rebound effect

The rebound effect, or pharmaceutical rebound phenomenon, is the emergence or re-emergence of symptoms that were either absent or controlled while taking a medication, but appear when that same medication is discontinued, or reduced in dosage. In the case of re-emergence, the severity of the symptoms is often worse than pretreatment levels.{{cn|date=August 2022}}

Rebound insomnia is insomnia that occurs following discontinuation of sedative substances taken to relieve primary insomnia. Regular use of these substances can cause a person to become dependent on its effects in order to fall asleep. Therefore, when a person has stopped taking the medication and is 'rebounding' from its effects, they may experience insomnia as a symptom of withdrawal. Occasionally, this insomnia may be worse than the insomnia the drug was intended to treat.{{cite book | last = Reber | first = Arthur S. | author2 = Reber, Emily S. | title = Dictionary of Psychology | publisher = Penguin Reference | year = 2001 | url = https://archive.org/details/penguindictionar00rebe_0 | isbn = 0-14-051451-1 | url-access = registration }} Common medicines known to cause this problem are eszopiclone, zolpidem, and anxiolytics such as benzodiazepines and which are prescribed to people having difficulties falling or staying asleep.

Rebound depression may appear to arise in patients previously free of such an illness.{{cite journal|last=Lader|first=Malcolm|title=Anxiety or depression during withdrawal of hypnotic treatments|journal=Journal of Psychosomatic Research|date=January 1994|volume=38|issue=Supplement 1|pages=113–123|doi=10.1016/0022-3999(94)90142-2|pmid=7799243}}

Daytime rebound effects of anxiety, metallic taste, perceptual disturbances which are typical benzodiazepine withdrawal symptoms can occur the next day after a short-acting benzodiazepine hypnotic wears off. Rebound phenomena do not necessarily only occur on discontinuation of a prescribed dosage. Another example is early morning rebound insomnia which may occur when a rapidly eliminated hypnotic wears off which leads to rebounding awakeness forcing the person to become wide awake before he or she has had a full night's sleep. One drug which seems to be commonly associated with these problems is triazolam, due to its high potency and ultra short half life, but these effects can occur with other short-acting hypnotic drugs.{{cite journal |vauthors=Kales A, Soldatos CR, Bixler EO, Kales JD |title=Early morning insomnia with rapidly eliminated benzodiazepines |journal=Science |volume=220 |issue=4592 |pages=95–7 |date=April 1983 |pmid=6131538 |doi= 10.1126/science.6131538|bibcode=1983Sci...220...95K }}{{cite journal |vauthors=Lee A, Lader M |title=Tolerance and rebound during and after short-term administration of quazepam, triazolam and placebo to healthy human volunteers |journal=Int Clin Psychopharmacol |volume=3 |issue=1 |pages=31–47 |date=January 1988 |pmid=2895786 |doi= 10.1097/00004850-198801000-00002}}{{cite journal |author=Kales A |title=Quazepam: hypnotic efficacy and side effects |journal=Pharmacotherapy |volume=10 |issue=1 |pages=1–10; discussion 10–2 |year=1990 |pmid=1969151 |doi= 10.1002/j.1875-9114.1990.tb02545.x|s2cid=33505418 }} Quazepam, due to its selectivity for type1 benzodiazepine receptors and long half-life, does not cause daytime anxiety rebound effects during treatment, showing that half-life is very important for determining whether a nighttime hypnotic will cause next-day rebound withdrawal effects or not.{{cite journal |vauthors=Hilbert JM, Battista D |title=Quazepam and flurazepam: differential pharmacokinetic and pharmacodynamic characteristics |journal=J Clin Psychiatry |volume=52 Suppl |pages=21–6 |date=September 1991 |pmid=1680120 }} Daytime rebound effects are not necessarily mild but can sometimes produce quite marked psychiatric and psychological disturbances.{{cite journal| journal =Pharmacopsychiatry |date=May 1989 | volume =22| issue =3| pages =115–9| title =Can a rapidly-eliminated hypnotic cause daytime anxiety? | author =Adam K |author2=Oswald I | pmid =2748714| doi =10.1055/s-2007-1014592|s2cid=32045254 }}

Rebound effects from stimulants such as methylphenidate or dextroamphetamine include stimulant psychosis, depression and a return of ADHD symptoms but in a temporarily exaggerated form.{{cite journal |author=Garland EJ |title=Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats |journal=J. Psychopharmacol. (Oxford) |volume=12 |issue=4 |pages=385–95 |year=1998 |pmid=10065914 |doi= 10.1177/026988119801200410|s2cid=38304694 }}{{cite journal |author=Rosenfeld AA |title=Depression and psychotic regression following prolonged methylphenidate use and withdrawal: case report |journal=Am J Psychiatry |volume=136 |issue=2 |pages=226–8 |date=February 1979 |pmid=760559 |doi=10.1176/ajp.136.2.226 }}{{cite journal |vauthors=Smucker WD, Hedayat M |title=Evaluation and treatment of ADHD |journal=Am Fam Physician |volume=64 |issue=5 |pages=817–29 |date=September 2001 |pmid=11563573 |url=http://www.aafp.org/afp/20010901/817.html |access-date=2009-04-27 |archive-date=2008-05-13 |archive-url=https://web.archive.org/web/20080513200522/http://www.aafp.org/afp/20010901/817.html |url-status=dead }} Up to a third of ADHD children experience a rebound effect when methylphenidate is withdrawn.{{cite journal |vauthors=Riccio CA, Waldrop JJ, Reynolds CR, Lowe P |title=Effects of stimulants on the continuous performance test (CPT): implications for CPT use and interpretation |journal=J Neuropsychiatry Clin Neurosci |volume=13 |issue=3 |pages=326–35 |year=2001 |pmid=11514638 |doi=10.1176/appi.neuropsych.13.3.326 |url=http://neuro.psychiatryonline.org/cgi/content/full/13/3/326 |archive-url=https://archive.today/20120714094514/http://neuro.psychiatryonline.org/cgi/content/full/13/3/326 |url-status=dead |archive-date=2012-07-14 }}

Many antidepressants, including SSRIs, can cause rebound depression, panic attacks, anxiety, and insomnia when discontinued.{{cite journal |vauthors=Bhanji NH, Chouinard G, Kolivakis T, Margolese HC |title=Persistent tardive rebound panic disorder, rebound anxiety and insomnia following paroxetine withdrawal: a review of rebound-withdrawal phenomena |journal=Can J Clin Pharmacol |volume=13 |issue=1 |pages=e69–74 |year=2006 |pmid=16456219 |url=http://www.cjcp.ca/pdf/CJCP_04-032_e69.pdf |archive-url=https://web.archive.org/web/20060412100436/http://www.cjcp.ca/pdf/CJCP_04-032_e69.pdf |url-status=dead |archive-date=2006-04-12 }}

Sudden and severe emergence{{cite journal|last=Fernandez|first=Hubert H.|author2=Martha E. Trieschmann |author3=Michael S. Okun |title=Rebound psychosis: Effect of discontinuation of antipsychotics in Parkinson's disease|journal=Movement Disorders|date=3 Aug 2004|doi=10.1002/mds.20260|pmid=15390047|volume=20|issue=1|pages=104–105|s2cid=11574536}} or re-emergence{{cite journal|last=Moncrieff|first=Joanna|date=23 March 2006|title=Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse|journal=Acta Psychiatrica Scandinavica|publisher=John Wiley & Sons A/S|volume=114|issue=1|pages=3–13|issn=1600-0447|url=http://www3.interscience.wiley.com/journal/118626311/abstract|archive-url=https://archive.today/20130105081330/http://www3.interscience.wiley.com/journal/118626311/abstract|url-status=dead|archive-date=5 January 2013|access-date=3 May 2009|doi=10.1111/j.1600-0447.2006.00787.x|pmid=16774655|s2cid=6267180}} of psychosis may appear when antipsychotics are switched or discontinued too rapidly.

Rebound hypertension, above pre-treatment level, was observed after clonidine,{{cite journal|last=Metz|first=Stewart|author2=Catherine Klein |author3=Nancy Morton |title=Rebound hypertension after discontinuation of transdermal clonidine therapy|journal=The American Journal of Medicine|date=January 1987|volume=82|issue=1|pages=17–19|url=http://www.amjmed.com/article/0002-9343(87)90371-8/abstract|access-date=5 December 2012|doi=10.1016/0002-9343(87)90371-8|pmid=3026180}} and guanfacine{{cite journal |author=Vitiello B |title=Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function |journal=Child Adolesc Psychiatr Clin N Am |volume=17 |issue=2 |pages=459–74, xi |date=April 2008 |pmid=18295156 |pmc=2408826 |doi=10.1016/j.chc.2007.11.010 }} discontinuation.

Continuous usage of topical decongestants (nasal sprays) can lead to constant nasal congestion, known as rhinitis medicamentosa.

Denosumab inhibits osteoclast recycling, which results in the accumulation of pre-osteoclasts and osteomorphs. When denosumab therapy is discontinued, the induced cells quite quickly and abundantly differentiate into osteoclasts causing bone resorption (rebound effect) and increasing the risk of fractures. For improving mineral bone density and preventing fractures after denosumab discontinuation, bisphosphonate administration is recommended. [https://www.risksafety.ru/jour/article/view/435/1157] {{cite journal|vauthors=Velts NY, Velts OV, Alyautdin RN|title=Denosumab and the Rebound Effect: Current Aspects of Osteoporosis Therapy (Review).|journal=Safety and Risk of Pharmacotherapy|volume=12|issue=2|pages=190-200|doi=10.30895/2312-7821-2024-12-2-190-200|doi-access=free}}

Another example of pharmaceutical rebound is a rebound headache from painkillers when the dose is lowered, the medication wears off, or the drug is abruptly discontinued.{{cite journal |author=Maizels M |title=The patient with daily headaches |journal=Am Fam Physician |volume=70 |issue=12 |pages=2299–306 |date=December 2004 |pmid=15617293 }}

In 2022, reports of viral RNA and symptom rebound in people with COVID-19 treated with Paxlovid were published. In May, CDC even issued a health alert informing physicians about "Paxlovid rebounds", which received attention when US president Joe Biden experienced a rebound. The cause of the rebound is unclear however, since around a third of people with COVID-19 experience a symptom rebound regardless of treatment.{{Cite news |last=Reynolds Lewis |date=2022-08-02 |title=Covid rebound can happen even in people who haven't taken Paxlovid |language=en |url=https://www.nbcnews.com/health/health-news/covid-can-rebound-even-people-havent-taken-paxlovid-study-finds-rcna41218 |access-date=2022-08-04}}

Abrupt withdrawal of highly potent corticosteroids, such as clobetasol for psoriasis can cause a much more severe case of the psoriasis to develop. Therefore, withdrawal should be gradual, until very little actual medication is being applied.{{cn|date=August 2022}}

• Disuse supersensitivity
• Supersensitivity psychosis
• Physical dependence
• Rebound headache
• Drug withdrawal
• Unintended consequences

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{{Psychoactive substance use}}

Category:Clinical pharmacology

Category:Psychiatric diagnosis