ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Multimodal Antidepressant — Serotonin Modulator Pregnancy: Avoid — limited human data. Neonatal adaptation syndrome risk in third trimester (similar to SSRIs — tremor, feeding difficulties, respiratory distress). Use only if benefit clearly outweighs risk with specialist input.

Vortioxetine

Brand names: Brintellix, Trintellix

Adult dose

Dose: 10 mg once daily. Range: 5–20 mg/day
Route: Oral
Frequency: Once daily (with or without food)
Max: 20 mg/day
Major depressive disorder (MDD). Start 10 mg, assess at 2 weeks; increase to 20 mg if needed. Consider 5 mg if poorly tolerated (especially in elderly or CYP2D6 poor metabolisers). Start low in elderly (5–10 mg). Source: BNF 90; NICE NG222.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed for paediatric depression.

Dose adjustments

Renal

No dose adjustment required for any degree of renal impairment.

Hepatic

Severe hepatic impairment: not recommended (limited data). Mild-moderate: no dose adjustment.

Paediatric weight-based calculator

Not licensed for paediatric depression.

Clinical pearls

  • Multimodal mechanism: vortioxetine is not simply a SSRI. It inhibits serotonin reuptake transporter (SERT) AND modulates multiple 5-HT receptors simultaneously: 5-HT3/7/1D antagonist, 5-HT1B partial agonist, 5-HT1A agonist. This receptor modulation alters norepinephrine, dopamine, acetylcholine, histamine, and GABA release — explaining broader spectrum than standard SSRI.
  • Cognitive benefit — key differentiator: FOCUS trial and CONNECT trial showed vortioxetine improved cognitive function (processing speed, attention, executive function) in depressed patients — a domain not addressed by most antidepressants. Cognitive impairment is a core feature of depression often undertreated. NICE NG222 notes cognitive improvement as a feature of vortioxetine.
  • Nausea management: dose-limiting nausea at initiation. Strategy: start at 5–10 mg, take with food, consider first dose at bedtime. Nausea typically resolves in 1–2 weeks. If persistent, 5 mg for 2 weeks before uptitrating. Do NOT dismiss — nausea at 20 mg affects adherence.
  • CYP2D6 interaction — clinically critical: bupropion (used for smoking cessation or augmentation of vortioxetine) is a potent CYP2D6 inhibitor. Adding bupropion to vortioxetine DOUBLES vortioxetine plasma concentration. Must reduce vortioxetine to 5–10 mg if adding bupropion. Same applies to fluoxetine and paroxetine.
  • Discontinuation: gradual taper recommended (less severe than SSRIs/SNRIs but some discontinuation symptoms reported). Do not stop abruptly at 20 mg — taper over 1–2 weeks. Source: BNF 90; McIntyre et al. J Psychopharmacol 2014 (FOCUS trial); NICE NG222; MHRA SPC Brintellix.

Contraindications

  • Concurrent MAO inhibitors (serotonin syndrome — allow 14 days washout between MAOI and vortioxetine)
  • Concomitant with linezolid or IV methylene blue (both are MAOI-like)
  • Hypersensitivity to vortioxetine

Side effects

  • Nausea (most common — up to 30% at 20 mg; dose-dependent; typically resolves after 1–2 weeks; take with food if problematic)
  • Vomiting, constipation, dizziness
  • Sexual dysfunction (less than SSRIs — fewer 5-HT3 effects on sexual circuits)
  • Pruritus (mildly common)
  • Hyponatraemia (SIADH — class effect of serotonergic antidepressants; monitor sodium in elderly)
  • Serotonin syndrome (rare — with concurrent serotonergic drugs)

Interactions

  • MAO inhibitors: serotonin syndrome — contraindicated; 14-day washout required
  • Linezolid, methylene blue (IV): functional MAO inhibition — avoid
  • Strong CYP2D6 inhibitors (bupropion, fluoxetine, paroxetine): reduce vortioxetine dose by 50% — CYP2D6 is primary metabolic pathway
  • Strong CYP inducers (rifampicin, carbamazepine): increase vortioxetine dose up to 3-fold
  • Serotonergic drugs (tramadol, triptans, St John's Wort): additive serotonin syndrome risk

Monitoring

  • Depression rating scales (PHQ-9, MADRS) at 2 weeks (early response), 6 weeks (response), 12 weeks (remission target)
  • Nausea (first 2 weeks — tolerability check)
  • Serum sodium in elderly (hyponatraemia risk — check at 4 weeks if ≥65 years)
  • Cognitive function (clinician-rated or patient-reported — a specific benefit to track)
  • Sexual function (ask specifically at each review)

Reference: BNFc; BNF 90; Alvarez et al. Int J Neuropsychopharmacol 2014; McIntyre et al. J Psychopharmacol 2014 (FOCUS); NICE NG222; MHRA SPC Brintellix. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways