|Classification and external resources|
Opioid dependence is a medical diagnosis characterized by an individual's inability to stop using opiates (morphine, heroin, codeine, oxycodone, hydrocodone, etc.) even when objectively it is in his or her best interest to do so, and is a major component of opioid addiction. In 1964 the WHO Expert Committee on Drug Dependence introduced "dependence" as "A cluster of physiological, behavioural and cognitive phenomena of variable intensity, in which the use of a psychoactive drug (or drugs) takes on a high priority. The necessary descriptive characteristics are preoccupation with a desire to obtain and take the drug and persistent drug-seeking behaviour. Determinants and problematic consequences of drug dependence may be biological, psychological or social, and usually interact". The core concept of the WHO definition of "drug dependence" requires the presence of a strong desire or a sense of compulsion to take the drug; and the WHO and DSM-IV-TR clinical guidelines for a definite diagnosis of "dependence" require that three or more of the following six characteristic features be experienced or exhibited:
- A strong desire or sense of compulsion to take the drug;
- Difficulties in controlling drug-taking behaviour in terms of its onset, termination, or levels of use;
- A physiological withdrawal state when drug use is stopped or reduced, as evidenced by: the characteristic withdrawal syndrome for the substance; or use of the same (or a closely related) substance with the intention of relieving or avoiding withdrawal symptoms;
- Evidence of tolerance, such that increased doses of the drug are required in order to achieve effects originally produced by lower doses;
- Progressive neglect of alternative pleasures or interests because of drug use, increased amount of time necessary to obtain or take the drug or to recover from its effects;
- Persisting with drug use despite clear evidence of overtly harmful consequences, such as harm to the liver, depressive mood states or impairment of cognitive functioning.
According to position papers on the treatment of opioid dependence published by the United Nations Office on Drugs and Crime and the World Health Organization, care providers should not mistake opioid dependence for a weakness of character or will. Accordingly, detoxification alone does not constitute adequate treatment.
- 1 Causes
- 2 Symptoms of withdrawal
- 3 Treatment
- 4 Pharmacogenomics
- 5 Epidemiology
- 6 See also
- 7 References
- 8 External links
It has been demonstrated that most opioid-dependent patients suffer from at least one severe psychiatric comorbidity. Since opioids used in pain therapy rarely cause any of these conditions, they are assumed to have existed prior to the development of dependence. Opioids are known to have strong antidepressive, anxiolytic and antipsychotic effects and thus opioid dependence often develops as a result of self medication. Opioids are excellent acute pain medication, but it is their ability to produce euphoria that makes them attractive to addicts.
Furthermore some studies suggest a permanent dysregulation of the endogenous opioid receptor system after chronic exposure to opioids. A recent study has shown that an increase in BDNF, brain-derived neurotrophic factor, in the ventral tegmental area (VTA) in rats can cause opiate-naive rats to begin displaying opiate-dependent behavior, including withdrawal and drug-seeking behavior. It has been shown that when an opiate-naive person begins using opiates at levels inducing euphoria, this same increase in BDNF occurs.
Another recent study concluded to have shown "a direct link between morphine abstinence and depressive-like symptoms" and postulates "that serotonin dysfunction represents a main mechanism contributing to mood disorders in opiate abstinence".
Symptoms of withdrawal
|This section does not cite any references or sources. (February 2014)|
Symptoms of withdrawal from opiates include, but are not limited to:
- akathisia (uncomfortable feeling of inner restlessness)
- blocked nose
- bone pain
- chills (shivering)
- difficulty sleeping
- flu-like symptoms
- general feeling of being unwell (malaise)
- hot flushes
- hypoglycaemia (low blood sugar)
- joint pain
- muscle pain
- priapism (persistent, uncontrollable erection that is often unrelated to sexual desire)
- restless legs syndrome (uncomfortable feeling in your legs that cause you to need to move your legs to get some relief)
- runny nose
- skin rash or rashes
- tachycardia (rapid heartbeat)
- cravings for the drug
- concentration problems
- feeling agitated
- feeling irritable
- feeling restless
- memory problems
- mood changes such as depressed mood or edginess
- mood swings
- panic attacks
- suicide ideation
Depending on the quantity, type, frequency, and duration of opioid use, acute physical withdrawal symptoms last for as little as two to seven days (for short-acting opioids such as hydromorphone [Dilaudid] and oxycodone) and as long as seven to ten days for long-acting opioids such as buprenorphine and methadone. This initial withdrawal is characterized by the body attempting to regain homeostasis as a result of the brain's lack of opioid receptor activity. Since the mechanisms of opioid dependence and withdrawal are not fully understood, it is difficult to determine how long withdrawal symptoms will last or how severe they may be for different individuals.
Opioid dependence is a complex health condition that often requires long-term treatment and care. The treatment of opioid dependence is important to reduce its health and social consequences and to improve the well-being and social functioning of people affected. The main objectives of treating and rehabilitating persons with opioid dependence are to reduce dependence on illicit drugs; to reduce the morbidity and mortality caused by the use of illicit opioids, or associated with their use, such as infectious diseases; to improve physical and psychological health; to reduce criminal behaviour; to facilitate reintegration into the workforce and education system and to improve social functioning. The ultimate achievement of a drug free state is the ideal and ultimate objective but this is unfortunately not feasible for all individuals with opioid dependence, especially in the short term.
As no single treatment is effective for all individuals with opioid dependence, diverse treatment options are needed, including psychosocial approaches and pharmacological treatment.
Relapse following detoxification alone is extremely common, and therefore detoxification rarely constitutes an adequate treatment of substance dependence on its own. However, it is a first step for many forms of longer-term abstinence-based treatment. Both detoxification with subsequent abstinence-oriented treatment and substitution maintenance treatment are essential components of an effective treatment system for people with opioid dependence.
Current trends in the US reveal a significant increase of prescription opioid abuse compared to illicit opiates such as heroin. This development has also implications for the prevention, treatment and therapy of opioid dependence.
MMT (Methadone Maintenance Treatment), a form of opioid replacement therapy, reduces and/or eliminates the use of illicit opiates, the criminality associated with opiate use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with opiate injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with opiates. Methadone maintenance has been found to be medically safe and non-sedating. It is also indicated for pregnant women addicted to opiates. Methadone maintenance treatment is given to addicted individuals who feel unable to go the whole way and get clean. For those individuals who wish to completely move away from drugs, a methadone reduction program is indicated, where the individual is prescribed an amount of methadone which is titrated up until withdrawal symptoms subside, followed by a period of stability, the dose will then be gradually reduced until the individual is either free of the need for methadone or is at a level which allows a switch to a different opiate with an easier withdrawal profile, such as Suboxone. Methadone toxicity has been shown to be associated with specific phenotypes of CYP2B6.
Studies have shown buprenorphine to be a safer alternative over methadone in opiate replacement therapy, primarily due to its lower instance of overdose related deaths during the course of treatment. Buprenorphine sublingual preparations are often used in the management of opioid dependence (that is, dependence on heroin, oxycodone, hydrocodone, morphine, oxymorphone, fentanyl or other opioids). The Suboxone and Subutex preparations were approved for this indication by the United States Food and Drug Administration in October 2002. This was only possible due to the Drug Addiction Treatment Act of 2000 which overturned a series of 1914–1920 Supreme Court rulings that had found that maintenance and detox treatments were not a form of medical treatment. Although the rulings had the power of legal precedent prior to 2000, it is likely that they were not the intended interpretation of the laws passed originally by congress.
Naltrexone was approved by the FDA in 1984 for the treatment of opioid dependence. It is available both as an oral medication and as a monthly injectable (approved in 2010). Some authors question whether oral Naltrexone is as effective in the treatment of opioid dependence as methadone and buprenorphine mainly due to non-compliance. The monthly injectable naltrexone preparations have been designed to overcome the problems of compliance encountered with the oral formulation.
In Switzerland, Germany, the Netherlands, and the United Kingdom, longterm injecting drug users who do not benefit from methadone and other medication options are being treated with pure injectable diamorphine that is administered under the supervision of medical staff. For this group of patients, diamorphine treatment has proven superior in improving their social and health situation. Studies show that even after years of homelessness and delinquency and despite severe comorbidities, about half of the patients find employment within the first year of treatment.
LAAM was previously used to treat opioid dependence. In 2003 the drug's manufacturer discontinued production. There are no available generic versions. LAAM produced long lasting effects, which allowed the person receiving treatment to visit a clinic only three times per week, as opposed to daily as with methadone.[full citation needed]
Each of these treatments is experimental, and some remain quite far from having been proven to be effective.
- Medical cannabis
12-step support groups
While medical treatment may help with the initial symptoms of opioid withdrawal, once an opiate addict overcomes the first stages of withdrawal, a method for long-term preventative care is attendance at 12-step groups such as Alcoholics Anonymous or Narcotics Anonymous. Attendance and participation in a 12 step program is an effective way to obtain and maintain sobriety. Among primarily inner city minorities who had a "long severe history of (primarily) crack and/or heroin use", 51.7% of the individuals with continuous 12-step attendance had over 3 years of sustained abstinence, in contrast to 13.5% among those who had less than continuous 12-step attendance.
A genetic basis for the efficacy of opioids in the treatment of pain has been demonstrated for a number of specific variations; however, the evidence for clinical differences in opioid effects is ambiguous. The pharmacogenomics of the opioid receptors and their endogenous ligands has been the subject of intensive activity in association studies. These studies test broadly for a number of phenotypes, including opioid dependence, cocaine dependence, alcohol dependence, methamphetamine dependence/psychosis, response to naltrexone treatment, personality traits, and others. Major and minor variants have been reported for every receptor and ligand coding gene in both coding sequences, as well as regulatory regions. Newer approaches shift away from analysis of specific genes and regions, and are based on an unbiased screen of genes across the entire genome, which have no apparent relationship to the phenotype in question. These GWAS studies yield a number of implicated genes, although many of them code for seemingly unrelated proteins in processes such as cell adhesion, transcriptional regulation, cell structure determination, and RNA, DNA, and protein handling/modifying.
Currently there are no specific pharmacogenomic dosing recommendations for opioids due to a lack of clear evidence connecting genotype to drug effect, toxicity, or likelihood of dependence.
118A>G variant as an example of an opioid receptor variant
While over 100 variants have been identified for the opioid mu-receptor, the most studied mu-receptor variant is the non-synonymous 118A>G variant, which results in functional changes to the receptor, including lower binding site availability, reduced mRNA levels, altered signal transduction, and increased affinity for beta-endorphin. In theory, all of these functional changes would reduce the impact of exogenous opioids, requiring a higher dose to achieve the same therapeutic effect. This points to a potential for a greater addictive capacity in these individuals who require dosages to achieve pain control. However, evidence linking the 118A>G variant to opioid dependence is mixed, with associations shown in a number of study groups, but negative results in other groups. One explanation for the mixed results is the possibility of other variants which are in linkage disequilibrium with the 118A>G variant and thus contribute to different haplotype patterns that more specifically associate with opioid dependence.
Non-opioid receptor genes associated with opioid dependence
The preproenkephalin gene, PENK, encodes for the endogenous opiates that modulate pain perception, and are implicated in reward and addiction. (CA) repeats in the 3' flanking sequence of the PENK gene was associated with greater likelihood of opiate dependence in repeated studies. Variability in the MCR2 gene, encoding melanocortin receptor type 2 has been associated with both protective effects and increased susceptibility to heroin addiction. The CYP2B6 gene of the cytochrome P450 family also mediates breakdown of opioids and thus may play a role in dependence and overdose.
As of 2010 opioid use disorder resulted in about 43,000 deaths globally up from 8,900 in 1990.
- Benzodiazepine withdrawal syndrome
- Doctor shopping
- Opioid receptor
- Physical dependence
- Prescription drug abuse
- Walid–Robinson Opioid-Dependence Questionnaire
- Substitution maintenance therapy in the management of opioid dependence and HIV/AIDS prevention. World Health Organization. 2004. ISBN 92-4-159115-3.
- Chen, Kevin W.; Banducci, Annie N.; Guller, Leila; MacAtee, Richard J.; Lavelle, Anna; Daughters, Stacey B.; Lejuez, C.W. (2011). "An examination of psychiatric comorbidities as a function of gender and substance type within an inpatient substance use treatment program". Drug and Alcohol Dependence 118 (2–3): 92–9. doi:10.1016/j.drugalcdep.2011.03.003. PMC 3188332. PMID 21514751.
- Praveen, KT; Law, F; O'Shea, J; Melichar, J (2012). "Opioid dependence". American family physician 86 (6): 565–6. PMID 23062049.
- Vargas-Perez, H.; Ting-A-Kee, R.; Walton, C. H.; Hansen, D. M.; Razavi, R.; Clarke, L.; Bufalino, M. R.; Allison, D. W.; Steffensen, S. C. (2009). "Ventral Tegmental Area BDNF Induces an Opiate-Dependent-Like Reward State in Naive Rats". Science 324 (5935): 1732–34. doi:10.1126/science.1168501. PMC 2913611. PMID 19478142.
- Laviolette, Steven R.; Van Der Kooy, Derek (2001). "GABAA receptors in the ventral tegmental area control bidirectional reward signalling between dopaminergic and non-dopaminergic neural motivational systems". European Journal of Neuroscience 13 (5): 1009–15. doi:10.1046/j.1460-9568.2001.01458.x. PMID 11264674.
- Goeldner, Celia; Lutz, Pierre-Eric; Darcq, Emmanuel; Halter, Thomas; Clesse, Daniel; Ouagazzal, Abdel-Mouttalib; Kieffer, Brigitte L. (2011). "Impaired Emotional-Like Behavior and Serotonergic Function During Protracted Abstinence from Chronic Morphine". Biological Psychiatry 69 (3): 236–44. doi:10.1016/j.biopsych.2010.08.021. PMC 3014999. PMID 20947067.
- "Opioid Withdrawal". Opiate Addiction & Treatment Resource.
- Nicholls L, Bragaw L, Ruetsch C. (Feb 2010). "Opioid Dependence Treatment and guidelines". J Manag Care Pharm. 16 (1 Suppl B): S14–21. PMID 20146550.
- - Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence - World Health Organization
- Matthew Daubresse, Patrick P. Gleason, Yi Peng, Nilay D. Shah, Stephen T. Ritter, G. Caleb Alexander (2013). "Impact of a drug utilization review program on high-risk use of prescription controlled substances". Pharmacoepidemiology and Drug Safety. doi:10.1002/pds.3487.
- Amy Maxmen (June 2012), "Tackling the US pain epidemic". Nature News doi:10.1038/nature.2012.10766
- Joseph, H; Stancliff, S; Langrod, J (2000). "Methadone maintenance treatment (MMT): A review of historical and clinical issues". The Mount Sinai journal of medicine, New York 67 (5–6): 347–64. PMID 11064485.
- Connock, M; Juarez-Garcia, A; Jowett, S; Frew, E; Liu, Z; Taylor, RJ; Fry-Smith, A; Day, E; Lintzeris, N (2007). "Methadone and buprenorphine for the management of opioid dependence: A systematic review and economic evaluation". Health technology assessment 11 (9): 1–171, iii–iv. PMID 17313907.
- Bunten, H; Liang, W J; Pounder, D J; Seneviratne, C; Osselton, D (28 July 2010). "OPRM1 and CYP2B6 Gene Variants as Risk Factors in Methadone-Related Deaths". Clinical Pharmacology & Therapeutics 88 (3): 383–389. doi:10.1038/clpt.2010.127. PMID 20668445.
- Bell, J.R; Butler, B., Lawrence, A., Batey, R. & Salmelainen (2009). "Comparing overdose mortality associated with methadone and buprenorphine treatment". Drug and Alcohol Dependence 104 (1–2): 73–7. doi:10.1016/j.drugalcdep.2009.03.020. PMID 19443138.
- Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews 2011, Issue 4. PMID 21491383
- Haasen, C.; Verthein, U.; Degkwitz, P.; Berger, J.; Krausz, M.; Naber, D. (2007). "Heroin-assisted treatment for opioid dependence: Randomised controlled trial". The British Journal of Psychiatry 191: 55–62. doi:10.1192/bjp.bp.106.026112. PMID 17602126.
- http://relaunch.bundestag.de/bundestag/ausschuesse/a14/anhoerungen/113/stllg/ZIS.pdf[dead link]
- James W. Kalat, Biological Psychology.
- Brewer, C; H Rezae, C Bailey (1988). "Opioid withdrawal and naltrexone induction in 48-72 hours with minimal drop-out, using a modification of the naltrexone-clonidine technique". The British Journal of Psychiatry 153 (3): 340–343. doi:10.1192/bjp.153.3.340. PMID 3250670.
- Ling, W; L Amass, S Shoptaw, JJ Annon, M Hillhouse, D Babcock, G Brigham, J Harrer, M Reid, J Muir, B Buchan, D Orr, G Woody, J Krejci, D Ziedonis (2005). "A multi-center randomized trial of buprenorphine–naloxone versus clonidine for opioid, detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network". Addiction 100 (8): 1090–1100. doi:10.1111/j.1360-0443.2005.01154.x. PMC 1480367. PMID 16042639.
- Herman, BH; F Vocci, P Bridge (1995). "The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal: Medication development issues for opiate addiction". Neuropsychopharmacology 13 (4): 269–293. doi:10.1016/0893-133X(95)00140-9. PMID 8747752.
- Alper, KR; HS Lotsof, GMN Frenken, DJ Luciano, J Bastiaans (1999). "Treatment of Acute Opioid Withdrawal with Ibogaine". The American Journal of Addictions 8 (3): 234–243. doi:10.1080/105504999305848. PMID 10506904.
- Morel LJ, Giros B, Daugé V (2009). "Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats". Neuropsychopharmacology 34 (11): 2469–76. doi:10.1038/npp.2009.70. PMID 19553915. Lay summary – PhysOrg.com (7 July 2009).
- Raby, Wilfrid Noel; Carpenter, Kenneth M.; Rothenberg, Jami; Brooks, Adam C.; Jiang, Huiping; Sullivan, Maria; Bisaga, Adam; Comer, Sandra; Nunes, Edward V. (2009). "Intermittent Marijuana Use Is Associated with Improved Retention in Naltrexone Treatment for Opiate-Dependence". The American Journal on Addictions 18 (4): 301–8. doi:10.1080/10550490902927785. PMC 2753886. PMID 19444734.
- Boyer, Edward W.; Kavita M. Babu, Jessica E. Adkins, Christopher R. McCurdy, John H. Halpern (28 June 2008). "Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth)". Addiction 103 (6): 1048–1050. doi:10.1111/j.1360-0443.2008.02209.x. PMC 3670991. PMID 18482427.
- Sobey, PW; Parran Tv, TV; Grey, SF; Adelman, CL; Yu, J (2003). "The use of tramadol for acute heroin withdrawal: a comparison to clonidine". Journal of addictive diseases 22 (4): 13–25. doi:10.1300/J069v22n04_03. PMID 14723475.
- Threlkeld, M; Parran, TV; Adelman, CA; Grey, SF; Yu, J; Yu, Jaehak (2006). "Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study". The American journal on addictions 15 (2): 186–91. doi:10.1080/10550490500528712. PMID 16595358.
- Brigham, Gregory (2003). "12-Step Participation as a Pathway to Recovery: The Maryhaven Experience and Implications for Treatment and Research". Science & Practice Perspectives 2 (1): 43–51. PMC 2851040.
- Alexandre B. Laudet, Ph.D - PowerPoint PPT Presentation - 12-step attendance and involvement over 3 years on odds of sustained abstinence
- Manning, V; Best D., Faulkner N., Titherington E., Morinan A., Keaney F., Gossop M., Strang J. (November 2012). "Does active referral by a doctor or 12-Step peer improve 12-Step meeting attendance? Results from a pilot randomised control trial". Drug Alcohol Depend; Research study (NCBI Pubmed.gov) 126 (1-2): 131–7. doi:10.1016/j.drugalcdep.2012.05.004. PMID 22677458.
- Hall, F. Scott; Drgonova, Jana; Jain, Siddharth; Uhl, George R. (December 2013). "Implications of genome wide association studies for addiction: Are our a priori assumptions all wrong?". Pharmacology & Therapeutics 140 (3): 267–279. doi:10.1016/j.pharmthera.2013.07.006.
- Bruehl, Stephen; Apkarian, A. Vania; Ballantyne, Jane C.; Berger, Ann; Borsook, David; Chen, Wen G.; Farrar, John T.; Haythornthwaite, Jennifer A.; Horn, Susan D.; Iadarola, Michael J.; Inturrisi, Charles E.; Lao, Lixing; Mackey, Sean; Mao, Jianren; Sawczuk, Andrea; Uhl, George R.; Witter, James; Woolf, Clifford J.; Zubieta, Jon-Kar; Lin, Yu (February 2013). "Personalized Medicine and Opioid Analgesic Prescribing for Chronic Pain: Opportunities and Challenges". The Journal of Pain 14 (2): 103–113. doi:10.1016/j.jpain.2012.10.016. PMC 3564046. PMID 23374939.
- Khokhar, Jibran Y.; Ferguson, Charmaine S.; Zhu, Andy Z.X.; Tyndale, Rachel F. (February 2010). "Pharmacogenetics of Drug Dependence: Role of Gene Variations in Susceptibility and Treatment". Annual Review of Pharmacology and Toxicology 50 (1): 39–61. doi:10.1146/annurev.pharmtox.010909.105826.
- Lozano, R; Naghavi, Mohsen; Foreman, Kyle; Lim, Stephen; Shibuya, Kenji; Aboyans, Victor; Abraham, Jerry; Adair, Timothy; Aggarwal, Rakesh; Ahn, Stephanie Y; Almazroa, Mohammad A; Alvarado, Miriam; Anderson, H Ross; Anderson, Laurie M; Andrews, Kathryn G; Atkinson, Charles; Baddour, Larry M; Barker-Collo, Suzanne; Bartels, David H; Bell, Michelle L; Benjamin, Emelia J; Bennett, Derrick; Bhalla, Kavi; Bikbov, Boris; Abdulhak, Aref Bin; Birbeck, Gretchen; Blyth, Fiona; Bolliger, Ian; Boufous, Soufiane; Bucello, Chiara (Dec 15, 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. PMID 23245604.
- Opioid Dependence Treatment and guidelines
- Opiate Withdrawal Timeline