0
0

Chapter 22. Venlafaxine and Desvenlafaxine

Michael E. Thase, M.D.; Diane M. Sloan, Pharm.D.
DOI: 10.1176/appi.books.9781585623860.427499

Sections

Excerpt

The drug known as venlafaxine was first synthesized in the early 1980s and was found to block the uptake of serotonin (5-HT) and, with lower potency, norepinephrine (NE), in rat brain synaptosomal preparations (Muth et al. 1986). Subsequently, it was shown to have in vivo activity in animal models of depression and to have little affinity for muscarinic or histaminergic postsynaptic receptors (Bolden-Watson and Richelson 1993; Muth et al. 1986). As such, venlafaxine was predicted to have a better tolerability profile than the tricyclic antidepressants (TCAs). Several early randomized, controlled trials (RCTs) confirmed that venlafaxine had antidepressant effects comparable to those of TCAs, with fewer side effects attributable to anticholinergic and antihistaminergic activity (see, for example, T. R. Einarson et al. 1999). The initial formulation of venlafaxine—now known as venlafaxine immediate-release (IR)—was approved by the U.S. Food and Drug Administration (FDA) for treatment of depression in 1994. An extended-release (XR) formulation was introduced a little more than 3 years later. Generic formulations of venlafaxine IR began to be introduced in 2007.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 22–1. Chemical structure of venlafaxine hydrochloride.

FIGURE 22–2. Rate differences for remission and 95% confidence intervals for venlafaxine versus selective serotonin reuptake inhibitors (SSRIs).Remission is defined as a 17-item Hamilton Rating Scale for Depression (Ham-D-17) score of 7 or less for 33 of the 34 studies. One study (4229; Allard et al. 2004) did not use the Ham-D, and remission was defined as a Montgomery-Åsberg Depression Rating Scale score of 10 or less. Remission rate differences for the individual studies ranged from –7% to 31%; differences numerically favored venlafaxine in 28 studies (although only 5 reached statistical significance), with 6 studies numerically favoring the SSRIs.Source. Reprinted from Nemeroff CB, Entsuah R, Benattia I, et al.: "Comprehensive Analysis of Remission (COMPARE) With Venlafaxine Versus SSRIs." Biological Psychiatry 63:424–434, 2008. Copyright 2008, Elsevier. Used with permission.

References

Albert U, Aguglia E, Maina G, et al: Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study. J Clin Psychiatry 63:1004–1009, 2002
[PubMed]
 
Alfaro CL, Lam YW, Simpson J, et al: CYP2D6 inhibition by fluoxetine, paroxetine, sertraline, and venlafaxine in a crossover study: intraindividual variability and plasma concentration correlations. J Clin Pharmacol 40:58–66, 2000
[PubMed]
 
Allard P, Gram L, Timdahl K, et al: Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram. Int J Geriatr Psychiatry 19:1123–1130, 2004
[PubMed]
 
Allgulander C, Hackett D, Salinas E: Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Br J Psychiatry 179:15–22, 2001
[PubMed]
 
Allgulander C, Mangano R, Zhang J, et al: Efficacy of venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine. SAD 388 Study Group. Hum Psychopharmacol 19:387–396, 2004
[PubMed]
 
Alves C, Cachola I, Brandao J: Efficacy and tolerability of venlafaxine and fluoxetine in outpatients with major depression. Prim Care Psychiatry 5:57–63, 1999
 
Amchin J, Ereshefsky L, Zarycranski W, et al: Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe. J Clin Pharmacol 41:443–451, 2001
[PubMed]
 
Amsterdam J: Efficacy and safety of venlafaxine in the treatment of bipolar II major depressive episode. J Clin Psychopharmacol 18:414–417, 1998
[PubMed]
 
Baldomero EB, Ubago JG, Cercós CL, et al: Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study. Depress Anxiety 22:68–76, 2005
[PubMed]
 
Ball SE, Ahern D, Scatina J, et al: Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism: comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2. Br J Clin Pharmacol 43:619–626, 1997
[PubMed]
 
Ballus C, Quiros G, De Flores T, et al: The efficacy and tolerability of venlafaxine and paroxetine in outpatients with depressive disorders or dysthymia. Int Clin Psychopharmacol 15:43–48, 2000
[PubMed]
 
Banham ND: Fatal venlafaxine overdose. Med J Aust 169:445–448, 1998
[PubMed]
 
Benkert O, Szegedi A, Philipp M, et al: Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder. J Clin Psychopharmacol 26:75–78, 2006
[PubMed]
 
Bielski RJ, Ventura D, Chang CC: A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry 65:1190–1196, 2004
[PubMed]
 
Bitsios P, Szabadi E, Bradshaw CM: Comparison of the effects of venlafaxine, paroxetine and desipramine on the pupillary light reflex in man. Psychopharmacology (Berl) 143:286–292, 1999
[PubMed]
 
Bolden-Watson C, Richelson E: Blockade by newly developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 52:1023–1029, 1993
[PubMed]
 
Bose A, Korotzer A, Gommoll C, et al: Randomized placebo-controlled trial of escitalopram and venlafaxine XR in the treatment of generalized anxiety disorder. Depress Anxiety 25:854–861, 2008
 
Bradwejn J, Ahokas A, Stein DJ, et al: Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study. Br J Psychiatry 187:352–359, 2005
[PubMed]
 
Buckley NA, McManus PR: Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 325:1332–1333, 2002
[PubMed]
 
Cipriani A, Barbui C, Brambilla P, et al: Are all antidepressants really the same? The case of fluoxetine: a systematic review. J Clin Psychiatry 67:850–864, 2006
[PubMed]
 
Clayton AH, Pradko JF, Croft HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 63:357–366, 2002
[PubMed]
 
Clerc GE, Ruimy P, Verdeau-Palles J: A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. Int Clin Psychopharmacol 9:139–143, 1994
[PubMed]
 
Cohen LS, Soares CN, Lyster A, et al: Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder. J Clin Psychopharmacol 24:540–543, 2004
[PubMed]
 
Costa e Silva J: Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. J Clin Psychiatry 59:352–357, 1998
 
Cunningham LA: Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group. Ann Clin Psychiatry 9:157–164, 1997
[PubMed]
 
Davidson JR, DuPont RL, Hedges D, et al: Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 60:528–535, 1999
[PubMed]
 
Davidson J, Watkins L, Owens M, et al: Effects of paroxetine and venlafaxine XR on heart rate variability in depression. J Clin Psychopharmacol 25:480–484, 2005
[PubMed]
 
Davidson J, Baldwin D, Stein DJ, et al: Treatment of posttraumatic stress disorder with venlafaxine extended release: a 6-month randomized controlled trial. Arch Gen Psychiatry 63:1158–1165, 2006a
 
Davidson J, Rothbaum BO, Tucker P, et al: Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study. J Clin Psychopharmacol 26:259–267, 2006b
 
Deecher DC, Beyer CE, Johnston G, et al: Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 318:657–665, 2006
[PubMed]
 
DeMartinis NA, Yeung PP, Entsuah R, et al: A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder. J Clin Psychiatry 68:677–688, 2007
[PubMed]
 
De Nayer A, Geerts S, Ruelens L, et al: Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. Int J Neuropsychopharmacol 5:115–120, 2002
 
Diaz-Martinez A, Benassinni O, Ontiveros A, et al: A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients. Clin Ther 20:467–476, 1998
[PubMed]
 
Dierick M, Ravizza L, Realini R, et al: A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuropsychopharmacol Biol Psychiatry 20:57–71, 1996
[PubMed]
 
Einarson A, Fatoye B, Sarkar M, et al: Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry 158:1728–1730, 2001
[PubMed]
 
Einarson TR, Arikian SR, Casciano J, et al: Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials. Clin Ther 21:296–308, 1999
[PubMed]
 
Emslie GJ, Findling RL, Yeung PP, et al: Venlafaxine ER for the treatment of pediatric subjects with depression: results of two placebo-controlled trials. J Am Acad Child Adolesc Psychiatry 46:479–488, 2007
[PubMed]
 
Entsuah AR, Rudolph RL, Hackett D, et al: Efficacy of venlafaxine and placebo during long-term treatment of depression: a pooled analysis of relapse rates. Int Clin Psychopharmacol 11:137–145, 1996
[PubMed]
 
Entsuah R, Gao B: Global benefit-risk evaluation of antidepressant action: comparison of pooled data for venlafaxine, SSRIs, and placebo. CNS Spectr 7:882–888, 2002
[PubMed]
 
Feighner JP, Entsuah A, McPherson MK: Efficacy of once-daily venlafaxine extended release (XR) for symptoms of anxiety in depressed outpatients. J Affect Disord 47:55–62, 1998
[PubMed]
 
Ferguson JM, Khan A, Mangano R, et al: Relapse prevention of panic disorder in adult outpatient responders to treatment with venlafaxine extended release. J Clin Psychiatry 68:58–68, 2007
[PubMed]
 
Freeman EW, Rickels K, Yonkers KA, et al: Venlafaxine in the treatment of premenstrual dysphoric disorder. Obstet Gynecol 98:737–744, 2001
[PubMed]
 
Gelenberg AJ, Lydiard RB, Rudolph RL, et al: Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: a 6-month randomized controlled trial. JAMA 283:3082–3088, 2000
[PubMed]
 
Guelfi JD, White C, Hackett D, et al: Effectiveness of venlafaxine in patients hospitalized for major depression and melancholia. J Clin Psychiatry 56:450–458, 1995
[PubMed]
 
Guelfi JD, Ansseau M, Timmerman L, et al: Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features. J Clin Psychopharmacol 21:425–431, 2001
[PubMed]
 
Hackett D, Haudiquet V, Salinas E: A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder. Eur Psychiatry 18:182–187, 2003
[PubMed]
 
Haddad PM: Antidepressant discontinuation syndromes. Drug Saf 24:183–197, 2001
[PubMed]
 
Harvey AT, Rudolph RL, Preskorn SH: Evidence of the dual mechanisms of action of venlafaxine. Arch Gen Psychiatry 57:503–509, 2000
[PubMed]
 
Howell C, Wilson AD, Waring WS: Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases. Br J Clin Pharmacol 64:192–197, 2007
[PubMed]
 
Howell SR, Husbands GE, Scatina JA, et al: Metabolic disposition of 14C-venlafaxine in mouse, rat, dog, rhesus monkey and man. Xenobiotica 23:349–359, 1993
[PubMed]
 
Ilett KF, Hackett LP, Dusci LJ, et al: Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Br J Clin Pharmacol 45:459–462, 1998
[PubMed]
 
Ilett KF, Kristensen JH, Hackett LP, et al: Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Br J Clin Pharmacol 53:17–22, 2002
[PubMed]
 
Keller MB, Trivedi MH, Thase ME, et al: The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: outcomes from the acute and continuation phases. Biol Psychiatry 62:1371–1379, 2007a
 
Keller MB, Trivedi MH, Thase ME, et al: The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: outcomes from the 2-year and combined maintenance phases. J Clin Psychiatry 68:1246–1256, 2007b
 
Kelsey JE: Dose-response relationship with venlafaxine. J Clin Psychopharmacol 16:21S–26S, 1996
 
Kennedy SH, Eisfeld BS, Dickens SE, et al: Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 61:276–281, 2000
[PubMed]
 
Khan A, Fabre LF, Rudolph R: Venlafaxine in depressed outpatients. Psychopharmacol Bull 27:141–144, 1991
[PubMed]
 
Khan A, Upton GV, Rudolph RL, et al: The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. J Clin Psychopharmacol 18:19–25, 1998
[PubMed]
 
Kim TS, Pae CU, Yoon SJ, et al: Comparison of venlafaxine extended release versus paroxetine for treatment of patients with generalized anxiety disorder. Psychiatry Clin Neurosci 60:347–351, 2006
[PubMed]
 
Klamerus KJ, Maloney K, Rudolph RL, et al: Introduction of a composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite. J Clin Pharmacol 32:716–724, 1992
[PubMed]
 
Klamerus KJ, Parker VD, Rudolph RL, et al: Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics. Pharmacotherapy 16:915–923, 1996
[PubMed]
 
Kocsis JH, Thase ME, Trivedi MH, et al: Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT Study. J Clin Psychiatry 68:1014–1023, 2007
[PubMed]
 
Kunsman GW, Kunsman CM, Presses CL, et al: A mixed-drug intoxication involving venlafaxine and verapamil. J Forensic Sci 45:926–928, 2000
[PubMed]
 
Levin GM, Nelson LA, DeVane CL, et al: A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir. Psychopharmacol Bull 35:62–71, 2001
[PubMed]
 
Liebowitz MR, Gelenberg AJ, Munjack D: Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry 62:190–198, 2005a
 
Liebowitz MR, Mangano RM, Bradwejn J, et al: A randomized controlled trial of venlafaxine extended release in generalized social anxiety disorder. SAD Study Group. J Clin Psychiatry 66:238–247, 2005b
 
Long C, Crifasi J, Maginn D, et al: Comparison of analytical methods in the determination of two venlafaxine fatalities. J Anal Toxicol 21:166–169, 1997
[PubMed]
 
Magni G, Hackett D: An open label evaluation of the long-term safety and clinical acceptability of venlafaxine in depressed patients. Clin Neuropharmacol 15 (suppl 1):323B, 1992
 
March JS, Entusah AR, Rynn M, et al: A randomized controlled trial of venlafaxine ER versus placebo in pediatric social anxiety disorder. Biol Psychiatry 62:1149–1154, 2007
[PubMed]
 
McAlpine DE, O'Kane DJ, Black JL, et al: Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clin Proc 82:1065–1068, 2007
[PubMed]
 
McGrath PJ, Stewart JW, Fava M, et al: Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 163:1531–1541, 2006
[PubMed]
 
McPartlin GM, Reynolds A, Anderson C, et al: A comparison of once-daily venlafaxine XR and paroxetine in depressed outpatients treated in general practice. Prim Care Psychiatry 4:127–132, 1998
 
Mehtonen OP, Sogaard J, Roponen P, et al: Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. J Clin Psychiatry 61:95–100, 2000
[PubMed]
 
Mendels J, Johnston R, Mattes J, et al: Efficacy and safety of bid doses of venlafaxine in a dose-response study. Psychopharmacol Bull 29:169–174, 1993
[PubMed]
 
Mines D, Hill D, Yu H, Novelli L: Prevalence of risk factors for suicide in patients prescribed venlafaxine, fluoxetine, and citalopram. Pharmacoepidemiol Drug Saf 14:367–372, 2005
[PubMed]
 
Montejo AL, Llorca G, Izquierdo JA, et al: Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. J Clin Psychiatry 62:10–21, 2001
[PubMed]
 
Montgomery SA, Andersen HF: Escitalopram versus venlafaxine XR in the treatment of depression. Int Clin Psychopharmacol 21:297–309, 2006
[PubMed]
 
Montgomery SA, Entsuah R, Hackett D, et al: Venlafaxine versus placebo in the preventive treatment of recurrent major depression. Venlafaxine 335 Study Group. J Clin Psychiatry 65:328–36, 2004a
 
Montgomery SA, Huusom AK, Bothmer J: A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology 50:57–64, 2004b
 
Muth EA, Haskins JT, Moyer JA, et al: Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative. Biochem Pharmacol 35:4493–4497, 1986
[PubMed]
 
Nemeroff CB, Thase ME, EPIC 014 Study Group: A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. J Psychiatr Res 41:351–359, 2007
[PubMed]
 
Nemeroff CB, Entsuah R, Benattia I, et al: Comprehensive Analysis of Remission (COMPARE) with venlafaxine versus SSRIs. Biol Psychiatry 63:424–434, 2008
[PubMed]
 
Nimatoudis I, Zissis NP, Kogeorgos J, et al: Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder: a double-blind, randomized, placebo controlled study. Int Clin Psychopharmacol 19:331–336, 2004
[PubMed]
 
Owen JR, Nemeroff CB: New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine. Depress Anxiety 7 (suppl 1):24–32, 1998
 
Owens MJ, Morgan WN, Plott SJ, Nemeroff CB: Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 283:1305–1322, 1997
[PubMed]
 
Pae CU, Lim HK, Ajwani N, et al: Extended-release formulation of venlafaxine in the treatment of post-traumatic stress disorder. Expert Rev Neurother 7:603–615, 2007
[PubMed]
 
Parsons AT, Anthony RM, Meeker JE: Two fatal cases of venlafaxine poisoning. J Anal Toxicol 20:266–268, 1996
[PubMed]
 
Perahia DG, Pritchett YL, Kajdasz DK, et al: A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res 42:22–34, 2008
[PubMed]
 
Poirier M-F, Boyer P: Venlafaxine and paroxetine in treatment-resistant depression: double-blind, randomised comparison. Br J Psychiatry 175:12–16, 1999
[PubMed]
 
Pollack MH, Worthington JJ 3rd, Otto MW, et al: Venlafaxine for panic disorder: results from a double-blind, placebo-controlled study. Psychopharmacol Bull 32:667–670, 1996
[PubMed]
 
Pollack MH, Lepola U, Koponen H, et al: A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. Depress Anxiety 24:1–14, 2007a
 
Pollack M, Mangano R, Entsuah R, et al: A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder. Psychopharmacology (Berl) 194:233–342, 2007b
 
Post RM, Altshuler LL, Leverich GS, et al: Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry 189:124–131, 2006
[PubMed]
 
Preskorn SH: Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 56:12–21, 1995
[PubMed]
 
Rauch SL, O'Sullivan RL, Jenike MA: Open treatment of obsessive-compulsive disorder with venlafaxine: a series of ten cases. J Clin Psychopharmacol 16:81–84, 1996
[PubMed]
 
Rickels K, Pollack MH, Sheehan DV, et al: Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 157:968–974, 2000
[PubMed]
 
Rickels K, Mangano R, Khan A: A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder. J Clin Psychopharmacol 24:488–496, 2004
[PubMed]
 
Rubino A, Roskell N, Tennis P, et al: Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study. BMJ 334:242, 2007
[PubMed]
 
Rudolph RL, Feiger AD: A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord 56:171–181, 1999
[PubMed]
 
Rudolph RL, Entsuah R, Aguiar L, et al: Early onset of antidepressant activity of venlafaxine compared with placebo and fluoxetine in outpatients in a double-blind study (abstract). Eur Neuropsychopharmacol 8:S142, 1998a
 
Rudolph RL, Entsuah R, Chitra R: A meta-analysis of the effects of venlafaxine on anxiety associated with depression. J Clin Psychopharmacol 18:136–44, 1998b
 
Rudolph RL, Fabre LF, Feighner JP, et al: A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry 59:116–122, 1998c
 
Rush AJ, Trivedi MH, Wisniewski SR, et al: Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. STAR*D Study Team. N Engl J Med 354:1231–1242, 2006
[PubMed]
 
Rynn MA, Riddle MA, Yeung PP, et al: Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials. Am J Psychiatry 164:290–300, 2007
[PubMed]
 
Schatzberg A, Roose S: A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry 14:361–370, 2006
[PubMed]
 
Schweizer E, Weise C, Clary C, et al: Placebo-controlled trial of venlafaxine for the treatment of major depression. J Clin Psychopharmacol 11:233–236, 1991
[PubMed]
 
Septien-Velez L, Pitrosky B, Padmanabhan SK, et al: A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol 22:338–347, 2007
[PubMed]
 
Shams ME, Arneth B, Hiemke C, et al: CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharmacol Ther 31:493–502, 2006
[PubMed]
 
Shang Y, Gibbs MA, Marek GJ, et al: Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single photon emission computed tomography imaging study. J Clin Psychopharmacol 27:71–75, 2007
[PubMed]
 
Shelton RC, Haman KL, Rapaport MH, et al: A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. J Clin Psychiatry 67:1674–1681, 2006
[PubMed]
 
Shrivastava RK, Cohn C, Crowder J, et al: Long-term safety and clinical acceptability of venlafaxine and imipramine in outpatients with major depression. J Clin Psychopharmacol 14:322–329, 1994
[PubMed]
 
Siepmann T, Ziemssen T, Mueck-Weymann M, et al: The effects of venlafaxine on autonomic functions in healthy volunteers. J Clin Psychopharmacol 27:687–691, 2007
[PubMed]
 
Silverstone PH, Ravindran A: Once-daily venlafaxine extended-release (XR) compared with fluoxetine in outpatients with depression and anxiety. J Clin Psychiatry 60:22–28, 1999
[PubMed]
 
Simon JS, Aguiar LM, Kunz NR, et al: Extended-release venlafaxine in relapse prevention for patients with major depressive disorder. J Psychiatr Res 38:249–257, 2004
[PubMed]
 
Sir A, D'Souza RF, Uguz S, et al: Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. J Clin Psychiatry 66:1312–1320, 2005
[PubMed]
 
Smith D, Dempster C, Glanville J, et al: Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry 180:396–404, 2002
[PubMed]
 
Stahl SM, Entsuah R, Rudolph RL: Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry 52:1166–1174, 2002
[PubMed]
 
Stein MB, Pollack MH, Bystritsky A, et al: Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial. Psychopharmacology (Berl) 177:280–288, 2005
[PubMed]
 
Thase ME: Antidepressant options: venlafaxine in perspective. J Clin Psychopharmacol 16:10S–18S, 1996
 
Thase ME: Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group. J Clin Psychiatry 58:393–398, 1997
[PubMed]
 
Thase ME: Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry 59:502–508, 1998
[PubMed]
 
Thase ME: Treatment of anxiety disorders with venlafaxine XR. Expert Rev Neurother 6:269–282, 2006
[PubMed]
 
Thase ME, Friedman ES, Howland RH: Venlafaxine and treatment-resistant depression. Depress Anxiety 12:55–62, 2000
[PubMed]
 
Thase ME, Entsuah AR, Rudolph RL: Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 178:234–221, 2001
[PubMed]
 
Thase ME, Clayton AH, Haight BR, et al: A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability. J Clin Psychopharmacol 26:482–488, 2006a
 
Thase ME, Shelton RC, Khan A: Treatment with venlafaxine extended release after SSRI nonresponse or intolerance: a randomized comparison of standard- and higher-dosing strategies. J Clin Psychopharmacol 26:250–258, 2006b
 
Tiller J, Johnson G, O'Sullivan B, et al: Venlafaxine: a long-term study (abstract). Clin Neuropharmacol 14:342B, 1992
 
Troy SM, Schultz RW, Parker VD, et al: The effect of renal disease on the disposition of venlafaxine. Clin Pharmacol Ther 56:14–21, 1994
[PubMed]
 
Troy SM, Lucki I, Peirgies AA, et al: Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and diazepam. J Clin Pharmacol 35:410–419, 1995a
 
Troy SM, Parker VD, Fruncillo RJ, et al: The pharmacokinetics of venlafaxine when given in a twice-daily regimen. J Clin Pharmacol 35:404–409, 1995b
 
Troy SM, Parker VD, Hicks DR, et al: Pharmacokinetic interaction between multiple-dose venlafaxine and single-dose lithium. J Clin Pharmacol 36:175–181, 1996
[PubMed]
 
Troy SM, DiLea C, Martin PT, et al: Pharmacokinetics of once-daily venlafaxine extended release (XR) in healthy volunteers. Curr Ther Res 58:504–514, 1997a
 
Troy SM, Parker VP, Hicks DR, et al: Pharmacokinetics and effect of food on the bioavailability of orally administered venlafaxine. J Clin Pharmacol 37:954–61, 1997b
 
Troy SM, Turner MB, Unruh M, et al: Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and ethanol. J Clin Pharmacol 37:1073–1081, 1997c
 
Tylee A, Beaumont G, Bowden MW, et al: A double-blind, randomized, 12-week comparison of the safety and efficacy of venlafaxine and fluoxetine in moderate to severe major depression in general practice. Prim Care Psychiatry 3:51–58, 1997
 
Tzanakaki M, Guazzelli M, Nimatoudis I, et al: Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Int Clin Psychopharmacol 15:29–34, 2000
[PubMed]
 
Vaishnavi SN, Nemeroff CB, Plott SJ, et al: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry 55:320–322, 2004
[PubMed]
 
Vieta E, Martinez-Aran A, Goikolea JM, et al: A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. J Clin Psychiatry 63:508–512, 2002
[PubMed]
 
Whyte IM, Dawson AH, Buckley NA: Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM 96:369–374, 2003
[PubMed]
 
Zanardi R, Franchini L, Serretti A, et al: Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study. J Clin Psychiatry 61:26–29, 2000
[PubMed]
 
+

CME Activity

Add a subscription to complete this activity and earn CME credit.
Sample questions:
1.
A 42-year-old man with recurrent major depressive disorder (MDD) is referred to you by his primary care physician for evaluation because the patient has not responded to two adequate trials of selective serotonin reuptake inhibitors (SSRIs). You decide to prescribe venlafaxine extended release (XR). Which of the following statements concerning the prescription of venlafaxine XR is true?
2.
The mechanism of action of both venlafaxine and desvenlafaxine is
3.
Although venlafaxine is approved by the U.S. Food and Drug Administration (FDA) only for the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder, double-blind and single-blind randomized, controlled clinical trials of venlafaxine monotherapy have shown it to be effective in all of the following additional conditions except
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 3.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 23.  >
What Your Patients Need to Know About Psychiatric Medications, 2nd Edition > Chapter 18.  >
What Your Patients Need to Know About Psychiatric Medications, 2nd Edition > Chapter 26.  >
Topic Collections
Psychiatric News
PubMed Articles
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation