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Psychopharmacology book

Serotonin Discontinuation Syndrome

Serotonin Discontinuation Syndrome / Antidepressant "Withdrawal"

Serotonergic antidepressants are nonaddictive, but “withdrawal” symptoms may occur upon discontinuation, especially if the course of treatment has been > 2 months. Serotonin discontinuation syndrome includes flu-like symptoms, irritability, and unusual sensations described as “brain zaps”. Serotonin withdrawal is unpleasant but not physically dangerous. It is more likely with serotonergics of short half-life, such as paroxetine (Paxil), venlafaxine (Effexor), and fluvoxamine (Luvox).  Discontinuation syndrome is problematic even with extended-release Effexor XR. These unpleasant side effects can be avoided if the antidepressant is tapered to discontinue. Some patients may require a long-tail taper over several months to avoid serotonin withdrawal symptoms.

Serotonin discontinuation syndrome Paroxetine PAXIL by Dr Jason Cafer MD
Antidepressant discontinuation syndrome / serotonin withdrawal Venlafaxine / Effexor by Dr Jason Cafer MD

Linear tapering


Psychiatrists have traditionally tapered off antidepressants linearly, for instance decreasing from 40 mg to 30 mg x 1 week, then 20 mg x 1 week, then 10 mg x 1 week. Linear tapers are not ideal, often providing minimal benefit over abrupt discontinuation for avoiding serotonin withdrawal symptoms.


Hyperbolic tapering


Horowitz & Taylor in The Lancet Psychiatry (June 2019) explain a more effective approach, referred to as the hyperbolic taper (as traditionally used to get off of benzodiazepines). Hyperbolic tapering involves a quick decrease to the usual starting dose, then a long-tail taper over a period of months, getting down to tiny doses well below the therapeutic range. 

hyperbolic tapering of serotonergic antidepressant by Dr Jason Cafer MD

To get low-enough doses you need to use a compounding pharmacy, liquid formulations, or chop tablets into tiny fragments. Capsules are not ideal, but a patient who understands the concept could open them, discard an inexact fraction of the medication, and reassemble.   


Among SSRIs, liquid formulations are available for citalopram, escitalopram, fluoxetine, and sertraline (but not for fluvoxamine or paroxetine). 


For the nitty gritty on parabolic tapering, Refer to my favorite newsletter, The Carlat Psychiatry Report (Drs Sazima & Aiken, Jun/Jul 2019).

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