Antidepressant Withdrawal (Discontinuation) Syndrome

Antidepressant Withdrawal (Discontinuation) Syndrome is a clinically important phenomenon to monitor for. Different antidepressants will have different discontinuation side effects.[1] Psychiatric symptoms of discontinuation such as anxiety and agitation, crying spells, or irritability are also sometimes misdiagnosed as a depressive relapse.

Is it Discontinuation Syndrome or a Relapse?

Antidepressant discontinuation symptoms can be differentiated from a depressive relapse by the time of onset. Discontinuation symptoms typically start 1 to 3 days after the treatment is stopped, whereas relapse symptoms are unlikely to become evident for another 2 to 3 weeks. Discontinuation symptoms are also unlikely to occur in patients who have been on antidepressants for less than 7 weeks. In addition, discontinuation symptoms will also resolve within a couple of days after the antidepressant is restarted. Patients who have a history of antidepressant non-adherence, who have experienced discontinuation symptoms in the past, or who have treatment-emergent anxiety are at highest risk for experiencing discontinuation phenomena.[2] It is also important to note that the time to recurrence for depression is much faster when antidepressants are discontinued rapidly rather than gradually.[3]


The mnemonic FINISH can be used to remember the symptoms of antidepressant discontinuation. Also don't forget that depressive and anxiety symptoms can also be signs of discontinuation syndrome.
  • F - Flu-like symptoms
  • I - Insomnia
  • N - Nausea
  • I - Imbalance
  • S - Sensory disturbances
  • H - Hyperarousal
  • Venlafaxine and paroxetine are the antidepressants that most commonly cause withdrawal symptoms.
    • Venlafaxine has a very short half-life, withdrawal symptoms can occur as quick as within missing one dose. The noradrenergic effects of venlafaxine contribute to the withdrawal symptoms and symptoms described as “brain zaps.”
    • Paroxetine is very potent and the most anticholinergic SSRI. Thus, when it is discontinued, it can cause cholinergic rebound symptoms which can include agitation, anxiety, insomnia, sialorrhea.
  • Generally, fluoxetine and vortioxetine have very long half-lives, which make withdrawal symptoms much less likely.[4]
  • Bupropion also has a relatively low rate of withdrawal and the symptoms tend to be mild.
  • Management of these symptoms include reassuring the patient that the symptoms are likely to be short-lived and mild. For acute symptoms, the antidepressant should be restarted with an even slower taper.
  • In some circumstances where the discontinuation symptoms are severe, one additional strategy is to substitute the original antidepressant with fluoxetine, which has a long half-life.
    • The original antidepressant can be tapered first, and then fluoxetine tapered, to lower the likelihood of discontinuation symptoms.[5]
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  • More conservative tapering schedules suggest a 10% reduction of the dose by 10% every 1 to 4 weeks.
  • For example, the The Horowitz–Taylor method suggests that tapering should be done in a hyperbolic manner to achieve a linear reduction of receptor occupancy to prevent withdrawal.[6]
    • This means the dose needs to be reduced by half, then by half of that, and so on.
    • The traditional formulations of antidepressants make the later stages of formulating the doses more challenging as a hyperbolic taper involves the use of very low dosages
    • The use of oral solutions or tapering strips have been reported to help facilitate tapering in individuals with significant withdrawal symptoms.[7]
  • There remains little data about what the long-term effects of antidepressants are, and there are few long-term efficacy studies that have been performed.[8][9]