Major depressive disorder, anhedonia and agomelatine: an open-label study.
ABSTRACT Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p<.05), HAM-A(p<.01), SHAPS (p<.05), LSEQ (p<.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.
Full-textDOI: · Available from: Domenico De Berardis, Jul 07, 2015
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ABSTRACT: Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled.Journal of Pineal Research 08/2011; 52(4):365-75. DOI:10.1111/j.1600-079X.2011.00962.x · 7.81 Impact Factor
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ABSTRACT: Anhedonia, or markedly diminished interest or pleasure, is a hallmark symptom of major depression, schizophrenia and other neuropsychiatric disorders. Over the past three decades, the clinical definition of anhedonia has remained relatively unchanged, although cognitive psychology and behavioral neuroscience have expanded our understanding of other reward-related processes. Here, we review the neural bases of the construct of anhedonia that reflects deficits in hedonic capacity and also closely linked to the constructs of reward valuation, decision-making, anticipation and motivation. The neural circuits subserving these reward-related processes include the ventral striatum, prefrontal cortical regions, and afferent and efferent projections. An understanding of anhedonia and other reward-related constructs will facilitate the diagnosis and treatment of disorders that include reward deficits as key symptoms.Trends in Neurosciences 12/2011; 35(1):68-77. DOI:10.1016/j.tins.2011.11.005 · 12.90 Impact Factor
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ABSTRACT: Ethanol withdrawal syndrome is characterized by somatic and behavioral symptoms, including increased anxiety and anhedonia. In animal models, however, there are many studies on the anxiogenic effects occurring during the first 24h after ethanol withdrawal, while anhedonia has been overlooked. Recently, we have found that amphetamine withdrawal reduced novelty seeking and enhanced environmental habituation in mice, two motivation-related behaviors. We now investigate the effects of withdrawal from ethanol, a drug of abuse with a different pharmacological profile, on these two motivation-related behaviors. Swiss male mice (3months old) were treated with 1.8g/kg ethanol for 21 consecutive days in their home cages. Seven days after ethanol withdrawal, mice were tested in a free-choice novelty apparatus containing one familiar and one novel compartment. Novelty-seeking behavior was assessed by comparing time spent in the novel compartment versus the familiar compartment, whereas environmental habituation was concomitantly evaluated by the time-response curve of total locomotion (novel+familiar). Novelty seeking was decreased and environmental habituation was enhanced during ethanol withdrawal. These anhedonic responses were not associated with concurrent changes in the anxiety-like behavior of mice (as confirmed in the elevated plus-maze test). We propose that the concomitant evaluation of novelty-seeking behavior and environmental habituation can be useful to study the behavioral consequences not only of amphetamine withdrawal but also of ethanol withdrawal. Furthermore, the present data support recent clinical findings that suggest the occurrence of protracted anhedonia well beyond the limited period immediately following the abrupt cessation of ethanol intake.Pharmacology Biochemistry and Behavior 12/2011; 101(1):132-7. DOI:10.1016/j.pbb.2011.12.013 · 2.82 Impact Factor