Antidepressant discontinuation syndrome and discontinuing antidepressants in adults

INTRODUCTION — 

Patients who stop their antidepressants are at risk for the discontinuation syndrome, especially if they abruptly stop the drug, taper it too quickly, or switch to a new antidepressant with a different pharmacodynamic profile [1-6]. Some studies use the term “withdrawal symptoms,” “withdrawal reaction,” or “withdrawal syndrome” instead of discontinuation syndrome [7-9]. In addition, some investigators draw a distinction between discontinuation symptoms and the discontinuation syndrome [8].

It appears that many patients abruptly discontinue their antidepressant [3,5,8,10]. Although discontinuation symptoms are generally mild and self-limiting, some cases are severe [8,10], which has given rise to online forums [11].

This topic discusses the antidepressant discontinuation syndrome and deprescribing antidepressants without switching to another drug. Choosing an alternative treatment for depressed patients unresponsive to their current treatment, as well as switching antidepressant drugs, are discussed separately. (See "Unipolar depression in adults: Choosing treatment for resistant depression" and "Switching antidepressant medications in adults".)

ANTIDEPRESSANT DISCONTINUATION SYNDROME — 

The antidepressant discontinuation syndrome is a normal physiologic response that can occur after patients are treated with an antidepressant for a sufficient length of time (eg, four weeks) and then stop the medication [2]. Recognition of the antidepressant discontinuation syndrome extends as far back as 1959 [12,13].

Incidence

Overall — Given the widespread use of antidepressants, many patients are affected by the discontinuation syndrome [10]. In meta-analyses of randomized trials of patients who stop taking an antidepressant, the estimated incidence of the discontinuation syndrome is 24 to 28 percent, with severe symptoms occurring in 2.8 percent [8]. Among patients who stop taking placebo, the discontinuation syndrome occurs in 16 to 17 percent.

Although some earlier studies reported higher rates, these may be attributed to limitations in study methods [8,10,14-16].

Drug specific incidence — The estimated incidence of antidepressant discontinuation symptoms for patients stopping specific drugs is described in the table (table 1), which is based upon meta-analyses, other studies, expert opinion, and clinical experience [8,17].

All antidepressants can cause the discontinuation syndrome, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, atypical antidepressants, serotonin modulators, tricyclics, and monoamine oxidase inhibitors [1,2,6,8,18-23]. Although discontinuation symptoms have been best characterized in patients with unipolar depression, they can occur in patients taking antidepressants regardless of diagnosis [6,18-20,24].

Factors that make some antidepressants more likely to cause the discontinuation syndrome include shorter antidepressant elimination half-life (eg, <24 hours) and lack of an active metabolite [1-7,18,20,24-30]. Other factors are nonlinear antidepressant pharmacokinetics and lower receptor binding affinity of the antidepressant.

As an example, the relatively low incidence of any discontinuation symptoms with fluoxetine is attributed to its relatively long elimination half-life and that of its active metabolite [4,17]. By contrast, abrupt discontinuation of venlafaxine commonly causes discontinuation symptoms due to its relatively short elimination half-life and that of its active metabolite desvenlafaxine [23,26,31]. Although venlafaxine extended-release has a longer elimination half-life than venlafaxine immediate release, the extended formulation half-life is nonetheless relatively short.

Other risk factors — Other risk factors for the antidepressant discontinuation syndrome, beyond the specific antidepressant that is stopped, include the following [1-7,18,20,24-30]:

●Prior history of discontinuation symptoms

●Anxiety symptoms at the onset of antidepressant treatment

●Longer duration of treatment at therapeutic doses (eg, at least four to eight weeks)

●Higher antidepressant doses and serum concentrations prior to discontinuation

●Interrupting treatment for at least a few days (eg, one to four)

●Abrupt discontinuation of the antidepressant (ie, no taper)

●Tapering the medication too quickly (eg, ≤7 days)

●Switching to a new antidepressant with a different pharmacodynamic profile

●Concurrent centrally acting medications (eg, antihypertensives, antihistamines, or antipsychotics)

In addition, patients who are genetically predisposed to rapidly metabolizing medications may perhaps be at greater risk of discontinuation symptoms [2]. It is also possible that discontinuation symptoms may arise if the patient switches from a branded formulation to a generic, due to differences in bioequivalence [25].

Sociodemographic factors such as age and sex do not appear to be risk factors for discontinuation symptoms.

Pathogenesis — The pathophysiology of the antidepressant discontinuation syndrome is not clear. For SSRIs, the association between shorter elimination half-life and increased frequency and severity of discontinuation symptoms suggests that reduced availability of serotonin in the brain is involved in the syndrome [24,32]. During SSRI treatment, the density and sensitivity of serotonin receptors are downregulated, which may leave patients vulnerable to a deficiency of serotonin when SSRIs are stopped [18].

Other neurotransmitters such as acetylcholine, dopamine, glutamate, and norepinephrine may also be involved in the discontinuation syndrome, given the wide range of symptoms that can occur as part of the syndrome, as well as the effect that serotonergic neurons have upon other neurotransmitter systems [18,24,32].

In addition, polymorphisms in neurotransmitter receptor genes and in hepatic enzyme genes that affect the rate of antidepressant metabolism may perhaps be related to discontinuation symptoms [2,33]. Psychologic factors, including negative expectations that amplify discontinuation symptoms (nocebo effects), also may have a role [18,34,35].

Clinical features

●Onset – Onset of the antidepressant discontinuation syndrome typically occurs within a few (eg, one to four) days of abruptly stopping antidepressants or tapering them too quickly [2-4,6,8,20,24]. However, symptoms may not emerge until one or more weeks have elapsed since the last dose, especially for drugs with relatively long elimination half-lives, such as fluoxetine.

●Symptoms – The antidepressant discontinuation syndrome is characterized by a wide range of new-onset somatic and neuropsychiatric symptoms that can occur in any combination; some reviews have identified approximately 50 to 80 symptoms across 10 organ systems [1,2,6,18,20,24]. None of the symptoms are pathognomonic. In most cases, discontinuation symptoms differ from any adverse effects that occurred during active treatment with the antidepressant.

Based upon results from multiple studies, the most common discontinuation symptoms appear to be [2-5,14,18,20,23,24,26]:

•Dizziness

•Headache

•Insomnia

•Irritability

•Nausea

Other common discontinuation symptoms include [1-5,14,18,20,23,24,26]:

•Agitation

•Anxiety

•Chills without fever

•Diaphoresis

•Dysphoria

•Fatigue

•Lethargy

•Myalgias

•Rhinorrhea

•Sensory disturbances such as:

-Paresthesias

-Electric shock-like sensations

•Tremor

•Vivid dreams

Less common or rare symptoms include anorexia [23], loss of balance [1,18,19,25], cognitive impairment [1,18,19], crying spells [4], dry mouth [23], loose stools/diarrhea [1,14,18,19,23,24], extrapyramidal symptoms [1], hypertension [36], hypomania and mania [37,38], psychosis (eg, auditory and visual hallucinations) [39-41], sexual dysfunction [42], somnolence [23], suicidal ideation [14], tinnitus [2,20], and vomiting [1,4,5,18].

In addition to the symptoms described above, abruptly stopping tricyclics may lead to akathisia, cardiac arrhythmia, and parkinsonism [19,43,44], whereas abruptly stopping monoamine oxidase inhibitors is infrequently associated with delirium and myoclonic jerks [21,43,45,46].

●Severity and course of illness – The antidepressant discontinuation syndrome is usually mild and dissipates spontaneously over one to three weeks; however, more distressing symptoms can persist for a month or longer [1-3,6,8,14,18,20,24]. Symptoms can interfere with functioning, and may rarely lead to hospitalization, particularly if discontinuation occurs abruptly. Some patients may be reluctant to discontinue their antidepressant because symptoms are aversive, whereas other patients may become alarmed and refuse subsequent treatment with antidepressants.

Although protracted discontinuation symptoms have been described (eg, six months), this literature is typically based upon case reports and online surveys [17].

Diagnosis — The diagnosis of the antidepressant discontinuation syndrome is not standardized, in part due to the heterogeneity of methods (eg, assessment procedures) that were used across studies, some of which are low quality [8,24].

Diagnosis of the syndrome requires one or more symptoms, such as dizziness, headache, insomnia, irritability, and nausea, which occur when treatment with antidepressants that have been taken continuously for at least several (eg, four) weeks is interrupted, abruptly discontinued, or tapered too quickly [1-7,17,18,20,24,30]. The syndrome typically is self-limited when untreated and resolves after restarting the antidepressant. Thus, the diagnosis is supported or confirmed if the symptoms resolve with management, either on their own by watchful waiting or by reinstating the discontinued drug. (See 'Management' below.)

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) describes the clinical features of the antidepressant discontinuation syndrome in the section entitled “Medication-Induced Movement Disorders and Other Adverse Effects of Medication” [2]. However, DSM-5-TR does not provide specific criteria for diagnosing the syndrome. In addition, the World Health Organization’s International Classification of Diseases 11^th Revision (ICD-11), does not include the discontinuation syndrome [9,47].

Differential diagnosis — Although the discontinuation syndrome can resemble other disorders, the syndrome can be distinguished from them as follows:

●Substance-related and addictive disorders – The adverse effects of stopping antidepressants (eg, dysphoria, insomnia, and nausea) can overlap with symptoms that arise from stopping substances such as alcohol, opioids, or stimulants; nevertheless, the antidepressant discontinuation syndrome differs from substance-related and addiction disorders in multiple ways [1,2,6,32,39]:

•Antidepressants are not addictive in that they do not cause euphoric or reinforcing effects, and patients do not neglect important occupational or social activities due to using antidepressants. Rather, antidepressants often improve functioning.

•Patients do not crave antidepressants or spend a large amount of time obtaining or using antidepressants; in addition, they generally do not escalate the dose unless directed to do so by the prescribing clinician.

•Antidepressants do not have street market value among individuals with substance-related and addictive disorders.

●Recurrence of the underlying disorder – Among patients who are successfully treated with antidepressants, another risk of stopping the medication is recurrence of the underlying disorder [2,8,48].

Some symptoms of the antidepressant discontinuation syndrome, including dysphoria, fatigue, and insomnia, can also occur in patients with recurrences of anxiety and depressive disorders [1,2,6,17,18,20,24]. However, other symptoms of the discontinuation syndrome, such as dizziness, nausea, and paresthesias, are not characteristic of anxiety and depressive disorders. Furthermore, resuming the discontinued antidepressant generally resolves the discontinuation syndrome within days (eg, one to three), whereas relapses of anxiety and depressive disorders often require weeks or months to remit after reintroducing the antidepressant or may require a different treatment.

Additional information about recurrence in the absence of maintenance treatment is discussed separately. (See "Major depressive disorder in adults: Continuation and maintenance treatment", section on 'Relapse/recurrence in the absence of treatment'.)

●General medical disorders – Discontinuation symptoms may also be mistaken for general medical conditions [6,24,25]. One case report described discontinuation symptoms from paroxetine that were initially mistaken for stroke [49], and another case report described evaluation and treatment by a neurologist and otolaryngologist for symptoms induced by stopping fluoxetine [50].

Prevention — When starting treatment with an antidepressant, patients are instructed to avoid skipping doses for a few consecutive days (eg, one to four) or abruptly stopping antidepressants on their own [17,24,51]. In addition, we educate patients about the potential for the antidepressant discontinuation syndrome and its specific symptoms. (See 'Clinical features' above.)

Patients may be reassured to learn that discontinuation symptoms are not unique to antidepressants and do not indicate that antidepressants cause addiction or dependence [2]. We also discuss the possibility that patients may experience symptoms that are not due to discontinuing the antidepressant, but rather, are nonspecific or are due to the patient’s expectations [10].

If discontinuation of the antidepressant is indicated, we typically taper the dose. (See 'Approach to discontinuing antidepressants' below.)

However, as an alternative, shared decision-making may lead a patient to remain on an antidepressant rather than discontinue it [10].

Management

Mild symptoms — Mild discontinuation symptoms that occur either while tapering an antidepressant, or after abruptly stopping it, are usually managed with reassurance and watchful waiting.

Moderate to severe symptoms

During a drug taper — If the discontinuation syndrome occurs in the context of tapering the antidepressant, management options include [6,17,18,51,52]:

●Extend the duration of the taper – If moderate to severe discontinuation symptoms occur during a two- to four-week taper, clinicians can extend the duration of the taper (eg, discontinue the antidepressant over 6 to 12 weeks). In addition, the antidepressant dose can be tapered by a fixed percent (eg, approximately 25 percent) rather than fixed amount. Thus, the absolute amount of each dose decrease is progressively smaller, until the last several doses, at which point the same small decrements are prescribed. As an example, sertraline 150 mg/day can be tapered using a liquid formulation as follows:

•Week 1 – 110 mg/day

•Week 2 – 80 mg/day

•Week 3 – 60 mg/day

•Week 4 – 45 mg/day

•Week 5 – 35 mg/day

•Week 6 – 25 mg/day

•Week 7 – 15 mg/day

•Week 8 – 10 mg/day

•Week 9 – 5 mg/day

•Week 10 – 5 mg/day

•Week 11 – Stop

Liquid formulations are available in the United States for slowly tapering other SSRIs, including citalopram, escitalopram, fluoxetine, and paroxetine. However, liquid formulations are not available for desvenlafaxine, duloxetine, fluvoxamine, levomilnacipran, milnacipran, and venlafaxine, as well as bupropion, mirtazapine, nefazodone, trazodone, vilazodone, and vortioxetine.

Alternatively, if moderate to severe discontinuation symptoms occur during a two- to four-week taper, patients may choose to continue the same tapering schedule or abruptly stop the drug. Some patients may prefer more severe symptoms for a relatively short time, rather than less intense symptoms for a longer time.

●Switch to an alternative agent with a lower risk of discontinuation syndrome – For patients who have difficulty tapering off an SSRI (eg, paroxetine), venlafaxine, or desvenlafaxine, a reasonable alternative is to immediately switch to fluoxetine 10 to 20 mg per day; fluoxetine can then be tapered over one to two weeks. (See 'Taper medications' below.)

After a drug taper — If moderate to severe symptoms arise after the drug is tapered and stopped, the antidepressant is restarted at the dose at which there were no symptoms; the discontinuation syndrome should resolve within a few days (eg, one to three). The taper is then recommenced at a slower pace than the initial taper (eg, 6 to 12 weeks), and the antidepressant dose can be decreased by a fixed percent (eg, 25 percent) with each reduction until the last several doses, at which point small decrements are prescribed.

After abrupt discontinuation — For patients who develop the antidepressant discontinuation syndrome after abruptly stopping treatment, we resume the medication at the dose that was used prior to discontinuation [1,2,18,24]. If discontinuation is indicated, we progressively taper the antidepressant. (See 'Taper medications' below.)

However, if restarting the same antidepressant is contraindicated (eg, it was abruptly stopped due to rash or patient declines), we suggest using another antidepressant with a similar pharmacodynamic profile. As an example, fluoxetine can be substituted for paroxetine. When the discontinuation symptoms abate, we progressively taper the antidepressant if indicated. (See 'Taper medications' below.)

If patients refuse to restart an antidepressant, it is reasonable to prescribe a short course (eg, one to two weeks) of a benzodiazepine such as clonazepam or lorazepam [46,53]. As an example, clonazepam is started at 0.25 to 0.5 mg once or twice daily and titrated up to 1 mg two or three times daily, based upon response and side effects. Following resolution of discontinuation symptoms, clonazepam is tapered by 20 to 25 percent every week.

Very severe symptoms — Rarely, patients with episodes of the antidepressant discontinuation syndrome require hospitalization, especially if it includes severe symptoms such as mania and/or psychosis [1]. For manic or psychotic symptoms, we suggest using standard treatments, such as a second-generation antipsychotic (eg, risperidone or quetiapine). (See "Bipolar mania and hypomania in adults: Choosing pharmacotherapy" and "Psychosis in adults: Initial management".)

APPROACH TO DISCONTINUING ANTIDEPRESSANTS

Indications for discontinuing antidepressants — Following a clinical assessment and discussion with the patient, discontinuing antidepressant medications may be indicated for the following reasons:

●Successful acute and maintenance treatment – Acute and maintenance phase treatment may be successful such that patients recover for a substantial length of time (eg, two years). For those patients who are not at an elevated risk of recurrence, it is reasonable to discontinue pharmacotherapy. (See "Major depressive disorder in adults: Continuation and maintenance treatment", section on 'Duration'.)

●Pregnancy – Discontinuation of antidepressants is common among patients who anticipate becoming pregnant, and patients with either a planned or unintended pregnancy.

●Imminent surgery or medical emergency.

●Sequential treatment – Patients with unipolar major depression who successfully complete acute phase pharmacotherapy may switch to psychotherapy for maintenance treatment; this strategy is called sequential treatment. (See "Major depressive disorder in adults: Continuation and maintenance treatment", section on 'Sequential treatment'.)

●Lack of tolerability or efficacy – Patients with acute psychiatric disorders who do not tolerate or respond satisfactorily to an antidepressant drug, administered at a therapeutic dose for sufficient duration, may discontinue the antidepressant and start psychotherapy or neuromodulation.

The present topic discusses discontinuing antidepressants without switching to another antidepressant. Switching antidepressant drugs is discussed separately. (See "Switching antidepressant medications in adults".)

Education for patients — As part of discontinuing antidepressants, we educate patients about the possibility of the discontinuation syndrome. This includes informing them that most patients do not experience any symptoms, and describing potential symptoms that may occur, especially the most common ones: dizziness, headache, insomnia, irritability, and nausea. In addition, we tell patients that if discontinuation symptoms occur, they are usually mild and dissipate spontaneously over one to three weeks. (See 'Clinical features' above.)

We then instruct patients how to taper the antidepressant by providing a tapering schedule, reassure them that tapering the antidepressant over a sufficient time can generally prevent discontinuation symptoms, and instruct patients to not [17,24,51]:

●Taper the medication too quickly

●Interrupt taking their medication for a few days (eg, one to four)

●Abruptly stop their medication

Further, we inform patients to call us if problematic discontinuation symptoms arise and tell them that there are multiple ways to manage the symptoms.

Following education, we then discontinue the antidepressant, typically by progressively tapering the dose.

Taper medications

●Progressively taper the dose – For patients who are treated with an antidepressant and are stopping the drug without switching to another antidepressant, we progressively taper the antidepressant. Prior to onset of the taper, we assess whether any symptoms that may occur during the taper (eg, headache or insomnia) are present at baseline, to avoid later attributing them to discontinuation of the antidepressant.

•Duration of the taper – The duration of the taper depends upon the length of time that the patient has continuously taken the drug:

-At least several (eg, four to eight) weeks – For many antidepressants that are prescribed for at least several weeks, we minimize discontinuation symptoms by progressively tapering the dose by a fixed amount or percent for at least two to four weeks (table 2) [1,24,54,55]. However, as indicated in the table, some antidepressants require less time for tapering and discontinuation, and for a few antidepressants, multiple tapering schedules can be used, depending upon the patient’s sensitivity to adverse effects such as the discontinuation syndrome.

-Shorter time (eg, two to three weeks) – For patients who are treated with antidepressants for a shorter time, the drug can be tapered over one to two weeks.

-Less than two weeks – For patients treated less than two weeks, the drug can be tapered over one week or abruptly stopped.

This approach is consistent with multiple treatment guidelines [6,17,56].

The specific duration of the taper additionally depends upon the clinical urgency for discontinuing the drug and the drug’s elimination half-life. Abrupt discontinuation may be necessary in some situations (eg, severe adverse effect, unintended pregnancy, or emergency surgery). 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 or more weeks if it is practical.

Although some studies report tapering schedules lasting for nine months or longer [18], this is not standard practice and according to at least one treatment guideline, there is insufficient evidence to recommend this approach [17].

•Assessing symptoms that occur while tapering the antidepressant – Despite correctly tapering their antidepressant, patients may develop symptoms that suggest the discontinuation syndrome. In patients with suspected discontinuation symptoms, we generally ask open-ended questions such as, “How have you felt since stopping the drug, have you had any new problems?” [19]. For patients who report new onset symptoms, clinicians should rule out other causes, such as psychiatric disorders, general medical conditions, or concurrent drugs [2,24].

Assessment instruments can improve detection of discontinuation symptoms [8], but they are not part of routine clinical practice. In some studies of the discontinuation syndrome, investigators used the Discontinuation-Emergent Signs and Symptoms checklist, which includes 43 items and is administered by the clinician or self-report [19,57]. These studies defined the discontinuation syndrome as the presence of a minimum number of signs and symptoms (eg, at least two or four) [8]; however, there is no established cutoff.

The frequency of assessment depends upon the severity of symptoms. We interview patients with mild to moderate symptoms every two to four weeks until symptoms resolve, and patients with severe symptoms weekly.

•Management of discontinuation symptoms – For patients who suffer discontinuation symptoms despite a progressive taper, management depends upon whether the symptoms occur during the taper or after it is completed, and the severity of symptoms. (See 'Management' above.)

●Selective serotonin reuptake inhibitors (SSRIs) – SSRIs are perhaps the most prescribed antidepressants. To prevent onset of the antidepressant discontinuation syndrome with SSRIs, tapering over two to four weeks prior to discontinuation works well for the large majority of patients. However, fluoxetine can be tapered over one to two weeks due to the relatively long elimination half-life of the parent drug (up to six days) and its active metabolite norfluoxetine (4 to 16 days) [4,24,29,58]. Alternatively, it is reasonable to abruptly stop fluoxetine, based upon randomized trials [27,57,59,60].

Patients who have difficulty tapering off of escitalopram, fluvoxamine, or paroxetine over two to four weeks may benefit from immediately switching to fluoxetine 10 to 20 mg per day [17]. 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.

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

●Efficacy – Evidence supporting a progressive taper for discontinuing antidepressant drugs includes randomized trials [61,62]. As an example:

•A 10-week randomized trial compared duloxetine (mean dose 108 mg/day) with placebo for 10 weeks in patients with acute generalized anxiety disorder [63]. Afterwards, study drugs were tapered and stopped over one to two weeks, depending upon the dose at the onset of tapering. Among the 194 patients who entered the drug-tapering phase, the incidence of one or more discontinuation symptoms was comparable with duloxetine and placebo (19 and 15 percent).

•A pooled analysis of six randomized trials, lasting eight or nine weeks, compared duloxetine with placebo in patients with acute major depression (n = 870) [55]. Following abrupt discontinuation of treatment, the incidence of one or more discontinuation symptoms was greater with duloxetine than placebo (44 versus 23 percent).

However, a meta-analysis did not find a difference in the incidence of antidepressant discontinuation symptoms between studies that tapered the medication and studies that did not [8]. However, much of the data were low quality, heterogeneity in study designs and the specific antidepressants studies was large, and the results were based upon indirect comparisons. The investigators cautioned against drawing any firm conclusions, and acknowledged that most guidelines recommend tapering antidepressants.

Adjust coprescribed medications — Discontinuing an antidepressant may necessitate dose adjustments of coprescribed medications because some antidepressants affect the metabolism of other drugs. As an example, bupropion, fluoxetine, and paroxetine each potently inhibit the hepatic cytochrome enzyme CYP2D6. Specific interactions of antidepressants with other medications may be determined using the drug interactions program included in UpToDate.

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".)

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 5^th to 6^th 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 10^th to 12^th 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 prescription drug prices in the United States (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Antidepressant discontinuation syndrome

•Incidence

-Overall – Randomized trials indicate that among patients who stop taking an antidepressant, the estimated incidence of the discontinuation syndrome is 24 to 28 percent, with severe symptoms occurring in 2.8 percent. Among patients who stop taking placebo, the discontinuation syndrome occurs in 16 to 17 percent. (See 'Overall' above.)

-Drug specific – The estimated incidence of antidepressant discontinuation symptoms for patients stopping specific drugs is described in the table (table 1). (See 'Drug specific incidence' above.)

•Clinical features – Onset of the antidepressant discontinuation syndrome typically occurs within a few (eg, one to four) days of abruptly stopping antidepressants or tapering them too quickly. The most common discontinuation symptoms appear to be:

-Dizziness

-Headache

-Insomnia

-Irritability

-Nausea

The discontinuation syndrome is usually mild and dissipates spontaneously over one to three weeks. However, more distressing symptoms can persist for a month or longer. (See 'Clinical features' above.)

•Prevention – To prevent the antidepressant discontinuation syndrome, we educate patients to not interrupt or abruptly stop their medication. If discontinuation of the antidepressant is indicated, we typically taper the dose. (See 'Prevention' above and 'Approach to discontinuing antidepressants' above.)

•Management

-Mild symptoms – Mild discontinuation symptoms that occur either while tapering an antidepressant, or after abruptly stopping it, are usually managed with reassurance and watchful waiting.

-Moderate to severe symptoms – If moderate to severe discontinuation symptoms occur while tapering the antidepressant, management options include extending the duration of the taper or switching to an alternative agent with a lower risk of the discontinuation syndrome. If symptoms arise after the drug is tapered and stopped, the antidepressant is restarted at the dose at which there were no symptoms, and the taper is then recommenced at a slower pace than the initial taper.

(See 'Management' above.)

●Discontinuing antidepressants

•Indications for discontinuation – Indications for discontinuing antidepressant medications include successful acute and maintenance treatment, pregnancy, and imminent surgery. (See 'Indications for discontinuing antidepressants' above.)

•Education – As part of discontinuing antidepressants, we educate patients about the possibility of the discontinuation syndrome. (See 'Education for patients' above.)

•Taper medications – For patients who are treated with an antidepressant and are stopping the drug without switching to another antidepressant, we progressively taper the antidepressant. The duration of the taper depends in part upon the length of time that the patient has continuously taken the drug. For most patients who are discontinuing an antidepressant after at least four to eight weeks of use, and are stopping the drug without switching to another antidepressant, we suggest tapering the dose over at least two to four weeks (Grade 2C). Exceptions include those drugs that are less likely to cause the antidepressant discontinuation syndrome (table 2). (See 'Taper medications' above.)