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]

Mnemonic

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]

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.