Agomelatine: a review for general practitioners

Abstract

The 24-hour rhythms of life, including the timing of sleep induction, wakefulness, hormone secretion, thermoregulation, glucose homeostasis and fat metabolism, are governed by external environmental time signals AbstractAgomelatine is a novel melatonergic antidepressant that restores disrupted biological rhythms, essentially by resetting the circadian clock. Two different, non-monoaminergic, and possibly synergistic pathways, appear to be involved in its mechanism of action. Agomelatine is a melatonin 1 (MT 1 ) and melatonin 2 (MT 2 ) receptor agonist and serotonin (5-hydroxytryptamine) 2C (5-HT 2C ) receptor antagonist. It is effective in treating moderate-to-severe depression, alleviating the symptoms of anxiety, and restoring the disrupted sleep patterns that often result from this potentially devastating disease. Agomelatine is generally well tolerated with little, if any, propensity for antidepressant-induced sexual dysfunction, weight gain, or discontinuation reactions. However, it has the potential to cause temporary hepatotoxicity, and liver functions need to be monitored as a result. Clinically, meaningful drug interactions are unlikely, with the exception of co-administered potent cytochrome P 1A2 (CYP1A2) enzyme inhibitors, which may increase agomelatine's plasma levels significantly. Agomelatine represents an interesting addition to the antidepressant market.Peer reviewed.

Novel drugs in depression - A new hope

“…After 2 weeks of treatment, if further clinical improvement is required, the dose may be increased to 50 mg once daily, taken as a single dose of two tablets in the evening. [13] Cautions and contraindications • Agomelatine is contraindicated in patients taking ciprofloxacin or fluvoxamine (potent inhibitors of CYP1A2), as these agents increase the plasma concentration of agomelatine • Agomelatine is contraindicated in people with cirrhosis or active liver disease, as evidences are available in literature for rising liver enzymes levels due to long-term consumption of agomelatine [2,13] • Caution should be exercised in patients suffering from renal failure, as plasma levels of agomelatine may increase by 25% in patients with renal impairment • Agomelatine should be discontinued in patients with symptoms of bipolar affective disorder, mania, or hypomania • In pregnant and lactating women, agomelatine is to be used with extreme caution, as its effects on human fertility are unknown.…”

“…[2] TCAs such as imipramine, amitriptyline, desipramine are the inhibitors of neuronal transport (reuptake) of norepinephrine (NE) and serotonin (5HT), which leads to an antidepressant effect by increasing the level of NE and 5HT in the synaptic space. However, various evidences are now available for pharmacological actions of TCAs on additional receptors, i.e.…”

“…[1] It is the third major cause of burden from disease and accounts for 4.5% of all human disability. [2] Depression will become second leading cause of disability for all age groups by 2020 and is expected to become the leading cause of disability in industrialized countries by 2030. [3] It is mostly predisposed by genetic influences, low self-esteem, chronic psychosocial adversities and lack of social and family support.…”

A comparative study of the clinical efficacy and safety of agomelatine with escitalopram in major depressive disorder patients: A randomized, parallel-group, phase IV study

“…[ 1 ] Depression would be the leading cause of disability in industrialized countries by 2030[ 2 ] and accounts for 4.5% of all human disabilities. [ 3 ] Major depressive disorder (MDD) is diagnosed when symptoms last for a minimum period of 2 weeks. [ 4 ] The circadian rhythm disruption is involved in the pathophysiology of depression.…”

Comparative efficacy of agomelatine versus sertraline in major depressive disorder in Himalayan region of India

“…The two theories are not mutually exclusive, and have arisen from attempts to elucidate the mechanisms of action of serendipitously discovered, as well as more innovative antidepressants. 9 Most antidepressant agents act by increasing the availability of the monoamines at neuronal synapses, particularly in the locus coeruleus (noradrenaline) and raphe nucleus (serotonin). The pioneering tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) inhibit their reuptake and metabolism, respectively.…”