Physical dependence

Physical dependence is a physical condition caused by chronic

use of a tolerance-forming drug, in which abrupt or gradual drug Addiction and dependence
withdrawal causes unpleasant physical symptoms.[5][6] Physical glossary[1][2][3][4]
dependence can develop from low-dose therapeutic use of certain
medications such as benzodiazepines, opioids, antiepileptics and addiction – a biopsychosocial
antidepressants, as well as the recreational misuse of drugs such as disorder characterized by
alcohol, opioids and benzodiazepines. The higher the dose used, persistent use of drugs (including
the greater the duration of use, and the earlier age use began are alcohol) despite substantial harm
predictive of worsened physical dependence and thus more severe and adverse consequences
withdrawal syndromes. Acute withdrawal syndromes can last
days, weeks or months. Protracted withdrawal syndrome, also addictive drug – psychoactive
known as post-acute-withdrawal syndrome or "PAWS", is a low- substances that with repeated
grade continuation of some of the symptoms of acute withdrawal, use are associated with
typically in a remitting-relapsing pattern, often resulting in relapse significantly higher rates of
and prolonged disability of a degree to preclude the possibility of substance use disorders, due in
lawful employment. Protracted withdrawal syndrome can last for large part to the drug's effect on
months, years, or depending on individual factors, indefinitely. brain reward systems
Protracted withdrawal syndrome is noted to be most often caused
dependence – an adaptive state
by benzodiazepines.[7] To dispel the popular misassociation with
addiction, physical dependence to medications is sometimes associated with a withdrawal
compared to dependence on insulin by persons with diabetes.[8] syndrome upon cessation of
repeated exposure to a stimulus
(e.g., drug intake)
drug sensitization or reverse
Contents
tolerance – the escalating effect
Symptoms of a drug resulting from repeated
Treatment administration at a given dose

Drugs that cause physical dependence drug withdrawal – symptoms

that occur upon cessation of
Rebound syndrome
repeated drug use
See also
physical dependence –
References dependence that involves
External links persistent physical–somatic
withdrawal symptoms (e.g.,
fatigue and delirium tremens)
Symptoms psychological dependence –
dependence that involves
Physical dependence can manifest itself in the appearance of both
emotional–motivational
physical and psychological symptoms which are caused by
withdrawal symptoms (e.g.,
physiological adaptions in the central nervous system and the brain
due to chronic exposure to a substance. Symptoms which may be dysphoria and anhedonia)
experienced during withdrawal or reduction in dosage include reinforcing stimuli – stimuli that
increased heart rate and/or blood pressure, sweating, and increase the probability of
tremors.[9] More serious withdrawal symptoms such as confusion,
seizures, and visual hallucinations indicate a serious emergency repeating behaviors paired with
and the need for immediate medical care. Sedative hypnotic drugs them
such as alcohol, benzodiazepines, and barbiturates are the only
rewarding stimuli – stimuli that
commonly available substances that can be fatal in withdrawal due
the brain interprets as
to their propensity to induce withdrawal convulsions. Abrupt
withdrawal from other drugs, such as opioids can cause an intrinsically positive and
extremely painful withdrawal that is very rarely fatal in patients of desirable or as something to
general good health and with medical treatment, but is more often approach
fatal in patients with weakened cardiovascular systems; toxicity is sensitization – an amplified
generally caused by the often-extreme increases in heart rate and response to a stimulus resulting
blood pressure (which can be treated with clonidine), or due to from repeated exposure to it
arrhythmia due to electrolyte imbalance caused by the inability to
eat, and constant diarrhea and vomiting (which can be treated with substance use disorder – a
loperamide and ondansetron respectively) associated with acute condition in which the use of
opioid withdrawal, especially in longer-acting substances where substances leads to clinically and
the diarrhea and emesis can continue unabated for weeks, although functionally significant
life-threatening complications are extremely rare, and nearly non- impairment or distress
existent with proper medical management.
tolerance – the diminishing
effect of a drug resulting from
Treatment repeated administration at a
given dose
Treatment for physical dependence depends upon the drug being
withdrawn and often includes administration of another drug, especially for substances that can be
dangerous when abruptly discontinued or when previous attempts have failed.[10] Physical dependence is
usually managed by a slow dose reduction over a period of weeks, months or sometimes longer depending
on the drug, dose and the individual.[7] A physical dependence on alcohol is often managed with a cross
tolerant drug, such as long acting benzodiazepines to manage the alcohol withdrawal symptoms.

Drugs that cause physical dependence

All µ-opioids with any (even slight) agonist effect, such as (partial list) morphine, heroin,
codeine, oxycodone, buprenorphine, nalbuphine, methadone, and fentanyl, but not agonists
specific to non-µ opioid receptors, such as salvinorin A (a k-opioid agonist), nor opioid
antagonists or inverse agonists, such as naltrexone (a universal opioid inverse agonist)[11]
All GABA agonists and positive allosteric modulators of both the GABA-A ionotropic
receptor and GABA-B metabotropic receptor subunits, including (partial list):
alcohol (alcoholic beverage) (cf. alcohol dependence, alcohol withdrawal, delirium
tremens)[12]
barbiturates such as phenobarbital, sodium thiopental and secobarbital
benzodiazepines such as diazepam (Valium), lorazepam (Ativan), and alprazolam
(Xanax) (see benzodiazepine dependence and benzodiazepine withdrawal syndrome)
nonbenzodiazepine hypnotics (z-drugs) such as zopiclone and zolpidem.[13]
gamma-hydroxybutyric acid (GHB) and 1,4-butanediol[14]
carisoprodol (Soma) and related carbamates (tybamate and meprobamate)
baclofen (Lioresal) and its non-chlorinated analogue phenibut
chloral hydrate
glutethimide
clomethiazole
methaqualone (Quaalude)
 nicotine (tobacco) (cf. nicotine withdrawal)[15][16]
gabapentinoids such as gabapentin (Neurontin), pregabalin (Lyrica), and phenibut (Noofen),
which are inhibitors of α2δ subunit-containing VDCCs[17][18]
antiepileptic drugs such as valproate, lamotrigine, tiagabine, vigabatrin, carbamazepine and
oxcarbazepine, and topiramate[17][19][20]
antipsychotic drugs such as clozapine, risperidone, olanzapine, haloperidol, thioridazine,
etc.[21]
commonly prescribed antidepressants such as the selective serotonin reuptake inhibitors
(SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (cf. SSRI/SNRI
withdrawal syndrome)[22][23][24]
blood pressure medications, including beta blockers such as propanolol and alpha-
adrenergic agonists such as clonidine[25][26]
androgenic-anabolic steroids[27][28]
glucocorticoids[29]

Rebound syndrome
A wide range of drugs whilst not causing a true physical dependence can still cause withdrawal symptoms
or rebound effects during dosage reduction or especially abrupt or rapid withdrawal.[30][31] These can
include caffeine,[32] stimulants,[33][34][35][36] steroidal drugs and antiparkinsonian drugs.[37] It is debated
whether the entire antipsychotic drug class causes true physical dependency, a subset, or if none do.[38]
But, if discontinued too rapidly, it could cause an acute withdrawal syndrome.[39] When talking about illicit
drugs rebound withdrawal, especially with stimulants, it is sometimes referred to as "coming down" or
"crashing".

Some drugs, like anticonvulsants and antidepressants, describe the drug category and not the mechanism.
The individual agents and drug classes in the anticonvulsant drug category act at many different receptors
and it is not possible to generalize their potential for physical dependence or incidence or severity of
rebound syndrome as a group so they must be looked at individually. Anticonvulsants as a group however
are known to cause tolerance to the anti-seizure effect.[40] SSRI drugs, which have an important use as
antidepressants, engender a discontinuation syndrome that manifests with physical side effects; e.g., there
have been case reports of a discontinuation syndrome with venlafaxine (Effexor).[24]

See also
Drug tolerance
Psychological dependence
Rebound insomnia
Substance dependence

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External links
National Institutes of Health MedlinePlus Encyclopedia (https://www.nlm.nih.gov/medlineplu
s/ency/article/001522.htm#Definition)

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