QUICKmedicine app

antidepressants (stopping or switching treatment)
You have 3 open access pages left.
UK healthcare workers and students can get FREE subscriptions... click here.

 
   

Stopping antidepressant treatment

  • the timing of when to stop antidepressant treatment is discussed in menu item below (length of antidepressant treatment)
  • patients should be advised not to stop treatment suddenly or omit doses - patients should also be forewarned about possible symptoms that may occur when treatment is discontinued
  • Drug and Therapeutics Bulletin (1) advises:
    • after a 'standard' 6-8 months treatment it is recommended that treatment should be tapered off over a 6-8 week period
    • if the patient has been on maintenance therapy then an even more gradual tapering e.g. by 1/4 of the treatment dose every 4-6 weeks, is advised
    • if a treatment course has lasted less than 8 weeks then discontinuation over 1-2 weeks is considered safe
  • this contrasts with the Maudsley prescribing guidelines (2) which recommend that antidepressants should be withdrawn slowly, preferably over four weeks, by weekly increments for example,
    Drug maintenance dose (mg/day) dose after 1st week (mg/day) dose after 2nd week (mg/day) dose after 3rd week (mg/day) dose after 4th week (mg/day)
    amitriptyline 150 100 50 25 Nil
    paroxetine 30 20 10 5 (liquid) Nil
    trazadone 450 300 150 75 Nil

    If withdrawal symptoms occur then the rate of drug withdrawal should be slowed or (if the drug has been stopped) the patient should be given reassurance that symptoms rarely last more than 1-2 weeks (2).

  • NICE also suggest a four week period for withdrawal of antidepressant treatment (3):
    • stopping or reducing antidepressants
      • advise people that discontinuation symptoms may occur on stopping, missing doses or, occasionally, reducing the dose of the drug. Explain that these are usually mild and self-limiting over about 1 week, but can be severe, particularly if the drug is stopped abruptly
      • normally, gradually reduce the dose over 4 weeks (this is not necessary with fluoxetine). Reduce the dose over longer periods for drugs with a shorter half-life (for example, paroxetine and venlafaxine)
      • advise the person to see their practitioner if they experience significant discontinuation symptoms. If symptoms occur:
        • monitor them and reassure the person if symptoms are mild
        • consider reintroducing the original antidepressant at the dose that was effective (or another antidepressant with a longer half-life from the same class) if symptoms are severe, and reduce the dose gradually while monitoring symptoms
      • for detailed guidance then consult the full guideline (3)

Swapping antidepressant treatment (2):

  • when swapping from one antidepressant to another, abrupt withdrawal should usually be avoided. Cross-tapering is preferred, where the dose of the ineffective or poorly tolerated drug is slowly reduced while the new drug is slowly introduced for example,
      week 1week 2week 3week 4
    withdrawing dosulepin150 mg od100mg od50 mg od25 mg odNil
    introducing citalopramNil10 mg od10mg od20 mg od20 mg od

Antidepressant use: swapping and stopping

The table below has been adapted from the Maudsley prescribing guidelines (2). However it is recommended that local prescribing guidelines and/or specialist psychiatric advice must be consulted when swapping antidepressant medication. Also the specific summary of product characteristics for each of the antidepressants involved should be consulted. It has been noted that there are no clear guidelines on switching antidepressants, so caution is required (2).

changing from to tricyclics to citalopram/escitalopram to fluoxetine to paroxetine to sertraline to venlafaxine to mirtazapine
tricyclics (TCA) cross taper cautiously halve dose and add citalopram (or escitalopram) then slow withdrawal halve dose and add fluoxetine then slow withdrawal halve dose and add paroxetine then slow withdrawal halve dose and add sertraline then slow withdrawal cross taper cautiously starting with 37.5 mg per day cautious cross-tapering recommended (4)
citalopram/escitalopram cross taper cautiously   withdraw citalopram (escitalopram) then start fluoxetine withdraw citalopram (escitalopram) and then start paroxetine at 10 mg per day withdraw citalopram (escitalopram) and then start sertraline at 25 mg per day withdraw and then start venlafaxine at 37.5 mg per day. Increase very slowly cautious cross-tapering recommended (4)
fluoxetine stop fluoxetine. Start tricyclic at very low dose and increase very slowly stop fluoxetine. Wait 4-7 days; start citalopram at 10mg per day (or escitalopram 5mg per day) and increase slowly   stop fluoxetine. Wait 4-7 days; start paroxetine at 10mg per day and increase slowly stop fluoxetine. Wait 4-7 days; start sertraline at 25 mg per day and increase slowly stop fluoxetine. Wait 4-7 days; start venlafaxine at 37.5 mg per day. Increase very slowly cautious cross-tapering recommended, start mirtazapine at 15mg daily (4)
paroxetine cross taper cautiously with very low dose of tricyclic withdraw paroxetine then start citalopram 10mg per day (or escitalopram 5mg per day) withdraw paroxetine then start fluoxetine   withdraw paroxetine then start sertraline at 25 mg per day withdraw paroxetine. Start venlafaxine at 37.5 mg per day. Increase very slowly cautious cross-tapering recommended (4)
sertraline cross taper cautiously with very low dose of tricyclic withdraw sertraline then start citalopram 10mg per day (or escitalopram 5mg per day) withdraw sertraline then start fluoxetine withdraw sertraline then start paroxetine 10mg per day   withdraw sertraline then start venlafaxine at 37.5 mg per day cautious cross-tapering recommended (4)
venlafaxine cross taper cautiously with very low dose of tricycli cross taper cautiously. Start with citalopram 10 mg per day (or escitalopram 5mg per day) crosss taper cautiously. Start with 20 mg every other day cross taper cautiously. Start with 10 mg per day. cross taper cautiously. Start with 25 mg per day   cautious cross-tapering recommended (4)
mirtazapine cautious cross-tapering recommended, using very low starting dose for tricyclic (4) cautious cross-tapering recommended (4)

cautious cross-tapering recommended (4)

cautious cross-tapering recommended (4) cautious cross-tapering recommended (4) cautious cross-tapering recommended (4)  
stopping/withdrawing of particular antidepressants

ticyclics

reduce over four weeks (4)

citalopram/escitalopram

reduce over one to four weeks (4)

 

fluoxetine

at 20mg per day - just stop

at 40 mg per day, reduce over four weeks

paroxetine

reduce over four weeks, or longer if necessary *

sertraline

reduce dose gradually over one to four weeks (4)

venlafaxine

reduce over four weeks or longer if necessary (2,4)

mirtazapine

reduce dose gradually over 4 weeks (4)

 

NICE guidance regarding switching antidepressants is less detailed (3):

  • do not switch to, or start, dosulepin
    • because evidence supporting its tolerability relative to other antidepressants is outweighed by the increased cardiac risk and toxicity in overdose
  • when switching to another antidepressant, which can normally be achieved within 1 week when switching from drugs with a short half life, consider the potential for interactions in determining the choice of new drug and the nature and duration of the transition. Exercise particular caution when switching:
    • from fluoxetine to other antidepressants, because fluoxetine has a long half-life (approximately 1 week)
    • from fluoxetine or paroxetine to a TCA, because both of these drugs inhibit the metabolism of TCAs; a lower starting dose of the TCA will be required, particularly if switching from fluoxetine because of its long half-life
    • to a new serotonergic antidepressant or MAOI, because of the risk of serotonin syndrome
    • from a non-reversible MAOI: a 2-week washout period is required (other antidepressants should not be prescribed routinely during this period).

Notes:

  • do not co-administer clomipramine and SSRIs or venlafaxine

  • when switching between one SSRI and another, some consider cross-tapering the doses generally not to be necessary (5,6)
    • selective serotonin reuptake inhibitors (SSRIs) overlap in their mechanism of action, and the new SSRI will usually prevent discontinuation symptoms that may occur when the first SSRI is stopped. Substituting a new SSRI at the relatively equivalent dose of the former SSRI is typically well-tolerated , though starting the new SSRI at a lower dose may also be considered since patients occasionally have idiosyncratic side effects to particular SSRIs (5)
    • the New Zealand formularly guidance (6) supports no need for cross-tapering for switching between short acting SSRIs (citalopram, escitalopram, paroxetine, sertraline) - but for switches from fluoxetine then it supports the Maudsley guidance and states
      • stop fluoxetine, wait 4 - 7 days, start SSRI at low dose (low dose= citalopram 10mg/day; escitalopram 5mg/day; paroxetine 10mg/day; sertraline 25mg/day)
    • the effects of the first SSRI are likely to be so similar to that of the second one, that the second SSRI will reduce the discontinuation effects of the first (2). The abrupt switch between SSRIs may still produce discontinuation symptoms, and vigilance is still advised. In cases where discontinuation symptoms arise a short period of dose tapering is recommended before starting a different SSRI

  • * withdrawal effects may be more pronounced. Slow withdrawal over 1-2 months may be necessary

Reference:

  1. Drug and Therapeutics Bulletin (1999); 37 (7):49-52.
  2. The Maudsley Prescribing Guidelines 2001; 6th Ed, p64 - 65.
  3. NICE (October 2009). Depression
  4. MIMS - Switching and Withdrawing Antidepressants (Accessed 6/8/13).
  5. UptoDate - Antidepressant medication in adults: Switching and discontinuing medication (Accessed 6/8/13)
  6. Using the New Zealand Formulary : Guide for switching antidepressants (Accessed 6/8/13)

Links: