268:, dizziness, and electric-shock-like experiences in the brain, often described by people who have them as brain zaps. These "brain zaps" have been described as an electric shock felt in the skull, potentially triggered by lateral eye movement, and at times accompanied by vertigo, pain, or dissociative symptoms. Some individuals consider it as a pleasant experience akin to an orgasm, however it is more often reported as an unpleasant experience that interferes with daily function. Mood disturbances such as
558:
360:. There is evidence that antidepressant discontinuation syndrome may be related to the half-life of SSRIs. Antidepressants with a lower half-life, such as Venlafaxine, have been implicated in higher incidences of withdrawal symptoms and more severe withdrawal symptoms. There may be a link between lower
390:
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
516:
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. In December 2014, class certification was denied. A second attempt at certification in 2015
326:
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). It also found that the safety information provided by the manufacturer not only neglected important
288:
has been reported to have a higher incidence in withdrawal symptoms after discontinuation when compared to other SNRIs. Venlafaxine has also been implicated to create withdrawal symptoms regardless of dosage. Venlafaxine has been implicated in causing the most severe withdrawal symptoms after
255:
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. Commonly reported symptoms include flu-like symptoms (nausea, vomiting, diarrhea, headaches, sweating) and sleep disturbances
238:
Approximately 15–50% of people who suddenly stop an antidepressant develop an antidepressant discontinuation syndrome. The condition is generally not serious, though about half of people with symptoms describe them as severe. Many restart antidepressants due to the severity of the symptoms.
491:
and negative outcomes. 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.
458:, interest grew as well in discontinuation syndromes. 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.
525:
The mechanisms of antidepressant withdrawal syndrome have not yet been conclusively identified. 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
391:
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
414:
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
465:, to evaluate all the research available prior to 2004. 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.
447:(MAOIs), SSRIs, and SNRIs. As of 2001, at least 21 different antidepressants, covering all the major classes, were known to cause discontinuation syndromes. The problem has been poorly studied, and most of the literature has been case reports or small
1548:. Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression: An Update of the 2007 Comparative Effectiveness Review (Report). Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality.
2182:
242:
Antidepressant discontinuation syndrome is a relatively new phenomenon, with its discovery in the 1950s. There is still little research on this syndrome; most of the research is conflicting or consists only of clinical trials.
411:, 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.
1899:
Schatzberg, A.F., Haddad, P., Kaplan, E.M., Lejoyeux, M., Rosenbaum, J.F., Young, A.H., Zajecka, J. (1997). "Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation
Consensus panel".
374:
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
479:, 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
335:
Most cases of discontinuation syndrome may last between one and four weeks and resolve on their own. Occasionally symptoms can last up to one year. They typically resolve within a day of restoring the medication.
895:
Henssler, J.; Schmidt, Y.; Schmidt, U.; Schwarzer, G.; Bschor, T.; Baethge, C. (2024). "Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis". The Lancet
Psychiatry.
1986:
Nielsen, M., Hanse, E.H., Gøtzsche, P.C. (2012). "What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors".
2229:
1385:
2128:
Damsa, C., Bumb, A., Bianchi-Demicheli, F., et al. (August 2004). "'Dopamine-dependent' side effects of selective serotonin reuptake inhibitors: a clinical review".
2224:
475:
In the late 1990s, some investigators thought that the fact that symptoms emerged when antidepressants were discontinued might mean that antidepressants were causing
209:
1564:"Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved"
1061:"Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved"
1623:"Withdrawal Syndrome Following Discontinuation of 28 Antidepressants: Pharmacovigilance Analysis of 31,688 Reports from the WHO Spontaneous Reporting Database"
461:
Heightened media attention and continuing public concerns led to the formation of an expert group on the safety of selective serotonin reuptake inhibitors in
327:
information about managing discontinuation syndrome, but also explicitly advised against opening capsules, a practice required to gradually taper dosage.
231:. Treatment may include restarting the medication and slowly decreasing the dose. People may also be switched to the long acting antidepressant
1621:
Gastaldon C, Schoretsanitis G, Arzenton E, Raschi E, Papola D, Ostuzzi G, Moretti U, Seifritz E, Kane JM, Trifirò G, Barbui C (December 2022).
205:
356:
The underlying reason for its occurrence is unclear, though the syndrome appears similar to withdrawal from other psychotropic drugs such as
227:
Methods of prevention include gradually decreasing the dose among those who wish to stop, though it is possible for symptoms to occur with
487:, and other psychotropic drugs. As such, some researchers advocate the term withdrawal over discontinuation, to communicate the similar
604:
571:
357:
2080:
828:
781:"A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based?"
1968:
512:
label omitted important information about "brain zaps" and other symptoms upon cessation. Eli Lilly moved for dismissal per the "
220:(TCAs). The risk is greater among those who have taken the medication for longer and when the medication in question has a short
427:
problems. The symptoms usually develop from birth to days after delivery and usually resolve within days or weeks of delivery.
345:
2244:
1501:
Tamam L, Ozpoyraz N (January–February 2002). "Selective
Serotonin Reuptake Inhibitor Discontinuation Syndrome: A Review".
1257:"27.3 The Effectiveness of SSRIs for Treatment of OCD in Children and Adolescents: A Systematic Review and Meta-Analysis"
387:) and then tapering, and eventually discontinuing, from that drug can decrease the severity of symptoms in some cases.
444:
277:
213:
443:(TCA), in the late 1950s, and each new class of antidepressants has brought reports of similar conditions, including
1874:
154:
256:(insomnia, nightmares, constant sleepiness). Sensory and movement disturbances have also been reported, including
2110:
217:
158:
92:
1875:"Report of the CSM Expert Working Group on the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants"
1873:
Expert Group on the Safety of
Selective Serotonin Reuptake Inhibitors (SSRIs) (December 2004). Weller IV (ed.).
322:
A 2009 Advisory
Committee to the FDA found that online anecdotal reports of discontinuation syndrome related to
2234:
488:
440:
273:
543:
596:
2062:
966:
675:
Warner CH, Bobo W, Warner C, Reid S, Rachal J (1 August 2006). "Antidepressant discontinuation syndrome".
109:
1153:"Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review"
908:"Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants"
454:
With the explosion of use and interest in SSRIs in the late 1980s and early 1990s, focused especially on
505:
2023:"Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review"
1772:
1386:"Cymbalta (Duloxetine) Discontinuation Syndrome: Issues of Scope, Severity, Duration & Management"
1726:
919:
513:
376:
1969:
WHO Expert
Committee on Drug Dependence – Thirty-third Report / WHO Technical Report Series 915
1295:
395:), and then tapering and discontinuing that drug. In severe cases, hospitalization may be required.
348:(post-acute-withdrawal syndrome, or PAWS) lasting over 18 months has been reported with paroxetine.
546:, and since neurotransmitters are an interrelated system, dysregulation of one affects the others.
361:
228:
2239:
1526:
1483:
1002:
59:
20:
1929:"Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria"
272:, anxiety, or agitation are also reported, as are cognitive disturbances such as confusion and
224:. The underlying reason for its occurrence is unclear. The diagnosis is based on the symptoms.
2145:
2044:
2003:
1950:
1909:
1753:
1699:
1691:
1660:
1642:
1603:
1585:
1518:
1475:
1433:
1364:
1315:
1276:
1237:
1219:
1180:
1172:
1133:
1092:
994:
986:
937:
878:
824:
802:
746:
684:
563:
527:
257:
194:
178:
174:
162:
99:
64:
47:
2137:
2034:
1995:
1940:
1850:
1842:
1809:
1743:
1735:
1650:
1634:
1593:
1575:
1510:
1467:
1423:
1354:
1346:
1307:
1268:
1227:
1211:
1164:
1123:
1082:
1072:
1036:
978:
945:
927:
868:
860:
792:
736:
728:
469:
468:
With the lack of a definition based on consensus criteria for the syndrome, a panel met in
2106:
484:
480:
1296:"Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem"
407:
and have the potential to affect the fetus and newborn, including an increased chance of
197:. The problem usually begins within three days and may last for several weeks or months.
923:
1972:
1945:
1928:
1855:
1830:
1748:
1722:"Antidepressant use in pregnancy: a critical review focused on risks and controversies"
1721:
1655:
1622:
1598:
1563:
1359:
1334:
1232:
1087:
1060:
950:
907:
873:
848:
741:
716:
539:
448:
252:
2218:
1999:
1471:
182:
1487:
1006:
1530:
1112:"Neurological complications of psychiatric drugs: clinical features and management"
416:
906:
Johnston JA, Nelson DR, Bhatnagar P, Curtis SE, Chen Y, MacKrell JG (2021-02-23).
932:
797:
780:
204:
A discontinuation syndrome can occur after stopping any antidepressant including
1256:
424:
420:
408:
341:
285:
1680:"Physiologic mechanisms underlying the antidepressant discontinuation syndrome"
1638:
1545:
1272:
557:
2201:
2196:
2191:
1428:
1411:
1041:
1024:
553:
472:, in 1997 to form a draft definition, which other groups continued to refine.
455:
436:
392:
384:
380:
364:
receptor availability and symptoms of antidepressant discontinuation syndrome.
337:
323:
232:
52:
1846:
1695:
1646:
1589:
1580:
1437:
1280:
1223:
1176:
1077:
990:
941:
864:
531:
476:
281:
269:
221:
198:
170:
2149:
2048:
2007:
1954:
1757:
1703:
1679:
1664:
1607:
1522:
1479:
1368:
1319:
1241:
1184:
1152:
1137:
1096:
998:
967:"Brain Zaps: An Underappreciated Symptom of Antidepressant Discontinuation"
882:
806:
750:
688:
161:
following its continuous use of at least a month. The symptoms may include
16:
Flu-like symptoms that happen after discontinuing antidepressant medication
1913:
1311:
823:(5th ed.). American Psychiatric Association. 2013. pp. 712–714.
153:, is a condition that can occur following the interruption, reduction, or
2141:
982:
535:
509:
404:
293:
166:
1814:
1797:
732:
1739:
1514:
1350:
1335:"Recognition and management of antidepressant discontinuation syndrome"
1200:"Status Cataplecticus Precipitated by Abrupt Withdrawal of Venlafaxine"
1199:
849:"A review of the management of antidepressant discontinuation symptoms"
462:
265:
190:
114:
2174:
2039:
2022:
1215:
1168:
2186:
284:
has been observed. Over fifty symptoms have been reported. The SNRI
261:
122:
1458:
Haddad PM (March 2001). "Antidepressant discontinuation syndromes".
1261:
Journal of the
American Academy of Child & Adolescent Psychiatry
1128:
1111:
251:
People with antidepressant discontinuation syndrome have been on an
2111:"Learned intermediary doctrine doesn't bar claim at pleading stage"
1151:
Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J (2018).
1412:"Recognising and managing antidepressant discontinuation symptoms"
1025:"Recognising and managing antidepressant discontinuation symptoms"
821:
Diagnostic and statistical manual of mental disorders : DSM-5
186:
118:
1544:
Gartlehner G, Hansen RA, Morgan LC, et al. (December 2011).
435:
Antidepressant discontinuation symptoms were first reported with
2081:"Lilly Fights Cymbalta 'Brain Zaps' Suit, Saying It Warned Docs"
292:
To simplify identifying the principal signs and symptoms, the
1971:(Report). World Health Organization. 2003. Archived from
67:, trouble sleeping, nausea, poor balance, sensory changes
2021:
Fava, G.A., Gatti, A, Belaise, C., et al. (2015).
1294:
Rizcalla M, Kowalkovski B, Prozialeck WA (2020-02-20).
289:
cessation of use, possibly due to its short half-life.
1391:. U.S. Food and Drug Administration (FDA). 9 June 2009
344:
seem to be particularly difficult to discontinue, and
276:. In cases associated with sudden discontinuation of
1927:
Black, K., Shea, C., Dursun, S., Kutcher, S. (2000).
1880:. Medicines and Healthcare Products Regulatory Agency
1453:
1451:
1449:
1447:
2164:
451:; incidence is hard to determine and controversial.
379:, switching to a drug with a longer half-life (e.g.
2168:
136:
128:
108:
98:
87:
79:
71:
58:
46:
38:
33:
2079:
1720:Byatt N, Deligiannidis KM, Freeman MP (Feb 2013).
403:Antidepressants, including SSRIs, can cross the
1054:
1052:
1018:
1016:
8:
2230:Serotonin–norepinephrine reuptake inhibitors
2064:Jennifer L Saavedra v. Eli Lilly and Company
1868:
1866:
971:The Primary Care Companion for CNS Disorders
502:Jennifer L Saavedra v. Eli Lilly and Company
315:Sensory disturbances, including “brain zaps”
210:serotonin–norepinephrine reuptake inhibitors
2199:Monoamine-oxidase-inhibitor antidepressants
1798:"'Brain shivers': from chat room to clinic"
2165:
1410:Haddad PM, Anderson IM (1 November 2007).
853:Therapeutic Advances in Psychopharmacology
670:
668:
666:
664:
662:
660:
658:
656:
654:
652:
650:
648:
646:
644:
642:
500:In 2013, a proposed class action lawsuit,
30:
2194:Tricyclic and tetracyclic antidepressants
2038:
1944:
1854:
1813:
1747:
1654:
1597:
1579:
1427:
1358:
1231:
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1040:
949:
931:
872:
842:
840:
796:
774:
772:
770:
768:
766:
764:
762:
760:
740:
717:"Antidepressant discontinuation syndrome"
710:
708:
706:
704:
702:
700:
698:
640:
638:
636:
634:
632:
630:
628:
626:
624:
622:
169:, nausea, poor balance, sensory changes,
1715:
1713:
1339:Journal of Psychiatry & Neuroscience
591:
589:
587:
2225:Selective serotonin reuptake inhibitors
1023:Haddad PM, Anderson IM (October 2007).
583:
235:which can then be gradually decreased.
206:selective serotonin reuptake inhibitors
147:Antidepressant discontinuation syndrome
34:Antidepressant discontinuation syndrome
1557:
1555:
2204:Other and unspecified antidepressants
1380:
1378:
779:Davies J, Read J (4 September 2018).
7:
721:Canadian Medical Association Journal
597:"Antidepressant Withdrawal Syndrome"
847:Wilson E, Lader M (December 2015).
715:Gabriel M, Sharma V (29 May 2017).
1684:The Journal of Clinical Psychiatry
1204:Journal of Clinical Sleep Medicine
1198:Wang J, Greenberg H (2013-07-15).
896:doi:10.1016/S2215-0366(24)00133-0.
605:The University of British Columbia
572:Benzodiazepine withdrawal syndrome
151:antidepressant withdrawal syndrome
42:Antidepressant withdrawal syndrome
14:
1416:Advances in Psychiatric Treatment
1029:Advances in Psychiatric Treatment
2000:10.1111/j.1360-0443.2011.03686.x
1472:10.2165/00002018-200124030-00003
1333:Bhat V, Kennedy S (2017-07-01).
1157:Psychotherapy and Psychosomatics
556:
1300:Journal of Osteopathic Medicine
965:Papp A, Onton JA (2018-12-20).
2078:Overley J (January 29, 2013).
1:
1110:Haddad PM, Dursun SM (2008).
346:prolonged withdrawal syndrome
140:15–50% (with sudden stopping)
1829:Aronson J (8 October 2005).
1678:Blier P, Tremblay P (2006).
933:10.1371/journal.pone.0247683
798:10.1016/j.addbeh.2018.08.027
530:that regulate mood, such as
445:monoamine oxidase inhibitors
214:monoamine oxidase inhibitors
603:. Therapeutics Initiative,
2261:
2115:Rebecca Tushnet's 43(B)log
1639:10.1007/s40264-022-01246-4
1273:10.1016/j.jaac.2020.09.006
18:
1568:Frontiers in Pharmacology
1429:10.1192/apt.bp.105.001966
1042:10.1192/apt.bp.105.001966
677:American Family Physician
496:2013 class action lawsuit
218:tricyclic antidepressants
159:antidepressant medication
93:antidepressant medication
1847:10.1136/bmj.331.7520.824
1796:Christmas, M.B. (2005).
1581:10.3389/fphar.2013.00045
1255:Khan AM (October 2020).
1078:10.3389/fphar.2013.00045
865:10.1177/2045125315612334
489:physiological dependence
441:tricyclic antidepressant
370:Prevention and treatment
19:Not to be confused with
2067:– via Justia.com.
544:gamma-aminobutyric acid
1771:Stutz B (2007-05-06).
504:, was brought against
399:Pregnancy and newborns
132:Gradual dose reduction
110:Differential diagnosis
1933:J Psychiatry Neurosci
1312:10.7556/jaoa.2020.030
2245:Withdrawal syndromes
2142:10.4088/JCP.v65n0806
2109:(December 9, 2013).
2027:Psychother Psychosom
1802:Psychiatric Bulletin
1773:"Self-Nonmedication"
1727:Acta Psychiatr Scand
983:10.4088/PCC.18m02311
514:learned intermediary
1975:on August 30, 2009.
1831:"Bottled lightning"
1815:10.1192/pb.29.6.219
1503:Advances in Therapy
1116:Hum Psychopharmacol
924:2021PLoSO..1647683J
785:Addictive Behaviors
733:10.1503/cmaj.160991
431:Culture and history
419:, rapid breathing,
362:5-hydroxytryptamine
83:Few weeks to months
1740:10.1111/acps.12042
1515:10.1007/BF02850015
1351:10.1503/jpn.170022
1122:(Suppl 1): 15–26.
508:claiming that the
247:Signs and symptoms
201:may rarely occur.
175:intrusive thoughts
21:Serotonin syndrome
2212:
2211:
2130:J Clin Psychiatry
2040:10.1159/000370338
1902:J Clin Psychiatry
1690:(Suppl 4): 8–13.
1633:(12): 1539–1549.
1562:Renoir T (2013).
1216:10.5664/jcsm.2848
1169:10.1159/000491524
1059:Renoir T (2013).
564:Psychiatry portal
528:neurotransmitters
303:Flu-like symptoms
179:depersonalization
163:flu-like symptoms
144:
143:
104:Based on symptoms
100:Diagnostic method
65:Flu-like symptoms
28:Medical condition
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470:Phoenix, Arizona
449:clinical studies
167:trouble sleeping
31:
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2235:Antidepressants
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409:miscarriage
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286:venlafaxine
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2219:Categories
1782:2010-05-24
1395:17 October
578:References
437:imipramine
393:fluoxetine
385:citalopram
381:fluoxetine
338:Paroxetine
324:duloxetine
233:fluoxetine
195:depression
129:Prevention
53:Psychiatry
2240:Syndromes
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1988:Addiction
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1647:1179-1942
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1281:0890-8567
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1177:1423-0348
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532:serotonin
506:Eli Lilly
477:addiction
377:half-life
352:Mechanism
312:Imbalance
282:psychosis
270:dysphoria
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222:half-life
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199:Psychosis
171:akathisia
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550:See also
536:dopamine
521:Research
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331:Duration
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294:mnemonic
280:, acute
229:tapering
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