Difficulty withdrawing SSRI/SNRI

Convert to long-acting SSRI, then reduce and stop.¹⁴³ Reduce the total daily dose in a stepwise fashion to: paroxetine 20mg, venlafaxine 75mg, duloxetine 30mg daily (see SSRI and SNRI, above). Then convert to an approximate dose equivalent* of fluoxetine, citalopram or sertraline (Step 1), using standard capsules, tablets or liquid. Switch by taking the last dose of paroxetine/venlafaxine/duloxetine today, and then starting the new dose of fluoxetine tomorrow at the same time of day.^80,20 Then stabilise on that dose for three to seven days then stop, as per previously reported.^144,146 For example, duloxetine 30mg daily changed to fluoxetine 20mg daily and continued for three to seven days then stopped. However, some individuals may prefer or need slower reductions.

Half-lives and time to almost complete elimination - Selective serotonin re-uptake inhibitors (SSRIs)^49,147

*Active metabolites

**Paroxetine and venlafaxine are associated with a greater incidence of withdrawal effects. There are mixed reports of discontinuation symptoms with Duloxetine.

Half-lives and time to almost complete elimination - Serotonin and noradrenaline re-uptake inhibitors (SNRIs)^49,147

*Active metabolites

The half-life of an antidepressant determines if it is appropriate for alternate day dosing. In general, most medication effects will be considered negligible/insignificant after three half-lives and will be eliminated from the individual`s system after five half-lives, but there are exceptions to this.

Citalopram, escitalopram, fluoxetine and sertraline all have long half-lives (see table above: Half-lives and time to almost complete elimination - SSRIs). If active metabolites are considered this can be up to 48 days (3 x 16 days) for fluoxetine. Therefore, alternate day (48 hour) dosing is possible with these drugs.

Venlafaxine and duloxetine are inappropriate for alternate day dosing due to their short half-life. For some people it may be appropriate to switch from ordinary release twice daily dosing of venlafaxine to once daily modified release (MR) preparations, to allow further reduction prior to stopping. For example, venlafaxine 37.5mg twice daily to 75mg MR once daily, then reducing to 37.5mg MR daily before stopping.¹⁴⁸

Paroxetine causes more withdrawal/discontinuation effects than sertraline even though their half-lives are comparable.¹⁴⁹ This is due to complex pharmacokinetics.¹⁵⁰ The high affinity of paroxetine for muscarinic receptors can lead to cholinergic rebound, contributing to withdrawal/discontinuation syndrome.¹⁵¹

Example conversion from short half-life antidepressant: Duloxetine (30mg), Paroxetine (20mg, daily dose) or Venlafaxine MR 75mg (37.5mg twice daily) to SSRI with long half-life

Steps: the rate of withdrawal will vary with individual needs e.g. weekly to four weekly reductions for some.

† Consider risk of interactions for two weeks after stopping

1. Some community pharmacies may not stock 1ml graduated 5ml oral syringes, but they can order if given advance notice. 
2. Citalopram 40mg/ml drops and escitalopram 20mg/ml drops are not recommended due to the difficulty with accurately measuring small doses with drops.
3. Sertraline liquid is not recommended as it is unlicensed in the UK, and individuals may experience oral numbness on their tongue and mouth due to the anaesthetic effects of non-tablet formulations.

* Approximate dose equivalents and switching considerations:^18,49,134

Due to inter-patient variability and differing half-lives, this means that these are approximate dose equivalents, not exact equivalence.

• The drug and dose equivalents can never be exact and should be interpreted considering your clinical knowledge and the individual’s needs.
• Drug interactions and drug-disease interactions should be considered
• Fluoxetine liquid may be required for a few individuals that require or prefer a slower reduction at weekly to four weekly intervals.