10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

Official reprint from UpToDate®

www.uptodate.com ©2021 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Discontinuing antidepressant medications in adults

Authors: Michael Hirsch, MD, Robert J Birnbaum, MD, PhD
Section Editor: Peter P Roy-Byrne, MD
Deputy Editor: David Solomon, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Apr 2021. | This topic last updated: May 09, 2020.

INTRODUCTION

Patients who discontinue their antidepressants after a therapeutic course are at risk for
discontinuation symptoms, especially if they are not starting a new antidepressant with a
similar pharmacodynamic profile.

Discontinuing antidepressants without switching to another drug is discussed in this topic.

Switching antidepressants is discussed separately. (See "Switching antidepressant medications
in adults".)

DISCONTINUATION SYMPTOMS

Abruptly stopping or rapidly tapering antidepressants often causes adverse effects, especially if
a new drug with overlapping pharmacodynamic activity is not started. The constellation of
discontinuation effects, sometimes referred to as a "discontinuation syndrome," has been best
characterized in patients who abruptly stop selective serotonin reuptake inhibitors (SSRIs). The
most common discontinuation symptoms include [1-4]:

● Dizziness
● Fatigue
● Headache
● Nausea

Other common discontinuation symptoms include [1-4]:

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 1/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

● Agitation
● Anxiety
● Chills
● Diaphoresis
● Dysphoria
● Insomnia
● Irritability
● Myalgias
● Paresthesias
● Rhinorrhea
● Tremor

Less common symptoms include electric-like shocks [3], ataxia [1,3], auditory and visual
hallucinations [5,6], and hypertension [7].

Onset of discontinuation symptoms typically occurs within a few (eg, one to four) days of
abruptly stopping antidepressants or tapering them rapidly (eg, one to seven days) [1,4,5,8-11].
Although symptoms are usually mild and dissipate over one to two weeks without specific
treatment, distressing symptoms can persist for a month or longer, interfere with functioning,
and may rarely lead to hospitalization.

Reviews estimate that among patients treated with antidepressants, discontinuation symptoms
occur in approximately 20 to 33 percent [11]; however, the incidence of symptoms varies widely
across studies [12]. Discontinuation symptoms are a potential problem with most
antidepressants if they are abruptly stopped or rapidly tapered [3,11]. Symptoms may emerge
after missing a single dose, but this is unusual. It is conceivable that discontinuation symptoms
may arise if the patient switches from a branded formulation to a generic, due to differences in
bioequivalence [1].

Factors that appear to be associated with more frequent and severe discontinuation symptoms
include [1,2,8,11,13,14]:

● Shorter antidepressant elimination half-life (eg, <24 hours)

● Nonlinear antidepressant pharmacokinetics
● Anxiety symptoms at the onset of antidepressant treatment
● Higher antidepressant doses
● Longer duration of treatment at therapeutic doses (eg, ≥5 to 8 weeks)
● Prior history of discontinuation symptoms

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 2/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

Discontinuation symptoms can occur with any SSRI, but the frequency and severity of
symptoms appear to vary according to the drug’s elimination half-life [2,15]. Randomized trials
indicate that the likelihood of discontinuation symptoms is as follows [4,8,11,16-22]:

● Least risk of symptoms – Fluoxetine

● Intermediate risk – Citalopram, escitalopram, and sertraline
● Greatest risk – Paroxetine

A study of clinician initiated reports of adverse effects found that discontinuation symptoms
occurred 10 times more often with paroxetine than sertraline, and 100 times more often with
paroxetine than fluoxetine [5].

Observational studies suggest that the risk of discontinuation symptoms with fluvoxamine is
high and comparable to that of paroxetine [3,12,23], which is consistent with the elimination
half-life of fluvoxamine (approximately 15 hours). A retrospective study found that among
patients treated with fluvoxamine (n = 43) or paroxetine (n = 50), the frequency of
discontinuation symptoms was comparable (14 and 20 percent of patients) [24].  

Euthymic patients who abruptly stop antidepressants or taper them too quickly are also at risk
for suffering depressive symptoms, in addition to discontinuation symptoms [2,8,16-20]. As an
example, patients (n = 395) with unipolar major depression who responded to treatment with
fluoxetine 20 mg/day were randomly assigned to abruptly stop the drug and substitute placebo,
or to continue fluoxetine [8]. Recurrence of depression occurred in more patients who abruptly
stopped fluoxetine, compared with patients who did not (39 versus 17 percent). Another
randomized trial found that among 28 patients who discontinued their antidepressants, suicidal
ideation occurred in 4 (14 percent) [2]. Additional information about recurrence in the absence
of maintenance treatment is discussed separately. (See "Unipolar depression in adults:
Continuation and maintenance treatment", section on 'Relapse/recurrence in the absence of
treatment'.)

It may be difficult to distinguish a discontinuation syndrome from relapse of depression

because some of the symptoms are the same, such as dysphoria, fatigue, and insomnia [1].
However, resolution of symptoms within a few days of restarting the antidepressant or after one
to two weeks of watchful waiting is more consistent with a discontinuation syndrome than
depressive relapse.

In addition, discontinuation symptoms may be mistaken for other medical conditions [1]. One
case report described discontinuation symptoms from paroxetine that were initially mistaken
for stroke [25].

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 3/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

Case reports describe mania/hypomania following abrupt withdrawal of antidepressants,

tapered discontinuation, or a decrease in dose [26].

Most studies assess discontinuation symptoms with the Discontinuation Emergent Signs and
Symptoms checklist, which includes 43 items and is administered by the clinician or by self-
report [3]. However, this is not standard clinical practice.

STANDARD APPROACH

Education about the potential for and nature of discontinuation symptoms at the onset of
treatment may prevent patients from skipping doses or abruptly stopping antidepressants on
their own and help reduce anxiety should adverse discontinuation effects occur [1,9,10,27].
Included in the education is the point that discontinuation symptoms are not unique to
antidepressants and do not indicate that antidepressants cause addiction or dependence.

For patients who are treated with an antidepressant for at least several (eg, three to five) weeks,
and are stopping the drug without switching to another antidepressant, the standard approach
to minimize discontinuation symptoms is to progressively taper (reduce) the dose by a fixed
amount or percent for at least two to four weeks [27-29]. For patients who are treated with
antidepressants for a briefer time period (eg, one to three) weeks, the drug can be tapered over
one to two weeks, and for patients treated for seven days or less, the drug can be abruptly
stopped. This standard approach is consistent with multiple treatment guidelines [9-11,30,31].

The specific duration of the taper depends primarily upon the clinical urgency and the drug’s
elimination half-life. Abrupt discontinuation may be necessary in some clinical situations (eg,
severe adverse side effect or unintended pregnancy). Drugs with a longer half-life (eg, ≥24
hours) can generally be tapered over two to three weeks, whereas drugs with shorter half-lives
(eg, <24 hours) are tapered over four weeks if it is practical. For patients who suffer
discontinuation symptoms despite a gradual taper, the duration of the taper is extended
beyond four weeks, and depends upon the pace that the patient can tolerate.

Management of discontinuation symptoms depends upon their severity and time of onset:

● Mild discontinuation symptoms that occur despite a gradual taper are managed with
reassurance and watchful waiting [1,11,27].

● If moderate to severe discontinuation symptoms occur during a two to four week taper,
clinicians can decrease the pace and taper the drugs over 6 to 12 weeks.

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 4/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

● If moderate to severe symptoms arise after the drug is stopped, the antidepressant is
restarted at the dose at which there were no symptoms, and the taper is recommenced at a
pace slower than the initial taper [1,11,27].

● Alternatively, for patients who have difficulty tapering off of a selective serotonin reuptake
inhibitor (SSRI) (eg, paroxetine) or venlafaxine, it is reasonable to immediately switch to
fluoxetine 10 to 20 mg per day; the fluoxetine can then be tapered off, typically without
discontinuation effects [9-11,14,27,32] (see 'SSRIs' below). If patients are adamantly
opposed to restarting an antidepressant, it is reasonable to prescribe a short course (eg,
one to two weeks) of a benzodiazepine [33].

Evidence supporting the standard approach to discontinuing antidepressant drugs is limited:

● A small randomized trial compared tapering over 3 days with tapering over 14 days in
patients who were treated with citalopram, fluoxetine, paroxetine, or venlafaxine (n = 28),
and found that the incidence of discontinuation and depressive symptoms was comparable
(approximately 46 percent in each group) [2].

● A retrospective study of patients treated with SSRIs (n = 66) found that more
discontinuation symptoms occurred in patients who abruptly stopped their
antidepressants, compared with patients who tapered their drugs over 2 to 16 weeks (12
versus 6 symptoms) [34].

● A prospective observational study of euthymic patients who discontinued their

antidepressants (n = 224) found that the median time to recurrence of depression was
shorter in patients who discontinued their antidepressant over one to seven days,
compared with patients who discontinued their antidepressant over 14 or more days (three
versus eight months) [15].

Discontinuation of an antidepressant may necessitate dose adjustments of co-prescribed

medications because some antidepressants affect the metabolism of other drugs. As an
example, fluoxetine potently inhibits the hepatic cytochrome enzyme CYP2D6. Specific
interactions of antidepressants with other medications may be determined using the Lexicomp
drug interactions tool (Lexi-Interact Online) included in UpToDate.

DRUG SPECIFIC APPROACH

Each section below describes discontinuation of specific antidepressants and aspects that may
vary from the standard approach.

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 5/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

SSRIs — Tapering selective serotonin reuptake inhibitors (SSRIs) over two to four weeks prior to
discontinuation works well for the large majority of patients (see 'Standard approach' above).
Fluoxetine is least likely to cause discontinuation symptoms due to its relatively long elimination
half-life and is tapered over a one to two week period; a reasonable alternative is to abruptly
stop the drug. Paroxetine is most likely to cause symptoms and is discontinued over three to
four weeks [29]. As an example, paroxetine 50 mg per day is tapered to 40 mg per day for week
1, 30 mg per day for week 2, 20 mg per day for week 3, and 10 mg per day for week 4. The drug
is then stopped.

Patients who have difficulty tapering off of paroxetine or other SSRIs may benefit from
immediately switching to fluoxetine 10 to 20 mg per day [9,10,27,32]. Patients switched to
fluoxetine 20 mg per day continue the dose for one to two weeks after the discontinuation
symptoms have abated, decrease the dose to 10 mg per day for one to two weeks, and then
stop the drug. Patients switched to fluoxetine 10 mg per day continue the dose for one to two
weeks after the discontinuation symptoms have resolved, after which fluoxetine is stopped. For
patients who have difficulty discontinuing fluoxetine 10 mg per day, a liquid formulation is
available for administering 5 mg per day for one to two weeks before stopping the drug.

Although we usually taper and discontinue fluoxetine over one to two weeks, the elimination
half-life of fluoxetine (1 to 3 days) and its active metabolite norfluoxetine (4 to 16 days) are so
long that some clinicians abruptly discontinue fluoxetine [1,14]. Evidence supporting abrupt
discontinuation includes randomized trials that found discontinuation symptoms were
comparable for fluoxetine and placebo when placebo was abruptly substituted for fluoxetine
[16,17]. As an example, one trial enrolled patients (n = 395) treated with fluoxetine 20 mg per
day for 12 weeks and randomly assigned them to either continue fluoxetine or to abruptly
substitute placebo for fluoxetine [8]. The incidence of new or worsened adverse events was
comparable with fluoxetine and placebo (32 and 27 percent of patients). Dizziness occurred in
more patients receiving placebo than fluoxetine (5 versus 1 percent), but the symptom was mild
and self limited. A subsequent randomized trial in patients treated with fluoxetine (n = 37; mean
dose 29 mg/day) for a mean duration of one year found that placebo substitution did not cause
any discontinuation symptoms [18].

The pharmacology, administration, and side effects of SSRIs are discussed separately. (See
"Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects".)

SNRIs — Abrupt discontinuation or a rapid taper of most serotonin-norepinephrine reuptake

inhibitors (SNRIs) often causes discontinuation symptoms (see 'Discontinuation symptoms'
above); thus, SNRIs are usually tapered gradually prior to discontinuation. Discontinuation

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 6/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

symptoms may be more likely to occur with desvenlafaxine or venlafaxine than other SNRIs [9-
11].

● Desvenlafaxine – Abrupt discontinuation of desvenlafaxine 50 mg/day or 100 mg/day may

cause symptoms [35,36]. For patients treated with higher doses who decide to stop the
medication and are not switching to another antidepressant, we suggest tapering the drug
over two to four weeks to reduce the risk of discontinuation symptoms (such as dizziness,
headache, insomnia, irritability, and nausea) [29,36]. (See 'Discontinuation symptoms'
above and 'Standard approach' above.)

● Duloxetine – We suggest tapering the dose over two to four weeks to reduce
discontinuation symptoms [29]. Some studies indicate that two weeks is sufficient [14].
Abrupt discontinuation of duloxetine or placebo in randomized trials found that dizziness,
nausea, and headache occurred more often with duloxetine [28].  

● Levomilnacipran – We suggest that doses greater than 40 mg per day be tapered and
discontinued over two to four weeks, consistent with procedures in the registration trials
[37].

● Milnacipran – Although abrupt discontinuation of milnacipran does not appear to cause a

discontinuation syndrome [38], we nevertheless suggest tapering the drug over one to two
weeks [39].

● Venlafaxine – We suggest tapering the daily dose by 37.5 to 75 mg each week over four
weeks to reduce discontinuation symptoms [1,14,29]. Patients who have difficulty tapering
off of venlafaxine may benefit from switching to fluoxetine 10 to 20 mg per day; the
fluoxetine can then be tapered off, typically without discontinuation effects [9,10,27,32].
(See 'SSRIs' above.)

Abrupt discontinuation of venlafaxine commonly causes discontinuation symptoms due to

its relatively short half-life (approximately 5 hours) and that of its active metabolite
desvenlafaxine (approximately 11 hours) [2,13,15,40-42]. The discontinuation symptoms of
venlafaxine are similar to, but can be more severe, than those produced by discontinuation
of SSRIs. As an example, a randomized trial that compared venlafaxine with escitalopram
found that after the drugs were abruptly stopped, venlafaxine led to more discontinuation
symptoms, including agitation, diaphoresis, dizziness, fatigue, nausea, restlessness, and
tremor [21].

The pharmacology, administration, and side effects of SNRIs are discussed separately. (See
"Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 7/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

effects".)

Atypical antidepressants — Atypical antidepressants include drugs that are not related to each
other or to other drug classes.

● Agomelatine – Abrupt cessation of agomelatine 25 mg per day does not cause

discontinuation symptoms [43]. For patients taking agomelatine 50 mg per day, we suggest
tapering the dose to 25 mg for one week before stopping the drug.

● Bupropion – Although discontinuation symptoms from bupropion are uncommon,

nevertheless, we taper the drug over two weeks before stopping it, consistent with prudent
care (see 'Standard approach' above). One case report described discontinuation
symptoms, including anxiety, headache, insomnia, irritability, and myalgias [44]. (See
'Discontinuation symptoms' above.)

● Mirtazapine – We suggest tapering the dose over two to four weeks. One report described a
case in which abrupt cessation of mirtazapine led to discontinuation symptoms, including
anxiety, dizziness, insomnia, nausea, and paresthesias [45]; another case report described
severe anxiety in the form of new onset panic attacks when mirtazapine was abruptly
withdrawn [46].

The pharmacology, administration, and side effects of atypical antidepressants are discussed
separately. (See "Atypical antidepressants: Pharmacology, administration, and side effects".)

Serotonin modulators

● Nefazodone – We suggest tapering the dose over two to four weeks to reduce
discontinuation symptoms (see 'Standard approach' above). Two case reports described
abrupt cessation or rapid tapering of nefazodone, which resulted in adverse
discontinuation effects, including anxiety, diaphoresis, dizziness, headache, insomnia,
myalgias, and nausea [47,48]. (See 'Discontinuation symptoms' above.)

● Trazodone – Trazodone is gradually tapered over two to four weeks prior to discontinuation.
Rapid or abrupt discontinuation may be followed by discontinuation symptoms, including
anxiety, headache, myalgia, nausea, and weakness [49,50].

● Vilazodone – Discontinuation symptoms due to abrupt discontinuation of vilazodone have

not been described. Nevertheless, for patients who take 20 to 40 mg per day, we suggest
tapering the dose down to 10 mg per day over one to two weeks, prior to discontinuation
[51].

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 8/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

● Vortioxetine – Clinicians can abruptly discontinue vortioxetine 10 mg per day, consistent

with procedures in the registration trials, which found no discontinuation symptoms at that
dose [52]. For patients taking 15 or 20 mg per day, we suggest decreasing the dose to 10
mg per day for one week before stopping the drug; the registration trials found that
abruptly discontinuing a dose of 15 or 20 mg caused dizziness, headache, mood lability,
muscle tension, and rhinorrhea in approximately 5 percent of patients.

The pharmacology, administration, and side effects of serotonin modulators are discussed
separately. (See "Serotonin modulators: Pharmacology, administration, and side effects".)

Tricyclics — Tricyclic (and tetracyclic) antidepressants are generally tapered over two to four
weeks [14,53] (see 'Standard approach' above). Abrupt discontinuation can cause
discontinuation symptoms, including agitation, anxiety, chills, diaphoresis, headache, insomnia,
irritability, malaise, myalgia, and nausea (see 'Discontinuation symptoms' above), and may
rarely cause akathisia, cardiac arrhythmia, and parkinsonism [3,54,55].

The pharmacology, administration, and side effects of tricyclics are discussed separately. (See
"Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects".)

MAOIs — Monoamine oxidase inhibitors (MAOIs) are generally tapered for at least four weeks
prior to stopping the drug [14]. Moderate to severe discontinuation symptoms that arise while
tapering phenelzine or tranylcypromine are managed by resuming the daily dose at which there
were no symptoms, and then tapering the dose more slowly (eg, phenelzine by 15 mg or
tranylcypromine by 10 mg every two weeks [14,54]). Abruptly stopping MAOIs can cause
discontinuation symptoms, including anxiety, agitation, insomnia, chills, diaphoresis, headache,
irritability, malaise, and nausea [12,33,54,56] (see 'Discontinuation symptoms' above). In
addition, reports have described more serious discontinuation symptoms, including delirium,
myoclonic jerks, and psychosis.

The pharmacology, administration, and side effects of MAOIs are discussed separately. (See
"Monoamine oxidase inhibitors (MAOIs): Pharmacology, administration, safety, and side
effects".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Depressive disorders".)

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&sou… 9/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.”
The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on “patient info” and the keyword(s) of interest.)

● Basics topics (see "Patient education: Coping with high drug prices (The Basics)")

● Beyond the Basics topics (see "Patient education: Depression in adults (Beyond the Basics)"
and "Patient education: Depression treatment options for adults (Beyond the Basics)" and
"Patient education: Coping with high drug prices (Beyond the Basics)")

SUMMARY

● Abruptly stopping or rapidly tapering antidepressants often causes discontinuation

symptoms, including agitation, anxiety, chills, diaphoresis, dizziness, dysphoria, fatigue,
headache, insomnia, irritability, myalgias, nausea, paresthesias, rhinorrhea, and tremor.
(See 'Discontinuation symptoms' above.)

● Factors that appear to be associated with more frequent and severe discontinuation
symptoms include shorter antidepressant elimination half-life (eg, <24 hours), higher
antidepressant doses, and longer duration of treatment at therapeutic doses (eg, ≥5 to 8
weeks). (See 'Discontinuation symptoms' above.)

● Education about the potential for and nature of discontinuation symptoms at the onset of
treatment may prevent patients from abruptly stopping antidepressants on their own and
help reduce anxiety should adverse discontinuation effects occur. For patients who are
treated with an antidepressant for at least several (eg, three to five) weeks, and are
stopping the drug without switching to another antidepressant, the standard approach to

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 10/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

minimize discontinuation symptoms is to taper the dose for at least two to four weeks. (See
'Standard approach' above.)

● Mild discontinuation symptoms that occur are managed with reassurance. If moderate to
severe discontinuation symptoms occur during a two to four week taper, clinicians can
decrease the pace and taper the drugs over 6 to 12 weeks. If disturbing symptoms arise
after the drug is stopped, the antidepressant is restarted at the dose at which there were
no symptoms, and the taper recommences at a pace slower than the initial taper.
Alternatively, for patients who have difficulty tapering off of a selective serotonin reuptake
inhibitor or venlafaxine, it is reasonable to immediately switch to fluoxetine 10 to 20 mg per
day; the fluoxetine can then be tapered off. (See 'Standard approach' above.)

● Abrupt discontinuation of most serotonin-norepinephrine reuptake inhibitors (SNRIs) often

causes discontinuation symptoms; thus, SNRIs are usually tapered gradually prior to
discontinuation. Discontinuation symptoms may be more likely to occur with
desvenlafaxine or venlafaxine than other SNRIs. (See 'SNRIs' above.)  

● Discontinuation symptoms and tapering schedules vary among atypical antidepressants

and serotonin modulators. (See 'Atypical antidepressants' above and 'Serotonin modulators'
above.)

● Tricyclic antidepressants are generally tapered over two to four weeks. (See 'Tricyclics'
above.)

● Monoamine oxidase inhibitors (MAOIs) are generally tapered for at least four weeks prior to
stopping the drug. (See 'MAOIs' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Warner CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Fam

Physician 2006; 74:449.

2. Tint A, Haddad PM, Anderson IM. The effect of rate of antidepressant tapering on the
incidence of discontinuation symptoms: a randomised study. J Psychopharmacol 2008;
22:330.
3. Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J
Clin Psychiatry 2006; 67 Suppl 4:14.

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 11/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

4. Fava GA, Gatti A, Belaise C, et al. Withdrawal Symptoms after Selective Serotonin Reuptake
Inhibitor Discontinuation: A Systematic Review. Psychother Psychosom 2015; 84:72.

5. Price JS, Waller PC, Wood SM, MacKay AV. A comparison of the post-marketing safety of
four selective serotonin re-uptake inhibitors including the investigation of symptoms
occurring on withdrawal. Br J Clin Pharmacol 1996; 42:757.

6. Yasui-Furukori N, Kaneko S. Hallucination induced by paroxetine discontinuation in patients

with major depressive disorders. Psychiatry Clin Neurosci 2011; 65:384.
7. Astorne Figari WJ, Herrmann S, Akogyeram C, Qian Q. New onset hypertension following
abrupt discontinuation of citalopram. Clin Nephrol 2014; 82:202.

8. Zajecka J, Fawcett J, Amsterdam J, et al. Safety of abrupt discontinuation of fluoxetine: a

randomized, placebo-controlled study. J Clin Psychopharmacol 1998; 18:193.
9. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Maj
or Depressive Disorder, Third Edition. October, 2010. http://psychiatryonline.org.pbidi.una
m.mx:8080/guidelines (Accessed on November 06, 2015).

10. American Psychiatric Association. Practice Guideline for the Treatment of Patients with
Major Depressive Disorder, Third Edition. Am J Psychiatry 2010; 167 (supplement):1.
11. National Institute for Health and Care Excellence (NICE). Depression: The Treatment and Ma
nagement of Depression in Adults (Updated Edition). Clinical Guideline 90. October, 2009. h
ttp://www.nice.org.uk/guidance/cg90 (Accessed on November 06, 2015).

12. Lejoyeux M, Adès J. Antidepressant discontinuation: a review of the literature. J Clin

Psychiatry 1997; 58 Suppl 7:11.
13. Rosenbaum JF, Zajecka J. Clinical management of antidepressant discontinuation. J Clin
Psychiatry 1997; 58 Suppl 7:37.

14. Ogle NR, Akkerman SR. Guidance for the discontinuation or switching of antidepressant
therapies in adults. J Pharm Pract 2013; 26:389.
15. Baldessarini RJ, Tondo L, Ghiani C, Lepri B. Illness risk following rapid versus gradual
discontinuation of antidepressants. Am J Psychiatry 2010; 167:934.
16. Judge R, Parry MG, Quail D, Jacobson JG. Discontinuation symptoms: comparison of brief
interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol 2002;
17:217.

17. Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor
discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 1998; 44:77.
18. Michelson D, Fava M, Amsterdam J, et al. Interruption of selective serotonin reuptake
inhibitor treatment. Double-blind, placebo-controlled trial. Br J Psychiatry 2000; 176:363.
https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 12/16
10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

19. Hindmarch I, Kimber S, Cockle SM. Abrupt and brief discontinuation of antidepressant
treatment: effects on cognitive function and psychomotor performance. Int Clin
Psychopharmacol 2000; 15:305.

20. Markowitz JS, DeVane CL, Liston HL, Montgomery SA. An assessment of selective serotonin
reuptake inhibitor discontinuation symptoms with citalopram. Int Clin Psychopharmacol
2000; 15:329.
21. Montgomery SA, Huusom AK, Bothmer J. A randomised study comparing escitalopram with
venlafaxine XR in primary care patients with major depressive disorder.
Neuropsychobiology 2004; 50:57.
22. Baldwin DS, Cooper JA, Huusom AK, Hindmarch I. A double-blind, randomized, parallel-
group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment
discontinuation with escitalopram and paroxetine in patients with major depressive
disorder. Int Clin Psychopharmacol 2006; 21:159.

23. Black DW, Wesner R, Gabel J. The abrupt discontinuation of fluvoxamine in patients with
panic disorder. J Clin Psychiatry 1993; 54:146.
24. Coupland NJ, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal. J Clin
Psychopharmacol 1996; 16:356.

25. Haddad PM, Devarajan S, Dursun SM. Antidepressant discontinuation (withdrawal)

symptoms presenting as 'stroke'. J Psychopharmacol 2001; 15:139.
26. Andrade C. Antidepressant-withdrawal mania:a critical review and synthesis of the
literature. J Clin Psychiatry 2004; 65:987.

27. Schatzberg AF, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome:
consensus panel recommendations for clinical management and additional research. J Clin
Psychiatry 2006; 67 Suppl 4:27.
28. Perahia DG, Kajdasz DK, Desaiah D, Haddad PM. Symptoms following abrupt
discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect
Disord 2005; 89:207.
29. Labbate LA, Fava M, Rosenbaum JF, Arana GW. Drugs for the treatment of depression. In: H
andbook of Psychiatric Drug Therapy, Sixth Edition, Lippincott Williams & Wilkins, Philadelp
hia 2010. p.54.

30. Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety
Treatments (CANMAT) clinical guidelines for the management of major depressive disorder
in adults. III. Pharmacotherapy. J Affect Disord 2009; 117 Suppl 1:S26.

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 13/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

31. Bauer M, Pfennig A, Severus E, et al. World Federation of Societies of Biological Psychiatry
(WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update
2013 on the acute and continuation treatment of unipolar depressive disorders. World J
Biol Psychiatry 2013; 14:334.

32. Benazzi F. SSRI discontinuation syndrome treated with fluoxetine. Int J Geriatr Psychiatry
1998; 13:421.
33. Haddad PM. Antidepressant discontinuation syndromes. Drug Saf 2001; 24:183.

34. van Geffen EC, Hugtenburg JG, Heerdink ER, et al. Discontinuation symptoms in users of
selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt
discontinuation. Eur J Clin Pharmacol 2005; 61:303.
35. Yang LP, Plosker GL. Desvenlafaxine extended release. CNS Drugs 2008; 22:1061.

36. Montgomery SA, Fava M, Padmanabhan SK, et al. Discontinuation symptoms and
taper/poststudy-emergent adverse events with desvenlafaxine treatment for major
depressive disorder. Int Clin Psychopharmacol 2009; 24:296.
37. Palmer EC, Binns LN, Carey H. Levomilnacipran: A New Serotonin-Norepinephrine Reuptake
Inhibitor for the Treatment of Major Depressive Disorder. Ann Pharmacother 2014;
48:1030.
38. Vandel P, Sechter D, Weiller E, et al. Post-treatment emergent adverse events in depressed
patients following treatment with milnacipran and paroxetine. Hum Psychopharmacol
2004; 19:585.

39. Kyle JA, Dugan BD, Testerman KK. Milnacipran for treatment of fibromyalgia. Ann
Pharmacother 2010; 44:1422.
40. Fava M, Mulroy R, Alpert J, et al. Emergence of adverse events following discontinuation of
treatment with extended-release venlafaxine. Am J Psychiatry 1997; 154:1760.

41. Parker G, Blennerhassett J. Withdrawal reactions associated with venlafaxine. Aust N Z J

Psychiatry 1998; 32:291.
42. Wellington K, Perry CM. Venlafaxine extended-release: a review of its use in the
management of major depression. CNS Drugs 2001; 15:643.

43. Montgomery SA, Kennedy SH, Burrows GD, et al. Absence of discontinuation symptoms
with agomelatine and occurrence of discontinuation symptoms with paroxetine: a
randomized, double-blind, placebo-controlled discontinuation study. Int Clin
Psychopharmacol 2004; 19:271.
44. Berigan TR, Harazin JS. Bupropion-Associated Withdrawal Symptoms: A Case Report. Prim
Care Companion J Clin Psychiatry 1999; 1:50.

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 14/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

45. Benazzi F. Mirtazapine withdrawal symptoms. Can J Psychiatry 1998; 43:525.

46. Klesmer J, Sarcevic A, Fomari V. Panic attacks during discontinuation of mirtazepine. Can J
Psychiatry 2000; 45:570.

47. Rajagopalan M, Little J. Discontinuation symptoms with nefazodone. Aust N Z J Psychiatry

1999; 33:594.
48. Benazzi F. Nefazodone withdrawal symptoms. Can J Psychiatry 1998; 43:194.

49. Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in
depression and therapeutic potential in other disorders. Drugs Aging 1994; 4:331.
50. Otani K, Tanaka O, Kaneko S, et al. Mechanisms of the development of trazodone
withdrawal symptoms. Int Clin Psychopharmacol 1994; 9:131.
51. McCormack PL. Vilazodone: a review in major depressive disorder in adults. Drugs 2015;
75:1915.

52. Zhang J, Mathis MV, Sellers JW, et al. The US Food and Drug Administration's perspective on
the new antidepressant vortioxetine. J Clin Psychiatry 2015; 76:8.
53. Garner EM, Kelly MW, Thompson DF. Tricyclic antidepressant withdrawal syndrome. Ann
Pharmacother 1993; 27:1068.

54. Dilsaver SC. Withdrawal phenomena associated with antidepressant and antipsychotic
agents. Drug Saf 1994; 10:103.
55. Ceccherini-Nelli A, Bardellini L, Cur A, et al. Antidepressant withdrawal: prospective
findings. Am J Psychiatry 1993; 150:165.

56. Gahr M, Schönfeldt-Lecuona C, Kölle MA, Freudenmann RW. Withdrawal and

discontinuation phenomena associated with tranylcypromine: a systematic review.
Pharmacopsychiatry 2013; 46:123.
Topic 105323 Version 7.0

Contributor Disclosures
Michael Hirsch, MD Nothing to disclose Robert J Birnbaum, MD, PhD Grant/Research/Clinical Trial
Support: Eli Lilly. Peter P Roy-Byrne, MD Employment: Mass Medical Society. David Solomon,
MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 15/16

10/5/2021 Discontinuing antidepressant medications in adults - UpToDate

https://www-uptodate-com.pbidi.unam.mx:2443/contents/discontinuing-antidepressant-medications-in-adults/print?search=venlafaxine switch&topicRef=1716&so… 16/16