Rebound effect

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The rebound effect, or 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.

Contents

Definition

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.[ citation needed ]

Examples

Sedative hypnotics

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. [1] 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. [2]

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. [3] [4] [5] 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. [6] Daytime rebound effects are not necessarily mild but can sometimes produce quite marked psychiatric and psychological disturbances. [7]

Stimulants

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. [8] [9] [10] Up to a third of ADHD children experience a rebound effect when methylphenidate is withdrawn. [11]

Antidepressants

Many antidepressants, including SSRIs, can cause rebound depression, panic attacks, anxiety, and insomnia when discontinued. [12]

Antipsychotics

Sudden and severe emergence [13] or re-emergence [14] of psychosis may appear when antipsychotics are switched or discontinued too rapidly.

Alpha-2 adrenergic agents

Rebound hypertension, above pre-treatment level, was observed after clonidine, [15] and guanfacine [16] discontinuation.

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

Humanized antibodies

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. [17]

Other medications

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. [18]

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. [19]

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.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially known as "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and was made available in 1960 by Hoffmann–La Roche, which followed with the development of diazepam (Valium) three years later, in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Hypnotic</span> Drug whose use induces sleep

Hypnotic, or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness).

<span class="mw-page-title-main">Insomnia</span> Disorder causing trouble with sleeping

Insomnia, also known as sleeplessness, is a sleep disorder where people have trouble sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, irritability, and a depressed mood. It may result in an increased risk of accidents of all kinds as well as problems focusing and learning. Insomnia can be short term, lasting for days or weeks, or long term, lasting more than a month. The concept of the word insomnia has two possibilities: insomnia disorder (ID) and insomnia symptoms, and many abstracts of randomized controlled trials and systematic reviews often underreport on which of these two possibilities the word insomnia refers to.

A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.

<span class="mw-page-title-main">Lorazepam</span> Benzodiazepine medication

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. It is also used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated. It is also used, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given orally, transdermally, intravenously (IV), or intramuscularly When given by injection, onset of effects is between one and thirty minutes and effects last for up to a day.

<span class="mw-page-title-main">Sedative</span> Drug that reduces excitement without inducing sleep

A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Flurazepam</span> Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals, was one of the first benzodiazepine hypnotic medications to be marketed.

<span class="mw-page-title-main">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, stimulants, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.

<span class="mw-page-title-main">Nonbenzodiazepine</span> Class of psychoactive drugs

Nonbenzodiazepines, sometimes referred to colloquially as Z-drugs, are a class of psychoactive, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as for treating insomnia and anxiety.

<span class="mw-page-title-main">Quazepam</span> Benzodiazipine

Quazepam, sold under the brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia, including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.

<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.

<span class="mw-page-title-main">Loprazolam</span> Benzodiazepine

Loprazolam (triazulenone) marketed under many brand names is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It is licensed and marketed for the short-term treatment of moderately-severe insomnia.

<span class="mw-page-title-main">Benzodiazepine withdrawal syndrome</span> Signs and symptoms due to benzodiazepine discontinuation in physically dependent persons

Benzodiazepine withdrawal syndrome is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.

Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after withdrawal from alcohol, opiates, benzodiazepines, antidepressants, and other substances. Infants born to mothers who used substances of dependence during pregnancy may also experience a PAWS. While PAWS has been frequently reported by those withdrawing from opiate and alcohol dependence, the research has limitations. Protracted benzodiazepine withdrawal has been observed to occur in some individuals prescribed benzodiazepines.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

<span class="mw-page-title-main">Effects of long-term benzodiazepine use</span>

The effects of long-term benzodiazepine use include drug dependence as well as the possibility of adverse effects on cognitive function, physical health, and mental health. Long-term use is sometimes described as use not shorter than three months. Benzodiazepines are generally effective when used therapeutically in the short term, but even then the risk of dependency can be significantly high. There are significant physical, mental and social risks associated with the long-term use of benzodiazepines. Although anxiety can temporarily increase as a withdrawal symptom, there is evidence that a reduction or withdrawal from benzodiazepines can lead in the long run to a reduction of anxiety symptoms. Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slow withdrawal is recommended for long-term users. Not everyone, however, experiences problems with long-term use.

<span class="mw-page-title-main">Antipsychotic switching</span> Process of transferring between antipsychotics

Antipsychotic switching refers to the process of switching out one antipsychotic for another antipsychotic. There are multiple indications for switching antipsychotics, including inadequate efficacy and drug intolerance. There are several strategies that have been theorized for antipsychotic switching, based upon the timing of discontinuation and tapering of the original antipsychotic and the timing of initiation and titration of the new antipsychotic. Major adverse effects from antipsychotic switching may include supersensitivity syndromes, withdrawal, and rebound syndromes.

References

  1. ↑ Reber, Arthur S.; Reber, Emily S. (2001). Dictionary of Psychology . Penguin Reference. ISBN   0-14-051451-1.
  2. ↑ Lader, Malcolm (January 1994). "Anxiety or depression during withdrawal of hypnotic treatments". Journal of Psychosomatic Research. 38 (Supplement 1): 113–123. doi:10.1016/0022-3999(94)90142-2. PMID   7799243.
  3. ↑ Kales A, Soldatos CR, Bixler EO, Kales JD (April 1983). "Early morning insomnia with rapidly eliminated benzodiazepines". Science. 220 (4592): 95–7. Bibcode:1983Sci...220...95K. doi:10.1126/science.6131538. PMID   6131538.
  4. ↑ Lee A, Lader M (January 1988). "Tolerance and rebound during and after short-term administration of quazepam, triazolam and placebo to healthy human volunteers". Int Clin Psychopharmacol. 3 (1): 31–47. doi:10.1097/00004850-198801000-00002. PMID   2895786.
  5. ↑ Kales A (1990). "Quazepam: hypnotic efficacy and side effects". Pharmacotherapy. 10 (1): 1–10, discussion 10–2. doi:10.1002/j.1875-9114.1990.tb02545.x. PMID   1969151. S2CID   33505418.
  6. ↑ Hilbert JM, Battista D (September 1991). "Quazepam and flurazepam: differential pharmacokinetic and pharmacodynamic characteristics". J Clin Psychiatry. 52 Suppl: 21–6. PMID   1680120.
  7. ↑ Adam K; Oswald I (May 1989). "Can a rapidly-eliminated hypnotic cause daytime anxiety?". Pharmacopsychiatry. 22 (3): 115–9. doi:10.1055/s-2007-1014592. PMID   2748714. S2CID   32045254.
  8. ↑ Garland EJ (1998). "Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats". J. Psychopharmacol. (Oxford). 12 (4): 385–95. doi:10.1177/026988119801200410. PMID   10065914. S2CID   38304694.
  9. ↑ Rosenfeld AA (February 1979). "Depression and psychotic regression following prolonged methylphenidate use and withdrawal: case report". Am J Psychiatry. 136 (2): 226–8. doi:10.1176/ajp.136.2.226. PMID   760559.
  10. ↑ Smucker WD, Hedayat M (September 2001). "Evaluation and treatment of ADHD". Am Fam Physician. 64 (5): 817–29. PMID   11563573. Archived from the original on 2008-05-13. Retrieved 2009-04-27.
  11. ↑ Riccio CA, Waldrop JJ, Reynolds CR, Lowe P (2001). "Effects of stimulants on the continuous performance test (CPT): implications for CPT use and interpretation". J Neuropsychiatry Clin Neurosci. 13 (3): 326–35. doi:10.1176/appi.neuropsych.13.3.326. PMID   11514638. Archived from the original on 2012-07-14.
  12. ↑ Bhanji NH, Chouinard G, Kolivakis T, Margolese HC (2006). "Persistent tardive rebound panic disorder, rebound anxiety and insomnia following paroxetine withdrawal: a review of rebound-withdrawal phenomena" (PDF). Can J Clin Pharmacol. 13 (1): e69–74. PMID   16456219. Archived from the original (PDF) on 2006-04-12.
  13. ↑ Fernandez, Hubert H.; Martha E. Trieschmann; Michael S. Okun (3 Aug 2004). "Rebound psychosis: Effect of discontinuation of antipsychotics in Parkinson's disease". Movement Disorders. 20 (1): 104–105. doi:10.1002/mds.20260. PMID   15390047. S2CID   11574536.
  14. ↑ Moncrieff, Joanna (23 March 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica. 114 (1). John Wiley & Sons A/S: 3–13. doi:10.1111/j.1600-0447.2006.00787.x. ISSN   1600-0447. PMID   16774655. S2CID   6267180. Archived from the original on 5 January 2013. Retrieved 3 May 2009.
  15. ↑ Metz, Stewart; Catherine Klein; Nancy Morton (January 1987). "Rebound hypertension after discontinuation of transdermal clonidine therapy". The American Journal of Medicine. 82 (1): 17–19. doi:10.1016/0002-9343(87)90371-8. PMID   3026180 . Retrieved 5 December 2012.
  16. ↑ Vitiello B (April 2008). "Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function". Child Adolesc Psychiatr Clin N Am. 17 (2): 459–74, xi. doi:10.1016/j.chc.2007.11.010. PMC   2408826 . PMID   18295156.
  17. ↑ Velts NY, Velts OV, Alyautdin RN. "Denosumab and the Rebound Effect: Current Aspects of Osteoporosis Therapy (Review)". Safety and Risk of Pharmacotherapy. 12 (2): 190–200. doi:10.30895/2312-7821-2024-12-2-190-200.
  18. ↑ Maizels M (December 2004). "The patient with daily headaches". Am Fam Physician. 70 (12): 2299–306. PMID   15617293.
  19. ↑ Reynolds Lewis (2022-08-02). "Covid rebound can happen even in people who haven't taken Paxlovid" . Retrieved 2022-08-04.
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