Venlafaxine

Aka: Venlafaxine, Effexor, Venlafaxine Withdrawal

1. See Also
   1. Desvenlafaxine (Pristiq)
   2. Serotonin Norepinephrine Reuptake Inhibitor (SNRI)
   3. SNRI Overdose
2. Indications
   1. Major Depression including refractory cases
      1. Considered to be second-line agent
   2. Generalized Anxiety Disorder
   3. Obsessive Compulsive Disorder
   4. Post-Traumatic Stress Disorder
3. Mechanism
   1. Similar activity as Tricyclic Antidepressants
   2. Serotonin Norepinephrine Reuptake Inhibitor
      1. Selective Serotonin Reuptake Inhibitor (<150 mg/day)
      2. Both Serotonin and Norepinephrine Reuptake Inhibitor (>150 mg/day)
   3. Minimally inhibits Dopamine uptake
4. Pharmacokinetics
   1. Half life: 5 to 11 hours
5. Background
   1. Cost (2013)
      1. Venlafaxine ER (Effexor XR): $20 per month
      2. Desvenlafaxine (Pristiq or the ER base): $140-160 per month
6. Preparations: Venlafaxine
   1. Venlafaxine regular release (Effexor)
      1. Available as 25, 37.5, 75, 100 mg tablets (scored)
      2. Start: 25 mg PO tid
      3. Effective dose: 150-225 mg per day divided bid to tid
      4. Maximum dose: 375 mg per day
      5. Disadvantages: More adverse effects than Effexor XR
      6. Advantages: May be dosed once daily since metabolites offer similar duration to Effexor XR
   2. Venlafaxine extended release (Effexor XR)
      1. Available as 37.5, 75, 150 mg (capsules)
      2. Start: 37.5 to 75 mg orally daily
      3. Maximum: 225 mg orally daily
7. Preparations: Desvenlafaxine
   1. Pristiq (Desvenlafaxine Succinate)
      1. Active metabolite of Effexor XR
      2. No added benefit over Effexor XR and with possibly more adverse effects
      3. Reference
         1. (2008) Prescriber's Letter 15(5): 28
   2. Desvenlafaxine ER (extended-release base preparation)
      1. Equivalent to Pristiq (but requires specific instructions to pharmacist to allow substitution)
      2. As with Pristiq, no significant benefit when compared with Venlafaxine XR (which is generic and much less expensive)
   3. References
      1. (2013) Presc Lett 20(7):40
8. Adverse Effects: Prominent Withdrawal symptoms
   1. See also Antidepressant Withdrawal
   2. Symptoms start 1-3 days after stopping medication (mild symptoms may have onset within hours of missed pill)
      1. Dizziness
      2. Irritability
      3. Insomnia
      4. Headache
      5. Gastrointestinal upset
      6. Ataxia or Vertigo
      7. Paresthesias (including shock-like Sensations)
      8. Tachycardia
      9. Fever
   3. Effexor taper schedule
      1. Reduce dose 25 mg/day every 5-7 days
      2. Taper to 25-50 mg/day before stopping
   4. Effexor XR taper schedule
      1. Reduce dose 37.5 to 75 mg per day every 7 days
      2. Taper to 37.5 mg/day before stopping
   5. Alternatives to tapering with Effexor
      1. Start Sertraline (Zoloft) 50 mg orally daily on stopping Effexor
9. Adverse Effects (higher with regular release Effexor)
   1. Anticholinergic (less than Tricyclic Antidepressants)
      1. Dizziness
      2. Somnolence
      3. Dry Mouth
   2. Nausea or Vomiting
      1. May be severe and limit dosing
      2. Start therapy at 25 mg per day
   3. Increased Blood Pressure
      1. Only seen with total daily doses 300 mg or higher
   4. Less Sexual Dysfunction than Prozac, Zoloft, Paxil
      1. Sexual Dysfunction in 10-15% of cases
      2. Similar to Luvox and Celexa
      3. See Antidepressant Induced Sexual Dysfunction
   5. More stimulating (anxiogenic) than sedating
      1. Agitation or Insomnia may occur
   6. Decreased appetite and Weight loss may occur
10. Drug Interactions
    1. Minimal Cytochrome P450 interactions
11. References
    1. Mishler and Lovecchio (2017) Crit Dec Emerg Med 31(11): 15-20
    2. (1997) Am J Psych 154:1760 [PubMed]
    3. Sundberg (1995) Depression Primary Care, PGM, p. 45-57