Agomelatine is used for the treatment of major depressive disorder in adults, particularly in patients who do not respond well to or cannot tolerate selective serotonin reuptake inhibitors (SSRIs). It is also helpful in preventing relapse.

Agomelatine acts as an agonist at melatonin receptors (MT₁ and MT₂) and as an antagonist at 5-HT₂C receptors. It does not affect monoamine uptake and shows no significant affinity for α, β adrenergic, histaminergic, cholinergic, dopaminergic, or benzodiazepine receptors. It helps restore normal circadian rhythms and increases the release of noradrenaline and dopamine in the frontal cortex without altering serotonin levels.

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.

Agomelatine is mainly metabolized by CYP1A2 (about 90%) and partly by CYP2C9/19. Drugs that affect these enzymes may alter the bioavailability of agomelatine. Strong CYP1A2 inhibitors, such as fluvoxamine and ciprofloxacin, can significantly increase agomelatine levels; therefore, their combined use is contraindicated.

Agomelatine should not be used in patients with hypersensitivity to the drug or its excipients. It is also contraindicated in patients with liver impairment (such as cirrhosis or active liver disease) or when liver enzymes exceed three times the upper normal limit. Concomitant use with strong CYP1A2 inhibitors is also contraindicated.

Common side effects include headache, nausea, and diarrhea. Agomelatine may increase liver enzyme levels; therefore, liver function should be monitored before starting treatment and periodically thereafter. It is contraindicated in patients with hepatic impairment. Studies indicate that sexual dysfunction rates are similar to placebo.

Use in pregnancy: There is limited clinical data regarding agomelatine use during pregnancy. Animal studies have not shown direct harmful effects, but caution is advised when prescribing to pregnant women.

Use in lactation: It is unknown whether agomelatine passes into human breast milk. Animal studies suggest excretion into milk, so breastfeeding should be discontinued if treatment is necessary.

Patients should be monitored closely, especially those at risk of liver injury or taking hepatotoxic drugs. Liver function tests should be performed before starting treatment and periodically during therapy.

Treatment should not be initiated if ALT or AST levels are more than three times the upper normal limit. Use with caution in elderly patients (≥75 years) due to limited data, and it is not recommended for elderly patients with dementia.

It is also not recommended for individuals under 18 years of age. Caution is advised in patients with a history of bipolar disorder, mania, or hypomania.

Experience with overdose is limited. Reported symptoms include drowsiness and upper abdominal pain. There is no specific antidote; treatment involves symptomatic care and monitoring under medical supervision.

Atypical antidepressant.

Dispense only on prescription. Store below 30°C in a cool and dry place, protected from light. Keep out of reach of children.