Agotin

Agorest is indicated for the major depressive disorder in adults especially in non-responders and intolerant to selective serotonin reuptake inhibitors (SSRIs) including prevention of relapse.

The effective dose of agomelatine is 25 mg per day given once at bed time for two weeks and can be increased to 50 mg per day in patients with inadequate response. Night time dosing is recommended because agomelatine improves the quality of sleep without day time sedation. For oral administration with or without food. Most adult patients should take a dosage of 25 mg (one tablet) daily. It is usually taking prior to bed time. If no improvement is noticed after two weeks, the dosage can be increased to 50 mg (two tablets) daily.
Children under 18 years
: Should be given only on medical advice.
Use in children and adolescents
: Agomelatine is not recommended in the treatment of depression in patients <18 years since safety and efficacy of agomelatine have not been established in this age group. In clinical trials among children and adolescents treated with other antidepressants, suicide-related behavior (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behavior and anger) were more frequently observed compared to those treated with placebo.
Use in the elderly
: The efficacy and safety of agomelatine (25 to 50 mg/day) have been established in elderly patients with MDD (aged <75 years). As  efficacy has not been established in every elder patients aged >75 years agomelatine should not be used in this patient group.

The commonly reported adverse effects in the clinical trials of Agorest are headache, nausea and diarrhea. It is found to increase the level of liver enzymes and so monitoring of enzyme level is warranted before starting therapy and therefore every 6 weeks. It is also contraindicated in patients with hepatic impairment. A meta-analysis of the treatment emergent sexual dysfunction with antidepressants has revealed that it has no significant difference with placebo.

Caution should be exercised before starting treatment and close surveillance should be performed throughout the treatment period in all patients, especially if hepatic injury risk factors or concomitant medicinal products associated with risk of hepatic injury are present. Baseline liver function tests should be undertaken in all patients and treatment should not be initiated in patients with baseline values of ALT and/or AST >3 times upper limit of normal.
Agorest should be used with caution in the elderly (≥75 years) due to lack of clinical data. Agorest should not be used for the treatment of major depressive episodes in elderly patients with dementia since the safety and efficacy of Agorest have not been established in these patients.
Agorest is not recommended in the treatment of depression in patients under 18 years of age. Agorest should be used with caution in patients with a history of bipolar disorder, mania or hypomania.

Agomelatine is a melatonergic agonist (MT
1
and MT2 receptors) and 5-HT
2C
antagonist. Binding studies indicate that agomelatine has no effect on monoamine uptake and no affinity for a, (3 adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors. Agomelatine resynchronises circadian rhythms in animal models of circadian rhythm disruption. Agomelatine increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin.