Venlafaxine (Effexor) versus ...

Venlafaxine vs. Escitalopram (Lexapro)

Major depressive disorder

Escitalopram is at least as effective as venlafaxine XR and significantly better tolerated 8. Escitalopram has a faster onset of antidepressant effects 9.

Results of double-blind comparison of escitalopram and venlafaxine ER for major depressive disorder 8. Venlafaxine Escitalopram
225 mg/day
20 mg/day
Mean changes from baseline to endpoint in MADRS total score
Remission rates at endpoint
Response rates
Treatment-emergent adverse events
Discontinuation due to adverse events

Generalized anxiety disorder (GAD)

Venlafaxine XR seems to be more effective than escitalopram for the treatment of GAD 10.

Results of randomized placebo-controlled trial of escitalopram and venlafaxine XR for GAD 10. Venlafaxine Escitalopram
75-225 mg/day
10-20 mg/day
Mean change from baseline at week 8 in HAMA total score
Mean change from baseline at week 8 using Last Observation Carried Forward approach
Discontinuation due to adverse events

Side effects

Escitalopram appears to be significantly better tolerated than venlafaxine XR 8.

Withdrawal symptoms

Venlafaxine is associated with significantly higher rate of discontinuation symptoms than escitalopram 8, 9.

Escitalopram provides a more cost-effective first-line treatment of depression than generic venlafaxine XR 4.

Venlafaxine vs. Sertraline (Zoloft)

Major depressive disorder

Venlafaxine therapy results in higher response and remission rates than sertraline therapy in the major depressive disorder 19, 20.

Results of randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder 20. Venlafaxine XR Sertraline
Maximum study dosage
225 mg/day
150 mg/day
Final scores on the primary or secondary measures (Quality of Life Enjoyment and Satisfaction Questionnaire; 17-item Hamilton Rating Scale for Depression) No significant differences, both antidepressants led to significant improvement in depressive symptoms and quality-of-life measures
Responders percentage
Remitters percentage
Response rates in patients who achieved the maximum dose of drug and maintained it for 3 weeks
Remission rates in patients who achieved the maximum dose of drug and maintained it for 3 weeks

Results of randomized, double-blind comparison of venlafaxine and sertraline for major depressive disorder 19. Venlafaxine Sertraline
Mean HAM-D, MADRS, or CGI scores
No significant differences
HAM-D response rate at week 8
HAM-D score less than 10 at week 8
Remission rate (HAM-D score < 10) at week 8
Discontinuation rate
Most common adverse events nausea, headache, sweating nausea, headache, diarrhea

Bipolar depression

There is a significantly increased risk of switches into hypomania or mania with venlafaxine compared with sertraline treatment 7.

Effects on depression, cognition and daily living in Alzheimer patients

Sertraline may provide a superior effectiveness in relation to depressive, cognitive, and behavioral symptoms in Alzheimer patients than venlafaxine 2.

Side effects

Venlafaxine is associated with the risk of blood pressure increase 9. Antidepressant-induced sexual dysfunction occurs more frequently with sertraline, than with venlafaxine 21.

Discontinuation syndrome

Sertraline may be associated with a lower symptom burden during treatment discontinuation 22.


Venlafaxine vs. Paroxetine (Paxil)

Major depressive disorder

In clinical study venlafaxine showed some evidence of superiority to paroxetine in the treatment-resistant depression. In patients with non-chronic treatment-resistant depression the response rate was 51.9% for venlafaxine and 32.7% for paroxetine, and a remission was achieved in 42.3% of venlafaxine-treated and 20.0% of paroxetine-treated patients 13.

Venlafaxine appears to have a higher rate of response and remission in patients with depressive disorder or dysthymia. In clinical study a response was achieved in 55% of patients on venlafaxine and 29% on paroxetine after 6 weeks of treatment. After 12 weeks, significantly more patients in the venlafaxine group had a HAM-D remission score of 8 or less (59% versus 31%) 14.

Results of randomized, single-blind, comparison of venlafaxine with paroxetine for resistant depression in elderly patients 11. Venlafaxine Paroxetine
Dose range
75-300 mg/day
10-60 mg/day
Remission rate at week 8
Mean Hamilton Rating Scale for Depression change
Mean Geriatric Depression Scale change
Mean Clinical Global Impression Scale change
Conclusion: Remission rates were higher for venlafaxine and tolerability was acceptable for both antidepressants.

Obsessive-compulsive disorder

Paroxetine is more efficacious than venlafaxine in the treatment of nonresponders to a previous SSRI trial 15.

Panic disorder

In randomized controlled trial patients treated with venlafaxine ER had significantly greater mean Panic Disorder Severity Scale score improvement than patients treated with the paroxetine and a significantly higher proportion of patients free of full symptom panic attacks (70% vs 58.3%) 16.

Social anxiety disorder

Venlafaxine ER appears to be effective treatment for SAD, with efficacy and tolerability comparable to paroxetine. In clinical study after 12 week of the treatment response rates were 58.6% for the venlafaxine ER and 62.5% for paroxetine 17.

Bipolar depression

Paroxetine and venlafaxine are both effective and safe in the treatment of depressive breakthrough episodes in bipolar disorder. There is a slightly higher risk for switch to mania or hypomania with venlafaxine 18.

Side effects

Paroxetine causes more side effects in comparison with venlafaxine23.

Venlafaxine vs. Mirtazapine (Remeron)

Major depressive disorder

Mirtazapine and venlafaxine are similarly effective for the treatment of overall symptoms of depression, and both antidepressants may be useful for somatic (bodily) symptoms of depression 12. Mirtazapine appears to have higher response and remission rates than venlafaxine 1.

Mirtazapine orally disintegrating tablets (ODT) have a faster onset of antidepressant efficacy than venlafaxine XR 3.

Side effects

Mirtazapine is associated with significantly fewer dropouts due to adverse events 1.

Venlafaxine vs. Trazodone (Desyrel)

Major depressive disorder

Venlafaxine can produce more improvement in the cognitive disturbance and retardation factors on the Hamilton Rating Scale for Depression. Trazodone is more effective against the sleep disturbance factor 6. Trazodone efficiency in comparison to venlafaxine is faster, so trazodone is characterized by potentially quicker beginning of activity in patients with depression disorders 5.

Side effects

Venlafaxine is most likely to cause nausea, whereas trazodone is associated with the most dizziness and somnolence 6. Libido decrease is common side effect with venlafaxine treatment 5.

Further reading
  • 1. Guelfi JD, Ansseau M, Timmerman L, Kørsgaard S; Mirtazapine-Venlafaxine Study Group. Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features. J Clin Psychopharmacol. 2001 Aug;21(4):425-31. PubMed
  • 2. Mokhber N, Abdollahian E, Soltanifar A, Samadi R, Saghebi A, Haghighi MB, Azarpazhooh A. Comparison of sertraline, venlafaxine and desipramine effects on depression, cognition and the daily living activities in Alzheimer patients. Pharmacopsychiatry. 2014 Jul;47(4-5):131-40. PubMed
  • 3. Benkert O, Szegedi A, Philipp M, Kohnen R, Heinrich C, Heukels A, van der Vegte-Senden M, Baker RA, Simmons JH, Schutte AJ. 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. 2006 Feb;26(1):75-8. PubMed
  • 4. Nordström G, Danchenko N, Despiegel N, Marteau F. Cost-effectiveness evaluation in Sweden of escitalopram compared with venlafaxine extended-release as first-line treatment in major depressive disorder. Value Health. 2012 Mar-Apr;15(2):231-9. PubMed
  • 5. Florkowski A, Gruszczynski W, Galecki P, Zboralski K, Kolodziejska I, Mikolajczyk I. Trazodone and venlafaxine in treatment of depressive disorders. Pol Merkur Lekarski. 2005 May;18(107):556-9. PubMed
  • 6. Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, Diamond BI, Fischer DE, Hearst E. A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol. 1994 Apr;14(2):99-106. PubMed
  • 7. Post RM, Altshuler LL, Leverich GS, Frye MA, Nolen WA, Kupka RW, Suppes T, McElroy S, Keck PE, Denicoff KD, Grunze H, Walden J, Kitchen CM, Mintz J. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006 Aug;189:124-31. PubMed
  • 8. 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. 2004 Sep;65(9):1190-6. PubMed
  • 9. Montgomery SA, Huusom AK, Bothmer J. A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology. 2004;50(1):57-64. PubMed
  • 10. Bose A, Korotzer A, Gommoll C, Li D. Randomized placebo-controlled trial of escitalopram and venlafaxine XR in the treatment of generalized anxiety disorder. Depress Anxiety. 2008;25(10):854-61. PubMed
  • 11. Mazeh D, Shahal B, Aviv A, Zemishlani H, Barak Y. A randomized, single-blind, comparison of venlafaxine with paroxetine in elderly patients suffering from resistant depression. Int Clin Psychopharmacol. 2007 Nov;22(6):371-5. PubMed
  • 12. Kang EH, Lee IS, Chung SK, Lee SY, Kim EJ, Hong JP, Oh KS, Woo JM, Kim S, Park JE, Yu BH. Mirtazapine versus venlafaxine for the treatment of somatic symptoms associated with major depressive disorder: a randomized, open-labeled trial. Psychiatry Res. 2009 Sep 30;169(2):118-23. PubMed
  • 13. Poirier MF, Boyer P. Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison. Br J Psychiatry. 1999 Jul;175:12-6. PubMed
  • 14. Ballu's C, Quiros G, De Flores T, de la Torre J, Palao D, Rojo L, Gutie'rrez M, Casais L, Riesgo Y. The efficacy and tolerability of venlafaxine and paroxetine in outpatients with depressive disorder or dysthymia. Int Clin Psychopharmacol. 2000 Jan;15(1):43-8. PubMed
  • 15. Denys D, van Megen HJ, van der Wee N, Westenberg HG. A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder. J Clin Psychiatry. 2004 Jan;65(1):37-43. PubMed
  • 16. Pollack M, Mangano R, Entsuah R, Tzanis E, Simon NM. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder. Psychopharmacology (Berl). 2007 Jun 23. PubMed
  • 17. Liebowitz MR, Gelenberg AJ, Munjack D. Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry. 2005 Feb;62(2):190-8. PubMed
  • 18. Vieta E, Martinez-Ara'n A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M. A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. J Clin Psychiatry. 2002 Jun;63(6):508-12. PubMed
  • 19. Mehtonen OP, Sogaard J, Roponen P, Behnke K. Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. J Clin Psychiatry. 2000 Feb;61(2):95-100 PubMed
  • 20. Shelton RC, Haman KL, Rapaport MH, Kiev A, Smith WT, Hirschfeld RM, Lydiard RB, Zajecka JM, Dunner DL. A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. J Clin Psychiatry. 2006 Nov;67(11):1674-81. PubMed
  • 21. Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM. Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry. 2000 Apr;61(4):276-81. PubMed
  • 22. Sir A, D'Souza RF, Uguz S, George T, Vahip S, Hopwood M, Martin AJ, Lam W, Burt T. Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. J Clin Psychiatry. 2005 Oct;66(10):1312-20. PubMed
  • 23. Miskovic M. Comparison of tolerance of venlafaxine, paroxetine and amitriptyline in depression therapy. Med Arch. 2015 Apr;69(2):107-9. PubMed

Published: March 31, 2008
Last updated: February 25, 2017


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