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 showin ...
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 re ...
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 showin ...
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 t ...
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 enabl ...
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 a ban ...
. Occasionally, this insomnia may be worse than the insomnia the drug was intended to treat. Common medicines known to cause this problem are
eszopiclone
Eszopiclone, sold under the brand-name Lunesta among others such as Night Calm in Egypt, is a medication used in the treatment of insomnia. Evidence supports slight to moderate benefit up to six months. It is taken orally.
Common side effects i ...
,
zolpidem
Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behaviora ...
, 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 anxi ...
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, i ...
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
Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a p ...
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.
Quazepam
Quazepam, sold under 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 ...
, 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
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or ...
,
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, hea ...
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 extracellul ...
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 and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, 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 Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
s are
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, and c ...
, 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 decongestant Topical decongestants are decongestants applied directly to the nasal cavity. Their effectiveness by themselves in the common cold appears to have a small benefit in adults.
Topical decongestants should only be used by patients for a maximum of 5†...
s (''
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 syste ...
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
Rhinitis medicamentosa (or RM) is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) and certain oral medic ...
.
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 re ...
rebound is a
rebound headache
A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, c ...
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 COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
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 involv ...
s, such as
clobetasol
Clobetasol is a synthetic glucocorticoid corticosteroid. A propionate ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), a ...
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 complete ...
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
*
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 certai ...
*
Rebound headache
A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, c ...
*
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 with ...
*
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