Wednesday 2 August, 2006

How to change antidepressants

Posted in General Practice, Michael Tam, Psychiatry, Wards at 18:34 by Michael Tam

Original article by: Michael Tam :: Printer friendly

Although starting antidepressants is not outside the realm of common experience (1), the changing of antidepressants is shrouded in the aura of mystic voodoo that many consider to be best left to the psychiatrists. The reality, however, is that there isn’t much to it.

For the first line and most common antidepressants used (SSRIs except fluoxetine, mirtazapine, venlafaxine and the tricyclic antidepressants):

Taper the dose of the first antidepressant by 25% per day (with complete cessation in 4-7 days).

Start the second antidepressant 3 days after the cessation of the first.

When changing from one antidepressant to another, the key factor is the half life of the original drug. The longer the half life, the longer the “washout period” and the longer one has to wait before commencing the second drug. Similarly, the longer the half life or the first agent, the higher the likelihood of side-effects if the second agent is started too early.

I find the follow guide and its principles fairly useful (adapted from Holmwood C., Ilchef R. Effective use of antidepressants) (2):

Category A changeover (longest washout period)

  • Drugs:
  • General recommendations:
    • Gradual withdrawal generally unnecessary; discontinuation symptoms very unlikely.
    • Wait for at least 2 weeks after stopping before starting next antidepressant
  • Specific drug information:
    • fluoxetine – long half-life of parent drug and metabolite means a period of weeks is needed after it is stopped before another antidepressant can be started.
    • phenelzine and tranylcypromine – maintain drug and diet restrictions for 2-3 weeks after stopping.

Category B changover (intermediate washout period)

  • Drugs:
  • General recommendations:
    • Withdrawal gradually to prevent discontinuation symptoms (particularly if higher dose or long term use).
    • Usually reduce dose by 25% per day (when switching).
    • Wait 2-4 days after stopping before starting next antidepressant.
  • Specific drug information:
    • SSRIs – the potential for discontinuation symptoms is probably greater with paroxetine than other SSRIs.

Category C changeover (shortest washout period)

  • Drugs:
  • General recommendations:
    • Wait for 1-2 days after stopping before starting next antidepressant.
  • Specific drug information:
    • moclobemide – discontinuation symptoms not reported.
    • venlafaxine – withdraw gradually to prevent discontinuation symptoms (discontinuation syndrome is similar to SSRIs).

Reference article

(1) Su M. How to start antidepressants [electronic article]. The Medicine Box. Last updated: 19 June 2006. [Link]

(2) Holmwood C., Ilchef R. (reviewers). Effective use of antidepressants. National Prescribing Service Limited. Last updated: November 2005.

Please read the disclaimer


  1. Connie said,

    My doctor had me stop taking 150mg Zoloft one day and start Cymbalta 30mg the next day. No tapering off, nothing. I have more depression and body pain for no explainable reason than I’ve had in years. I know I need to call the doctor but??? Just too blah to do it.

  2. Michael Tam said,

    Dear Connie,

    I think that you’ve hit the nail on the head. You need to go see your regular doctor.

    • melody said,

      are cymbalta and zoloft closely related enough to switch from one to the other in one day?

      • Michael Tam said,

        Unless there was a pressing reason to do so, it would be preferable not to change between Cymbalta (duloxetine) and Zoloft (sertraline) in such a manner.


  3. jason said,

    my doctor has swapped me from effexor-xr 300mg in morning to pritiq desvenlafaxine 50mg in the morning with one day break from the effexor is this ok

    • Michael Tam said,

      Dear jason,

      Venlafaxine to desvenlafaxine is somewhat of a special case given that they are almost the same drug. The described change over is quick but probably not unreasonable.

  4. Tammy said,

    I had been taking Cymbalta 90mg for a couple years & it didn’t seem to be working anymore so I gradually weaned myself down to 30mg a day. I went to see my Dr. and he decided to put me on 150mg of Welbutrin starting the next day. I never completely stopped the Cymbalta though and now I’m having major mood swings and am tired all the time. Will this go away? I’ve been taking the Welbutrin for 4 days now.

  5. Michael Tam said,

    Dear Tammy,

    It sounds like there is some degree of confusion over your medication regimen. In this situation, it would be best to discuss your management with your regular practitioner.

  6. grace said,

    I have been on Paxil for quite some time. I am now on 60 mgs and the doctor is thinking of switching me to zoloft. The doctor said I should get down to 20 mgs and then he can make the switch and then ween me off the Paxil. I think it is call cross over. Is this effective or the best way to go? I am so confused.

    • grace said,

      What I am saying is the he wants me to take Paxil (20 mgs) and Zoloft at the same time. Then ween me off the Paxil.

    • Michael Tam said,

      This wouldn’t be the usual recommended method of changing over antidepressants but there are times when a crossover may be preferred.

      It would be best to discuss this with your regular medical practitioner.

      • Grace said,

        Since Paxil has a smaller half life would it be possible to switch from 20 mgs of paxil one day to 50 mgs of Zoloft the next day and have no effects? I am being treated by a general intern. I am going to seek other opinions before switching.

  7. Amy said,

    Have been taking Zoloft for 10 years. Dr wants me to try Lexapro. He wants me to stop taking Zoloft Monday and start taking 5mg of Lexapro Monday. Is this too fast? I am worried about discontinuation syndrome, but Dr insists it is safe. I have doubts.


    • Michael Tam said,

      Changing antidepressants in that manner would minimise the likelihood of discontinuation syndrome at the increased risk of serotonin syndrome.

      If you have any concerns about our medication therapy, you should discuss this with your regular medical practitioner.

  8. margi winters said,

    My doctor is changing me from 75mg of ventafaxine to 50mg of sertraline.
    In seven days the sertraline will be taken twice a day. One morning I took the
    ventafaxine and the next morning the sertraline. On the second day of sertraline I am having heart papitations. I am anxious about this change. How long will it
    take my body to adjust to the change.? I have been on antidepressants for 28 yrs.
    I am worried about over use of the drug and if it harms a person in the long run.

  9. caroline said,

    Dear Tam

    Am so pleased to have found this site as i am very nervous about switching medication as am being prescribed by a General Practitioner whp seemed very unsure herself as to how to do it, changing her mind twice when instructing me.

    Have been on max dose of Lofepramine (Amitriptilyne made me too sleepy) for past year, my depression has worsened after having a baby 3 months ago. Have been taking 1 tablet (75mg) in morning and 2 at night. Doctor is switching me to Ventlafaxine (slow release) 75mg. She said to start off by just taking my 2 usual lofepramine at night and instead of my morning dose, to take venlafaxine instead. She said to come back to see her after 1 week. I have not started it yet as am concerned about side effects etc. I am also taking 28mg methadone.

    Some years ago effexor was prescribed but I panicked after taking just one tablet, as my pupils went huge and I felt like I was starting to withdraw (I was on a high dose of morphine on this occassion).

    Had tried Citalapram previous to tricyclics, which had no effect. So I think my GP is giving me this as a last resort. Your knowledge on the subject would be greatly appreciated. Thanks in advance for your time.


    • Michael Tam said,

      Dear Caroline,

      Firstly: read the disclaimer

      I normally try to avoid doing a “crossover” when changing antidepressants due to the risk of side-effects and serotonin syndrome. I have no experience with lofepramine as it is not licensed for use in Australia. However, it would fit under the “Category B changeover” in the above article.

      It would be impossible for me to comment specifically on your situation as I don’t have any of the clinical information. Please consider discussing your concerns with your regular GP.

      Yours sincerely,
      Michael Tam

  10. EC said,

    I just started Luvox 2 weeks ago, can I just stop?

    • Michael Tam said,

      I would strongly suggest that you contact your regular doctor before discontinuing your medication.

  11. coeus said,

    Hi Michael,

    I have only been on Pristiq for approximately 2-3 weeks now as indicated for my anxiety. I’ve been deliberating a fair bit about whether to change over to Lexapro or Amitriptyline.

    In my case, the Amitriptyline would be aimed at my chronic tension-type headache. Conversely, the Lexapro has an indication for Generalised Anxiety Disorder (GAD). Obviously, there’s a trade-off here.

    In your opinion, would you suggest the Amitriptyline over the Lexapro since the chronic tension-type headache is stirring a bit more anxiety?


    • Michael Tam said,

      I would strongly suggest you have this discussion with your regular physician. Although amitriptyline has some theoretical benefits in this setting, it also has a greater burden of side-effects. It would generally not be logical to swap and change antidepressant medication without good indication.

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