User:Sintegral/Opioid use disorder

Excerpt from article: Opioid use disorder

= Opioid use disorder =

Medications
Opioid replacement therapy (ORT) involves replacing an opioid, such as heroin, with a longer acting but less euphoric opioid. Commonly used drugs for ORT are methadone or buprenorphine which are taken under medical supervision. , buprenorphine/naloxone is preferentially recommended, as the addition of the opioid antagonist naloxone is believed to reduce the risk of abuse via injection or insufflation without causing impairment.

The driving principle behind ORT is the program's capacity to facilitate a resumption of stability in the user's life, while the patient experiences reduced symptoms of drug withdrawal and less intense drug cravings; a strong euphoric effect is not experienced as a result of the treatment drug. In some countries (not the US, or Australia), regulations enforce a limited time for people on ORT programs that conclude when a stable economic and psychosocial situation is achieved. (People with HIV/AIDS or hepatitis C are usually excluded from this requirement.) In practice, 40–65% of patients maintain abstinence from additional opioids while receiving opioid replacement therapy and 70–95% can reduce their use significantly. Along with this is a concurrent elimination or reduction in medical (improper diluents, non-sterile injecting equipment), psychosocial (mental health, relationships), and legal (arrest and imprisonment) issues that can arise from the use of illegal opioids. Clonidine or lofexidine can help treat the symptoms of withdrawal.

Participation in methadone and buprenorphine treatment reduces the risk of mortality due to overdose. The starting of methadone and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies. ORT has proven to be the most effective treatment for improving the health and living condition of people experiencing illegal opiate use or dependence, including mortality reduction and overall societal costs, such as the economic loss from drug-related crime and healthcare expenditure. ORT is endorsed by the World Health Organization, United Nations Office on Drugs and Crime and UNAIDS as being effective at reducing injection, lowering risk for HIV/AIDS, and promoting adherence to antiretroviral therapy.

Buprenorphine and methadone work by reducing opioid cravings, easing withdrawal symptoms, and blocking the euphoric effects of opioids via cross-tolerance, and in the case of buprenorphine, a high-affinity partial agonist, also due to opioid receptor saturation. It is this property of buprenorphine that can induce acute withdrawal when administered before other opioids have left the body. Naltrexone, a μ-opioid receptor antagonist, also blocks the euphoric effects of opioids by occupying the opioid receptor, but it does not activate it, so it does not produce sedation, analgesia, or euphoria, and thus it has no potential for abuse or diversion.

In the United States, since March 2020 as a result of the COVID-19 pandemic, buprenorphine may be dispensed via telemedicine.

Methadone
Methadone maintenance treatment (MMT), a form of opioid replacement therapy, reduces and/or eliminates the use of illegal opiates, the criminality associated with opiate use, and allows patients to improve their health and social productivity. Methadone is a μ-opioid receptor agonist. If initial doses during the beginning of treatment are too high or are concurrent with illicit opioid use, this may present an increased risk of death from overdose. 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 is medically safe and non-sedating. It is also indicated for pregnant women addicted to opiates. For individuals who wish to completely move away from drugs, they can start a methadone reduction program. A methadone reduction program is where an individual is prescribed an amount of methadone which is increased until withdrawal symptoms subside, after 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.

Some impairment in cognition has been demonstrated in those using methadone. Currently, 55 countries worldwide use methadone replacement therapy, while some countries such as Russia do not.

Buprenorphine
Buprenorphine is a partial opioid receptor agonist. Unlike methadone and other full opioid receptor agonists, buprenorphine is less likely to cause respiratory depression due to its ceiling effect. Treatment with buprenorphine may be associated with reduced mortality. Buprenorphine under the tongue is often used to manage opioid dependence. Preparations were approved for this use in the United States in 2002. Some formulations of buprenorphine incorporate the opiate antagonist naloxone during the production of the pill form to prevent people from crushing the tablets and injecting them, instead of using the sublingual (under the tongue) route of administration.

[SINTEGRAL EDIT] In order to reduce the harm associated with buprenorphine injection, it is available in a sublingual formulation that combines buprenorphine with the opioid receptor antagonist naloxone in a 4:1 ratio (ie. 8 mg/2 mg).This sublingual formulation is commonly administered as a flat, orange film with a grainy texture that is rectangular with dimensions of approximately 2.1 cm. length by 1.2 cm width. As a partial agonist with high receptor affinity and modest efficacy, buprenorphine has a ceiling effect after afer dosage levels around 16 mg, although doses of up to 32 mg are prescribed in some cases. While it may induce euphoria similar to methadone in addicts that have not accumulated tolerance, attempts to increase euphoria or achieve intoxication through dose escalation beyond 32 mg are generally ineffective. [SINTEGRAL EDIT]

Other opioids
Evidence of effects of heroin maintenance compared to methadone are unclear as of 2010. A Cochrane review found some evidence in opioid users who had not improved with other treatments. In Switzerland, Germany, the Netherlands, and the United Kingdom, long-term injecting drug users who do not benefit from methadone and other medication options may be treated with injectable heroin that is administered under the supervision of medical staff. Other countries where it is available include Spain, Denmark, Belgium, Canada, and Luxembourg.

Dihydrocodeine in both extended-release and immediate-release form are also sometimes used for maintenance treatment as an alternative to methadone or buprenorphine in some European countries. Dihydrocodeine is an opioid agonist. It may be used as a second line treatment. A 2020 systematic review found low quality evidence that dihydrocodeine may be no more effective than other routinely used medication interventions in reducing illicit opiate use. An extended-release morphine confers a possible reduction of opioid use and with fewer depressive symptoms but overall more adverse effects when compared to other forms of long-acting opioids. Retention in treatment was not found to be significantly different. It is used in Switzerland and more recently in Canada.

Naltrexone
Naltrexone is an opioid receptor antagonist used for the treatment of opioid addiction. Naltrexone is not as widely used as buprenorphine or methadone for OUD due to low rates of patient acceptance, non-adherence due to daily dosing, and difficulty achieving abstinence from opioids before beginning treatment. Additionally, dosing naltrexone after recent opioid use could lead to precipitated withdrawal. Conversely, naltrexone antagonism at the opioid receptor can be overcome with higher doses of opioids. Naltrexone monthly IM injections received FDA approval in 2010, for the treatment of opioid dependence in abstinent opioid users.