Agomelatine

Agomelatine is a novel antidepressant that acts as an MT1 and MT2 melatonergic agonist and 5-HT2C antagonist. It treats major depressive episodes, resynchronizes circadian rhythms, and improves sleep architecture without causing daytime sedation or sexual dysfunction.

Major depressive disorder in adults, particularly in non-responders or those intolerant to SSRIs, including the prevention of relapse.

Atypical anti-depressant drugs

Melatonergic Receptor Agonist & 5-HT2C Antagonist

Agomelatine acts on MT1 and MT2 receptors and antagonizes 5-HT2C receptors, leading to increased noradrenaline and dopamine release in the frontal cortex while having no effect on extracellular serotonin levels.

Combines melatonergic agonism and 5-HT2C antagonism to restore circadian rhythm synchronization and enhance frontocortical dopaminergic and noradrenergic neurotransmission.

25 mg once daily at bedtime. If no clinical improvement is observed after 2 weeks, the dose may be increased to 50 mg once daily at bedtime.

For oral administration with or without food. Take prior to bedtime.

Take as soon as remembered if before bedtime. Do not double doses to make up for a missed dose.

Common: Headache, nausea, diarrhea, fatigue, and dizziness. Potentially increases liver enzymes (transaminases). Low incidence of sexual dysfunction.

Perform baseline liver function tests (LFTs) and monitor periodically (e.g., at 6 weeks). Use with caution in patients with a history of mania or bipolar disorder.

Hepatic impairment (cirrhosis or active liver disease), ALT/AST >3 times the upper limit of normal, and concomitant use of potent CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin).

Concomitant use with potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) dramatically increases agomelatine exposure (up to 60-fold) and is strictly contraindicated.

No significant interaction with food. Alcohol consumption should be avoided.

No adequate clinical data on pregnant women. Prescribe with caution only if potential benefit outweighs risk.

Pregnancy Category: Antidepressant Precaution — always consult a doctor before taking during pregnancy.

Unknown whether excreted in human milk. Discontinue breastfeeding if treatment with agomelatine is necessary.

Not recommended in children and adolescents under 18 years of age due to lack of safety/efficacy data and risk of suicidal behavior.

Established efficacy in adults <75 years. Not recommended in patients ≥75 years or elderly patients with dementia.

Contraindicated in patients with hepatic impairment. No major adjustment required in renal impairment, but caution advised.

Overdosage leads to drowsiness and epigastric pain. Manage with symptomatic treatment and clinical monitoring.

Store below 30°C in a cool, dry place. Protect from light and moisture. Keep out of reach of children.

Agomelatine (C15H17NO2)