Venlafaxine (Effexor) vs Paroxetine (Paxil)

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

Venlafaxine advantages over Paroxetine

  • Unlike paroxetine venlafaxine does not significantly inhibit CYP enzymes.
  • Venlafaxine has higher remission rate than paroxetine in the treatment of depression.
  • Lower risk of weight gain than with paroxetine.

Paroxetine advantages over Venlafaxine

  • Paroxetine is available in suspension formulation.
  • Among the SRIs, which all have anti-anxiety effects, paroxetine holds the reputation of having the most consistent anxiolytic effects.
  • SSRIs are less toxic than venlafaxine in overdose.
  • No risk of increased blood pressure.


Venlafaxine Paroxetine
Brand names
• Effexor®
• Effexor XR®
• Paxil®
• Paxil® CR
• Brisdelle®
effexor xr pills paxil cr pills
Drug class
• Antidepressant, antianxiety agent
• Serotonin-norepinephrine reuptake inhibitor (SNRI) • Selective serotonin reuptake inhibitor (SSRI)
Dose formulations
• Tablets
• Tablets, extended release
• Capsule, extended release
• Tablets
• Capsules
• Tablets, extended release
• Oral suspension
Legal status
• Rx only
• Not a controlled drug
FDA-approved indications
• Depressive disorder
• Generalized anxiety
• Social anxiety disorder
• Panic disorder
  • Hot Flashes
• Obsessive compulsive disorder
• Posttraumatic stress disorder
• Premenstrual dysphoric disorder
"Off-label" uses
• Hot flashes
• Somatization disorder
• Neuropathic pain
• Premenstrual dysphoric disorder
• Premature ejaculation
Mechanism of action
• Venlafaxine inhibits the reuptake of serotonin and norepinephrine.
• The reuptake effects of venlafaxine are dose dependent. At low doses it blocks only serotonin neurotransmission. At higher doses venlafaxine blocks neurotransmission of both serotonin and noradrenaline.
• Paroxetine is the most potent inhibitor of the serotonin reuptake of all currently available antidepressants.
• Paroxetine produces moderate anticholinergic effects.
• 5 hours
• 11 hours for active metabolite O-desmethylvenlafaxine
• 21 hours
Oral bioavailability
• 45% • 50%
Metabolism, Elimination
• Venlafaxine is metabolized in the liver via the CYP2D6 to its active metabolite, O-desmethylvenlafaxine.
• 87% of venlafaxine dose is excreted by the kidneys.
• Paroxetine undergoes extensive ‎hepatic‎ metabolism by CYP2D6.
• Paroxetine is oxidized to inactive metabolites which are then conjugated and inactivated.
• About 64% of the paroxetine dose is excreted in the urine; 36% in the faeces.
• Concurrent use with monoamine oxidase inhibitors or within 14 days of stopping an MAOI.
• Hypersensitivity to venlafaxine • Hypersensitivity to paroxetine
• Concurrent use with pimozide, thioriazine
Side effects
• Paroxetine causes more side effects in comparison with venlafaxine9.
• Headache
• Nausea
• Insomnia
• Asthenia
• Dizziness
• Ejaculation problems
• Somnolence
• Dry mouth
• Sweating
• Anorexia
• Increased blood pressure
• Nausea
• Somnolence
• Sweating
• Tremor
• Weakness
• Dry mouth
• Insomnia
• Constipation
• Ejaculation problems
• Weight gain
Pregnancy category

Venlafaxine vs Paroxetine for Hot Flashes

Antidepressants represent a useful alternative to hormone therapy as they allow to avoid serious risks of estrogen-dependent conditions.

Paroxetine and venlafaxine are the most studied and most effective antidepressants used for the management hot flashes. Both antidepressants can reduce the frequency and severity of hot flashes in menopausal as well as post-menopausal women.

Paroxetine is rated as most effective SSRI. And venlafaxine is rated as the most useful SNRI.

Currently Brisdelle® (paroxetine) is the only FDA-approved medication for hot flashes.

Venlafaxine appears to provide more immediate symptom relief than paroxetine, but has a higher rate of side effects, most notably nausea and constipation. On the other hand, paroxetine usually provides more significant reduction in hot flash frequency.

Dosage for hot flashes1:

  • Brisdelle®: 7.5 mg per day
  • Paroxetine or paroxetine ER: 10–25 mg per day
  • Venlafaxine XR: 37.5–150 mg per day

Helpful non-pharmaceutical measures that may be practiced along with taking the medication, include physical activity, weight loss, relaxation techniques, vitamins, ginseng.

Venlafaxine vs Paroxetine for Depression

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 2.

Venlafaxine appears to have a higher rate of response and remission in patients with depression 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%) 3.

Results of randomized, single-blind, comparison of venlafaxine with paroxetine for resistant depression in elderly 4. 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.

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 8.

Venlafaxine vs Paroxetine for Obsessive-Compulsive Disorder

Paroxetine is more efficacious than venlafaxine in the treatment of SSRI-resistant OCD5.

Venlafaxine vs Paroxetine for Panic Attacks

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%) 6.

Venlafaxine vs Paroxetine for Social Anxiety

Venlafaxine ER appears to be effective treatment for social anxiety, 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 7.

Further reading


  • 1. Stubbs C, Mattingly L, Crawford SA, Wickersham EA, Brockhaus JL, McCarthy LH. Do SSRIs and SNRIs reduce the frequency and/or severity of hot flashes in menopausal women. J Okla State Med Assoc. 2017 May;110(5):272-274 PubMed
  • 2. Poirier MF, Boyer P. Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison. Br J Psychiatry. 1999 Jul;175:12-6. PubMed
  • 3. 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
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. 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
  • 8. 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
  • 9. Miskovic M. Comparison of tolerance of venlafaxine, paroxetine and amitriptyline in depression therapy. Med Arch. 2015 Apr;69(2):107-9. PubMed

Published: February 05, 2018
Last updated: February 05, 2018


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