty, Vancouvet; 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 25mg 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 50mg/day) with venlafaxine (75 150mg/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 [l] L6o H et al. Int Clin Psychopharmacol. 2002; 17:239 247.
•
Efficacy/tolerance profile of agomelatine and practical use in depressed patients
F. Rouillon *. Hopital Andr& Cheneviet; Department of Psychiatty,
Cr&teil, 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 placebocontrolled 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, placebocontrolled 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
$660
pressant 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 MT 1 and MT2 receptors. Moreover, agomelatineunlike 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.
•
Clinical efficacy of agomelatine in depression: the evidence
J. Den Boer*, F. Bosker, Y. Meesters. Groningen 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 [l] L6o H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17: 239 247.
~ T h e
benefits of agomelatine beyond antidepressant efficacy: impact on sleep
R. Lam*. Mood Disorders Centre, Univ. of British Columbia, Dept. of Psychiatty, Vancouvet; 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 25mg 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 50mg/day) with venlafaxine (75 150mg/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 [l] L6o H et al. Int Clin Psychopharmacol. 2002; 17:239 247.
•
Efficacy/tolerance profile of agomelatine and practical use in depressed patients
F. Rouillon *. Hopital Andr& Cheneviet; Department of Psychiatty,
Cr&teil, 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 placebocontrolled 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, placebocontrolled 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