Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I 2004. Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study

Imperial College University of London, London, UK.
International Clinical Psychopharmacology (Impact Factor: 2.46). 10/2004; 19(5):271-80. DOI: 10.1097/01.yic.0000137184.64610.c8
Source: PubMed


The effects of an abrupt interruption of agomelatine, a new melatonergic/serotonergic antidepressant, were explored in a double-blind, placebo-controlled study. Paroxetine was used as active control. After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day, sustained remitted depressed patients were randomized for 2 weeks, under double-blind conditions, to placebo or to their initial antidepressant treatment. Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms (DESS) checklist. One hundred and ninety-two sustained remitted patients were randomized to the 2-week discontinuation period. Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine. Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms, during the first week, compared to those who continued with paroxetine (respective mean number of emergent symptoms: 7.3+/-7.1 and 3.5+/-4.1, P<0.001). No significant difference was shown between the continuing and interrupting groups in the second week of discontinuation. By contrast to paroxetine, abrupt cessation of agomelatine is not associated with discontinuation symptoms.

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    • "Further limitations of the CHRONOS study were the short-term nature of the treatment and the fact that there were no follow-up visits after the end of the treatment period. However, it should be pointed out that previous randomized, double-blind trials have demonstrated the efficacy of long-term treatment with agomelatine in prevention of relapse27 and the absence of discontinuation symptoms following abrupt cessation of treatment with agomelatine.28 "
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    ABSTRACT: CHRONOS was a large naturalistic study designed to evaluate the effectiveness and safety of agomelatine in the management of patients with major depression in routine clinical practice. Patients (n=6,276) with a moderate or severe major depressive episode without psychotic symptoms were treated initially as outpatients (80.2%) or in psychiatric facilities (19.8%) in 54 regions of the Russian Federation. Patients received a flexible-dosing regimen of agomelatine 25 mg or 50 mg once daily for 8 weeks, with frequent study visits (weeks 1, 2, 3, 4, 6, and 8). Patients (mean age 44 years, 72.6% female) showed progressive improvement on the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score from 22±6.9 at baseline to 4.7±4.7 at week 8 (P<0.0001). The proportion of responders (HAMD-17 decrease of ≥50%) was 90.1% and the proportion of remitters (HAMD-17 <7) was 79.1% at week 8. All individual HAMD-17 item scores improved rapidly, and the change relative to baseline was significant (P<0.0001) at week 1 and at each subsequent visit in all cases. There were corresponding rapid improvements in Clinical Global Impression Severity and Improvement scores. In the subgroup of patients with more severe illness (HAMD-17 ≥21 at baseline; n=3,478), the proportions of responders and remitters were 92.4% and 72.8%, respectively, at week 8. Agomelatine was effective and well tolerated in a large sample of depressed patients in an observational treatment setting, and showed a rapid onset of benefit across all HAMD-17 items.
    Neuropsychiatric Disease and Treatment 04/2014; 10:631-639. DOI:10.2147/NDT.S58994 · 1.74 Impact Factor
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    • "Discontinuation symptoms in MDD have been evaluated in only one randomized, double-blind, placebo controlled study, with paroxetine as the active comparator [142]. No significant differences were present in the Discontinuation-Emergent Signs and Symptoms scale (DESS) between patients who stopped or continued agomelatine treatment. "
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    ABSTRACT: Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in "real world" clinical practice will be also discussed.
    International Journal of Molecular Sciences 06/2013; 14(6):12458-83. DOI:10.3390/ijms140612458 · 2.86 Impact Factor
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    • "Discontinuation rates for the comparison of agomelatine, venlafaxine, sertraline, fluoxetine and escitalopram were derived from head-to-head clinical trials comparing the therapies [20-23]. The frequency of discontinuation symptoms was set to zero for agomelatine because a randomized clinical trial conducted to examine the effect of an abrupt interruption of agomelatine [27] concluded that there was an absence of discontinuation symptoms in agomelatine-treated patients, whilst discontinuation symptoms were detected in paroxetine-treated patients. Another study aimed to evaluate discontinuation symptoms in depression and anxiety disorders showed no significant difference between paroxetine and venlafaxine [30]. "
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    ABSTRACT: Background Major depressive disorder (MDD) constitutes an important public health problem, as it is highly prevalent in the industrialized world and it is associated with substantial economic consequences for patients, health care providers, insurance and social security organizations and employers. To conduct an economic evaluation comparing agomelatine with other commonly used alternatives for treating patients with major depressive disorder (MDD) in Greece. Methods An existing international Markov model designed to evaluate the cost-effectiveness of agomelatine was adapted to the Greek setting. It reflects six different health states, in which patients may move on a monthly basis. The analysis was undertaken from a societal perspective. Transition probabilities, utilities and costs assigned to each health state were extracted from the published literature, government sources and expert opinion. Data reflects the year 2012 and was discounted using a rate of 3.5%. Probabilistic analysis was undertaken to deal with uncertainty. Results Base case analyses revealed that agomelatine is a dominant therapy for MDD relative to escitalopram, fluoxetine and sertraline, and it appeared to be cost-effective compared to venlafaxine (ICER: €547/QALY). Agomelatine remained a dominant treatment against generic sertraline and fluoxetine, and it appeared to be a cost-effective alternative compared to generic venlafaxine and escitalopram (ICER: €1,446/QALY and €3,303/QALY, respectively). Excluding the indirect cost from the analysis, agomelatine remained a cost-effective alternative over all comparators. In the probabilistic sensitivity analysis agomelatine was dominant in 44.5%, 89.6%, 70.6% and 84.6% of simulated samples against branded venlafaxine, escitalopram, fluoxetine and sertraline, respectively. Conclusion The present evaluation indicates that agomelatine is either a dominant or a cost-effective alternative relative to branded or generic alternatives, in Greece.
    BMC Health Services Research 05/2013; 13(1):173. DOI:10.1186/1472-6963-13-173 · 1.71 Impact Factor
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