Auvelity
Auvelity
Generic Name
Auvelity
Mechanism
- Partial agonist at 5‑HT₁A receptors – modulates serotonergic tone.
- Partial agonist at dopamine D₂ receptors – helps rebalance dopaminergic activity.
- Antagonist at 5‑HT₂A receptors – reduces serotonin‑mediated hallucinogenic effects.
- The combined actions produce a *serotonin‑dopamine activity modulation* that decreases depressive symptoms while minimizing classic antipsychotic adverse effects.
Auvelity therefore functions as an atypical antipsychotic tailored for depression, offering mood‑stabilizing benefits without extensive metabolic disruption.
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Pharmacokinetics
| Parameter | Detail |
| Absorption | ~70 % oral bioavailability; rapid absorption; peak plasma ~1–3 h post‑dose. |
| Distribution | Highly protein‑bound (∼97 %); extensive CNS penetration. |
| Metabolism | Predominantly CYP2D6; secondary CYP3A4; subject to genetic polymorphisms. |
| Elimination | Half‑life ≈ 51 h; steady state achieved ~2 weeks. |
| Excretion | Primarily fecal (≈ 60 %); minor renal (~30 %). |
| Drug interactions | Strong CYP2D6 inhibitors (e.g., fluoxetine) ↑ exposure; CYP3A4 inhibitors (e.g., ketoconazole) moderately ↑ exposure. |
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Indications
- Adjunctive therapy for major depressive disorder in adults with partial or no response to an SSRI/SNRI.
- Off‑label uses (subject to clinician judgment) include bipolar depression and certain anxiety disorders, but data are limited.
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Dosing
| Regimen | Typical dosing pattern |
| Initial dose | *Auvelity* 0.5 mg orally once daily at bedtime. |
| Titration | Increase by 0.5 mg increments every 7 days to a maximum of 2 mg/day (1 + 1 mg). |
| Maintenance | 0.5–2 mg/day, divided as 1 mg BID or 2 mg QD per tolerance. |
| Administration time | Prefer evenings to minimise insomnia; may take with or without food. |
*Special populations*:
• CYP2D6 poor metabolizers: start at 0.25 mg/day.
• Hepatic impairment (Child‑Pugh B): titrate cautiously; avoid >2 mg/day.
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Monitoring
| Parameter | Frequency |
| Baseline depression severity | Prior to initiation |
| Suicidal ideation | Every visit for 2 months |
| Weight & BMI | Every 6 weeks |
| Metabolic panel (glucose, lipids) | Every 3 months |
| ECG (if risk factors present) | Baseline & 4 weeks if QT prolongation risk |
| Liver function tests | Baseline; repeat if hepatic disease suspected |
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Clinical Pearls
1. Add‑on strategy: *Auvelity* is best reserved for patients who have not achieved remission after 6–8 weeks of a conventional SSRI/SNRI—avoid monotherapy.
2. Slow titration reduces akathisia: advance dose in 1 week increments; consider lorazepam for early akathisia.
3. CYP2D6 phenotype matters: Genotype screening can prevent overdosing in poor metabolizers; alternative dosing (0.25 mg) reduces risk.
4. Minimal metabolic impact: Compared with other atypical antipsychotics, *Auvelity* shows the lowest weight‑gain risk—ideal for weight‑conscious patients.
5. Psychomotor vigilance: Patients often report increased energy; monitor for potential mania in bipolar‑suspected cases.
6. Interaction with serotonergic drugs: Pairing with triptans, MAOIs, or other SSRIs can trigger serotonin syndrome—use caution.
7. Pediatric data are lacking: Despite efficacy in adults, *Auvelity* is not approved for adolescents and should be avoided outside clinical trials.
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