Overview
Agomelatine is an atypical antidepressant with a novel mechanism of action, acting as a melatonin receptor agonist and serotonin 5-HT2C receptor antagonist. It is used primarily for the treatment of major depressive episodes in adults. Unlike many antidepressants, it has minimal sexual side effects and does not typically cause weight gain or discontinuation symptoms.
Mechanism of Action
Agomelatine acts as an agonist at melatonin MT1 and MT2 receptors, which helps resynchronize circadian rhythms often disrupted in depression. It also acts as an antagonist at serotonin 5-HT2C receptors, which increases the release of dopamine and norepinephrine in the prefrontal cortex without affecting serotonin levels.
Indications
- Major depressive episodes in adults
Dosage
The recommended dose is 25 mg once daily at bedtime. After two weeks, if there is insufficient improvement, the dose may be increased to 50 mg once daily at bedtime. Liver function tests should be performed before starting treatment and periodically during treatment.
Contraindications
- Hepatic impairment (cirrhosis or active liver disease)
- Concomitant use with potent CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin)
- Hypersensitivity to agomelatine or any excipient
Side Effects
- Headache
- Dizziness
- Somnolence
- Insomnia
- Migraine
- Nausea
- Diarrhea
- Constipation
- Abdominal pain
- Back pain
- Fatigue
- Anxiety
- Increased liver enzymes (ALT, AST)
Interactions
- Potent CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) increase agomelatine exposure and are contraindicated.
- Moderate CYP1A2 inhibitors (e.g., propranolol, enoxacin) may increase agomelatine exposure; consider dose adjustment.
- Agomelatine is a weak inhibitor of CYP1A2, CYP2C9, and CYP2C19; monitor drugs metabolized by these enzymes.
- Alcohol may enhance sedative effects.