31st January 2024

Opiates

Background

Opioids are classed as substances derived from the opium poppy and a range of synthetic and semi-synthetic compounds that primarily act on the μ opioid receptor. Examples include heroin, morphine and codeine. They all have analgesic effects and suppress respiration, which in some cases can be beneficial, e.g., use of Oramorph to treat shortness of breath as part of palliative symptom management. However, they are one of the most widely abused substances worldwide and have a dangerous side effect profile. Management of overdose, intoxication and withdrawal can be challenging and requires an MDT approach.

Presentation

Acute intoxication with opioids causes euphoria and sedative effects. Nausea, vomiting, dizziness, bradycardia, miosis and respiratory depression can also occur, especially if an IV preparation of opioid is used.

Opiate withdrawal can cause fatigue, coryzal symptoms, restlessness and irritability. Tremor, hypertension, tachycardia, nausea and mydriasis may also be seen. Withdrawal from IV heroin typically starts around six hours after injection and peaks at 36 to 48 hours. Scales available to rate opioid withdrawal severity include the Clinical Opiate Withdrawal Scale (COWS) and the Short Opiate Withdrawal Scale (SOWS)

Opioid dependence can be defined by the following ICD-10 criteria:

• Feeling the need/desire to take opioids (prescribed or otherwise)
• An inability to control the level or cessation of opioids
• Withdrawal symptoms  if opioids are not used for a period
• Opioid tolerance development
• Social withdrawal due to opioid use and needing to spend time both recovering from the side effect profile and obtaining more opioids
• Continuing to use opioids despite evidence of their negative effect, e.g., low mood

Diagnosis 

Diagnosis of acute opioid intoxication or withdrawal is largely clinical; however, urine sample testing can be used. Buprenorphine can be detected for 1-2 weeks post ingestion, methadone for 3-4 days, opiates like morphine for 2-3 days, and oxycodone for 1-2 days. Opioid dependence can be identified by considering the above ICD-10 criteria described.

Differential diagnosis

The physical symptoms of intoxication, such as nausea and vomiting, could mimic cerebellar syndromes, and the depressive effects can also mimic the action of benzodiazepines. Withdrawal symptoms such as tachycardia could present similarly to an arrhythmia, and should be explored via appropriate investigation, e.g., ECG.

Management

Opioid overdose

Overdose can be managed with naloxone if needed, for example, for patients presenting with reduced GCS at risk of airway compromise. This should be given in a stepwise approach to avoid precipitating withdrawal, due to the risk of recurrence of dangerous levels of sedation when the naloxone effect subsides (about 30-60 mins). Individuals with heroin dependence should be given overdose awareness training and take-home naloxone alongside opioid substitution therapy to increase safety practices.

Opioid withdrawal

Lofexidine is a non-opioid alpha-adrenergic agonist that can be used to manage symptoms of opioid withdrawal. NICE recommends its use for patients who have declined opioid substitution, wish to detoxify quickly or have only mild or uncertain dependence. Side effects include dry mouth and drowsiness, hypotension and bradycardia.

Opioid substitution

Opioid substitution (via a service referral) should be considered if the following criteria are met:

1. Regular opiate use (often daily).
2. Convincing evidence of current dependence.
3. Ability to comply with the substitution regimen.
4. Not receiving opioid substitution from an alternative source/clinician.

Methadone or buprenorphine can be used as opioid substitution treatment for opioid dependence. Initiation of treatment should be titrated to achieve a dose that avoids intoxication, withdrawal and leads to complete cessation of illicit opioid use. For methadone, this typically takes two to four weeks, but titration of buprenorphine is usually faster. In general, a typical starting dose of methadone would be 10-30mg, and a typical starting dose of buprenorphine would be 4-8 mg. An average maintenance dose of methadone would be between 60 and 120 mg daily, and an average maintenance dose of buprenorphine would be between 12 and 16 mg daily.

Methadone has full agonist properties and is a liquid preparation. Tablet form is available for special circumstances, e.g., to reduce nausea and vomiting. Ultra-long-acting forms like depot aren’t approved for UK use yet. It has a half-life of 13-50 hours, so delayed toxicity can occur; therefore, careful monitoring and dose adjustment are needed during initiation. Buprenorphine is a sublingual tablet with partial agonist and antagonist properties. There is a risk of precipitated withdrawal if the first dose is given when circulating opioids are still present due to the antagonist properties; therefore, the first dose should be given when withdrawal begins (6-12 hours after last opioid use). Both are metabolised by P450 enzymes so prone to drug interactions.

NICE recommends both methadone and buprenorphine. Evidence suggests buprenorphine is associated with lower incidence of fatal overdose during the start of treatment initiation but that more patients remain engaged with treatment when methadone is used. Other factors to consider when choosing which to initiate would include patient preference, any previous treatment failure and existing medication/alcohol interactions. Once established on maintenance treatment, the risk of death by overdose is considerably lower than prior to treatment.

When patients on community opioid substitution are admitted to hospital it is important to independently clarify the patient’s dose and when their last dose was supervised to have been taken (with their key worker and pharmacy). Once this has been confirmed if they have been regularly taking the prescribed medication the same dose can be continued. They should also be given information about drug treatment services, blood-borne virus infections and how to prevent drug overdose. This is termed harm reduction and is an important part of opioid management to consider.

References

• Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. UK: Department of Health; 2017.
• Stringer S, Church L, Keynejad R, Hurn J. Psychiatry P.R.N.: Principles, reality, next steps. Oxford: Oxford University Press; 2020.
• Opioid dependence [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://cks.nice.org.uk/topics/opioid-dependence/ 
• The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines [Internet]. World Health Organization. World Health Organization; 1992 [cited 2022Dec3]. Available from: https://apps.who.int/iris/handle/10665/37958