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It has been reported that over two-thirds of the patient don't achieve remission on their first antidepressant medication, which often necessitates a switch.

Even if you have been taking medication for years, sometimes switching can be beneficial so you're not alone in this situation.

There are multiple strategies that can be used when switching from one antidepressant to another, so be sure to talk to your doctor about the best method.

There are many studies and guidelines that have evaluated how to safely change antidepressants as it is a common need, and I go over those in the next sections.

Switching From Zoloft To Effexor

As discussed, there are several strategies to safely switch antidepressants that studies have suggested.


It is important to note that there is no 'single' recommended way to safely switch from Zoloft (sertraline) to Effexor (venlafaxine). A variety of methods can be used, including:

  • Direct switch
  • Cross-taper
  • Taper with wash-out switch

A direct switch refers to:

  • Your current antidepressant being stopped, with your new antidepressant, initiated the next day.

A cross-taper refers to:

  • Your current antidepressant is gradually reduced and stopped.
  • The new antidepressant is started at a low dose at some point during the taper of the first antidepressant. This means you will be taking both antidepressants at the same time.
  • The dose of the second (new) antidepressant is increased slowly to the therapeutic dose while the first (old) antidepressant is slowly decreased and discontinued.

A taper with wash-out switch refers to:

  • The first antidepressant is gradually reduced and stopped.
  • This is followed by a 'drug-free' interval, which can last for several days to several weeks. This allows time for the old antidepressant to leave your system.
  • After the wash-out period, the new antidepressant is started according to its dose recommendation.

The strategy employed depends on several factors, and each has positives and negatives.

For example, the 'taper with washout' method is the most conservative and likely the safest in terms of adverse drug reactions but increases the risk of symptom recurrence of the condition being treated.

A 'direct switch' is the easiest to employ and can be effective when switching to an antidepressant with a similar mechanism of action. However, there is a small increase in the risk of adverse drug effects.

Zoloft To Effexor Recommendations

All of the above tapering methods have been used when switching from Zoloft to Effexor. Most studies don't specifically state a Zoloft to Effexor switch, but rather a more general SSRI (the class which contains Zoloft) to Effexor switch.

Studies published the New England Journal of Medicine and Journal of Clinical Psychology have reported using the 'direct switch' method safely and effectively. In both studies:

  • The initial SSRI agent was stopped, with Effexor initiated the next day.

A different study recommends that if you are on a high dose of your SSRI, then it may be safer to taper it down before starting on Effexor, to avoid side effects.

To reiterate, there isn't one recommended method when switching from Zoloft to Effexor. The method employed depends on many factors and should be based on a discussion with your doctor.

The method your doctor is recommending isn't uncommon, especially since Effexor has serotonin effects, like Zoloft. In addition, when employing a 'direct switch' method, the new agent is typically started at a low dose, which 37.5 mg of Effexor is. Be sure to talk with your doctor regarding your concerns and options.


  • There are several strategies that have been suggested to safely switch from Zoloft to Effexor.
  • These strategies include a direct switch (with no taper), a 'cross-taper' and a taper with wash-out period.
  • There is no 'single' recommended strategy and you should discuss your options with your doctor.

  • References
    1. To Abruptly Cross Over or Not: That Is the Question in SSRI Conversion. Semantics Scholar
    2. Switching antidepressants for treatment-resistant major depression. PubMed
    3. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. PubMed
    4. Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial. PubMed