Drug withdrawal

Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome,[1] 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 withdrawal to occur, one must have first developed a form of drug dependence. This may occur as physical dependence, psychological dependence or both. Drug dependence develops from consuming one or more substances over a period of time.

Dependence arises in a dose-dependent manner and produces withdrawal symptoms that vary with the type of drug that is consumed. For example, prolonged use of an antidepressant medication is likely to cause a rather different reaction when discontinued compared to discontinuation of an opioid, such as heroin. Withdrawal symptoms from opiates include anxiety, sweating, vomiting, and diarrhea. Alcohol withdrawal symptoms include irritability, fatigue, shaking, sweating, and nausea. Withdrawal from nicotine can cause irritability, fatigue, insomnia, headache, and difficulty concentrating. Many prescription and legal nonprescription substances can also cause withdrawal symptoms when individuals stop consuming them, even if they were taken as directed by a physician.

The route of administration, whether intravenous, intramuscular, oral or otherwise, can also play a role in determining the severity of withdrawal symptoms.[citation needed] There are different stages of withdrawal as well; generally, a person will start to feel bad (crash or come down), progress to feeling worse, hit a plateau, and then the symptoms begin to dissipate. However, withdrawal from certain drugs (barbiturates, benzodiazepines, alcohol, glucocorticoids) can be fatal.[citation needed] While it is seldom fatal to the user, withdrawal from opiates (and some other drugs) can cause miscarriage, due to fetal withdrawal. The term "cold turkey" is used to describe the sudden cessation of use of a substance and the ensuing physiologic manifestations.

The symptoms from withdrawal may be even more dramatic when the drug has masked prolonged malnutrition, disease, chronic pain, infections (common in intravenous drug use), or sleep deprivation, conditions that drug abusers often develop as a secondary consequence of the drug. When the drug is removed, these conditions may resurface and be confused with withdrawal symptoms. Genes that encode for the alpha5 nicotinic acetylcholine receptor affect nicotine and alcohol withdrawal symptoms.

Effect on homeostasis

Homeostasis is the body's ability to maintain a certain chemical equilibrium in the brain and throughout the body. For example, the function of shivering in response to cold is to produce heat maintaining internal temperature at around 37 °C (98.6 °F). Homeostasis is impacted in many ways by drug usage and withdrawal. The internal systems perpetuate homeostasis by using different counter-regulatory methods in order to create a new state of balance based on the presence of the drug in the system.[2] These methods include adapting the body's levels of neurotransmitters, hormones, and other substances present to adjust for the addition of the drug to the body.[3]


Addiction and dependence glossary[4][5][6]
  • addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
  • addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
  • dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal – symptoms that occur upon cessation of repeated drug use
  • physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
  • psychological dependence – dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome)
  • reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
  • rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization – an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose

Examples (and ICD-10 code) of withdrawal syndrome include:

Prescription medicine

As noted above, many drugs should not be stopped abruptly[8] without the advice and supervision of a physician, especially if the medication induces dependence or if the condition they are being used to treat is potentially dangerous and likely to return once medication is stopped, such as diabetes, asthma, heart conditions and many psychological or neurological conditions, like epilepsy, depression, hypertension, schizophrenia and psychosis. The stopping of antipsychotics in schizophrenia and psychoses needs monitoring.[9] The stopping of antidepressants for example, can lead to antidepressant discontinuation syndrome. With careful physician attention, however, medication prioritization and discontinuation can decrease costs, simplify prescription regimens, decrease risks of adverse drug events and poly-pharmacy, focus therapies where they are most effective, and prevent cost-related under-use of medications.[10]

Medication Appropriateness Tool for Comorbid Health Conditions in Dementia[11] (MATCH-D) warns that people with dementia are more likely to experience adverse effects, and to monitor carefully for withdrawal symptoms when ceasing medications for these people as they are both more likely to experience symptoms and less likely to be able to reliably report symptoms.[12]

Anti-hypertensive drugs

The latest evidence does not have evidence of an effect due to discontinuing vs continuing medications used for treating elevated blood pressure or prevention of heart disease in older adults on all-case mortality and incidence of heart attack.[13] The findings are based on low quality evidence suggesting it may be safe to stop anti-hypertensive medications. However, older adults should not stop any of their medications without talking to a healthcare professional.[13]

See also


  1. ^ "MeSH Browser". meshb.nlm.nih.gov. Archived from the original on 30 July 2020. Retrieved 7 February 2020.
  2. ^ Koob GF (May 1996). "Drug addiction: the yin and yang of hedonic homeostasis". Neuron. 16 (5): 893–6. doi:10.1016/S0896-6273(00)80109-9. PMID 8630244. S2CID 7053540.
  3. ^ "What Causes Drug Withdrawal?". Laguna Treatment Hospital. Archived from the original on 2018-10-13. Retrieved 2018-10-12.
  4. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN 9780071481274.
  5. ^ Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
  6. ^ Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". New England Journal of Medicine. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMC 6135257. PMID 26816013. Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
    Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.
  7. ^ "Opiate and opioid withdrawal". MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. Archived from the original on 2019-12-08. Retrieved 2019-11-20.
  8. ^ Peter Lehmann, ed. (2002). Coming off Psychiatric Drugs. Germany: Peter Lehmann Publishing. ISBN 978-1-891408-98-4. Archived from the original on 2019-05-28. Retrieved 2022-05-06.
  9. ^ Joint Formulary Committee, BMJ, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 978-0-85369-845-6. Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
  10. ^ Alexander GC, Sayla MA, Holmes HM, Sachs GA (April 2006). "Prioritizing and stopping prescription medicines". CMAJ. 174 (8): 1083–4. doi:10.1503/cmaj.050837. PMC 1421477. PMID 16606954.
  11. ^ "MATCH-D Medication Appropriateness Tool for Comorbid Health conditions during Dementia". www.match-d.com.au. Archived from the original on 2019-05-18. Retrieved 2019-06-01.
  12. ^ Page AT, Potter K, Clifford R, McLachlan AJ, Etherton-Beer C (October 2016). "Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel". Internal Medicine Journal. 46 (10): 1189–1197. doi:10.1111/imj.13215. PMC 5129475. PMID 27527376.
  13. ^ a b Reeve E, Jordan V, Thompson W, Sawan M, Todd A, Gammie TM, et al. (June 2020). "Withdrawal of antihypertensive drugs in older people". The Cochrane Database of Systematic Reviews. 2020 (6): CD012572. doi:10.1002/14651858.cd012572.pub2. PMC 7387859. PMID 32519776.