Physical dependence

Last updated
Addiction and dependence glossary [1] [2] [3]
  • 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

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. [4] [5] 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. [6] To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes. [7]

Contents

Symptoms

Physical dependence can manifest itself in the appearance of both physical and psychological symptoms which are caused by physiological adaptions in the central nervous system and the brain due to chronic exposure to a substance. Symptoms which may be experienced during withdrawal or reduction in dosage include increased heart rate and/or blood pressure, sweating, and tremors. [8] More serious withdrawal symptoms such as confusion, seizures, and visual hallucinations indicate a serious emergency and the need for immediate medical care. Sedative hypnotic drugs such as alcohol, benzodiazepines, and barbiturates are the only commonly available substances that can be fatal in withdrawal due to their propensity to induce withdrawal convulsions. Abrupt withdrawal from other drugs, such as opioids can cause an extremely painful withdrawal that is very rarely fatal in patients of general good health and with medical treatment, but is more often fatal in patients with weakened cardiovascular systems; toxicity is generally caused by the often-extreme increases in heart rate and blood pressure (which can be treated with clonidine), or due to arrhythmia due to electrolyte imbalance caused by the inability to eat, and constant diarrhea and vomiting (which can be treated with loperamide and ondansetron respectively) associated with acute opioid withdrawal, especially in longer-acting substances where the diarrhea and emesis can continue unabated for weeks, although life-threatening complications are extremely rare, and nearly non-existent with proper medical management.

Treatment

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. [9] 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. [6] 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

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

Related Research Articles

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

Benzodiazepines, colloquially 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, 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, who soon followed with diazepam (Valium) 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">Diazepam</span> Benzodiazepine sedative

Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. Orally, effects begin after 15 to 60 minutes.

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.

Colloquially known as "downers", depressants or central depressants are drugs that lower neurotransmission levels, or depress or reduce arousal or stimulation in various areas of the brain. Depressants do not change the mood or mental state of others. Stimulants, or "uppers", increase mental or physical function, hence the opposite drug class from depressants are stimulants, not antidepressants.

Self-medication, sometime called do-it-yourself (DIY) medicine, is a human behavior in which an individual uses a substance or any exogenous influence to self-administer treatment for physical or psychological conditions, for example headaches or fatigue.

<span class="mw-page-title-main">Opioid use disorder</span> Medical condition

Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Opioid withdrawal symptoms include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood. Addiction and dependence are important components of opioid use disorder.

Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal and that necessitates the re-consumption of the drug. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. ΔFosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence.

<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">Benzodiazepine withdrawal syndrome</span> Signs and symptoms due to benzodiazepines 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.

<span class="mw-page-title-main">Alcohol detoxification</span> Abrupt cessation of alcohol intake

Alcohol detoxification is the abrupt cessation of alcohol intake in individuals that have alcohol use disorder. This process is often coupled with substitution of drugs that have effects similar to the effects of alcohol in order to lessen the symptoms of alcohol withdrawal. When withdrawal does occur, it results in symptoms of varying severity.

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.

Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms - such as anxiety or anhedonia - upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exposure to certain psychoactive substances or behaviors, which leads to an individual requiring further exposure to avoid withdrawal symptoms, as a result of negative reinforcement. Neuronal counter-adaptation is believed to play a role in generating withdrawal symptoms, which could be mediated through changes in neurotransmitter activity or altered receptor expression. Environmental enrichment and physical activity can attenuate withdrawal symptoms.

<span class="mw-page-title-main">Alcohol withdrawal syndrome</span> Medical condition

Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. More severe symptoms may include seizures, and delirium tremens (DTs); which can be fatal in untreated patients. Symptoms start at around 6 hours after last drink. Peak incidence of seizures occurs at 24-36 hours and peak incidence of delirium tremens is at 48-72 hours.

<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">Substance use disorder</span> Continual use of drugs (including alcohol) despite detrimental consequences

Substance use disorder (SUD) is the persistent use of drugs despite the substantial harm and adverse consequences to one's own self and others, as a result of their use. In perspective, the effects of the wrong use of substances that are capable of causing harm to the user or others, have been extensively described in different studies using a variety of terms such as substance use problems, problematic drugs or alcohol use, and substance use disorder. The National Institute of Mental Health (NIMH) states that "Substance use disorder (SUD) is a treatable mental disorder that affects a person's brain and behavior, leading to their inability to control their use of substances like legal or illegal drugs, alcohol, or medications. Symptoms can be moderate to severe, with addiction being the most severe form of SUD". Substance use disorders (SUD) are considered to be a serious mental illness that fluctuates with the age that symptoms first start appearing in an individual, the time during which it exists and the type of substance that is used. It is not uncommon for those who have SUD to also have other mental health disorders. Substance use disorders are characterized by an array of mental/emotional, physical, and behavioral problems such as chronic guilt; an inability to reduce or stop consuming the substance(s) despite repeated attempts; operating vehicles while intoxicated; and physiological withdrawal symptoms. Drug classes that are commonly involved in SUD include: alcohol (alcoholism); cannabis; opioids; stimulants such as nicotine, cocaine and amphetamines; benzodiazepines; barbiturates; and other or unknown substances.

<span class="mw-page-title-main">Addiction</span> Disorder resulting in compulsive behaviours

Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behaviour that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use often alters brain function in ways that perpetuate craving, and weakens self-control. This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological factors that are implicated in addiction's development. Classic signs of addiction include compulsive engagement in rewarding stimuli, preoccupation with substances or behavior, and continued use despite negative consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification, coupled with delayed deleterious effects.

<span class="mw-page-title-main">Psychoactive drug</span> Chemical substance that alters nervous system function

A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug is a chemical substance that changes the function of the nervous system and results in alterations of perception, mood, cognition, and behavior. These substances may be used medically, recreationally, for spiritual reasons, or for research. Some categories of psychoactive drugs may be prescribed by physicians and other healthcare practitioners because of their therapeutic value.

<span class="mw-page-title-main">Opioid withdrawal</span> Withdrawal symptoms of opiates

Opioid withdrawal is a set of symptoms arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, nausea, vomiting, diarrhea, sweating, and an increased heart rate. Opioid use triggers a rapid adaptation in cellular signalling pathways that means, when rapidly withdrawn, there can be adverse physiological effects. All opioids, both recreational drugs and medications, when reduced or stopped, can lead to opioid withdrawal symptoms. When withdrawal symptoms are due to recreational opioid use, the term opioid use disorder is used, whereas when due to prescribed medications, the term prescription opioid use disorder is used. Opioid withdrawal can be helped by the use of opioid replacement therapy, and symptoms may be relieved by the use of medications including lofexidine and clonidine.

<span class="mw-page-title-main">Prescription drug addiction</span> Medical condition

Prescription drug addiction is the chronic, repeated use of a prescription drug in ways other than prescribed for, including using someone else’s prescription. A prescription drug is a pharmaceutical drug that may not be dispensed without a legal medical prescription. Drugs in this category are supervised due to their potential for misuse and substance use disorder. The classes of medications most commonly abused are opioids, central nervous system (CNS) depressants and central nervous stimulants. In particular, prescription opioid is most commonly abused in the form of prescription analgesics.

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ "Definition of physical dependence - NCI Dictionary of Cancer Terms". 2011-02-02. Retrieved 2015-02-18.
  5. ↑ "All about Addiction". Medical News Today. Retrieved 2015-02-18.
  6. 1 2 Landry MJ, Smith DE, McDuff DR, Baughman OL (1992). "Benzodiazepine dependence and withdrawal: identification and medical management". J Am Board Fam Pract. 5 (2): 167–75. PMID   1575069.
  7. ↑ "Withdrawal From Antidepressants: Symptoms, Causes, Treatments". WebMD. Retrieved 2016-02-20. These symptoms are not technically the same thing as physical "withdrawal" from a drug.... Unlike drug withdrawal, antidepressant discontinuation effects are not related to addiction but can reflect physiological consequences of stopping a drug, just as when someone with diabetes stops insulin.
  8. ↑ "Drug addiction (substance use disorder)". Mayo Clinic. Retrieved 4 October 2020.
  9. ↑ Jain, Raka; Majumder, Pradipta; Gupta, Tina (January 2013). "Pharmacological Intervention of Nicotine Dependence". BioMed Research International. 2013: 278392. doi: 10.1155/2013/278392 . ISSN   2314-6133. PMC   3891736 . PMID   24490153.
  10. ↑ Trang T, Sutak M, Quirion R, Jhamandas K (May 2002). "The role of spinal neuropeptides and prostaglandins in opioid physical dependence". Br. J. Pharmacol. 136 (1): 37–48. doi:10.1038/sj.bjp.0704681. PMC   1762111 . PMID   11976266.
  11. ↑ Kozell L, Belknap JK, Hofstetter JR, Mayeda A, Buck KJ (July 2008). "Mapping a locus for alcohol physical dependence and associated withdrawal to a 1.1 Mb interval of mouse chromosome 1 syntenic with human chromosome 1q23.2-23.3". Genes, Brain and Behavior . 7 (5): 560–7. doi: 10.1111/j.1601-183X.2008.00391.x . PMID   18363856.
  12. ↑ Sikdar S; Ayonrinde, O.; Sampson, E. (July 1998). "Physical dependence on zopiclone. Prescribing this drug to addicts may give rise to iatrogenic drug misuse". BMJ. 317 (7151): 146. doi:10.1136/bmj.317.7151.146. PMC   1113504 . PMID   9657802.
  13. ↑ Galloway GP, Frederick SL, Staggers FE, Gonzales M, Stalcup SA, Smith DE (January 1997). "Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence". Addiction. 92 (1): 89–96. doi:10.1111/j.1360-0443.1997.tb03640.x. PMID   9060200.
  14. ↑ Alvis, Bret D.; Sobey, Christopher M. (January 2017). "Oral Baclofen Withdrawal Resulting in Progressive Weakness and Sedation Requiring Intensive Care Admission". The Neurohospitalist. 7 (1): 39–40. doi:10.1177/1941874416637404. ISSN   1941-8744. PMC   5167087 . PMID   28042369.
  15. ↑ Kawazoe, Shingo; Shinkai, Takahiro (September 2015). "[Nicotine dependence]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 73 (9): 1516–1521. ISSN   0047-1852. PMID   26394514.
  16. ↑ Baker, Timothy B.; Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Smith, Stevens S.; Loh, Wei-Yin; Bolt, Daniel (November 2012). "Are Tobacco Dependence and Withdrawal Related Amongst Heavy Smokers? Relevance to Conceptualizations of Dependence". Journal of Abnormal Psychology. 121 (4): 909–921. doi:10.1037/a0027889. ISSN   0021-843X. PMC   3560396 . PMID   22642839.
  17. 1 2 Tran KT; Hranicky D; Lark T; Jacob Nj (June 2005). "Gabapentin withdrawal syndrome in the presence of a taper". Bipolar Disord. 7 (3): 302–4. doi:10.1111/j.1399-5618.2005.00200.x. PMID   15898970.
  18. ↑ Weingarten (2019). "Acute phenibut withdrawal: A comprehensive literature review and illustrative case report". Bosnian Journal of Basic Medical Sciences. Department of Anesthesiology and Perioperative Medicine, Mayo Clinic. 19 (2): 125–129. PMC   6535394 . PMID   30501608.
  19. ↑ Hennessy MJ, Tighe MG, Binnie CD, Nashef L (November 2001). "Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep". Neurology. 57 (9): 1650–4. doi:10.1212/WNL.57.9.1650. PMID   11706106. S2CID   22885837.
  20. ↑ Lazarova M, Petkova B, Staneva-Stoycheva D (December 1999). "Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal". Methods Find Exp Clin Pharmacol. 21 (10): 669–71. doi:10.1358/mf.1999.21.10.795757. PMID   10702963.
  21. ↑ Meyer, Jonathan M. (January 2011). "Pharmacotherapy of Psychosis and Mania". Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition (12 ed.). McGraw-Hill Education / Medical. p. 435. ISBN   9780071624428.
  22. ↑ Kora K, Kaplan P (2008). "[Hypomania/mania induced by cessation of antidepressant drugs]". Turk Psikiyatri Derg (in Turkish). 19 (3): 329–33. PMID   18791886.
  23. ↑ Tint A, Haddad PM, Anderson IM (May 2008). "The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study". J. Psychopharmacol. (Oxford). 22 (3): 330–2. doi:10.1177/0269881107087488. PMID   18515448.
  24. 1 2 Quaglio G, Schifano F, Lugoboni F (September 2008). "Venlafaxine dependence in a patient with a history of alcohol and amineptine misuse". Addiction. 103 (9): 1572–4. doi:10.1111/j.1360-0443.2008.02266.x. PMID   18636997.
  25. ↑ "MedlinePlus Medical Encyclopedia: Drug abuse and dependence" . Retrieved 2008-12-21.
  26. ↑ Karachalios GN, Charalabopoulos A, Papalimneou V, et al. (May 2005). "Withdrawal syndrome following cessation of antihypertensive drug therapy". Int. J. Clin. Pract. 59 (5): 562–70. doi: 10.1111/j.1368-5031.2005.00520.x . PMID   15857353. S2CID   31449302.
  27. ↑ Trenton AJ, Currier GW (2005). "Behavioural manifestations of anabolic steroid use". CNS Drugs. 19 (7): 571–95. doi:10.2165/00023210-200519070-00002. PMID   15984895. S2CID   32243658.
  28. ↑ Hartgens F, Kuipers H (2004). "Effects of androgenic-anabolic steroids in athletes". Sports Med. 34 (8): 513–54. doi:10.2165/00007256-200434080-00003. PMID   15248788. S2CID   15234016.
  29. ↑ Archived May 19, 2013, at the Wayback Machine
  30. ↑ Heh CW, Sramek J, Herrera J, Costa J (July 1988). "Exacerbation of psychosis after discontinuation of carbamazepine treatment". Am J Psychiatry. 145 (7): 878–9. doi:10.1176/ajp.145.7.878. PMID   2898213.
  31. ↑ Henssler J, Heinz A, Brandt L, Bschor T (May 2019). "Antidepressant Withdrawal and Rebound Phenomena". Deutsches Ärzteblatt Online. 116 (20): 355–361. doi:10.3238/arztebl.2019.0355. PMC   6637660 . PMID   31288917.
  32. ↑ Griffiths RR, Evans SM, Heishman SJ, et al. (December 1990). "Low-dose caffeine physical dependence in humans". J. Pharmacol. Exp. Ther. 255 (3): 1123–32. PMID   2262896.
  33. ↑ Lake CR, Quirk RS (December 1984). "CNS stimulants and the look-alike drugs". Psychiatr. Clin. North Am. 7 (4): 689–701. doi:10.1016/S0193-953X(18)30723-8. PMID   6151645.
  34. ↑ Sarampote CS, Efron LA, Robb AS, Pearl PL, Stein MA (2002). "Can stimulant rebound mimic pediatric bipolar disorder?". J Child Adolesc Psychopharmacol. 12 (1): 63–7. doi:10.1089/10445460252943588. PMID   12014597.
  35. ↑ Danke F (1975). "[Methylphenidate addiction--Reversal of effect on withdrawal]". Psychiatr Clin (Basel) (in German). 8 (4): 201–11. PMID   1208893.
  36. ↑ Cohen D, Leo J, Stanton T, et al. (2002). "A boy who stops taking stimulants for "ADHD": commentaries on a Pediatrics case study". Ethical Hum Sci Serv. 4 (3): 189–209. PMID   15278983.
  37. ↑ Chichmanian RM, Gustovic P, Spreux A, Baldin B (1993). "[Risk related to withdrawal from non-psychotropic drugs]". Thérapie (in French). 48 (5): 415–9. PMID   8146817.
  38. ↑ Tierney, Lawrence M.; McPhee, Stephen J.; Papadakis, Maxine A. (2008). Current medical diagnosis & treatment, 2008 . McGraw-Hill Medical. p.  916. ISBN   978-0-07-149430-4.
  39. ↑ BNF; British Medical Journal (2008). "Antipsychotic drugs". UK: British National Formulary. Retrieved 22 December 2008.
  40. ↑ Wolfgang Löscher; Dieter Schmidt (August 2006). "Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic Drugs". Epilepsia. 47 (8): 1253–1284. doi: 10.1111/j.1528-1167.2006.00607.x . PMID   16922870.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.