The presentation, diagnosis, and treatment of opioid dependence

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Reference: March-April 2025 | Issue 2 | Vol 18 | Page 11

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This module gives an expert overview of the presentation, diagnosis, and treatment of opioid dependence, with the latest Ireland-specific treatment guidelines and protocols

Opioid use disorder (OUD) defines the chronic use of opioid drugs (commonly heroin or opioid analgesic drugs) leading to clinically significant stress or impairment. People with OUD are at an increased risk of morbidity, mortality, and other adverse health and social conditions.¹ The condition affects over 16 million people worldwide with over 120,000 deaths annually attributed to opioids,² and many other negative societal outcomes.^3,4

OUD results in a strong compulsion to take opioids, an increase in opioid tolerance over time, and withdrawal symptoms when opioids are discontinued. In Ireland, the main opioid necessitating treatment from addiction services is heroin, but in the past 10-15 years there has been an increase in opioid analgesic dependence and the numbers seeking treatment.

Whilst exact prevalence data remains elusive, it is estimated that from 2006 to 2016 codeine use in Ireland increased 208 per cent.⁵ Because analgesic preparations containing codeine can be sold over-the-counter (OTC) the public perception often underestimates the potential harms of using these drugs regularly. The mainstay of treatment for OUD is opioid substitution treatment (OST). As of 2021, there were 12,657 people in receipt of OST in Ireland.⁶

Identifying OUD

Identifying patients who may potentially suffer from OUD is difficult because of the stigma associated with the condition. For this reason many sufferers find it difficult to present to their healthcare provider (HCP) and discuss options for treatment. It is important to adopt an empathic, non-judgemental approach to any patient who may present for treatment of an issue relating to addiction.

Given heroin is particularly demonised by society, it can often be difficult for patients to open up and talk about the issue. It is also important that any HCP encountering patients with potential OUD is in a position to either treat the problem or make an onward referral.

For HCPs, it is important that they are in a position to identify patients who present with potential opioid problems, particularly where the main reason for the consultation is seemingly unrelated to a potential addiction issue. As outlined, the two main opioids likely to result in problematic use are heroin and opioid analgesics (often codeine). Whilst there are commonalities to the pattern of use and sequelae of both types of opioid problem, the presentation and course of each addiction is often quite distinct.

Heroin addiction

The most common routes by which heroin is taken include injecting, snorting, and smoking (‘chasing’ or ‘chasing the dragon’). The physical consequences of injecting tend to be more severe than smoking or snorting, although the extent and impact of the addiction can be devastating regardless of route of use. Injecting exposes users to a higher risk of fatal overdose, soft tissue infections, deep vein thrombosis (DVT), and viral hepatitis and human immunodeficiency virus (HIV) transmission.

There may be evidence of track marks on arms, but unless the patient specifically reports a history of heroin use and their arms are not visible then it is difficult to pick this sign up. Respiratory complications of smoking heroin include tuberculosis and pneumonia and worsening pre-existing conditions such as asthma and chronic obstructive pulmonary disease.

Heroin addiction, like other chronic addictions, can result in debt, loss of employment and relationships, theft, and contact with the criminal justice system. When an addiction becomes overwhelming, sufferers become prone to various forms of exploitation to pay back drug debts (eg, prostitution, drug dealing, or drug ‘muling’).

Codeine analgesic addiction

Codeine analgesic formulations (mainly codeine-ibuprofen and codeine-paracetamol) are commonly sold OTC in Ireland. In response to growing concerns about the rising use of these medications and problems associated with long-term use, tighter restrictions have been implemented in the past decade.

The medication was once sold ‘front-of-shop’ and consumers could purchase the drug with little scrutiny. A change in the law moved the medication behind the counter so that people buying them had to request them from the pharmacist, while being asked a number of questions relating to safe and short-term use.

Long-term, excessive use of these medications exposes the user to some very serious complications such as stomach ulceration, perforation and bleeding, and renal damage (non-steroidal anti-inflammatory drugs), as well as liver damage (paracetamol).

Pathognomonic of this addiction is the need to travel to different pharmacies in order to secure the medication and stave off withdrawal symptoms. These medications are also not cheap. A severe addiction can cost a lot of money to maintain and push people into debt.

Screening and assessment

There are many different screening tools that can help identify potential opioid problems. One of the most well established, simple, and easy to administer tools is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), criteria for opioid dependence. This is an 11-item questionnaire examining various symptoms and patterns related to opioid use. The presence of two symptoms or more denotes the presence of OUD (see Figure 1) with greater number of symptoms being associated with increasing severity.

A thorough assessment is essential when patients are being commenced on OST. There are a number of internationally validated assessment tools. The National Addiction Centre, King’s College London, has developed a patient assessment guide which consists of 18 headings, covering various important aspects of the history including demographic information, current opioid/other drug/alcohol use, medical/psychiatric history, personal/social/family history, mini mental state examination, differential diagnosis, aetiology, and concluding with a formulation where a plan is made for management and treatment.

A urine test is helpful to establish the presence (or absence) of opioids such as methadone or heroin (morphine). Patients will often access methadone sold illicitly in the period before they commence treatment.

Induction of OST

When a diagnosis of OUD is made and an agreement arrived at to start OST, it is imperative that the induction is carried out safely. Methadone and buprenorphine induction are quite different processes, each medication presenting unique risks to the patient.

Methadone
Methadone is a full mµ opioid agonist with a half-life of 15-60 hours (mean 22 hours). It works by occupying opioid receptors and reduces withdrawal symptoms and craving. The optimum dose range is 60-120mg daily for most patients. A small subset will stabilise on doses smaller than 60mg and some will need greater than 120mg.

It is an oral solution usually containing a methadone concentration of 1mg/ml (although more concentrated versions are used in exceptional circumstances). The usual starting dose is 20-30mg with no more than a gradual 20-30mg dose increase in the first week of treatment. It takes about four to five half-lives to attain steady state serum methadone levels, so that the elimination of the drug is in balance with the amount of drug left in the body.⁷

In some cases, however, it can take much longer, making the person more susceptible to overdose if the methadone dose is inappropriately increased in that first week of treatment.^8,9

Once steady state is reached the person becomes opioid tolerant and this is protective against overdose, rendering heroin relatively ineffective if taken ‘on-top’ of methadone. Methadone treatment is often seen as the gold standard and has decades of research demonstrating its effectiveness in reducing overdose mortality.^10,11 It also reduces injecting and the transmission of bloodborne viruses such as hepatitis C and HIV.¹²

Buprenorphine
Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver Somniferum. It is a partial mµ opioid agonist. It is also a weak kappa receptor antagonist. It reaches a ‘ceiling’ effect at higher doses where escalating doses do not lead to a greater opioid effect. This is important because it results in less adverse effects (eg, respiratory depression) than full mµ agonists (eg, methadone).

Buprenorphine has high affinity for, but low intrinsic activity at, mµ opioid receptors and the high affinity is dose related. Buprenorphine displaces other full mµ opioid agonists from opioid receptors such as morphine and methadone, causing precipitated withdrawal if there is not a washout period of the current opioid prior to switching to buprenorphine.

Methadone to buprenorphine is a particularly tricky conversion as methadone takes a considerable length of time to clear from the system. It is advised that the dose of methadone should be reduced down to as low a dose as possible and no higher than 30mg, with this last dose been taken at least 24-48 hours before the first dose of buprenorphine. If the patient has been taking heroin, they should be advised to use it for the last time six to 12 hours before starting buprenorphine.

In practice, the use of the Clinical Opioid Withdrawal Scale (COWS) is a useful aid to check for objective signs of withdrawal, which should be present before commencing buprenorphine (Figure 3). In recent years microdosing with buprenorphine has allowed an uncomplicated conversion to take place on higher doses of methadone. This practice, however, has not reached Ireland yet.

In Ireland there are two buprenorphine/naloxone formulations licensed for use. Since 2007, suboxone has been used, and recently zubsolv has been made available. There are slight differences in the way the doses are delivered between the two formulations. Equivalent doses are shown in Figure 4.

Naloxone is added to buprenorphine to reduce the risk of misuse. When these products are taken as prescribed, sublingually, buprenorphine’s opioid effects do not allow naloxone to exert its opioid withdrawal effects. However, if the sublingual tablets are crushed and injected, naloxone dominates and can cause opioid withdrawal symptoms.¹³

Once satisfied the COWS score is at least seven, and there are some objective signs of opioid withdrawal present, then the first dose of buprenorphine can be given. Usually the first dose will be 4-8mg on the first day and this can be increased to 12-16mg on day two. Most patients will require doses in the 12-24mg range. Some may need more and some will require less.

Precipitated withdrawal

Precipitated opioid withdrawal results in the rapid onset of opioid withdrawal symptoms (which include aches and pains, nausea and vomiting, diarrhoea and abdominal cramps, dilated pupils, increased lacrimation, rhinorrhoea, yawning, piloerection, goosebumps on skin, etc) within an hour or two of taking the first dose of buprenorphine. The symptoms gradually subside over the next six to 24 hours. This occurs in about 9 per cent of cases of buprenorphine induction.¹⁴

Whilst good assessment and use of the COWS will reduce the risk of precipitated withdrawal, there can be cases where, despite a moderately high COWS score, withdrawal symptoms occur in the hours after taking the fist dose of buprenorphine.

An interesting case study in the Drug and Alcohol Review in 2021 discussed a buprenorphine induction where the patient presented in moderate opioid withdrawal (COWS score 16) and developed precipitated withdrawal. The culprit in this case was thought to have been a single dose of methadone taken a few days previously. The patient did not mention this in the history and said they had only been taking heroin. The precipitated withdrawal symptoms were successfully managed as an inpatient by monitoring symptoms and increasing the buprenorphine dose.¹⁵

Loss of tolerance

Tolerance describes the diminished response to a drug over the course of repeated or prolonged exposure. This mechanism allows physiological processes to achieve stability in a constantly changing environment. In the management of patients with OUD, the importance of opioid tolerance cannot be overstated.

Opioid tolerance differs for different opioids. For example, one of the great benefits of methadone is that within a couple of weeks of commencing treatment it will confer good opioid tolerance, which in turn will make heroin use less effective and reduce the risk of overdose.

There are a number of well-established times in the treatment journey of patients where they are at a significantly heightened risk of fatal overdose due to reduced opioid tolerance. The first occurs at the commencement of methadone treatment and in that period (7-10 days) until steady state is reached and tolerance is uncertain.^16,17

The second is when a patient leaves treatment (or any facility where they have been prescribed OST, eg, hospital or prison) and they have discontinued opioids. With reduced or lost tolerance they may not appreciate that they will be more sensitive to the respiratory depressant effects of heroin should they lapse. Injecting drug users are at a particularly high risk of fatal overdose in these circumstances.

The third circumstance where tolerance can fall is where patients on OST miss doses (usually due to non-attendance). The greater the number of days of OST missed, the greater the tolerance falls. This creates a problem when a pharmacist or doctor is faced with what re-starting dose to give. This tends to be more of an issue with methadone than buprenorphine as it has a greater propensity to cause respiratory depression.

Figure 5 is an algorithm that I formulated following discussion with many overseas addiction medicine colleagues and on the available experiences from a trawl of the literature. The key here is cautious re-induction of methadone doses and each case must be examined on its merits. A good knowledge of the patient’s history and clinical care is essential.

Measuring progress

As outlined earlier, OST has a well-established evidence-base in terms of improving the health of patients with OUD on a number of levels. As a patient progresses through treatment their progress should be assessed in a holistic way and with a view to making treatment accessible and not impeding their opportunity to progress in their life and seek educational and employment opportunities.

OST often gets criticised because patients seem to stay on the medication long-term (even though many patients with other chronic diseases remain on medication for many years, sometimes for life). Patients who wish to reduce their OST dose with a view to coming off their medication should be supported in doing so, but the risk of relapse following detoxification is high (72-88 per cent) and the overdose risk when tolerance is lost is significant. Patients need to be made aware of the risks and re-entry to OST should be seamless should they not succeed.^18,19

Urine testing has a role in assessing progress, but it is over relied upon by many prescribers. A fact borne out by a review of HSE addiction services in 2010. The report was particularly critical of using the results of urine tests to assess take-home OST dose suitability.²⁰ In any case, with the proliferation of newer psychoactive substances and other prescription drugs in the past 10 years, many of these substances will not be captured by a five panel drug screen, limiting the utility of urine testing even further.

Developing a good rapport with your patient, with honest, open dialogue makes it easier for patients to provide reliable information about their drug use. Key areas of assessment include regular attendance and good presentation and not being intoxicated or impaired. When patients are eligible for take-home OST doses, safe storage advice is essential, particularly where there are others in the home who are opioid-naïve (especially young children). Small amounts of methadone, taken unwittingly, can have fatal consequences.

Psychosocial support

Patients with OUD often suffer with comorbid psychiatric conditions. It is estimated that 65 per cent of patients have at least one mental health disorder. The risk is almost seven times higher than in the general population.²¹ There is also a high incidence of anxiety and affective disorders,²² sexual and physical abuse,²³ as well as post-traumatic stress disorders.²⁴ For this reason, it is particularly important to offer good wraparound psychosocial support with a multidisciplinary team approach from specialists in counselling, cognitive behavioural therapy, outreach, nursing, pharmacy, social care, psychology, and psychiatry.

Stigma

Heroin addiction is misunderstood by society. It is often viewed as a moral rather than a health issue. The treatment of heroin addiction (OST) is often as stigmastised and misunderstood as the addiction itself. OST is often depicted in a negative and a stereotypical way.

Pejorative descriptions such as ‘liquid handcuffs’, ‘substituting one addiction for another’ heap further stigma and shame on people who are trying to overcome addiction and usually a multitude of other issues.Labels such as ‘clean’ ‘dirty’ ‘junkie’ and ‘addict’ are degrading. We should view heroin addiction like any other chronic condition.

It is important to establish a good therapeutic alliance as you would when you approach patients suffering from any other condition. OUD should be no different. Punitive practices such as reducing OST doses or excluding patients from treatment for positive urine toxicology have no place in treatment.

Conclusion

Opioid use disorder is a chronic, relapsing, remitting condition which can be effectively treated with pharmacotherapy. The condition should be viewed like any other illness and not as a moral issue. Heroin addiction and the people suffering from it are often demonised by society and this prevents people from seeking treatment.

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