opioid use disorder essay
Opioid use disorder (OUD) is characterised by repeated use of opioids with harmful consequences (4). It is a complex and relapsing condition that may require long-term treatment and care. People with OUD should have access to medication for its management. Treatment including medication is associated with important social and clinical benefits, reduces overdose deaths and crime, and enables patients to positively contribute to society (10,18,24). Evidence-based, good quality treatment helps achieve recovery outcomes (3). In Europe, treatment options and guidelines differ by country; there is no common best practice guidance across Europe. Existing guidelines are not all up-to-date and do not provide day-to-day advice for physicians to inform best practice.
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Write My Essay For MeAccess to pharmacotherapy should be made available to all patients with OUD. Opioid agonist therapy (OAT), including methadone, buprenorphine or buprenorphine/ naloxone fixed dose combination is effective treatment for OUD, (7,18,19,21,23,24). The focus of this work is limited to methadone and buprenorphine: these are the most widely available treatments throughout Europe and considered as the most appropriate agonist therapies for use in OUD. This recommendation focuses on only these treatments; other treatment options are not considered here.
Methods
A group of 15 European experts in the treatment of OUD (see Appendix 1) developed practical recommendations for the treatment of OUD. Recent national and international guidelines published between May 2014 and Dec 2016 were identified and reviewed by searching key national sources and following expert recommendations. Their content provides the basis of the recommendations, supplemented by expert consensus from the Faculty of experts. Where evidence-based information is not available, expert consensus recommendations are provided for optimal pharmacotherapeutic options.
In total 15 guidelines were reviewed (Appendix 2). The recommendations describe the two most widely used and effective treatments in OUD (methadone and buprenorphine or buprenorphine/ naloxone) and provide practical recommendations for their optimal use in general, and in patients with more complex and hard-to-treat problems.
Treatment objectives
Patients and physicians should reach an agreement on treatment objectives (3,21), which are goals that are expected to be achieved from the treatment program (11). The broad goal of treating OUD is to improve the physical and psychological health (3,18,23) and to reduce health, social and economic harm to individuals and community (18).
From a health of the individual point of view, short-term goals include to avoid serious risk to health (18), cease or reduce dangerous illicit opioid use (3,11,14,18,19,23), cease exposure to risk from unsafe injecting therefore reducing risk of blood-borne virus transmission (3,13,18,19,23), address pre-existing health concerns (11), reduce overdose risk (23). From a social aspect, OUD treatment reduces substance-related criminal activity (3,18,23), and promotes re-integration to society (3,14,23), for example working, studying or participation in other activities (18), as well as enhancing quality of life for families and communities (25).
An important long-term goal may be to reach complete abstinence (3,14,18), but the complexities of OUD mean that this is not necessarily achieved (18). This is not a reason to limit access to care. Over emphasis on abstinence may, to some, devalue other achievable short term goals (18). Extended treatment may benefit some people to achieve improved social functions without necessarily ceasing illicit drug use (18,23). Progress for patients is often progressive and individual with some aiming to cease all drug use, others may not choose this path.
A range of interventions or treatment options, including psychosocial and pharmacological interventions are available: there is no single treatment that is effective for all individuals with OUD (35). OAT represents an important component of the overall management program aiming to provide safe, effective and consistent therapy (13,29). It is pragmatic and focused on realisable goals (23), and has been shown to be superior to withdrawal management regarding retention, sustained abstinence, reduced risk of morbidity and mortality (32). OAT often controls withdrawal symptoms and minimizes the craving for additional opioids (19,21). It is the most effective long-term strategy and can allow a “return-to-normal” physiological, psychological and societal functioning (7,13,25). Some patients are able to reach abstinence with significant support from both medical intervention and community-based services (22,29). Treatment of strategies including OAT and a combination of professional and peer-based support to assist patients and families in achieving positive outcomes in OUD.
Appropriate quality OAT for OUD is cost-effective and the return on investment from good quality OAT is better than from poor quality. It is important for decision-makers to focus on retaining investment in OAT and treatment in the wider context while also improving the quality of OAT (for example by ensuring sufficient dosing levels).
Treatment option: Methadone
Methadone is a long-acting synthetic opioid which as an oral formulation is effective in treating OUD (21). It prevents opioid withdrawal, reduces opioid craving and mitigates the euphoric effects of opioids such as heroin (11). Methadone is rapidly absorbed following oral administration; effects starts in 15- 45 min (18), peak plasma concentration and clinical effect reached at 2-6 hours, and has a half-life average 24-36 hours (range 4-90 hours) at steady state (11,18).
The pharmacokinetics of methadone with the variable individual response make safety an important concern in OAT. Methadone may accumulate and cause sedation and respiratory depression (11), with an increased toxicity, potentially lethal, by concomitant ingestion of alcohol and sedative-hypnotics such as benzodiazepines and Z drugs (11). Respiratory depression, including deaths may occur on treatment initiation or conversion to methadone (19). Management should be limited to those knowledgeable in the use of methadone for maintenance treatment of OUD.
Tolerance to the various effects of methadone could develop at different rates: rapid to the euphoric effect, less rapid to respiratory depression and slowest to autonomic side effects (11). Tolerance is lost in as little as 3 days. Cross-tolerance between methadone and other opioids is unpredictable.
• Methadone is an indicated treatment OUD in patients who are physiologically dependent on opioids (21)
• Methadone is administered orally either as a liquid or as a tablet commonly in the supervised setting (21)
• Methadone use should be monitored to prevent misuse and diversion (11,18,21); unsupervised dosing should be considered after the patient’s clinical response and behaviour indicates this is safe and appropriate
• The extended pharmacokinetics and individual response to methadone make the process of induction and achievement of stability highly variable: it may take 2-4 weeks (33)
• Methadone dosage:
– Starting dose should not exceed 30 mg daily and is often lower in some patients (11)
– Increment of doses should be stepwise based on “go low, go slow” with 10% or 5-10 mg changes (11,21,23) no more frequently than every 5 to 7 days (11,13,21) (and may need to be longer) – increments driven by the clinical response
– It is not recommended to alter the dose without an assessment and after each dose change it may take up to 5 days for methadone plasma levels to reach steady state (11)
– Optimal dose is critical to outcome (3), which is the lowest dose where a patient experiences minimum withdrawal, is clinically and socially stable, opioid-induced euphoria is prevented, and the patient is able to stay in treatment (21)
– The typical optimal dose is 60-120mg daily (13) but many factors (e.g. drug interactions, liver or renal failure) may affect methadone clearance so the optimal dose is highly variable (3)
– Doses of 60 mg/day or greater have been shown to be more effective than lower doses in patient retention, reduced unsanctioned opioid use, and less risk behaviour (11,13,18)
– Dividing doses is rarely used but may be beneficial for specific populations only such as during pregnancy, patients with rapid metabolism or pain management (13,23).
• Patients on methadone should be advised to avoid alcohol and over-the-counter sedating drugs (13). Depending on the individual case and risk profile, prescribers may limit or avoid prescribing any sedating drugs, including benzodiazepines, non-benzodiazepine hypnotics, anti-psychotics, antidepressants, and sedating antihistamines (13) and pay special attention to presence of such drugs in urine samples (33)
• Switching from methadone to another medication of OUD is appropriate if the patient experiences intolerable side effects or is not successful in attaining or maintaining treatment goals through the use of methadone (18,27)
• Advantages and disadvantages of methadone treatment (Table 1) should be considered in deciding if methadone is a suitable treatment
• Methadone is an important choice for treatment in patients who require treatment with daily monitoring, may continue to use other opioids or have intense addiction. Buprenorphine/ Naloxone is recommended in settings with increased risk of misuse or diversion
• Table 1 Advantages and disadvantages of methadone
Advantages
Potent opioid agonist with extensive treatment experience (33)
Potentially improved treatment retention in some patients, for example unstable patients or those more likely to cease therapy (32)
For people with high opioid tolerance, may be more appropriate (32)
No precipitated withdrawal; initiating treatment may be easier in patients continuing to use other opioids (32)
For patients with anxiety or other concurrent mental health problems such as schizophrenia sedative effects may be beneficial (23)
Disadvantages
Fatal overdose and toxicity risks (sedation and respiratory depression which in the most severe case may lead to hypoventilation, coma, bradycardia and death with risk of delayed toxicity occurring hours after exposure for the patient) (11,13,18,19,21,32,33)
May be associated with overdose risk in domestic settings for other parties including families and young children, with serious consequences (23)
Patients concurrently using alcohol, sedative hypnotics (e.g. benzodiazepines), stimulants, cocaine or any medication that interferes with methadone metabolism are at risk of methadone toxicity (18,19,33)
Unsupervised administration can lead to misuse and diversion (21)
Longer and more challenging initiation phase (11,13,19) with unpredictable patient responses over time which may be associated with increased induction treatment drop out (19)
Overdose risk high during first 2 weeks of initiation in the presence of sedatives and patients with low opioid tolerance or altered pharmacokinetics (11,13,19,23)
Associated with more clinically relevant drug interactions. Some medications (e.g., those used to treat HIV, tuberculosis and epilepsy) increase the clearance of methadone leading to a need for increased doses (18,32,33)
Liver & renal failure affect methadone clearance leading to requirement for variable doses (23)
Often requires daily supervision (18,21): this may limit autonomy and prevents patient undertaking work or participating in other daily activities such as study, caring, travel and socialising (32)
With office based treatment and “Take home dosing” there is risk of diversion & fatal toxicity (19,32) (e.g. if a child consumes it accidentally)
Cognitive impairment (18) and sedation may limit opportunities for work, study (7)
Risks for cardiac patients, (QTc prolongation and fatal torsades de pointes arrhythmia): Need for ECGs in patients using doses above 100 mg and patients with cardiac risk factors (11,13,18,19,33)
Other adverse effects include sleep apnoea, painful joints and bones, constipation, perspiration, endocrine effects, impact on sex hormones, dry mouth, dysphoria, dyspepsia, opioid-induced oedema, pruritus, weight gain, tooth damage (3,11,18,19,33)
Pharmacokinetics altered in pregnancy so increased need to alter dose during pregnancy (21)
Toxicity increased in the elderly (33)
Harder to transition from and longer more challenging discontinuation (18)
Treatment option: Buprenorphine and buprenorphine/ naloxone
Buprenorphine is a semi-synthetic opioid that is used to treat OUD (15). Buprenorphine is a partial opioid agonist which binds strongly at the mu opioid receptor with a higher binding affinity and lower intrinsic activity compared to most opioid agonists(23). For patients taking buprenorphine, the addition of other opioids may be ineffective in terms of euphoria (19).
It is recommended as an initial choice for patients requiring pharmacotherapy treatment for OUD primarily because of its favourable safety profile and potential for community-based management in the outpatient setting (7,18,22,33). The lower intrinsic activity of buprenorphine is associated with a ceiling effect of receptor activation – respiratory and central nervous system depression is significantly less with buprenorphine as compared to full opioid agonists. In adults, overdoses on buprenorphine alone are not normally fatal.
Buprenorphine exhibits a slower rate of association with, and dissociation from, opioid receptors resulting in a long duration of effect and limiting risk abstinence syndromes in adults on withdrawal. Buprenorphine may cause opioid withdrawal precipitation in individuals with tolerance to opioids higher than buprenorphine’s maximal effect (18,21). It also has a slow rate to associate with and dissociate from the opioid receptor, therefore preventing euphoria following additional opioid use on top (26).
Buprenorphine is available as a single agent or combined with naloxone. Buprenorphine-naloxone (Suboxone®, generics) combines buprenorphine and naloxone, an opioid antagonist (26). Naloxone administered intravenously to opioid-dependent persons, produces marked opioid antagonist effects and opioid withdrawal, reducing potential diversion and misuse. When naloxone is administered orally or sublingually to patients experiencing opioid withdrawal, little or no pharmacological effect is observed (26).
Buprenorphine is well absorbed when administrated sublingually, but has poor bioavailability when ingested orally due to first-pass hepatic metabolism (9,18). Sublingual administrated buprenorphine reaches peak concentration in 1-4 hours, with typical effects to continue to up to 12 hours at low does (2mg), but as long as 48-72 hours at higher doses (16 or 32mg) (18).
Buprenorphine and methadone when used at appropriate doses are equally effective in reducing illicit opioid use and risk behaviours (3). Evidence suggests buprenorphine and/ or buprenorphine/ naloxone is associated with reduced “on top” heroin use (3).
• Buprenorphine is administered as a sublingual tablet (18) and should be taken in conjunction with psychosocial therapy (21)
• Induction onto buprenorphine is normally relatively simple and is different to the induction with methadone, usually safer and easier (18,19,23); patients may reach maintenance doses more quickly (18,19,23,33)
• To reduce the risk of precipitated withdrawal symptoms, when starting buprenorphine, the first dose should be delayed until patients are experiencing mild or moderate withdrawal symptoms (18,21,23)
• Regular patient review is recommended for first few weeks to evaluate adequacy of dose and maintenance does should be achieved within the first one or two weeks (33)
• It has lower potential for misuse compared with full opioid agonists since it is effective in suppressing withdrawal symptoms but produces less euphoria (19,22). Kappa receptor antagonists may be beneficial in the treatment of mood and addictive disorder (18)
• It is recommended that physicians act to reduce chance of diversion, including frequent office visits, urine testing, and recalls visits for pill counts (21)
• Buprenorphine dosage:
– Optimal dose is critical to outcome (21)
– The starting dose is from 2-4mg up to 8 mg per day, depending on degree of tolerance to opioids and extent of opioid withdrawal at first dose (18,33)
– Dose should be increased by 2-4 mg each time. Once the initial dose is well tolerated it can be rapidly increased (19,23,33)
– Optimal doses following induction must be individualised according to patient responses and an optimal dose is critical to obtaining the best outcome (3)
– Doses of buprenorphine at the end of the first week to achieve stabilisation typically range from 12 to 24 mg/day (33) with the proportion of patients who relapse decreasing as the induction dose is increased
– Doses of at least 16 mg are associated with better outcomes, a greater reduction in on-top use of illicit drugs than doses <16 mg (1,16,28,36).
– Doses in excess of 24 mg per day ma
