Generic advice regarding dose reduction (tapering or stopping) of selective serotonin reuptake inhibitors (SSRIs) (SSRI)

Generic advice regarding dose reduction (tapering or stopping) of selective serotonin reuptake inhibitors (SSRIs) (SSRI)

• SSRIs exhibit a hyperbolic dose-response relationship (1,2)
  • brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose (2)
    • SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose
    • that is means that when reducing SSRI dose (1)
      • decreases to smaller doses cause larger change to serotonin receptor occupancy
      • because of this, traditional linear dose reductions (for example, reducing sertraline by 50 mg increments) cause increasingly large (or hyperbolic) changes to serotonin receptor inhibition and therefore more severe symptoms
      • this is an explanation as to why some patients may tolerate the early stages of their taper but towards the end, at lower doses, they experience withdrawal symptoms.

A proportionate taper is recommended by NICE and the Royal College of Psychiatrists to reduce the risk withdrawal symptoms (1)

• involves reductions as a proportion of the previous dose (such as 25%)
• note that some doses will not be available in tablet form so liquid preparations should be used
• too prevent withdrawal symptoms, tapering should take place over a long period of time, spanning months, or even years
• SSRIs with shorter half-lives, such as paroxetine and venlafaxine, require a longer taper

Skipping of doses in a tapering regime:

• as most SSRIs have a half-life of around 24 hours, skipping doses creates large changes to drug levels, and so increases the risk and/or severity of withdrawal (1)
  • it is advised that instead patients should follow a hyperbolic tapering regime outlined above
  • note though that fluoxetine has a longer half-life and therefore skipping doses remains an option, and is currently recommended by NICE

Reference:

• Palmer EG et al. Withdrawing from SSRI antidepressants: advice for primary care.British Journal of General Practice 2023; 73 (728): 138-140. DOI: 10.3399/bjgp23X732273
• Sorensen A et al. The relationship between dose and serotonin transporter occupancy of antidepressants-a systematic review. Mol Psychiatry. 2022 Jan;27(1):192-201.