Effexor
Effexor
Generic Name
Effexor
Mechanism
Effexor blocks the serotonin (5‑HT) and norepinephrine (NE) transporters (SERT, NET).
• Increases synaptic concentrations of 5‑HT and NE.
• At lower doses, primarily inhibits SERT; at higher doses, NET inhibition becomes more prominent.
• Modulates α₂‑adrenergic autoreceptors, which may enhance NE release.
Pharmacokinetics
| Parameter | Description |
| Absorption | Oral; ~80 % bioavailability. Peak serum concentration 1–2 h post‑dose. |
| Metabolism | Hepatic; extensive first‑pass via CYP2D6 → O‑desmethylvenlafaxine (active metabolite). |
| Elimination | Renal (≈70 %) and hepatic. Half‑life of ∼5 h; O‑desmethylvenlafaxine ~11 h. |
| Drug interactions | Strong CYP2D6 inhibitors (e.g., paroxetine) ↑ venlafaxine levels; SSRIs/MRIs increase risk of serotonin syndrome. |
Indications
- Major Depressive Disorder (MDD) (Adults, Adolescents 12–17 yrs with inadequate response to single‑agent therapy).
- Generalized Anxiety Disorder (GAD) (Adults, Adolescents 12–17 yrs).
- Chronic Pain Syndromes (off‑label: fibromyalgia, neuropathic pain).
Contraindications
Contraindications
• Known hypersensitivity to venlafaxine or any exipient.
• Concomitant use with monoamine oxidase inhibitors (MAO‑I) or ≥14 days after discontinuation.
Warnings
• Serotonin syndrome – with other serotonergic agents (SSRIs, SNRIs, TCAs).
• Hypertension – may raise systolic BP ↑20–30 mmHg; avoid in uncontrolled hypertension.
• Abrupt withdrawal – sudden cessation leads to discontinuation syndrome (nausea, agitation).
• Pregnancy/Lactation – Category C; use only if benefits outweigh risks.
Dosing
| Patient | Initial Dose | Titration | Maintenance | Max Dose |
| Adults | 37.5 mg PO once daily (first day) | 37.5 mg ↑ 75 mg/d after 2–3 days if needed | 75–225 mg/d (split 2×) | 375 mg/d |
| Adolescents (12–17 yrs) | 37.5 mg PO once daily | ↑ 37.5–75 mg/d after 3–5 days | 75–225 mg/d (split 2×) | 375 mg/d |
| Administration | Take with or without food; avoid grapefruit juice. | |||
| Extended‑Release (XR) | 37.5 mg once daily; titrate to 75–225 mg/day in 2‑step increments. |
Adverse Effects
- Common: nausea, dry mouth, dizziness, insomnia, somnolence, headache.
- Dose‑dependent: increased serum BP, sweating, increased sweating.
- Serious: serotonin syndrome, hypertensive crisis, QTc prolongation (rare), increased suicidal ideation in <25 yrs.
Monitoring
| Parameter | Frequency | Rationale |
| Blood pressure / heart rate | Baseline, day 7, then every 2–4 weeks if BP >140/90 mmHg | Detect hypertensive spikes |
| Weight | Baseline, monthly | Venlafaxine may alter appetite/weight |
| Serotonin syndrome signs | Continuous while on concomitant serotonergic drugs | Early detection |
| Renal/hepatic function | Every 3–6 months in CKD/CHD | Dose adjustment if impaired |
| Suicidality | Baseline, weekly during first 12 weeks, then every 3–4 weeks | Mandatory safety monitoring in younger patients |
Clinical Pearls
- Titration speed matters – Rapid ↑ in dose increases hypertension risk; prefer stepwise ↑ of 37.5 mg/d.
- EEG for patients with seizures – Venlafaxine can lower seizure threshold; use cautiously in seizure‑prone individuals.
- XR vs IR – The XR formulation has better titration tolerability but requires dosing once daily in the morning; the IR formulation can be split, useful for patients with morning insomnia.
- Withdrawal protocol – Taper by 25 % of maintenance dose every 1–2 weeks to avoid discontinuation syndrome.
- Serotonin syndrome signs – Hyperreflexia, clonus, temp >38 °C; treat promptly with discontinuation and supportive care.
- Use in pregnancy – Evidence suggests fetal growth restriction at ≥2nd trimester; weigh benefits vs risks.
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• *Reference‑friendly:*
• *FDA boxed warning for venlafaxine (2014).*
• *American Psychiatric Association – Practice Guidelines for the Treatment of Depression (2024).*
• *UpToDate: “Venlafaxine: clinical pharmacology and therapeutic options” (accessed 2025).*
Feel free to adapt dosing or monitoring in special populations based on institutional protocols.