[112] Antidepressant Withdrawal Syndrome

[112] Antidepressant Withdrawal Syndrome

Antidepressant drugs are associated with drug tolerance, dependence and a discontinuation syndrome similar to other drug classes such as the opiates and benzodiazepines. The effects of stopping any antidepressant should be more precisely termed “withdrawal syndrome” instead of “antidepressant discontinuation syndrome.”

What is it?

Antidepressant withdrawal syndrome refers to physical and psychological symptoms that occur when stopping, missing doses or reducing doses of any antidepressant.1,2 The mechanism has not been determined but various explanations have been proposed.3,4 Daily drug treatment can affect the availability of several neurotransmitters that can lead to many downstream physiological consequences. When drug treatment stops, the body’s adaptive changes take time to recalibrate, resulting in a period of possible symptoms.5

Clinical Features

  • Symptoms usually appear within a few days of stopping, or dose reduction.
  • Symptoms include anxiety, crying, dizziness, headache, increased dreaming, insomnia, irritability, myoclonus, nausea, electric shocks (zaps), tremor, flu-like symptoms, imbalance, and sensory disturbances.1
  • Most antidepressant withdrawal symptoms resolve within 2 weeks.1
  • Severe and prolonged withdrawal symptoms have been reported lasting weeks to months.5 Numerous cases are reported anecdotally in great detail online.1,2
  • Systematic Reviews

Two systematic reviews studied withdrawal reactions with selective serotonin reuptake inhibitors (SSRIs). The first review asked whether withdrawal reactions were different between benzodiazepines and SSRIs, and authors concluded the two were “very similar.” They strongly assert that SSRIs fulfill the criteria for tolerance and dependence in addition to a withdrawal syndrome.6 The second review studied withdrawal symptoms associated with SSRIs. That review found 15 RCTs, 4 open trials, 4 retrospective investigations and 38 case reports. It concluded that SSRIs should be added to the list of drugs where stopping can induce withdrawal symptoms. This list includes benzodiazepines, barbiturates and other psychotropic drugs.

What proportion of patients have withdrawal symptoms?

Antidepressant withdrawal symptoms have typically been identified by post-marketing adverse drug reports. They are more frequent than suggested from early drug approval trials.7 The drug monograph for duloxetine (Cymbalta), for example, reports each discontinuation-related symptom experienced by 1% or more patients at a higher rate than placebo in controlled trials8, but doesn’t provide the overall proportion of patients experiencing symptoms. A manufacturer-funded uncontrolled observational study reported that 51% of patients discontinuing duloxetine experienced one or more symptoms.9 In general, one to two-thirds of patients have at least one new symptom when abruptly discontinuing an antidepressant.10 When stopping is investigated in clinical trials, the Discontinuation Emergent Signs and Symptoms (DESS) checklist is often used.11 The incidence of withdrawal symptoms appears higher with short half-life antidepressants (e.g. paroxetine, venlafaxine) than from long half-life antidepressants (fluoxetine and its long-lived metabolite norfluoxetine).10 A major gap in the literature surrounding the DESS checklist is that improvement in symptoms after stopping is not captured.

Is there evidence for an optimal method of stopping antidepressants?

There are few controlled trials reporting methods for antidepressant discontinuation and resulting symptoms.11,13-30 Only one controlled trial directly compared a taper to an abrupt stop.22,23 In this, tapering reduced the rate of emerging withdrawal symptoms, but did not eliminate symptoms. One trial compared taper lengths and found a short taper may be no different than a longer taper.24 The studies relied upon un-validated means to quantify symptoms, primarily focused on new or worsening symptoms, and may be biased due to loss of blinding. Populations tended to be patients with moderate depression whose depression was somewhat reduced before the antidepressants were stopped. Despite the lack of evidence most antidepressant monographs and guidelines recommend a slow taper approach.1,31

When to taper or abruptly stop?

The optimal method of stopping antidepressants is currently unknown and withdrawal symptoms can happen unpredictably, despite tapering. Some considerations favouring abrupt stopping or tapering are shown in Table 1.

Table 1: Considerations for choosing a method of stopping antidepressants

Favours Taper Favours Abrupt Stopping
  • No toxicity from ongoing antidepressant therapy.
  • Short half-life of drug and metabolites (<24 hrs).
  • Previous antidepressant withdrawal symptoms.
  • Patient prefers autonomy of self-regulated taper.
  • Pregnancy and the safety of the antidepressant has not been established.
  • Important new drug may interact significantly with antidepressant.
  • Patient is experiencing troubling toxicity related to their antidepressant.
  • Treatment duration <6-8 weeks.32,33
  • Trial of tapering is prolonging the discomfort of withdrawal symptoms.
  • Long half-life of drug and metabolites.

EXAMPLE: Long-term paroxetine 40 mg daily is no longer indicated in a patient. A reasonable approach to discontinuation might be:

  • Reduce to paroxetine 30 mg daily x 1 week, then 20 mg daily x 1 week, then 10 mg daily x 1week, then 5 mg daily x 1 week, then stop.
  • If intolerable symptoms occur, increasing back to the previously tolerated dose and reducing more slowly (e.g. every 2-4 weeks) may help.

Other considerations

It is essential that patients are informed of the potential for antidepressant withdrawal symptoms before starting an antidepressant. For patients treated for depression, it is important they are aware of and monitored for a recurrence of depressive symptoms, or increased suicidality.24


  • Antidepressants should be added to the list of drugs associated with tolerance, dependence and a withdrawal syndrome.
  • Withdrawal symptoms occur in at least one-third of patients who stop.
  • Before starting an antidepressant, patients must be informed of the possibility of withdrawal symptoms. The requirements for informed consent are analogous to recommendations before initiating long-term opioid therapy.
  • Some symptoms may improve upon stopping but this is not captured in the studies of antidepressant withdrawal.
  • Any decision to abruptly stop or taper an antidepressant must consider the potential that recurrent depressive symptoms or increased suicidality may represent withdrawal or re-emergence of the original condition.

The draft of this Therapeutics Letter was submitted for review to 130 experts and primary care physicians in order to correct any inaccuracies and to ensure that the information is concise and relevant to clinicians.

The Therapeutics Initiative is funded by the BC Ministry of Health through a grant to the University of BC. The Therapeutics Initiative provides evidence-based advice about drug therapy, and is not responsible for formulating or adjudicating provincial drug policies.
ISSN 2369-8691 (Online) <||> ISSN 2369-8683 (Print)


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  • Mark McConnell
    Posted at 13:44h, 23 July Reply

    This is a very important topic, one often denied, and your treatment of it is very helpful. Thank you.

  • stitch
    Posted at 16:47h, 25 July Reply

    This is a huge disaster for all the millions of people hooked on a drug they were lied to about in regards to the dependence issues. Its not a small deal. 15,000 members belong to a forum called survivingantidepressants.org among many other online support groups, because they are being ostracized and gaslighted by their own doctors when arising these massive issues. They are fighting a deadly condition from the Iatrogenic (drug induced harm) from these pills. Its pure torture and a death sentence for many. This is a disaster of biblical proportions. The medical community should hang their heads in shame

    • Alan Cassels @ TI
      Posted at 16:00h, 01 November Reply

      It is quite possible many of the patients who take these drugs were not fully explained the issues related to dependence and withdrawal. This is part of the reason that we wrote this newsletter. We appreciate your feedback on this.
      cheers, Alan Cassels
      Communications Director, Therapeutics Initiative

  • Muddasir
    Posted at 10:15h, 29 October Reply

    Why doctors cause people to suffer by prescribing these detrimental pills , i have been going through hell which i can’t explain after tapering off the antidepressant & benzodiazepine , escitolopram & clonazepam

    • Alan Cassels @ TI
      Posted at 14:48h, 01 November Reply

      We believe with better knowledge of the potential withdrawal effects of antidepressants, doctors will be able to better counsel their patients who wish to stop these medications. That was the thrust of our newsletter #112 and we thank you for sharing your perspective.
      cheers, Alan Cassels
      Communications Director,
      Therapeutics Initiative

  • Hap Dossier
    Posted at 02:44h, 30 January Reply

    I had been taking 300mg per day, of venlafaxine for 5 years. I was taking this to (I suppose) help with the terrible time I was having getting off of tramadol . I tried a few times to get off venlafaxine, but the withdrawal symptoms were too severe. I, lately have been taking a CBD oil supplement to help getting off of mirapex, which I have been taking due to RLS.

    Following is how I am now managing to get off of venlafaxine: Two weeks ago I forgot to take my daily(AM) dose of 2ea 150mg of the time release venlafaxine. The next morning, I was getting brain zaps, anxiety, etc. the classic withdrawal symptoms, which is when I realized I had forgotten them the day before. I took only one of the 150mg pills, thinking I may as well try to get off this drug again. This time I decided to take one pill (or a portion thereof) ONLY if I had to have relief from the withdrawal.

    It has been 10 days since I took that one pill. I have had mild withdrawal symptoms, but they are/were very manageable. Those symptoms are gradually going away, and I feel now that I am free of that drug. In short, getting off venlafaxine was a snap! Why???

    Possible clues: I have recently stopped any sugar intake, and have been on a very low carb diet. I have continued to take CBD oil (about 20mg per day), Am taking green food supplement, Am taking super B complex, xtra b12, xtra vit c.

    I am a young 77 years old, don’t smoke or drink

    I am currently doing some research as to why I have been so easily able to “cold turkey” venlafaxine. I am elated, and hope my story will help others get off antidepressants. Feel free to Email me if you have questions.

    • Carl Stovel
      Posted at 10:21h, 03 April Reply

      I am a retired psychiatrist in Victoria, BC. During my thoroughly enjoyable career from 1974-2012, I had the privilege to participate in the lives of >8000 mentally ill (depression and bipolar illness) patients and their families. Most of these folks did well on various antidepressants, mainly sertraline (Zoloft) and venlafaxine (Effexor-XR) or mood stabilizers such as lithium, valproate (Epival), carbamazepine (Tegretol) and lamotrigine (Lamictal), and NEVER on the dangerous atypical antipsychotics.
      I would estimate that half of the patients who were prescribed venlafaxine (Effexor) were capable of stopping their medication precipitously/cold turkey. Of course, I always recommended a gradual reduction in any medication while monitoring return of illness symptoms and withdrawal symptoms. There was always a small cohort of patients who had extreme withdrawal effects. They were all successfully weaned of venlafaxine (Effexor) either by tapering more slowly by opening the 37.5 mg capsules and tapering the individual pellets, or adding long acting fluoxetine (Prozac) as the lower doses of venlafaxine (Effexor) 37.5-75 mg are reached. The fluoxetine (Prozac) essentially tapers itself.
      On a side note, I never ever prescribed paroxetine (Paxil) for a variety of compelling reasons.
      Carl Stovel MD, FRCPC
      Retired Psychiatrist
      Victoria, BC, Canada
      [No conflict of interest]

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