Opioid use disorder(OUD) is defined as a loss of control over opioid use leading to physical, psychological, and social consequences. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes diagnostic criteria for OUD that are universal across all drugs and are based on the presence of at least two of 11 criteria organized into four clusters: 1-Impaired control 2-Social impairment 3- Risky use 4- Pharmacologic dependence[3] Opioid abuse happens for different of reasons, including self-medication, use for reward, compulsive use due to addiction, and diversion for profit. treatment methods that balance chronic pain while reducing the risks for drug abuse, misuse, and distraction are strongly needed.[4][5]
Tolerance is the process whereby neuroadaptation occurs (through receptor desensitization) resulting in reduced drug effects. Tolerance is more pronounced for some effects than for others - tolerance occurs quickly to the effects on mood, itching, urinary retention, and respiratory depression, but occurs more slowly to the analgesia and other physical side effects. Impaired control leads to the use in bigger amounts or for longer periods of time than anticipated; persistent desire to reduce or stop use; many unsuccessful attempts to reduce or stop use; a significant amount of time spent using or recovering from the effects of the substance; a strong urge to use or crave the substance.[3]
Magnesium and zinc deficiency speed up the development of tolerance to opioids and relative deficiency of these minerals is quite common[11] due to low magnesium/zinc content in food and use of substances which deplete them including diuretics (such as alcohol, caffeine/theophylline) and smoking. Reducing intake of these substances and taking zinc/magnesium supplements may slow the development of tolerance to opiates.
Dependence is characterized by extremely unpleasant withdrawal symptoms that occur if opioid use is abruptly discontinued after tolerance has developed. The withdrawal symptoms include severe dysphoria, sweating, nausea, rhinorrhea, depression, severe fatigue, vomiting and pain. Slowly reducing the intake of opioids over days and weeks will reduce or eliminate the withdrawal symptoms.[12] The speed and severity of withdrawal depend on the half-life of the opioid — heroin and morphine withdrawal occur more quickly and are more severe than methadone withdrawal, but methadone withdrawal takes longer. The acute withdrawal phase is often followed by a protracted phase of depression and insomnia that can last for months. The symptoms of opioid withdrawal can also be treated with other medications, but with low efficacy.[13]
Addiction is the process whereby physical and/or psychological addiction develops to a drug - including opioids. The withdrawal symptoms can reinforce the addiction, driving the user to continue taking the drug. Psychological addiction is more common in people taking opioids recreationally, it is rare in patients taking opioids for pain relief.[14]
The 12 month prevalence of opioid use disorder is 370 per 100,000 (0.37%) in ages 18 years and older in the community population.[15]
In 2016, an estimated 26.8 million persons worldwide with OUD, up 47.3 percent from 1990. The highest prevalence was found in high-income North America, North Africa, and the Middle East.[16]
Variability in opioid prescribing in emergency departments is a risk factor.[17][18] The Centers for Disease Control and Prevention has studied risk factors[19].
Substance use disorders are linked to psychiatric problems; those who have one are more likely to have the other. Substance use causing mental diseases, people with psychiatric disorders using substances to manage symptoms, and common risk factors for both conditions are all possible explanations. The lifetime prevalence of comorbid psychiatric disorders in patients with OUD has been found to range between 24 and 86 percent, with mood and anxiety disorders being the most common axis I disorders and antisocialpersonality disorder being the most commonly diagnosed axis II condition. Determining whether a person has a substance-induced disorder or a basic psychiatric disorder can be difficult in people with co-occurring disorders.[20][21]
DSM-V Diagnostic Criteria for Opioid Use Disorder(OUD)[15][edit | edit source]
“
A. A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:
1. Opioids are often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of opioids to achieve intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of an opioid.
Note: This criterion is not considered to be met for those taking opioids solely under appropriate medical supervision.
11. Withdrawal, as manifested by either of the following:
a. The characteristic opioid withdrawal syndrome.
b. Opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.
Note: This criterion is not considered to be met for those individuals taking opioids solely under appropriate medical supervision .
Specify if:
In early remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use opioids,” maybe met).
In sustained remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion A4, “Craving, or a strong desire or urge to use opioids,” maybe met).
Specify if:
On maintenance therapy: This additional specifier is used if the individual is taking a prescribed agonist medication such as methadone or buprenorphine and none of the criteria for opioid use disorder have been met for that class of medication (except tolerance to, or withdrawal from, the agonist). This category also applies to those Individuals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist such as oral naltrexone or depot naltrexone.
In a controlled environment: This additional specifier is used if the individual is in an environment where access to opioids is restricted.
several methods of psychosocial interventions such as individual counseling or group therapy can benefit people with OUD. Clinicians in primary care can assist patients who are interested in these treatments in getting connected to them. there is limited evidence to recommend these kinds of interventions either alone or in combination with pharmacotherapy. Most of the surveys on these therapeutic interventions are used in conjunction with medication.[23][24]
long-term(maintenance) medication is still the first-line treatment for patients with OUD, and many patients prefer it. the evidence for the three medications that have been approved for the treatment of OUD- Methadone, Buprenorphine, Naltrexone- will be discussed in the following section. long-term maintenance therapy with agonists is the mainstay treatment for OUD.[25] a systematic review of 19 cohort studies in 2017 showed that pharmacotherapy with methadone and buprenorphine significantly reduces mortality for all reasons in the patients using opioidagonist comparing to the people without medical treatment.[26]
Buprenorphine is a highly effective long-acting partial opioid agonist for the treatment of OUD. Buprenorphine is available in different formulations in the USA. Most of them are combined with naloxone to avoid injection or intranasal use. sublingual tablets are available in 2, and 8 mg doses with or without naloxone. many patients may need doses above 16mg/day up to 32 mg. for those who do not respond to 32mg/day of buprenorphine, methadone therapy should be considered. long term maintenance treatment with buprenorphine is more effective than short-term or medically supervised withdrawal treatment.[27]Buprenorphine has a high tendency to bind to the receptor, which adds to its safety. however it can dislodge other narcotics and lead to unwanted withdrawal if given too soon after using an agonist.[28] to prevent this buprenorphine should be started when withdrawal symptoms begin in the patient. usually, after 8 to 12 hours of using short-acting opioids such as heroin, buprenorphine can be started with a low dose.[29]
Methadone is a highly effective long-acting agonist, which noticeably reduces the use of illicit opioid use.[25]. considering that methadone has a long half-life, the starting dose is at 30-40 mg/day and increases slowly until an effective therapeutic dose is reached. The goal and effective dose are to suppress opioidcraving and at the same time to avoid over-sedation. The studies show that higher doses of methadone( doses of at least 60-100 mg) are linked with maintaining treatment and reduction of overdosemortality.[30]
Naltrexone is an opiumantagonist, the newest medication for the treatment of OUD in primary care settings. The oral form has low efficacy. However, RCT studies have shown that the monthly injection of the intramuscular extended-release formulation is superior to the placebo and the oral form of naltrexone and reduces craving and relapse in patients with OUD.[31][32]
↑Kaye AD, Jones MR, Kaye AM, Ripoll JG, Galan V, Beakley BD, Calixto F, Bolden JL, Urman RD, Manchikanti L (February 2017). "Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse: Part 1". Pain Physician. 20 (2S): S93–S109. PMID28226333.
↑Buresh, Megan; Stern, Robert; Rastegar, Darius (2021-05-19). "Treatment of opioid use disorder in primary care". BMJ. BMJ: n784. doi:10.1136/bmj.n784. ISSN1756-1833.
↑Santillán R, Maestre JM, Hurlé MA, Flórez J. "Enhancement of opiate analgesia by nimodipine in cancer patients chronically treated with morphine: a preliminary report." Pain. 1994 Jul;58(1):129-32. PMID 7970835
↑Smith FL, Dombrowski DS, Dewey WL. "Involvement of intracellular calcium in morphine tolerance in mice." Pharmacology, Biochemistry, and Behavior. 1999 Feb;62(2):381-8. PMID 9972707
↑Larson AA, Kovács KJ, Spartz AK. "Intrathecal Zn2+ attenuates morphine antinociception and the development of acute tolerance." European Journal of Pharmacology. 2000 Nov 3;407(3):267-72. PMID 11068022
↑Wong CS, Cherng CH, Luk HN, Ho ST, Tung CS. "Effects of NMDA receptor antagonists on inhibition of morphine tolerance in rats: binding at mu-opioid receptors." Eur J Pharmacol. 1996 Feb 15;297(1-2):27-33. PMID 8851162
↑Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
↑Hermann D, Klages E, Welzel H, Mann K, Croissant B. Low efficacy of non-opioid drugs in opioid withdrawal symptoms. Addict Biol. 2005 Jun;10(2):165-9. PMID: 16191669
↑Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
↑ 15.015.115.2Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN0890425558.
↑Astals M, Domingo-Salvany A, Buenaventura CC, Tato J, Vazquez JM, Martín-Santos R, Torrens M (2008). "Impact of substance dependence and dual diagnosis on the quality of life of heroin users seeking treatment". Subst Use Misuse. 43 (5): 612–32. doi:10.1080/10826080701204813. PMID18393080.
↑Roncero C, Barral C, Rodríguez-Cintas L, Pérez-Pazos J, Martinez-Luna N, Casas M, Torrens M, Grau-López L (September 2016). "Psychiatric comorbidities in opioid-dependent patients undergoing a replacement therapy programme in Spain: The PROTEUS study". Psychiatry Res. 243: 174–81. doi:10.1016/j.psychres.2016.06.024. PMID27416536.
↑Tiet QQ, Leyva YE, Moos RH, Frayne SM, Osterberg L, Smith B (August 2015). "Screen of Drug Use: Diagnostic Accuracy of a New Brief Tool for Primary Care". JAMA Intern Med. 175 (8): 1371–7. doi:10.1001/jamainternmed.2015.2438. PMID26075352.
↑Timko, C; Debenedetti, A; Billow, R (2006). "Intensive referral to 12-Step self-help groups and 6-month substance use disorder outcomes". Addiction (Abingdon, England). 101 (5): 678–88. doi:10.1111/j.1360-0443.2006.01391.x. ISSN0965-2140. PMID16669901.
↑McAuliffe, William E. (1990). "A Randomized Controlled Trial of Recovery Training and Self-help for Opioid Addicts in New England and Hong Kong". Journal of Psychoactive Drugs. Informa UK Limited. 22 (2): 197–209. doi:10.1080/02791072.1990.10472544. ISSN0279-1072.
↑ 25.025.1Mattick, Richard P; Breen, Courtney; Kimber, Jo; Davoli, Marina (2014-02-06). "Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence". Cochrane Database of Systematic Reviews. Wiley. doi:10.1002/14651858.cd002207.pub4. ISSN1465-1858.
↑Sordo, Luis; Barrio, Gregorio; Bravo, Maria J; Indave, B Iciar; Degenhardt, Louisa; Wiessing, Lucas; Ferri, Marica; Pastor-Barriuso, Roberto (2017-04-26). "Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies". BMJ. BMJ: j1550. doi:10.1136/bmj.j1550. ISSN0959-8138.
↑Weinstein, Zoe M.; Kim, Hyunjoong W.; Cheng, Debbie M.; Quinn, Emily; Hui, David; Labelle, Colleen T.; Drainoni, Mari-Lynn; Bachman, Sara S.; Samet, Jeffrey H. (2017). "Long-term retention in Office Based Opioid Treatment with buprenorphine". Journal of Substance Abuse Treatment. Elsevier BV. 74: 65–70. doi:10.1016/j.jsat.2016.12.010. ISSN0740-5472.
↑Coe, Marion A.; Lofwall, Michelle R.; Walsh, Sharon L. (2019). "Buprenorphine Pharmacology Review: Update on Transmucosal and Long-acting Formulations". Journal of Addiction Medicine. Ovid Technologies (Wolters Kluwer Health). 13 (2): 93–103. doi:10.1097/adm.0000000000000457. ISSN1932-0620.
↑Vogel, Marc; Hämmig, Robert; Kemter, Antje; Strasser, Johannes; von Bardeleben, Ulrich; Gugger, Barbara; Walter, Marc; Dürsteler, Kenneth (2016). "Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the "Bernese method"". Substance Abuse and Rehabilitation. Informa UK Limited. Volume 7: 99–105. doi:10.2147/sar.s09919. ISSN1179-8467.
↑Faggiano, Fabrizio; Vigna-Taglianti, Federica; Versino, Elisabetta; Lemma, Patrizia (2003-07-21). "Methadone maintenance at different dosages for opioid dependence". Cochrane Database of Systematic Reviews. Wiley. doi:10.1002/14651858.cd002208. ISSN1465-1858.
↑Sullivan, Maria A.; Bisaga, Adam; Pavlicova, Martina; Carpenter, Kenneth M.; Choi, C. Jean; Mishlen, Kaitlyn; Levin, Frances R.; Mariani, John J.; Nunes, Edward V. (2019). "A Randomized Trial Comparing Extended-Release Injectable Suspension and Oral Naltrexone, Both Combined With Behavioral Therapy, for the Treatment of Opioid Use Disorder". American Journal of Psychiatry. American Psychiatric Association Publishing. 176 (2): 129–137. doi:10.1176/appi.ajp.2018.17070732. ISSN0002-953X.
↑Krupitsky, Evgeny; Nunes, Edward V; Ling, Walter; Illeperuma, Ari; Gastfriend, David R; Silverman, Bernard L (2011). "Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial". The Lancet. Elsevier BV. 377 (9776): 1506–1513. doi:10.1016/s0140-6736(11)60358-9. ISSN0140-6736.