ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Melatonin Receptor Agonist / 5-HT2C Antagonist Pregnancy: Avoid — insufficient data. Use sertraline in preference.

Agomelatine

Brand names: Valdoxan

Adult dose

Dose: 25mg OD at night initially; increase to 50mg OD at night after 2 weeks if inadequate response.
Route: Oral
Frequency: Once daily at bedtime
Max: 50mg OD
Unique mechanism: agonist at MT1/MT2 melatonin receptors AND antagonist at 5-HT2C receptors. Does not inhibit serotonin reuptake. Improves sleep architecture by resynchronising circadian rhythm. No sexual dysfunction (unlike SSRIs/SNRIs). No discontinuation syndrome. Hepatotoxicity is the key safety concern — LFT monitoring mandatory.

Paediatric dose

Route: Oral
Frequency: Once daily at night
Max: Not applicable
Not licensed under 18 years. Seek specialist child and adolescent psychiatry opinion.

Dose adjustments

Renal

No dose adjustment required.

Hepatic

Contraindicated in hepatic impairment (cirrhosis, hepatic failure, elevated baseline LFTs).

Clinical pearls

  • No sexual dysfunction and no discontinuation syndrome — key advantages over SSRIs/SNRIs; can be useful when sexual side effects are a major concern or when switching drugs
  • Hepatotoxicity: EMA mandated LFT monitoring — check at initiation, 3, 6, 12, and 24 weeks. Stop if LFTs >3× ULN
  • Efficacy comparable to SSRIs in meta-analyses but less robust long-term data — consider as alternative when sexual side effects preclude SSRI use
  • Smoking significantly reduces agomelatine efficacy (CYP1A2 induction) — be aware in heavy smokers

Contraindications

  • Hepatic impairment or elevated baseline LFTs
  • Concomitant strong CYP1A2 inhibitors (fluvoxamine — increases agomelatine levels 60-fold)
  • Hypersensitivity to agomelatine

Side effects

  • Hepatotoxicity (most important — monitor LFTs)
  • Nausea, dizziness
  • Headache
  • Somnolence
  • Back pain
  • Fatigue

Interactions

  • Fluvoxamine — contraindicated (strong CYP1A2 inhibitor; 60-fold increase in agomelatine AUC)
  • Ciprofloxacin, enoxacin (CYP1A2 inhibitors) — increase agomelatine exposure; avoid
  • Smoking — CYP1A2 inducer; reduces agomelatine levels significantly; dose adjustment may be needed on smoking cessation

Monitoring

  • LFTs (at 3, 6, 12, 24 weeks — mandatory)
  • Sleep quality (circadian rhythm improvement)
  • Mood response (re-evaluate at 8–12 weeks)

Reference: BNFc; BNF 90; EMA Agomelatine Assessment Report; NICE CG90 (Depression). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways