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The rebound effect, or rebound phenomenon, is the emergence or re-emergence of
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...
s 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.


Definition

The rebound effect, or
pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
rebound phenomenon, is the emergence or re-emergence of
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...
s 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.


Examples


Sedative hypnotics

Rebound insomnia is
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy ...
that occurs following discontinuation of
sedative 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 ...
substances taken to relieve primary insomnia. Regular use of these substances can cause a person to become
dependent A dependant is a person who relies on another as a primary source of income. A common-law spouse who is financially supported by their partner may also be included in this definition. In some jurisdictions, supporting a dependant may enab ...
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 Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * '' Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from ...
. Occasionally, this insomnia may be worse than the insomnia the drug was intended to treat. Common medicines known to cause this problem are eszopiclone, zolpidem, and
anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...
s such as
benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "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, ...
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. 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 Benzodiazepines (BZD, BDZ, BZs), sometimes called "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, ...
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 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 ...
, due to its high potency and ultra short half life, but these effects can occur with other short-acting
hypnotic drugs Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
. 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 Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
will cause next-day rebound withdrawal effects or not. Daytime rebound effects are not necessarily mild but can sometimes produce quite marked psychiatric and psychological disturbances.


Stimulants

Rebound effects from
stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
such as
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
or
dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and ...
include stimulant psychosis, depression and a return of ADHD symptoms but in a temporarily exaggerated form. Up to a third of ADHD children experience a rebound effect when methylphenidate is withdrawn.


Antidepressants

Many
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness ...
s, including
SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extrace ...
s, can cause rebound depression,
panic attacks Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...
,
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil Turmoil may refer to: * ''Turmoil'' (1984 video game), a 1984 video game released by Bug-Byte * ''Turmoil'' (2016 video game), a 2016 indie oil tycoon video ...
, and
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy ...
when discontinued.


Antipsychotics

Sudden and severe emergence or re-emergence of psychosis may appear when
antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range o ...
s are
switched Switched may refer to: * Switched (band), an American music group * ''Switched'' (novel), first book in the young adult Trylle series by Amanda Hocking * ''Switched!'' (American TV series) * ''Switched!'' (Singaporean TV series) * "Switched" (' ...
or discontinued too rapidly.


Alpha-2 adrenergic agents

Rebound hypertension, above pre-treatment level, was observed after
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, an ...
, and
guanfacine Guanfacine, sold under the brand name Tenex among others, is an oral medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD as well as being ...
discontinuation. Continuous usage of topical decongestants (''
nasal spray Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for s ...
s'') can lead to constant
nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathing. ...
, known as rhinitis medicamentosa.


Other medications

Another example of
pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
rebound is a rebound headache from painkillers when the dose is lowered, the medication wears off, or the drug is abruptly discontinued. In 2022, reports of viral RNA and symptom rebound in people with
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickl ...
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. Abrupt withdrawal of highly potent
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are in ...
s, such as
clobetasol Clobetasol is a synthetic glucocorticoid corticosteroid. A propionate ester of clobetasol, clobetasol propionate Clobetasol propionate is a corticosteroid used to treat skin conditions such as eczema, contact dermatitis, seborrheic dermatit ...
for
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complet ...
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.


See also

*
Disuse supersensitivity Disuse supersensitivity, also pharmacological disuse supersensitivity or pharmacological denervation supersensitivity, is the increased sensitivity by a postsynaptic cell because of decreased input by incoming axons, e.g., due to the exposure to a ...
*
Supersensitivity psychosis Dopamine supersensitivity psychosis is a hypothesis that attempts to explain the phenomenon in which psychosis (e.g. having hallucinations, which can mean hearing or seeing things that other people do not see or hear) occurs despite treatment with ...
*
Physical dependence 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 ...
* Rebound headache *
Drug withdrawal Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of wit ...
*
Unintended consequences In the social sciences, unintended consequences (sometimes unanticipated consequences or unforeseen consequences) are outcomes of a purposeful action that are not intended or foreseen. The term was popularised in the twentieth century by Ameri ...


References

{{Psychoactive substance use Clinical pharmacology Psychiatric diagnosis