Ingrezza
Ingrezza
Generic Name
Ingrezza
Mechanism
- Serotonin (5‑HT) reuptake inhibition (SERT inhibition) → ↑ synaptic 5‑HT.
- Receptor modulation:
- *5‑HT₃ antagonist* – reduces nausea and anxiety.
- *5‑HT₇ antagonist* – improves circadian rhythm & sleep regulation.
- *5‑HT₁A partial agonist* – supports anxiolytic and antidepressant effects.
- *5‑HT₁B partial agonist* – modulates presynaptic serotonergic tone.
- The combined effects yield enhanced serotonergic neurotransmission with a favorable cognitive‑enhancing profile.
Pharmacokinetics
| Parameter | Details |
| Route | Oral (PO) |
| Absorption | Tmax ≈ 2.5–3 h; high oral bioavailability (~85 %). |
| Distribution | ~30–40 % plasma protein binding; central nervous system penetration. |
| Metabolism | Hepatic; primarily CYP2D6 (≈ 70 %), with minor CYP3A4 involvement. |
| Elimination | Excreted as metabolites; half‑life ≈ 66 h (≈ 3 days). |
| Food Effect | Minimal; can be taken with or without food. |
Indications
- Adult Major Depressive Disorder (MDD) – effective as first‑line or switch therapy.
- Adjunctive therapy – not currently approved for use in anxiety disorders or other conditions.
Contraindications
| Contraindication | Warning |
| Known hypersensitivity to vortioxetine or any excipients. | Serotonin‑syndrome: avoid concomitant serotonergic drugs, MAO‑I, St. John’s wort, triptans, linezolid, etc. |
| Concurrent MAO‑I use within the last 14 days. | Hyponatremia: monitor serum sodium, particularly in elderly patients. |
| Severe hepatic impairment (Child‑Pugh C). | Suicidal ideation: regular assessment per FDA boxed warning. |
| • | Drug interactions: potent CYP2D6 inhibitors/inducers (e.g., quinidine, fluoxetine, rifampin) alter doses. |
> FDA boxed warning: Risk of increased suicidality in patients under 25 years; monitor closely.
Dosing
- Starting dose: 10 mg PO once daily (no loading dose).
- Titration: increase to 20 mg PO after 1 week if adequate response not achieved; can further titrate to 20 mg if tolerated.
- Maximum dose: 20 mg/day.
- Dose adjustments: none required for hepatic or renal impairment; however, if using CYP2D6 inhibitors, consider reducing the dose (e.g., 10 mg daily).
- Special populations:
- *Elderly*: same dosing; monitor for GI and somnolence.
- *Pregnancy / Lactation*: Category B, not recommended unless benefits outweigh risks.
Monitoring
| Parameter | Frequency | Rationale |
| Serum sodium | Baseline + 4–6 weeks | Detect hyponatremia early. |
| Suicidality screening | Baseline, week 1–4, and then monthly | FDA boxed warning compliance. |
| Liver function tests | Baseline, then 6‑8 weeks | Monitor hepatic metabolism. |
| Drug interaction screening | Prior to initiation | Identify potent CYP2D6 inhibitors/inducers. |
| QT interval | Baseline if on QT‑prolonging drugs | Rare but possible QTc extension. |
Clinical Pearls
- Cognitive Benefit: Vortioxetine consistently shows improvements in processing speed and executive function in MDD trials—useful for patients with cognitive complaints.
- Weight Profile: Lower propensity for weight gain and metabolic disturbance compared with many SSRIs and SNRIs.
- Sexual Function: Generally less sexual dysfunction than classic SSRIs; consider when patients express concerns about libido.
- Warfarin Interaction: Vortioxetine may increase INR; monitor clotting times in patients concurrently on warfarin.
- Elderly Precautions: Initiate at the lowest dose (10 mg) and titrate cautiously; watch for constipation and orthostatic hypotension.
- Avoid Poly‑Serotonergic Regimen: Combining with other serotonergic agents can precipitate syndrome; if medically necessary, taper the other agent first.
--
• *This drug card is intended for educational and reference purposes. Always refer to the latest prescribing information and local guidelines before initiating therapy.*