Hyperbolic dosing

When PET imaging data was used to examine serotonin receptor occupancy at various doses of selective serotonin reuptake inhibitors (SSRIs), it was found that the relationship between the SSRI dose and serotonin receptor occupancy was not linear. The study recommended that reducing SSRI doses “hyperbolically” would reduce the risk of discontinuation symptoms. This “hyperbolic” style of dose reduction involves making smaller dose reductions towards the end of the withdrawal period and is often applied when reducing and stopping benzodiazepines. 

This advice has been adapted by the newest National Institute for Health and Care Excellence (NICE) guidelines on antidepressants which are due to be released in May 2022 and recommend reducing the dose proportionally rather than by a fixed dose or linear reduction. As an example, the guidelines recommend reducing the dose in steps of 75 or 50 per cent of the previous dose so it could take several weeks or months to complete a full withdrawal. 

The guidelines highlight that the speed and duration of the withdrawal should be led by the person taking the medication and recommend continuing medications for at least six months after the remission of symptoms. The guidelines also emphasise the importance of the individual being monitored during the withdrawal period for any mood changes and discontinuation symptoms. The frequency of this monitoring will be decided dependent on clinical need. 

If mild discontinuation symptoms develop the NICE guidelines recommend offering reassurance and continuing to monitor for any change in symptoms. Further dose reductions are not recommended until the discontinuation symptoms have ceased. 

In individuals experiencing severe symptoms the guidelines recommend increasing the dose back up to the original dose and re-trying in the future with more gradual dose reductions. 

Antidepressants with short half-lives are most likely to cause severe discontinuation symptoms and, therefore, a longer withdrawal period with smaller dose reductions is necessary. 

Antidepressants with longer half-lives such as fluoxetine are associated with a lower risk of discontinuation symptoms, which is why the NICE guidelines recommend that fluoxetine can be stopped over a much shorter time frame.