Is Effexor better than Zoloft? (3+ comparisons)

In this article, we will compare Effexor with Zoloft to determine which one is more effective. We will also discuss the conditions in which Effexor and Zoloft are preferred, their mechanisms of action, and their side effects profiles.

Is Effexor better than Zoloft?

Effexor could be more effective than Zoloft for some individuals, depending on the specific needs and response of each patient to the medication. There are certain conditions in which Effexor performs better than Zoloft, and vice versa.

Therefore, the choice of antidepressants solely depends on your healthcare provider and how well you respond to a certain medication. Your doctor will evaluate your condition and prescribe the most appropriate antidepressant based on your response.

While recommending either Effexor or Zoloft, your doctor will consider your current symptoms, medical history, and your response to the treatment.

How does Effexor differ from Zoloft?

Effexor may differ from Zoloft in the following ways:

Mechanism of action

Effexor is a serotonin-norepinephrine inhibitor (SNRI) antidepressant that works by increasing serotonin, norepinephrine and dopamine in the brain by blocking their reuptake in brain cells. Due to the blocking of these neurotransmitters, Effexor is effective in treating patients with major depression (6).

In contrast, Zoloft is a selective serotonin reuptake inhibitor (SSRI) that works by inhibiting the serotonin reuptake in brain cells. This inhibition results in increased serotonin levels(5).

Serotonin is a chemical neurotransmitter in the brain which regulates mood, blocking its reuptake benefits patients with major depression by enhancing their mood.

Therapeutic benefits

Effexor and Zoloft are approved by the FDA for the following conditions:

Zoloft  Effexor
Major depressive disorder Depression
Social anxiety disorder Social anxiety disorder
Post-traumatic stress disorder Cataplexy (5)
Premenstrual dysphoric disorder Panic disorders
Obsessive-compulsive disorder
Panic disorder (6)

Common side effects

There are several side effects associated with both Effexor and Zoloft, however, we will list some commonly reported side effects in the below table:

Zoloft Effexor
Nausea Nausea
Diarrhoea Constipation
Difficulty sleeping Loss of appetite
Dry mouth Dry mouth
Drowsiness Fatigue
Fatigue (6) Sex-related problems
Sexual side effects Excessive sweating (5)

What are the conditions for which Effexor is preferred?

Effexor as a serotonin and norepinephrine reuptake inhibitor (SNRI), affects two important brain chemicals (serotonin and norepinephrine). Effexor works better than Zoloft which alters serotonin levels and treats depression.

Effexor may reduce depression symptoms more than SSRIs and more patients may respond well to Effexor as compared to Zoloft. Hence, suggesting that Effexor might be more effective in treating depression than SSRIs.

The effectiveness of Effexor might be because it affects both serotonin and norepinephrine in the brain, providing benefits over SSRIs in the treatment of depression (2).

Effexor was found to be more effective than Zoloft in helping patients feel better and preventing the return of depression. Patients taking other antidepressants, such as tricyclic antidepressants (TCAs) discontinue the treatment more often due to the side effects, but this is less common with Effexor(3).

In the cases of treatment-resistant depression, Effexor is more effective as compared to SSRIs including Zoloft. It helps patients feel better and remain symptom-free as compared to other antidepressants.

Effexor may also prevent the recurrence of depression, therefore Effexor is a better choice for patients who struggle to respond to other antidepressant treatments(3).

What are the conditions for which Zoloft is preferred?

Effexor and Zoloft both are effective in treating depression by improving a patient’s quality of life. However, Zoloft has an advantage in that it causes fewer withdrawal side effects and it was also associated with a lower incidence of raised blood pressure compared to Effexor.

Therefore, Zoloft may be a better choice for patients who are at risk of experiencing hypertension as a side effect (4). Additionally, Zoloft may be more effective in enhancing the mood, cognitive abilities, and daily functioning of Alzheimer’s patients with depression compared to Effexor(1).


The choice between Effexor and Zoloft as antidepressant medications depends on individual patient factors and specific clinical considerations. Both medications have their strengths and are effective in treating depression, but they may be preferred in different situations.

Ultimately, the decision between Effexor and Zoloft should be made by a qualified healthcare provider after a thorough examination of the patient’s condition, medical history and response to the medication.

It is essential to consider the specific needs of each patient to determine which antidepressant is the most suitable for their specific condition.

Was this helpful?

Thanks for your feedback!



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. doi: 10.1055/s-0034-1377041. Epub 2014 Jun 23. PMID: 24955552. Available from: 


Stahl SM, Entsuah R, Rudolph RL. Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry. 2002 Dec 15;52(12):1166-74. doi: 10.1016/s0006-3223(02)01425-7. PMID: 12488062. Available from: 


Bauer M, Tharmanathan P, Volz HP, Moeller HJ, Freemantle N. The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression: a meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):172-85. doi: 10.1007/s00406-008-0849-0. Epub 2009 Jan 22. PMID: 19165525. Available from: 


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. doi: 10.4088/jcp.v66n1015. PMID: 16259546. Available from: 


Singh D, Saadabadi A. Venlafaxine. 2022 Oct 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30570984. Available from: 


Singh HK, Saadabadi A. Sertraline. 2023 Feb 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 31613469. Available from: 

Find a supportive therapist who can help with Depression.

Discover the convenience of BetterHelp, an online therapy platform connecting you with licensed and accredited therapists specialized in addressing issues such as depression, anxiety, relationships, and more. Complete the assessment and find your ideal therapist within just 48 hours.


AskYourPharm is user-supported. We may earn a commission if you sign up for BetterHelp’s services after clicking through from this site