Teach me vortioxetine and ketamine-esketamine…introduction backgeound moa, phamacodynamics kinetics, uses, adr, contraindication, toxicity, abuse, discontinuation, guidelines for use, dosage formulation,indication,evidencebased trials,precaution, special population,drug interaction and eveyrthing related to it
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vortioxetine depression efficacy
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esketamine treatment-resistant depression
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That is the complete, evidence-based guide to both drugs. Here is a summary of what was covered:
What This Guide Covers
Vortioxetine (Trintellix)
- MOA: Multimodal - SERT inhibitor + 5-HT1A agonist + 5-HT3/7/1D antagonist + 5-HT1B partial agonist (with specific Ki values for each target)
- PK: 75% bioavailability, t½ 66 hours, CYP2D6 primary metabolism, 98-99% protein bound, no active metabolites, no CYP induction/inhibition
- Dosing: 5-20 mg/day oral; 20 mg/day is optimal (80% SERT occupancy)
- Special features: Procognitive effects (DSST), better sexual tolerability than SSRIs, low weight gain/sedation profile
- Drug interactions: Halve dose with CYP2D6 inhibitors; adjust with CYP inducers; 21-day MAOI washout
Ketamine/Esketamine (Spravato)
- MOA: NMDA receptor antagonism → GABAergic disinhibition → cortical glutamate surge → AMPA activation → BDNF/mTOR/synaptogenesis
- Esketamine: 4x greater NMDA affinity than R-ketamine; t½ ~5 hours; CYP3A4/2B6 metabolism
- Dosing: Esketamine IN 56-84 mg twice weekly (induction) then weekly; IV ketamine 0.5 mg/kg over 40 min (off-label gold standard)
- REMS: Esketamine ONLY in certified settings with 2-hour monitoring
- Key trials: ESCAPE-TRD (NEJM 2023) - superior to quetiapine; Janik et al. 2025 (JAMA Psychiatry) - monotherapy efficacy
- Abuse: Schedule III; "K-hole" at high doses; bladder toxicity with chronic use
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