Venlafaxine Hydrochloride

• Major Depressive Disorder (MDD):
  Approved for the treatment of major depressive episodes, including both single and recurrent episodes.
• Generalized Anxiety Disorder (GAD):
  Indicated for the management of excessive anxiety and worry associated with GAD.
• Social Anxiety Disorder (Social Phobia):
  Used to treat social anxiety disorder characterized by intense fear of social or performance situations.
• Panic Disorder (with or without agoraphobia):
  Approved for reducing the frequency and severity of panic attacks.
• Off-label Uses:
  Sometimes prescribed for obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and neuropathic pain, though not formally approved for these.

• Route: Oral (immediate-release tablets, extended-release tablets/capsules).
• Adults:
• Depression and Anxiety Disorders: Start with 37.5 mg once daily (extended-release) or 75 mg/day (immediate release in divided doses).
• Titrate gradually to 75–225 mg/day once daily (extended-release) or 75–375 mg/day divided doses (immediate release) based on response and tolerability.
• Panic Disorder: Typical target dose 150 mg/day.
• Elderly: Start at lower doses (37.5 mg/day), titrate carefully due to increased sensitivity.
• Pediatrics: Safety and efficacy not established.
• Renal Impairment: Dose reduction recommended in moderate to severe impairment.
• Hepatic Impairment: Start at lower doses; titrate cautiously.
• Administration: Take with food; immediate-release tablets usually given twice daily; extended-release once daily.
• Duration: Usually continued for several months; abrupt discontinuation should be avoided.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that increases the concentrations of serotonin (5-HT) and norepinephrine (NE) in the synaptic cleft by inhibiting their reuptake into presynaptic neurons. At lower doses, it primarily inhibits serotonin reuptake, while at higher doses, norepinephrine reuptake inhibition becomes more pronounced. This dual action enhances neurotransmission, leading to improved mood, reduced anxiety, and alleviation of depressive symptoms.

• Absorption: Well absorbed orally with peak plasma levels within 2–4 hours (immediate release) and 6–8 hours (extended release).
• Bioavailability: Approximately 45% due to first-pass metabolism.
• Distribution: Volume of distribution ~4 L/kg; plasma protein binding ~27%.
• Metabolism: Extensively metabolized in the liver by CYP2D6 to active metabolite O-desmethylvenlafaxine (ODV).
• Half-life: Venlafaxine ~5 hours; ODV ~11 hours.
• Excretion: Excreted mainly via urine (~87%) as metabolites and unchanged drug.

• Pregnancy: FDA category C. Animal studies show adverse effects at high doses; human data limited. Use only if benefits justify risks.
• Lactation: Excreted in breast milk; effects on nursing infants unknown. Caution advised.

• Antidepressant.
• Subclass: Serotonin-norepinephrine reuptake inhibitor (SNRI).

• Known hypersensitivity to venlafaxine or excipients.
• Concurrent or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs).
• Use with linezolid or intravenous methylene blue due to risk of serotonin syndrome.

• Suicidality: Increased risk in children, adolescents, and young adults; monitor closely.
• Serotonin Syndrome: Potentially life-threatening; risk increased when combined with other serotonergic drugs.
• Hypertension: Monitor blood pressure regularly; dose-related increases reported.
• Discontinuation Syndrome: Avoid abrupt cessation; taper gradually.
• Glaucoma: Use cautiously in patients with narrow-angle glaucoma.
• Seizure Risk: Caution in patients with seizure history.

• Common: Nausea, headache, dizziness, insomnia, dry mouth, sweating, somnolence, nervousness.
• Cardiovascular: Hypertension, tachycardia.
• Rare but serious: Serotonin syndrome, seizures, abnormal bleeding, hyponatremia, mania/hypomania.

• MAO inhibitors: Contraindicated; risk of serotonin syndrome.
• Other serotonergic agents (SSRIs, triptans, tramadol): Increased serotonin syndrome risk.
• CYP2D6 inhibitors: May increase venlafaxine levels.
• Anticoagulants/antiplatelets: Increased bleeding risk.
• Alcohol: May enhance CNS depressant effects.

• Guidelines reaffirm venlafaxine as a first-line agent for major depression and anxiety disorders.
• Recent warnings emphasize monitoring blood pressure and suicidality risk.
• No major changes in dosing or indications recently.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tightly closed and out of reach of children.