Ssri discontinuation or withdrawal syndrome
Antidepressant Discontinuation Syndrome | AAFP
CHRISTOPHER H. WARNER, MAJ, MC, USA, WILLIAM BOBO, LCDR, MC, USN, CAROLYNN WARNER, MAJ, MC, USA, SARA REID, CPT, USAF, MC, AND JAMES RACHAL, MAJ, USAF, MC
Am Fam Physician. 2006;74(3):449-456
Patient information: See related handout on antidepressant discontinuation syndrome, written by the authors of this article.
Author disclosure: Nothing to disclose.
Antidepressant discontinuation syndrome occurs in approximately 20 percent of patients after abrupt discontinuation of an antidepressant medication that was taken for at least six weeks.
Typical symptoms of antidepressant discontinuation syndrome include flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. These symptoms usually are mild, last one to two weeks, and are rapidly extinguished with reinstitution of antidepressant medication. Antidepressant discontinuation syndrome is more likely with a longer duration of treatment and a shorter half-life of the treatment drug. A high index of suspicion should be maintained for the emergence of discontinuation symptoms, which should prompt close questioning regarding accidental or purposeful self-discontinuation of medication. Before antidepressants are prescribed, patient education should include warnings about the potential problems associated with abrupt discontinuation. Education about this common and likely underrecognized clinical phenomenon will help prevent future episodes and minimize the risk of misdiagnosis.
Interruption of treatment with an anti-depressant medication is sometimes associated with an antidepressant discontinuation syndrome; in early reports it was referred to as a “withdrawal reaction.
”1 Symptoms of antidepressant discontinuation syndrome can include flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. All approved anti-depressant agents have had case reports or warnings from their manufacturers of such reactions occurring in response to either abrupt discontinuation or medication tapering.2 These medications include selective serotonin reuptake inhibitors (SSRIs),3 tricyclic antidepressants,4 monoamine oxidase inhibitors (MAOIs),5 and atypical agents such as venlafaxine (Effexor),6 mirtazapine (Remeron),7 trazodone (Desyrel),8 and duloxetine (Cymbalta).9
| Clinical recommendation | Evidence rating | References |
|---|---|---|
Maintain a high index of suspicion for antidepressant discontinuation syndrome. | C | 19 |
| Be alert to times when patients may need guidance on discontinuing an antidepressant or when they are likely to discontinue an antidepressant on their own. | C | 27,32 |
| Be sure to differentiate antidepressant discontinuation syndrome from relapse of depression and other psychiatric and medical conditions. | C | 19,27,28 |
| Gradually discontinue medication using one of the suggested tapering regimens (Table 5). | C | 16,17,21,22,27,28 |
The importance of understanding and recognizing antidepressant discontinuation syndrome is threefold: (1) though typically mild, antidepressant discontinuation syndrome symptoms are associated with significant discomfort, work absenteeism, other psychosocial problems, and may on rare occasions be severe enough to require hospitalization10–12; (2) failure to recognize antidepressant discontinuation syndrome may result in medical and psychiatric misdiagnosis, potentially exposing patients to unnecessary diagnostic investigations or potentially risky medical interventions; (3) patients may be unwilling to use psychotropic medications in the future, thereby increasing their vulnerability to future relapses of depressive or anxiety disorders.
Pathophysiology
Although several hypotheses exist, the definitive pathophysiologic explanation for antidepressant discontinuation syndrome remains unknown. Early reports of antidepressant discontinuation syndrome made heavy use of the term “withdrawal” to describe discontinuation symptoms; however, antidepressant medications are not believed to be habit forming and are not associated with drug-seeking behavior.13 Long-term use of SSRIs increases synaptic levels of serotonin through blockade of the serotonin reuptake pump, resulting in down-regulation of postsynaptic receptors.14
There is speculation concerning the possibility of a temporary deficiency of synaptic serotonin with abrupt withdrawal of an SSRI.15 This deficiency is compounded by the fact that down-regulated receptors will remain in their relatively hypoactive state for days to weeks.15
This is believed to result in antidepressant discontinuation syndrome directly or indirectly via downstream effects on other neurotransmitter systems (e.
g., norepinephrine, dopamine, and γ-amino-butyric acid) implicated in depressive and anxiety disorders.15
Because tricyclic antidepressants and MAOIs also are serotonergically active, the same mechanism is implicated for their respective antidepressant discontinuation syndromes; however, tricyclic antidepressants also affect the cholinergic system, so rapid discontinuation may cause signs of parkinsonism and problems with balance. Because MAOIs cause changes in the alpha2-adrenergic and dopaminergic receptors, their discontinuation may cause agitation and psychosis.
Epidemiology and Risk Factors
Because of the varied clinical presentation, transient nature, and lack of pathognomonic clinical features, there are relatively few data on incidence, prevalence, and other estimates of burden associated with antidepressant discontinuation syndrome. One observational study16 found that four of 45 patients (9 percent) given fluoxetine (Prozac) and 26 of 52 patients (50 percent) given paroxetine (Paxil) reported discontinuation symptoms, with a mean onset of two days and mean duration of five days.
A randomized controlled trial17 (RCT) comparing three SSRIs found a lower incidence of antidepressant discontinuation syndrome with fluoxetine (14 percent) than with paroxetine (66 percent) or sertraline (Zoloft) (60 percent). This study was limited by its open-label design and was sponsored by the manufacturer of fluoxetine. In addition, a retrospective chart review13 of 350 patients using SSRIs showed no significant added risk associated with age, sex, or diagnosis.
Perhaps the best evidence comes from an RCT18 that found mild to moderate antidepressant discontinuation symptoms in 35 percent of patients given paroxetine and 14 percent given placebo who were abruptly withdrawn from treatment after 12 weeks. The difference of approximately 20 percent between active treatment and placebo for one of the drugs most commonly associated with antidepressant discontinuation syndrome may provide an upper boundary for the probability of the condition.18
DURATION OF TREATMENT
Although unconfirmed by prospective clinical trials, case reports of antidepressant discontinuation syndrome reactions are rare among individuals who have received less than six to eight weeks of antidepressant treatment.
19 This generalization applies to antidepressant discontinuation syndrome that occurs in the settings of both abrupt and gradual antidepressant discontinuation. Such a time frame may be required to allow the synaptic changes that occur during long-term pharmacologic antidepressant treatment.
PHARMACOLOGIC PROFILE
For SSRIs, a relatively homogenous drug class, differences among the pharmacokinetic properties such as elimination half-life and metabolism may be the most clinically relevant (Table 1).20,21 Specifically, antidepressant discontinuation syndrome is more common in patients discontinuing agents with relatively short half-lives, such as paroxetine, than in those with longer half-lives, such as fluoxetine.13,16,17,19,22 In recent years, slow-, extended-, or controlled-release formulations of venlafaxine (Effexor XR), paroxetine (Paxil CR), and fluoxetine (Prozac Weekly) have become available. Although there are limited data concerning weekly fluoxetine, antidepressant discontinuation syndrome reactions have been reported with controlled-release paroxetine and extended-release venlafaxine.
14,23
| Drug | Dosage range (mg per day) | Half-life (hours) | Active metabolite? |
|---|---|---|---|
| Selective serotonin reuptake inhibitor | |||
| Citalopram (Celexa) | 10 to 60 | 35 | No |
| Escitalopram (Lexapro) | 10 to 30 | 27 to 32 | No |
| Fluoxetine (Prozac) | 20 to 80 | 84 to 144 | Yes |
| Paroxetine (Paxil) | 10 to 60 | 21 | No |
| Paroxetine CR (Paxil CR) | 12.5 to 62.5 | 15 to 20 | No |
| Sertraline (Zoloft) | 50 to 200 | 26 | Yes |
| Atypical antidepressant | |||
| Bupropion (Wellbutrin) | 75 to 450 | 12 to 30 | Yes |
| Buproprion SR (Wellbutrin SR) | 100 to 400 | 12 to 30 | Yes |
| Buproprion XL (Wellbutrin XL) | 150 to 450 | 12 to 30 | Yes |
| Duloxetine (Cymbalta)* | 40 to 60 | 11 to 16 | Yes |
| Mirtazapine (Remeron) | 15 to 45 | 20 to 40 | No |
| Trazodone (Desyrel) | 50 to 400 | 7. 1 | Yes |
| Venlafaxine (Effexor) | 75 to 450 | 3 to 13 | Yes |
| Venlafaxine XR (Effexor XR) | 75 to 450 | 3 to 13 | Yes |
| Monoamine oxidase inhibitors | |||
| Phenelzine (Nardil) | 15 to 90 | 1.2 | Yes |
| Tricyclic antidepressant* | |||
| Amitriptyline | 25 to 300 | 9 to 25 | Yes |
| Clomipramine (Anafranil) | 25 to 250 | 22 to 84 | No |
| Desipramine (Norpramin) | 25 to 300 | 14.3 to 24.7 | No |
| Doxepin (Sinequan) | 25 to 300 | 11 to 23 | No |
| Imipramine (Tofranil) | 25 to 300 | 10 to 16 | Yes |
| Nortriptyline (Pamelor) | 25 to 150 | 18. 2 to 35 | No |
Clinical Manifestations and Pathophysiology
CLINICAL MANIFESTATIONS
Antidepressant discontinuation syndrome involves a large number of psychological and physiological signs and symptoms. Case reports, audits of adverse drug reaction databases, and clinical trials report certain characteristic symptoms. These symptoms depend on the class of antidepressant used (Table 2).2,13,16,17,19,22,24,25 In a recent retrospective chart review13 of patients on antidepressants and two small, prospective, randomized controlled trials,16,24 patients' SSRIs were replaced with placebo for five days or their antidepressant medication was abruptly discontinued. All noted that the most common symptoms of SSRI withdrawal were dizziness, gastrointestinal upset, lethargy or anxiety/hyperarousal, dysphoria, sleep problems, and headache.13,16,24
| SSRI | Atypical antidepressant | Tricyclic antidepressant | MAOI | |
|---|---|---|---|---|
| General | ||||
| Flu-like symptoms | + | + | + | — |
| Headache | + | + | + | + |
| Lethargy | + | + | + | — |
| Gastrointestinal | ||||
| Abdominal cramping | + | — | + | — |
| Abdominal pain | + | — | + | — |
| Appetite disturbance | + | + | + | — |
| Diarrhea | + | + | — | |
| Nausea/vomiting | + | + | + | — |
| Sleep | ||||
| Insomnia | + | + | + | + |
| Nightmares | + | + | + | + |
| Balance | ||||
| Ataxia | + | — | + | — |
| Dizziness | + | + | + | — |
| Lightheadedness | + | — | + | — |
| Vertigo | + | + | + | — |
| Sensory | ||||
| Blurred vision | + | — | — | — |
| “Electric shock” sensations | + | + | — | — |
| Numbness | + | — | — | — |
| Paresthesia | + | + | — | — |
| Movement | ||||
| Akathisia | + | + | + | — |
| Myoclonic jerks | — | — | — | + |
| Parkinsonism | + | — | + | — |
| Tremor | + | — | + | — |
| Affective | ||||
| Aggression/irritability | + | — | — | + |
| Agitation | + | — | + | + |
| Anxiety | + | + | + | — |
| Low mood | + | + | + | + |
| Psychosis | ||||
| Catatonia | — | — | — | + |
| Delirium | — | — | — | + |
| Delusions | — | — | — | + |
| Hallucinations | — | — | — | + |
Antidepressant discontinuation syndrome is most often seen in the primary care office in association with SSRI discontinuation, because SSRIs are the most commonly prescribed class of antidepressant medications.
In 2000, a systematic review25 of 46 case reports of SSRI discontinuation proposed the diagnostic criteria listed in Table 3.25 The FINISH mnemonic (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal) was created to facilitate rapid recognition (Table 4).26 However, neither set of criteria25,26 has been formally validated.
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| Flu-like symptoms |
| Fatigue |
| Lethargy |
| General malaise |
| Muscle aches/headaches |
| Diarrhea |
| Insomnia |
| Nausea |
| Imbalance |
| Gait instability |
| Dizziness/lightheadedness |
| Vertigo |
| Sensory disturbances |
| Paresthesia |
| “Electric shock” sensations |
| Visual disturbance |
| Hyperarousal |
| Anxiety |
| Agitation |
Multiple case reports demonstrate that antidepressant discontinuation syndrome associated with tricyclic antidepressants closely mimics that of the SSRIs.
3,4 However, signs of parkinsonism and profound problems with balance appear to be especially characteristic of antidepressant discontinuation syndrome caused by tricyclic antidepressant discontinuation.3,4 Additionally, case reports have noted that the antidepressant discontinuation syndrome associated with MAOIs may involve more serious symptomatology such as aggressiveness, agitation, catatonia, severe cognitive impairment, or myoclonus and psychotic symptoms and may require more intensive management.4,5
ONSET AND COURSE
Discontinuation symptoms typically appear within three days of stopping antidepressant medication or initiating a medication taper, though it has been reported that reactions may occur within hours of the first missed dose.9 Untreated symptoms are usually mild and resolve spontaneously in one to two weeks.19 In rare but more serious cases involving psychosis, catatonia, or severe cognitive impairment, immediate psychiatric consultation may be required.
Diagnostic considerations
MAINTAIN A HIGH INDEX OF SUSPICION
Any uncomfortable symptoms reported by patients receiving antidepressants should prompt close questioning for missed doses, unreported downward adjustments in dosage, or outright medication discontinuation.
DIFFERENTIATION FROM RELAPSE
The symptoms of antidepressant discontinuation syndrome that are associated with most antidepressants share features of major depression, including dysphoria, appetite changes, sleep problems, cognitive problems, and fatigue. By focusing on symptoms that distinguish antidepressant discontinuation syndrome from depressive illness relapse (e.g., dizziness, “electric shock” sensations, “rushing” sensations in the head, headache, and nausea) and observing for rapid (i.e., within a few days) reversal of symptoms after restarting the antidepressant or complete resolution of symptoms in one to two weeks (highly uncharacteristic of a depressive relapse), a definitive diagnosis is fairly easy to make.
19,27 Depressive relapses or recurrences typically occur after at least two to three weeks or longer after cessation of medication and are most often marked by gradual worsening of depression, insomnia, and psychomotor symptoms.28
DIFFERENTIATION FROM OTHER CONDITIONS
Irritability, sleeplessness, and anxiety or agitation in a patient taking antidepressants may appropriately raise suspicion of an antidepressant-associated bipolar manic episode that must be distinguished from antidepressant discontinuation syndrome. The development of these symptoms should prompt close questioning about medication adherence, as previously mentioned. If such symptoms appear shortly after discontinuation or during dose reduction, rapid symptom resolution after restoring the antidepressant medication will lead to the correct diagnosis.
Antidepressant discontinuation syndrome also may be misdiagnosed as severe conditions including stroke, other neurologic conditions, infectious diseases, and adverse effects of other medications the patient is taking.
29 Antidepressant discontinuation syndrome has been reported when switching from one antidepressant agent to another.30 When the new agent has different pharmacologic mechanism reactions than the first agent, antidepressant discontinuation syndrome may be misinterpreted as intolerable side effects from the new medication.29
Prevention and management
USE OF ANTIDEPRESSANTS
For optimal treatment of most psychiatric conditions, and especially anxiety and depressive disorders, psychosocial interventions should be recommended along with or considered as alternatives to pharmacologic therapies. The all-too-common practice of “short-term” prescriptions for off-label, non–mental health reasons (e.g., irritable bowel syndrome, weight loss, headaches, insomnia) has been associated with early antidepressant discontinuation and may increase the risk of antidepressant discontinuation syndrome.31
PATIENTS AT RISK OF DISCONTINUATION
Patients may be tempted to discontinue their antidepressant medication after they begin to feel better, a practice that invites both early relapse of illness and antidepressant discontinuation syndrome.
Women may discontinue antidepressant use after discovering that they are pregnant. Ideally, patients should be counseled regarding the risks of illness relapse, the importance of treating symptoms to remission, the need for continuation and (where appropriate) maintenance pharmacotherapy, and the need for gradual discontinuation of medications before discontinuing care.27,32
DISCONTINUING MEDICATION
Although there are no clinical trials comparing abrupt discontinuation with tapered discontinuation of antidepressants, tapering is recommended by experts, based on the suspected pathophysiology of antidepressant discontinuation syndrome.33 Patients should be forewarned of the possibility of antidepressant discontinuation syndrome if antidepressants are discontinued, and that supervised tapering of medication over six to eight weeks may be required to minimize discontinuation symptoms. Several RCTs have shown that with abrupt cessation of antidepressants, symptoms can begin within days.
16,17,22 It may be possible to discontinue medication more quickly if doses are low; discontinuation may take longer (three months or more) after maintenance therapy. It may be possible to stop fluoxetine therapy without tapering. There are no clear, validated tapering recommendations. However, Table 527 offers one expert's recommendations for tapering rates.
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MANAGEMENT
If antidepressant discontinuation syndrome occurs and other serious causes of these symptoms have been ruled out, the physician should begin by providing reassurance to the patient that the condition is reversible, is not serious or life threatening, and will run its course within one to two weeks. The physician should then consider restarting the antidepressant medication with a slow dose taper or providing support if the patient desires not to restart the antidepressant.
Severe symptoms should resolve in fewer than three days, and often within 24 hours. If the antidepressant discontinuation syndrome occurs during a tapering of the antidepressant, consider restarting at the original dose and then taper at a slower rate. In cases where slow tapering is poorly tolerated, a medicine with a longer half-life such as fluoxetine may be substituted for the shorter half-life agent.
GENERIC DRUGS AND SUBSTITUTIONS
Not all formulations of the same drug are bioequivalent. Generic drugs are allowed up to a 20 percent difference. This may result in an unintended sudden reduction in drug concentration if a patient's medication is switched to a generic or alternative brand.
TRICYCLIC ANTIDEPRESSANTS
Antidepressant discontinuation syndrome symptoms caused by tricyclic antidepressants that suggest cholinergic rebound (e.g., parkinsonism and other problems with movement) may respond to short-term use of anticholinergic agents such as atropine (Atropisol) or benztropine (Cogentin).
This should be considered especially for patients who are opposed to restarting their tricyclic antidepressant.34
Going Off Antidepressants - Harvard Health Publishing
Coming off your medication can cause antidepressant withdrawal – and could set you up for a relapse of depression.
Can going off your medication cause antidepressant withdrawal symptoms (antidepressant discontinuation syndrome)? About 10% of women ages 18 and over take antidepressants. As many of us know, these medications can be a godsend when depression has robbed life of its joy and made it hard to muster the energy and concentration to complete everyday tasks. But as you begin to feel better and want to move on, how long should you keep taking the pills?
If you're doing well on antidepressants and not complaining of too many side effects, many physicians will renew the prescription indefinitely — figuring that it offers a hedge against a relapse of depression.
But side effects that you may have been willing to put up with initially — sexual side effects (decreased desire and difficulty having an orgasm), headache, insomnia, drowsiness, vivid dreaming, or just not feeling like yourself — can become less acceptable over time, especially if you think you no longer need the pills.
The decision to go off antidepressants should be considered thoughtfully and made with the support of your physician or therapist to make sure you're not stopping prematurely, risking a recurrence of depression. Once you decide to quit, you and your physician should take steps to minimize or avoid the discontinuation symptoms that can occur if such medications are withdrawn too quickly.
Why antidepressant withdrawal?
Antidepressants work by altering the levels of neurotransmitters — chemical messengers that attach to receptors on neurons (nerve cells) throughout the body and influence their activity. Neurons eventually adapt to the current level of neurotransmitters, and symptoms that range from mild to distressing may arise if the level changes too much too fast — for example, because you've suddenly stopped taking your antidepressant.
They're generally not medically dangerous but may be uncomfortable.
Among the newer antidepressants, those that influence the serotonin system — selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) — are associated with a number of withdrawal symptoms, often called antidepressant or SSRI discontinuation syndrome. Stopping antidepressants such as bupropion (Wellbutrin) that do not affect serotonin systems — dopamine and norepinephrine reuptake inhibitors — seems less troublesome overall, although some patients develop extreme irritability.
Having discontinuation symptoms doesn't mean you're addicted to your antidepressant. A person who is addicted craves the drug and often needs increasingly higher doses. Few people who take antidepressants develop a craving or feel a need to increase the dose. (Sometimes an SSRI will stop working — a phenomenon called "Prozac poop-out" — which may necessitate increasing the dose or adding another drug.
)
Antidepressant withdrawal can look like depressionDiscontinuation symptoms can include anxiety and depression. Since these may be the reason you were prescribed antidepressants in the first place, their reappearance may suggest that you're having a relapse and need ongoing treatment. Here's how to distinguish discontinuation symptoms from relapse:
If symptoms last more than a month and are worsening, it's worth considering whether you're having a relapse of depression. |
Antidepressant withdrawal symptoms
Neurotransmitters act throughout the body, and you may experience physical as well as mental effects when you stop taking antidepressants or lower the dose too fast. Common complaints include the following:
- Digestive. You may have nausea, vomiting, cramps, diarrhea, or loss of appetite.
- Blood vessel control. You may sweat excessively, flush, or find hot weather difficult to tolerate.
- Sleep changes. You may have trouble sleeping and unusual dreams or nightmares.
- Balance.
You may become dizzy or lightheaded or feel like you don't quite have your "sea legs" when walking. - Control of movements. You may experience tremors, restless legs, uneven gait, and difficulty coordinating speech and chewing movements.
- Unwanted feelings. You may have mood swings or feel agitated, anxious, manic, depressed, irritable, or confused — even paranoid or suicidal.
- Strange sensations. You may have pain or numbness; you may become hypersensitive to sound or sense a ringing in your ears; you may experience "brain-zaps" — a feeling that resembles an electric shock to your head — or a sensation that some people describe as "brain shivers."
As dire as some of these symptoms may sound, you shouldn't let them discourage you if you want to go off your antidepressant. Many of the symptoms of SSRI discontinuation syndrome can be minimized or prevented by gradually lowering, or tapering, the dose over weeks to months, sometimes substituting longer-acting drugs such as fluoxetine (Prozac) for shorter-acting medications.
The antidepressants most likely to cause troublesome symptoms are those that have a short half-life — that is, they break down and leave the body quickly. (See the chart "Antidepressant drugs and their half-lives.") Examples include venlafaxine (Effexor), sertraline (Zoloft), paroxetine (Paxil), and citalopram (Celexa). Extended-release versions of these drugs enter the body more slowly but leave it just as fast. Antidepressants with a longer half-life, chiefly fluoxetine, cause fewer problems on discontinuation.
Besides easing the transition, tapering the dose decreases the risk that depression will recur. In a Harvard Medical School study, nearly 400 patients (two-thirds of them women) were followed for more than a year after they stopped taking antidepressants prescribed for mood and anxiety disorders. Participants who discontinued rapidly (over one to seven days) were more likely to relapse within a few months than those who reduced the dose gradually over two or more weeks.
Antidepressant drugs and their half-lives* | ||
| Drug | Half out of body in | 99% out of body in |
| Serotonin reuptake inhibitors | ||
| paroxetine (Paxil) | 24 hours | 4. |
| sertraline (Zoloft) | 26 hours | 5.4 days |
| escitalopram (Lexapro) | 27 to 32 hours | 6.1 days |
| citalopram (Celexa) | 36 hours | 7.3 days |
| fluoxetine (Prozac) | Four to six days | 25 days |
| Serotonin and norepinephrine reuptake inhibitors | ||
| venlafaxine (Effexor) | 5 hours | 1 day |
| duloxetine (Cymbalta) | 12 hours | 2. |
| desvenlafaxine (Pristiq) | 12 hours | 2.5 days |
| Dopamine and norepinephrine reuptake inhibitor | ||
| bupropion (Wellbutrin) | 21 hours | 4.4 days |
| *Discontinuation symptoms typically start when 90% or more of the drug has left your system. Source: Adapted from Joseph Glenmullen, M.D., The Antidepressant Solution: A Step-by-Step Guide to Safely Overcoming Antidepressant Withdrawal, Dependence, and "Addiction" (Free Press, 2006). | ||
4 days
5 days
How to go off antidepressants
If you're thinking about stopping antidepressants, you should go step-by-step, and consider the following:
Take your time. You may be tempted to stop taking antidepressants as soon as your symptoms ease, but depression can return if you quit too soon. Clinicians generally recommend staying on the medication for six to nine months before considering going off antidepressants. If you've had three or more recurrences of depression, make that at least two years.
Talk to your clinician about the benefits and risks of antidepressants in your particular situation, and work with her or him in deciding whether (and when) to stop using them. Before discontinuing, you should feel confident that you're functioning well, that your life circumstances are stable, and that you can cope with any negative thoughts that might emerge. Don't try to quit while you're under stress or undergoing a significant change in your life, such as a new job or an illness.
Make a plan. Going off an antidepressant usually involves reducing your dose in increments, allowing two to six weeks between dose reductions. Your clinician can instruct you in tapering your dose and prescribe the appropriate dosage pills for making the change. The schedule will depend on which antidepressant you're taking, how long you've been on it, your current dose, and any symptoms you had during previous medication changes. It's also a good idea to keep a "mood calendar" on which you record your mood (on a scale of one to 10) on a daily basis.
Consider psychotherapy. Fewer than 20% of people on antidepressants undergo psychotherapy, although it's often important in recovering from depression and avoiding recurrence. In a meta-analysis of controlled studies, investigators at Harvard Medical School and other universities found that people who undergo psychotherapy while discontinuing an antidepressant are less likely to have a relapse.
Stay active. Bolster your internal resources with good nutrition, stress-reduction techniques, regular sleep — and especially physical activity. Exercise has a powerful antidepressant effect. It's been shown that people are far less likely to relapse after recovering from depression if they exercise three times a week or more. Exercise makes serotonin more available for binding to receptor sites on nerve cells, so it can compensate for changes in serotonin levels as you taper off SSRIs and other medications that target the serotonin system.
Seek support. Stay in touch with your clinician as you go through the process. Let her or him know about any physical or emotional symptoms that could be related to discontinuation. If the symptoms are mild, you'll probably be reassured that they're just temporary, the result of the medication clearing your system. (A short course of a non-antidepressant medication such as an antihistamine, anti-anxiety medication, or sleeping aid can sometimes ease these symptoms.
) If symptoms are severe, you might need to go back to a previous dose and reduce the levels more slowly. If you're taking an SSRI with a short half-life, switching to a longer-acting drug, like fluoxetine, may help.
You may want to involve a relative or close friend in your planning. If people around you realize that you're discontinuing antidepressants and may occasionally be irritable or tearful, they'll be less likely to take it personally. A close friend or family member may also be able to recognize signs of recurring depression that you might not perceive.
Complete the taper. By the time you stop taking the medication, your dose will be tiny. (You may already have been cutting your pills in half or using a liquid formula to achieve progressively smaller doses.) Some psychiatrists prescribe a single 20-milligram tablet of fluoxetine the day after the last dose of a shorter-acting antidepressant in order to ease its final washout from the body, although this approach hasn't been tested in a clinical trial.
Check in with your clinician one month after you've stopped the medication altogether. At this follow-up appointment, she or he will check to make sure discontinuation symptoms have eased and there are no signs of returning depression. Ongoing monthly check-ins may be advised.
Image: AlinaTraut/Getty Images
Antidepressant discontinuation syndrome: diagnosis, prevention and treatment
04/18/2017
UP TO ZMISTU NUMBER
Withdrawal symptoms may occur after discontinuation of any class of antidepressants. The largest number of publications is devoted to selective serotonin reuptake inhibitors (SSRIs), apparently due to the fact that drugs of this class are most often prescribed for the treatment of depressive disorders.
Usually these symptoms are mild and disappear on their own after a while. However, some patients may need to resume pharmacotherapy. This review briefly discusses the main clinical aspects of the antidepressant discontinuation syndrome.
This condition is also called antidepressant withdrawal syndrome, although this is not entirely correct. The appearance of symptoms after stopping therapy does not mean that the drug is addictive. Antidepressants do not have addictive potential and do not cause addiction. This is an important positive point that should be communicated to patients, since most people will stop taking the prescribed treatment as soon as possible in case of fear of becoming dependent on the drug. nine0003
Why is it important to recognize antidepressant withdrawal syndrome?
There are three reasons: discomfort for the patient, diagnostic problem and possible compliance problems.
Although withdrawal symptoms are rarely life-threatening, they are always associated with discomfort and some degree of psychosocial maladjustment. Hence the second problem: having experienced a withdrawal syndrome, the patient hardly agrees to any psychopharmacotherapy in the future. And finally, symptoms that occur in connection with the cessation of the action of an antidepressant can be mistaken for an exacerbation of a depressive disorder, another mental disorder, or a physical illness. nine0032 For example, consider two typical scenarios. Convinced of achieving remission of major depressive disorder, the doctor hurries to please the patient that the antidepressant can be stopped, but forgets to tell how to do it correctly. The patient takes everything literally and the next day forgets about the medicine. A week later, he develops withdrawal symptoms, and he addresses his complaints to a) the same psychiatrist who forgets to ask how the antidepressant was withdrawn and perceives the symptoms as a relapse of depression; b) to another specialist, for example, a neurologist, to whom he prefers not to report about treatment with a psychiatrist.
And the neurologist interprets these non-specific symptoms according to his competence. As a result, unnecessary examinations and possibly even treatment. nine0032 In addition, symptoms can be confused with side effects of a newly prescribed drug after discontinuation of an antidepressant, especially when switching between antidepressants with different mechanisms of action, for example, from paroxetine (SSRI) to bupropion (a dopamine and norepinephrine reuptake inhibitor). This can lead to the erroneous conclusion that the patient does not tolerate the new drug well. Symptoms of discontinuation of therapy may also be perceived as failure of therapy, especially irritability and anxiety. nine0032 Symptoms of discontinuation of antidepressant therapy can be divided into six categories: sensory symptoms, balance disorders, general somatic, affective, gastrointestinal symptoms, and sleep disorders (Fig.).
At first, information about the listed manifestations was accumulated from reports of clinical cases.
Then this problem was studied in prospective double-blind clinical trials in which patients were specifically randomized to the abolition of antidepressant therapy. nine0032 In English literature, a mnemonic device is used to memorize the spectrum of antidepressant withdrawal syndrome: the main symptoms are encrypted in the word FINISH.
F - from "flu-like" - flu-like symptoms;
I - insomnia;
N - from "nausea" - nausea;
I - from "imbalance" - imbalance;
S - sensory symptoms;
H - from "hyperarousal" - increased excitability, which reflects affective disorders.
It should be noted that the symptoms presented in the figure are mainly associated with discontinuation of SSRIs and serotonin and norepinephrine reuptake inhibitors. The spectrum of symptoms during withdrawal of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants has its own specifics. Thus, in the event of discontinuation of tricyclic antidepressants, sensory symptoms and balance disorders, as a rule, are not observed.
With the abolition of MAO inhibitors, symptoms may be more pronounced than after the abolition of SSRIs. Patients may experience a worsening of depressive and anxiety symptoms, an acute impairment of consciousness up to catatonia. nine0003
When do withdrawal symptoms appear and how long do they last?
They usually appear within the first week after stopping the antidepressant; according to studies, on average on the second day. Spontaneous resolution occurs at different times - from 1 day to 3 weeks, on average, patients continue to experience symptoms for 10 days.
What causes withdrawal syndrome?
The syndrome occurs when all classes of antidepressants are discontinued. The largest number of reports was recorded for paroxetine. The half-life of the drug from blood plasma is the indicator that correlates more than others with the risk of developing a withdrawal syndrome. In other words, the shorter the residual effect of the drug after the last dose, the higher the likelihood of symptoms.
nine0032 For example, fluoxetine has a half-life of 7 days, so this SSRI has the lowest risk of withdrawal. Paroxetine has an average half-life of 24 hours, hence the high risk of withdrawal syndrome, especially when the therapeutic dose is abruptly stopped.
Can antidepressant discontinuation syndrome be distinguished from relapse of depression?
Common symptoms include dysphoria, decreased appetite, sleep disturbances and fatigue. But there are also distinctive features—symptoms that are rarely seen in depression, such as sensory phenomena (paresthesias) as well as dizziness, headache, and nausea. In addition, in the case of withdrawal syndrome, a rapid (within 1 day) improvement can be observed when the drug is resumed, while recurrent depression does not respond so quickly to therapy. nine0003
Who is at risk for developing antidepressant withdrawal syndrome?
Typically, these are patients who begin to feel better after a few weeks of taking an antidepressant and are not sufficiently informed about the need for long-term maintenance therapy.
Women who find out they are pregnant during treatment may also abruptly stop taking the antidepressant for safety reasons.
How to stop antidepressants to minimize the risk of withdrawal? nine0013
Patients should be explained in an accessible form the features of the action of the prescribed antidepressant, the rules for increasing and gradually reducing the dose, and warn about a possible deterioration in well-being with an abrupt cessation of therapy. But at the same time, the words "withdrawal syndrome", "addiction", "addiction" should be avoided, since they can be perceived negatively and cause early termination of therapy. Sooner or later, that happy moment comes when it becomes clear that antidepressants can be abandoned. However, the withdrawal process, as a rule, takes several weeks, but in some cases even longer, especially if the patient's health worsens at the first steps of dose reduction. When prescribing fluoxetine, it is possible to cancel the drug without a gradual dose reduction, although it has not been specifically studied in studies.
nine0032 If possible, you should also discuss with the patient's relatives the creation of the most favorable conditions for the period of antidepressant withdrawal. Patients with major depressive disorder, as a rule, do not work and are at home, therefore they are not subjected to external psycho-emotional stress. It is optimal if the patient's close environment tries to create a positive atmosphere and tries to involve a family member in some kind of activity in order to distract from the perception of possible withdrawal symptoms. nine0003
How to help patients who complain of feeling worse after stopping antidepressants?
If this does happen, explain to the patient that the symptoms are not life-threatening and usually resolve within a few days. If the patient continues to experience symptoms and they reduce quality of life, it is common practice to restart the therapeutic dose of the antidepressant. In the future, you can again try to stop the drug through a very gradual dose reduction.
If this does not help, then it is possible to transfer the patient to fluoxetine-SSRI with the lowest risk of withdrawal syndrome, and then cancel it. nine0003
Literature
1. Haddad P.M., AndersonI.M. (2007). Recognizing and managing antidepressant discontinuation symptoms. Advances in Psychiatric treatment, 13(6): 447-457.
2. Warner C.H., Bobo W., Warner C., Reid S., Rachal J. (2006). Antidepressant discontinuation syndrome. American Family Physician, 74(3): 449-456.
3. Renoir T. (2013). Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved. Frontiers in Pharmacology, 4.
Prepared by Dmitry Molchanov
- Number:
- Thematic issue "Neurology, Psychiatry, Psychotherapy" No. 1 (40), March 2017
27.
12.2022 Psychiatry0003
Neurotic, stress-related and somatoform disorders (F40-F48) are the most widespread disorders of mental health in the practice of primary care physicians. The search for new tools for effective and non-invasive therapy of neurotic disorders (NR) is still relevant, but the remains of the latest psychopharmacological arsenal may not satisfy all the needs of patients. Pharmaceutical request Tenoten to affinity-purify antibodies to brain-specific protein S-100 in homeopathic dilutions. Modifying the functional activity of S-100, Tenoten can be stress-protective, anxiolytic, antidepressant, antiamnestic and neuroprotective. Based on the results of the program of preclinical and clinical trials, the drug can become an alternative to benzodiazepines in selected patients from HP ....
Antidepressant Discontinuation Syndrome - Neurology - LiveJournal
Terminology Issues .
This condition is also called antidepressant withdrawal syndrome, although this is not entirely correct. The appearance with symptoms after cessation of and antidepressant therapy () does not mean that the drug is addictive. Antidepressants do not have addictive potential (Latin "addictus" - addicted; English "addiction" - dependence, addiction, addiction) and do not cause dependence. This is an important positive point that should be communicated to patients, since most people will stop taking the prescribed treatment as soon as possible in case of fear of becoming dependent on the drug. nine0004 Relevance recognition (detection) in a patient with SPTA. [ 1 ] First, although withdrawal symptoms are rarely life threatening, they are always associated with discomfort and some degree of psychosocial maladaptation ( ! reduced quality of life). [ 2 ] Secondly, having experienced a withdrawal syndrome, the patient hardly agrees to any psycho-pharmacotherapy in the future.
[ 3 ] Third, symptoms associated with discontinuation of an antidepressant may be mistaken for an exacerbation of a depressive disorder, another mental or nervous system disorder, or a physical illness (for example, if the patient consults a neurologist whom he prefers not to inform about treatment by a psychiatrist, the neurologist interprets these non-specific symptoms according to his competence; as a result, unnecessary examinations and possibly even treatment). [ nine0124 4 ] Fourth, SPTA can be confused with the side effects of a newly prescribed drug after antidepressant withdrawal, especially when switching between antidepressants with different mechanisms of action (this can lead to the erroneous conclusion that the patient does not tolerate the new drug well).
SPTA risk categories . As a rule, these are patients who begin to feel better after a few weeks of taking an antidepressant and are not well informed about the need for long-term maintenance therapy.
Women who find out they are pregnant during treatment may also abruptly stop taking the antidepressant for safety reasons. nine0003
Clinic . SPTA is observed upon discontinuation of all classes of antidepressants. The half-life of the drug from blood plasma is the indicator that correlates more than others with the risk of developing a withdrawal syndrome. In other words, the shorter the residual effect of the drug after the last dose, the higher the likelihood of symptoms. For example, fluoxetine has a half-life of 7 days, so this representative of the SSRIs (selective serotonin reuptake inhibitors) has the lowest risk of developing a withdrawal syndrome. Paroxetine has an average half-life of 24 hours, hence the high risk of withdrawal syndrome, especially when the therapeutic dose is abruptly discontinued. nine0003
SPTA can be divided into six categories: [ 1 ] sensory symptoms, [ 2 ] balance disorders, [ 3 ] general somatic, [ 4 ] affective, [ 5 9012 symptoms5 ] and [ 6 ] sleep disorders:
It should be noted that the symptoms presented in the figure are mainly associated with discontinuation of SSRIs and serotonin and norepinephrine reuptake inhibitors.
The spectrum of symptoms during the abolition of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) has its own specifics. Thus, in the event of discontinuation of TCAs, sensory symptoms and balance disorders are usually not observed. With the abolition of MAO inhibitors, symptoms may be more pronounced than after the abolition of SSRIs. Patients may experience a worsening of depressive and anxiety symptoms, an acute impairment of consciousness up to catatonia. nine0004 In the English literature, a mnemonic device is used to memorize the SPTA spectrum; the main symptoms are encrypted in the word FINISH : F - from "flu-like" - flu-like symptoms; I - insomnia; N - from "nausea" - nausea; I - from "imbalance" - imbalance; S - sensory symptoms; H - from "hyperarousal" - increased excitability, which reflects affective disorders. PTAS usually appear within the first week after stopping the antidepressant; according to studies, on average on the second day.
Spontaneous resolution occurs at various times - from 1 day to 3 weeks, on average, patients continue to experience symptoms for 10 days (note: in the case of SPTA, you can see a rapid - within 1 day - improvement when the drug is resumed, while relapsing depression does not respond so quickly to therapy). nine0003
Principles for stopping antidepressant (how to minimize the risk of PTAS). Patients should be explained in an accessible form the features of the action of the prescribed antidepressant, the rules for increasing and gradually reducing the dose, and warn of a possible deterioration in well-being in the event of an abrupt cessation of therapy. But at the same time, the words “withdrawal syndrome”, “addiction”, “dependence” should be avoided, since they can be perceived negatively and cause early termination of therapy. Sooner or later, that happy moment comes when it becomes clear that antidepressants can be abandoned. However, the withdrawal process, as a rule, takes several weeks, but in some cases even longer, especially if the patient's well-being worsens in the first stages of dose reduction.
When prescribing fluoxetine, it is possible to cancel the drug without a gradual dose reduction, although it has not been specifically studied in studies. If possible, you should also discuss with the patient's relatives the creation of the most favorable conditions for the period of withdrawal of the antidepressant. Patients with major depressive disorder, as a rule, do not work and are at home, therefore they are not exposed to external psycho-emotional stress. Ideally, the patient's close environment will try to create a positive atmosphere and try to involve a family member in some kind of activity in order to distract from the perception of possible withdrawal symptoms. nine0003
If PTAS does occur, explain to the patient that these symptoms are not life threatening and usually resolve within a few days. If the patient continues to experience SPTA and they reduce quality of life, it is common practice to restart the therapeutic dose of the antidepressant. In the future, you can again try to stop the drug through a very gradual dose reduction.
