Desvenlafaxine
Desvenlafaxine
Generic Name
Desvenlafaxine
Brand Names
*Pristiq*) is a selective serotonin‑norepinephrine reuptake inhibitor (SNRI) used primarily for the treatment of major depressive disorder (MDD). The following drug card provides a concise, SEO‑friendly reference for students and clinicians.
Mechanism
- Reuptake inhibition:
- Serotonin (5‑HT) transporter (SERT) – ~80 % of its effect.
- Norepinephrine transporter (NET) – ~20 % of its effect.
- Result: Elevated synaptic 5‑HT and norepinephrine lead to improved mood, energy, and motivation.
- Distinctive feature: As a *secondary metabolite* of venlafaxine, it bypasses the need for hepatic CYP2D6 activation, resulting in a more consistent pharmacodynamic profile.
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Pharmacokinetics
- Absorption: Rapid oral absorption, peak plasma concentration ~4 h.
- Bioavailability: ~12 % (low, but not limiting for efficacy).
- Metabolism: Minimal CYP450 involvement; major metabolite is the inactive 4‑hydroxy‑desvenlafaxine.
- Half‑life: 11–13 h (steady‑state ~4 days).
- Excretion: Primarily renal (~63 %), rest via feces; no major accumulation after multiple doses.
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Indications
- Major Depressive Disorder (MDD) – adults, children ≥18 y.
- Dysthymia (as adjunct therapy).
- Off‑label: Generalized Anxiety Disorder, Social Anxiety Disorder (requires further evidence).
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Contraindications
| Category | Key Points |
| Contraindicated | Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. |
| Warnings |
• Serotonin syndrome – especially when combined with serotonergic agents. • Hypertension – caution in uncontrolled hypertensive patients. • Hyponatremia – risk in the elderly, patients on diuretics, or with renal impairment. |
| Precautions |
• Hepatic impairment – dose reduction (e.g., 25 mg QD) recommended. • Pregnancy – category C; use only if benefits outweigh risks. • QT prolongation – avoid in patients with congenital long QT or on other QT‑prolonging drugs. |
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Dosing
| Population | Initial Dose | Titration | Maintenance |
| Adults (≥18 y) | 50 mg once daily | Increase by 50 mg each week, max 200 mg/day (100 mg BID or 50 mg BID) | 50–200 mg/day; adjust for response & tolerability. |
| Children (≥13 y) | 25 mg once daily | Increase by 25 mg weekly | 25–100 mg/day. |
| Elderly | Same as adults; monitor for sedation & orthostatic hypotension. | ||
| Renal impairment | Dose‑adjust to maintain trough ≤ 150 µg/L. | Carefully reduce doses. | 25–50 mg/day preferred. |
| Not to be abruptly discontinued – taper over 2–4 weeks to avoid withdrawal syndrome. |
• Formulations: 50 mg and 100 mg tablets; 50 mg and 100 mg capsules.
• Administration tips: Take at same time daily; food has no impact on absorption.
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Adverse Effects
Common (≥10 %):
• Nausea
• Dry mouth
• Insomnia
• Headache
• Dizziness
Serious (≤2 %):
• Hyponatremia – monitor serum sodium, especially in >65 y.
• Hypertension – monitor BP at baseline and after dose escalation.
• Serotonin syndrome – symptoms: agitation, tremor, hyperreflexia, hyperthermia.
• QT prolongation – rare but serious; avoid in QT‑prolonging drug settings.
• Suicidal ideation – watch for emergent anxiety or mood changes in young patients.
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Monitoring
| Parameter | Frequency | Rationale |
| Baseline BP & HR | Prior to initiation | Detect hypertension risk |
| Serum sodium | Baseline, then every 4–6 weeks (or sooner if signs of hyponatremia) | Hyponatremia risk |
| Liver function tests | Baseline; then every 12 weeks if on >1 yr therapy | Hepatotoxicity monitoring |
| Renal function | Baseline; then every 12 weeks | Dose adjustment |
| Suicidal ideation | Baseline, then at each visit for first 6 months | FDA safety warnings |
| QT interval (ECG) | Baseline if QT risk medications | Detect arrhythmias |
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Clinical Pearls
- Active metabolite advantage: Desvenlafaxine bypasses CYP2D6, making dosing predictable across diverse genotypes—ideal for patients on heavy CYP2D6‑substrate regimens.
- Taste of productivity: While common side effects include insomnia, many patients report improved daytime alertness and reduced impulsivity after the first week.
- Desvenlafaxine vs. Venlafaxine: The latter can produce a “venlafaxine withdrawal syndrome” due to CYP2D6 metabolism. Desvenlafaxine’s stable mono‑dose avoids this, making it preferable for patients who miss doses.
- Hyponatremia monitoring: Even in the absence of symptoms, a routine sodium check at 4–6 weeks is sufficient to catch asymptomatic shifts.
- Pregnancy considerations: Although labeled Category C, clinical experience suggests that benefits often outweigh potential but unconfirmed risks. Consider sharing data with obstetric consult.
- Polypharmacy tip: Desvenlafaxine shows minimal drug–drug interactions; however, co‑prescribing with MAOIs, TMP‑SMX, or tramadol can amplify serotonin syndrome risk—check drug lists!
- Elderly dosing: Start low (25 mg QD) and titrate slowly, as autonomic instability can lead to orthostatic falls.
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• References (selected for quick lookup):
1. *FDA prescribing information – Pristiq*.
2. *UpToDate – Review of major depressive disorder pharmacotherapy, 2023*.
3. *American Journal of Psychiatry, 2005 – Pharmacokinetics of desvenlafaxine*.
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• *This drug card is for educational purposes; always consult updated prescribing sources before clinical use.*