Antidepressant discontinuation syndrome: Difference between revisions
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Revision as of 16:46, 22 March 2025
| Antidepressant discontinuation syndrome | |
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| Synonyms | Antidepressant withdrawal syndrome<ref name=TI2018/> |
| Pronounce | |
| Field | Psychiatry |
| Symptoms | Flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes<ref name=War2006/> |
| Complications | |
| Onset | Within 3 days<ref name=War2006/> |
| Duration | Few weeks to months<ref name=Gab2017/><ref name=Dav2018/> |
| Types | |
| Causes | Stopping of an antidepressant medication<ref name=War2006/><ref name=Gab2017/> |
| Risks | |
| Diagnosis | Based on symptoms<ref name=War2006/> |
| Differential diagnosis | Anxiety, mania, stroke<ref name=War2006/> |
| Prevention | Gradual dose reduction<ref name=War2006/> |
| Treatment | |
| Medication | |
| Prognosis | |
| Frequency | 20-50%(with sudden stopping)<ref name=Gab2017/><ref name=Dav2018/> |
| Deaths | |
Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication that was taken continuously for at least one month.<ref name="DSM5">,
Diagnostic and statistical manual of mental disorders : DSM-5., 5th edition, American Psychiatric Association, ISBN 9780890425541, Pages: 712–714,</ref> The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, and anxiety.<ref name=War2006/><ref name=Gab2017/><ref name=Dav2018>, A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based?, Addictive Behaviors, Vol. 97, pp. 111–121, DOI: 10.1016/j.addbeh.2018.08.027, PMID: 30292574,</ref> The problem usually begins within three days and may last for several months.<ref name=War2006/><ref name=Dav2018/> Rarely psychosis may occur.<ref name=War2006/>
A discontinuation syndrome can occur after stopping any antidepressant including selective serotonin re-uptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs).<ref name=War2006/><ref name=Gab2017/> The risk is greater among those who have taken the medication for longer and when the medication in question has a short half-life.<ref name=War2006/> The underlying reason for its occurrence is unclear.<ref name=War2006/> The diagnosis is based on the symptoms.<ref name=War2006/>
Methods of prevention include gradually decreasing the dose among those who wish to stop, though it is possible for symptoms to occur with tapering.<ref name=War2006/><ref name=Wil2015>,
A review of the management of antidepressant discontinuation symptoms, Therapeutic Advances in Psychopharmacology, Vol. 5(Issue: 6), pp. 357–68, DOI: 10.1177/2045125315612334, PMID: 26834969, PMC: 4722507,</ref><ref name=Dav2018 /> Treatment may include restarting the medication and slowly decreasing the dose.<ref name=War2006/> People may also be switched to the long acting antidepressant fluoxetine which can then be gradually decreased.<ref name=Wil2015/>
Approximately 20–50% of people who suddenly stop an antidepressant develop an antidepressant discontinuation syndrome.<ref name=War2006>,
Antidepressant discontinuation syndrome, American Family Physician, Vol. 74(Issue: 3), pp. 449–56, PMID: 16913164,</ref><ref name=Gab2017>, Antidepressant discontinuation syndrome, Canadian Medical Association Journal, Vol. 189(Issue: 21), pp. E747, DOI: 10.1503/cmaj.160991, PMID: 28554948, PMC: 5449237,</ref><ref name=Dav2018 /> The condition is generally not serious,<ref name=War2006/> though about half of people with symptoms describe them as severe.<ref name=Dav2018/> Some restart antidepressants due to the severity of the symptoms.<ref name=Dav2018/>
Signs and symptoms
People with antidepressant discontinuation syndrome have been on an antidepressant for at least four weeks and have recently stopped taking the medication, whether abruptly, after a fast taper, or each time the medication is reduced on a slow taper.<ref name=War2006/> Commonly reported symptoms include flu-like symptoms (nausea, vomiting, diarrhea, headaches, sweating) and sleep disturbances (insomnia, nightmares, constant sleepiness). Sensory and movement disturbances have also been reported, including imbalance, tremors, vertigo, dizziness, and electric-shock-like experiences in the brain, often described by people who have them as "brain zaps". Mood disturbances such as dysphoria, anxiety, or agitation are also reported, as are cognitive disturbances such as confusion and hyperarousal.
In cases associated with sudden discontinuation of MAO inhibitors, acute psychosis has been observed.<ref name=War2006/><ref name=Haddad2007>,
Recognising and managing antidepressant discontinuation symptoms, Advances in Psychiatric Treatment, Vol. 13(Issue: 6), pp. 447–57, DOI: 10.1192/apt.bp.105.001966,</ref><ref name=Renoir2013>Renoir T, Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved, Front Pharmacol, 2013, Vol. 4, DOI: 10.3389/fphar.2013.00045, PMID: 23596418, PMC: 3627130,</ref> Over fifty symptoms have been reported.<ref>, Neurological complications of psychiatric drugs: clinical features and management, Hum Psychopharmacol, 2008, Vol. 23(Issue: Suppl 1), pp. 15–26, DOI: 10.1002/hup.918, PMID: 18098217,</ref>
A 2009 Advisory Committee to the FDA found that online anecdotal reports of discontinuation syndrome related to duloxetine included severe symptoms and exceeded prevalence of both paroxetine and venlafaxine reports by over 250% (although acknowledged this may have been influenced by duloxetine being a much newer drug).<ref name=":0">
Cymbalta (Duloxetine) Discontinuation Syndrome: Issues of Scope, Severity, Duration & Management(link). '. U.S. Food and Drug Administration (FDA). 9 June 2009.
Accessed 17 October 2016.
</ref> It also found that the safety information provided by the manufacturer not only neglected important information about managing discontinuation syndrome, but also explicitly advised against opening capsules, a practice required to gradually taper dosage.<ref name=":0" />
Duration
Most cases of discontinuation syndrome may last between one and four weeks and resolve on their own.<ref name=War2006/> Occasionally symptoms can last up to one year.<ref name=Gab2017/> They typically resolve within a day of restoring the medication.<ref>,
Recognising and managing antidepressant discontinuation symptoms, Advances in Psychiatric Treatment, Vol. 13(Issue: 6), pp. 447–457, DOI: 10.1192/apt.bp.105.001966,</ref> Paroxetine and venlafaxine seem to be particularly difficult to discontinue, and prolonged withdrawal syndrome (post-acute-withdrawal syndrome, or PAWS) lasting over 18 months has been reported with paroxetine.<ref name="DrugSaf2001-Haddad" /><ref>, Selective Serotonin Reuptake Inhibitor Discontinuation Syndrome: A Review, Advances in Therapy, Vol. 19(Issue: 1), pp. 17–26, DOI: 10.1007/BF02850015, PMID: 12008858,</ref><ref name="2ndGenReview">Lua error in Module:Citation/CS1/Configuration at line 2088: attempt to index field '?' (a nil value).
</ref>
Mechanism
The underlying reason for its occurrence is unclear,<ref name=War2006/> though the syndrome appears similar to withdrawal from other psychotropic drugs such as benzodiazepines.<ref name=TI2018>
[112] Antidepressant Withdrawal Syndrome | Therapeutics Initiative(link). Therapeutics Initiative.
23 July 2018.
</ref>
Prevention and treatment
In some cases, withdrawal symptoms may be prevented by taking medication as directed, and when discontinuing, doing so gradually, although symptoms may appear while tapering. When discontinuing an antidepressant with a short half-life, switching to a drug with a longer half-life (e.g. fluoxetine or citalopram) and then tapering, and eventually discontinuing, from that drug can decrease the severity of symptoms.<ref name=Haddad2007/>
Treatment is dependent on the severity of the discontinuation reaction and whether or not further antidepressant treatment is warranted. In cases where further antidepressant treatment is prescribed, then the only option suggested may be restarting the antidepressant. If antidepressants are no longer required, treatment depends on symptom severity. If symptoms of discontinuation are severe, or do not respond to symptom management, the antidepressant can be reinstated and then withdrawn more cautiously, or by switching to a drug with a longer half life, (such as Prozac), and then tapering and discontinuing that drug.<ref name="DrugSaf2001-Haddad">Haddad, Peter M.,
Antidepressant discontinuation syndromes, Drug Safety, Vol. 24(Issue: 3), pp. 183–97, DOI: 10.2165/00002018-200124030-00003, PMID: 11347722,</ref> In severe cases, hospitalization may be required.<ref name=War2006/>
Pregnancy and newborns
Antidepressants, including SSRIs, can cross the placenta and have the potential to affect the fetus and newborn, including an increased chance of miscarriage, presenting a dilemma for pregnant women to decide whether to continue to take antidepressants at all, or if they do, considering if tapering and discontinuing during pregnancy could have a protective effect for the newborn.<ref name=Byatt>,
Antidepressant use in pregnancy: a critical review focused on risks and controversies, Acta Psychiatr Scand, Vol. 127(Issue: 2), pp. 94–114, DOI: 10.1111/acps.12042, PMID: 23240634, PMC: 4006272,</ref>
Postnatal adaptation syndrome (PNAS) (originally called "neonatal behavioral syndrome", "poor neonatal adaptation syndrome", or "neonatal withdrawal syndrome") was first noticed in 1973 in newborns of mothers taking antidepressants; symptoms in the infant include irritability, rapid breathing, hypothermia, and blood sugar problems. The symptoms usually develop from birth to days after delivery and usually resolve within days or weeks of delivery.<ref name=Byatt/>
Culture and history
Antidepressant discontinuation symptoms were first reported with imipramine, the first tricyclic antidepressant (TCA), in the late 1950s, and each new class of antidepressants has brought reports of similar conditions, including monoamine oxidase inhibitors (MAOIs), SSRIs, and SNRIs. As of 2001, at least 21 different antidepressants, covering all the major classes, were known to cause discontinuation syndromes.<ref name="DrugSaf2001-Haddad" /> The problem has been poorly studied, and most of the literature has been case reports or small clinical studies; incidence is hard to determine and controversial.<ref name="DrugSaf2001-Haddad" />
With the explosion of use and interest in SSRIs in the late 1980s and early 1990s, focused especially on Prozac, interest grew as well in discontinuation syndromes.<ref> Stutz, Bruce,
Self-Nonmedication Full text, New York Times, 2007-05-06,
</ref> Some of the symptoms emerged from discussion boards where people with depression discussed their experiences with the disease and their medications; "brain zaps" or "brain shivers" was one symptom that emerged via these websites.<ref name="Christmas">Christmas, M.B.,
'Brain shivers': from chat room to clinic, Psychiatric Bulletin, 2005, Vol. 29(Issue: 6), pp. 219–21, DOI: 10.1192/pb.29.6.219,</ref><ref name="Aronson">Aronson, J., Bottled lightning, BMJ, Vol. 331(Issue: 7520), DOI: 10.1136/bmj.331.7520.824, PMC: 1246084,</ref>
Heightened media attention and continuing public concerns led to the formation of an expert group on the safety of selective serotonin reuptake inhibitors in England, to evaluate all the research available prior to 2004.<ref name="CSMExpert"> Expert Group on the Safety of Selective Serotonin Reuptake Inhibitors (SSRIs). Report of the CSM Expert Working Group on the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants(link). {{{website}}}. Medicines and Healthcare Products Regulatory Agency. December 2004.
</ref>: iv The group determined that the incidence of discontinuation symptoms are between 5% and 49%, depending on the particular SSRI, the length of time on the medicine and abrupt versus gradual cessation.<ref name="CSMExpert"/>: 126–136
With the lack of a definition based on consensus criteria for the syndrome, a panel met in Phoenix, Arizona in 1997 to form a draft definition,<ref>Schatzberg, A.F.,
Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus panel, J Clin Psychiatry, 1997, Vol. 5u(Issue: 7), pp. 5–10, PMID: 9219487,</ref> which other groups continued to refine.<ref>Black, K., Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria, J Psychiatry Neurosci, 2000, Vol. 25(Issue: 3), pp. 255–61, PMID: 10863885, PMC: 1407715,</ref><ref name="who.int">Lua error in Module:Citation/CS1/Configuration at line 2088: attempt to index field '?' (a nil value).
</ref>
In the late 1990s, some investigators thought that the fact that symptoms emerged when antidepressants were discontinued might mean that antidepressants were causing addiction, and some used the term "withdrawal syndrome" to describe the symptoms. While people taking antidepressants do not commonly exhibit drug-seeking behavior, stopping antidepressants leads to similar symptoms as found in drug withdrawal from benzodiazapines, and other psychotropic drugs.<ref>,
What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors, Addiction, 2012, Vol. 105(Issue: 5), pp. 900–8, DOI: 10.1111/j.1360-0443.2011.03686.x, PMID: 21992148,</ref><ref>, Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review, Psychother Psychosom, 2015, Vol. 84(Issue: 2), pp. 72–81, DOI: 10.1159/000370338, PMID: 25721705,</ref> As such, some researchers advocate the term withdrawal over discontinuation, to communicate the similar physiological dependence and negative outcomes.<ref name="TI2018" /> Due to pressure from pharmaceutical companies who make anti-depressants, the term "withdrawal syndrome" is no longer used by drug makers, and thus, most doctors, due to concerns that they may be compared to other drugs more commonly associated with withdrawal.<ref name=War2006/>
2013 class action lawsuit
In 2013, a proposed class action lawsuit, Jennifer L Saavedra v. Eli Lilly and Company,<ref>Justia. Jennifer L Saavedra v. Eli Lilly and Company</ref> was brought against Eli Lilly claiming that the Cymbalta label omitted important information about "brain zaps" and other symptoms upon cessation.<ref name="Law360"> Overley, Jeff. Lilly Fights Cymbalta 'Brain Zaps' Suit, Saying It Warned Docs(link). {{{website}}}. Law360. January 29, 2013.
</ref> Eli Lilly moved for dismissal per the "learned intermediary doctrine" as the doctors prescribing the drug were warned of the potential problems and are an intermediary medical judgment between Lilly and patients; in December 2013 Lilly's motion to dismiss was denied.<ref>Rebecca Tushnet for Rebecca Tushnet's 43(B)log December 09, 2013 Learned intermediary doctrine doesn't bar claim at pleading stage</ref>
Research
The mechanisms of antidepressant withdrawal syndrome have not yet been conclusively identified.<ref name=War2006/><ref name=Renoir2013/> The leading hypothesis is that after the antidepressant is discontinued, there is a temporary, but in some cases, long-lasting, deficiency in the brain of one or more essential neurotransmitters that regulate mood, such as serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid, and since neurotransmitters are an interrelated system, dysregulation of one affects the others.<ref name=War2006/><ref>Damsa, C.,
"Dopamine-dependent" side effects of selective serotonin reuptake inhibitors: a clinical review, J Clin Psychiatry, Vol. 65(Issue: 8), pp. 1064–8, DOI: 10.4088/JCP.v65n0806, PMID: 15323590,</ref>
See also
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References
External links
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