Physical dependence: Wikis


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Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance [1] and where negative physical symptoms[2] of withdrawal result from abrupt discontinuation or dosage reduction.[3] Physical dependence can develop from low-dose therapeutic use of certain medications as well as misuse of recreational drugs such as alcohol. The higher the dose used typically the worse the physical dependence and thus the worse the withdrawal symptoms. Withdrawal symptoms can last days, weeks or months or occasionally longer and will vary according to the dose, the type of drug used and the individual person.[4]



Physical dependence can manifest itself in the appearance of both physical and psychological symptoms but 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. 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 or psychostimulants, can exaggerate mild to moderate neurotoxic side effects due to hyperthermia and generation of free radicals[5], but life-threatening complications are very rare.


Treatment for physical dependence depends upon the drug being withdrawn and often includes administration of another drug, especially for substances that can be dangerous when abruptly discontinued. 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.[4] 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.[17] These can include stimulants,[18][19][20][21], antidepressants,[22][23] anticonvulsants,[24][25][26] steroidal drugs and antiparkinsonian drugs.[27] Antipsychotics are another drug class that do not cause true physical dependency[28] but if discontinued too rapidly can cause an acute withdrawal syndrome.[29] Drugs like cocaine, marijuana, amphetamines, and hallucinogens can be associated with minimal physical dependence[30] but can still cause withdrawal or rebound symptoms. However, with sustained and heavy cocaine abuse signs of physiological dependence may occur.[31] When talking about illicit drugs rebound withdrawal is, especially with stimulants, 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 need to be looked at individually. Anticonvulsants as a group however are known to cause tolerance to the anti-seizure effect.[32] SSRI drugs, which have an important use as antidepressants, are not considered to cause physical dependence, but it's generally accepted that they cause a discontinuation syndrome. Due to this, in Europe these drugs cannot be advertised as "non-habit forming".[citation needed] There has however been case reports of dependence with venlafaxine (Effexor).[33]

See also


  1. ^ physical dependence at Dorland's Medical Dictionary
  2. ^ "Definition of physical dependence - NCI Dictionary of Cancer Terms". Retrieved 2008-12-21. 
  3. ^ "Drug Addiction". CNN. 
  4. ^ a b 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. 
  5. ^ Sharma HS, Sjöquist PO, Ali SF (2007). "Drugs of abuse-induced hyperthermia, blood-brain barrier dysfunction and neurotoxicity: neuroprotective effects of a new antioxidant compound H-290/51". Current pharmaceutical design 13 (18): 1903–23. PMID 17584116. 
  6. ^ Jed E. Rose (October 2007). "Multiple brain pathways and receptors underlying tobacco addiction". Biochemical Pharmacology 74 (8): 1263–1270. doi:10.1016/j.bcp.2007.07.039. 
  7. ^ 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. PMID 11976266.& PMC 1762111. 
  8. ^ Sikdar S (July 1998). "Physical dependence on zopiclone. Prescribing this drug to addicts may give rise to iatrogenic drug misuse". BMJ 317 (7151): 146. PMID 9657802.& PMC 1113504. 
  9. ^ 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. 
  10. ^ 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. PMID 9060200. 
  11. ^ 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. 
  12. ^ "MedlinePlus Medical Encyclopedia: Drug abuse and dependence". Retrieved 2008-12-21. 
  13. ^ 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. 
  14. ^ Trenton AJ, Currier GW (2005). "Behavioural manifestations of anabolic steroid use". CNS Drugs 19 (7): 571–95. PMID 15984895. 
  15. ^ Hartgens F, Kuipers H (2004). "Effects of androgenic-anabolic steroids in athletes". Sports Med 34 (8): 513–54. PMID 15248788. 
  16. ^
  17. ^ 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. PMID 2898213. 
  18. ^ Lake CR, Quirk RS (December 1984). "CNS stimulants and the look-alike drugs". Psychiatr. Clin. North Am. 7 (4): 689–701. PMID 6151645. 
  19. ^ 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. 
  20. ^ Danke F (1975). "[Methylphenidate addiction--Reversal of effect on withdrawal]" (in German). Psychiatr Clin (Basel) 8 (4): 201–11. PMID 1208893. 
  21. ^ 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. 
  22. ^ Kora K, Kaplan P (2008). "[Hypomania/mania induced by cessation of antidepressant drugs"] (in Turkish). Turk Psikiyatri Derg 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. ^ 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. PMID 11706106. 
  25. ^ 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. 
  26. ^ 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. PMID 10702963. 
  27. ^ Chichmanian RM, Gustovic P, Spreux A, Baldin B (1993). "[Risk related to withdrawal from non-psychotropic drugs]" (in French). Therapie 48 (5): 415–9. PMID 8146817. 
  28. ^ Tierney, Lawrence M.; McPhee, Stephen J.; Papadakis, Maxine A. (2008). Current medical diagnosis & treatment, 2008. McGraw-Hill Medical. pp. 916. ISBN 0-07-149430-8. 
  29. ^ BNF; British Medical Journal (2008). "Antipsychotic drugs". UK: British National Formulary. Retrieved 22 december 2008. 
  30. ^ "Addiction Disorders". Retrieved 2008-12-21. 
  31. ^ Gawin FH (February 1988). "Chronic neuropharmacology of cocaine: progress in pharmacotherapy". J Clin Psychiatry 49 Suppl: 11–6. PMID 3276669. 
  32. ^ Wolfgang Löscher and Dieter Schmidt (August 2006). "Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic Drugs". Epilepsia 47 (8): 1253–1284. 
  33. ^ 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. 

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