Primary prevention
Before starting any opioid therapy, efforts should be made to maximise use of non-pharmacological and non-opioid pharmacological therapies as appropriate. There is evidence that shows non-opioid therapies are at least as effective as opioid therapies for acute pain, and that they are preferred to opioid therapies for subacute and chronic pain.[30][31] This may have potential implications for further reducing the use of opioids in the accident and emergency department and in the community. New classes of drugs, such as the recently approved suzetrigine, a first-in-class non-opioid, non-addictive analgesic, may provide different methods of pain treatment in adults, thus preventing opioid overdose.[32] Opioid therapy should only be considered if expected benefits for pain and function are anticipated to outweigh risks to the patient.[31]
Clinicians prescribing opioids should identify treatment resources for opioid use disorder (OUD) in the community, and establish a network of referral options across the different levels of care that patients might need. This is to ensure prompt referral and treatment, if needed.[31]
The patient’s history of controlled substance prescriptions should be reviewed ideally before every opioid prescription, and at the very least, prior to the first prescription and then at 3-monthly intervals. This can help determine whether the patient is receiving opioid dosages from multiple prescribers, which puts them at increased risk of overdose. In the US, patient prescribing histories can be viewed via state Prescription Drug Monitoring Programs (PDMPs).[33] Using PDMPs to inform treatment decisions has changed prescribing behaviours and decreased opioid-related harms and treatment admissions.[34] However, PDMP-generated risk scores have not been validated against clinical outcomes such as overdose, and therefore should not take the place of clinical judgment.[31]
Patients who regularly use opioids (therapeutically or recreationally) should be educated about the dangers of overdose, especially after periods of abstinence. This education is associated with a reduction in death from overdose.[35] Patients at high risk, together with family members and caregivers, should be educated about the recognition and management of opioid overdose, including the administration of naloxone.[31][33][36][37]
The US Department of Health and Human Services (HSS) and Centers for Disease Control and Prevention (CDC) advise clinicians to strongly consider co-prescribing naloxone alongside opioids for the following groups:[31][38]
Those receiving opioids at high doses (50 mg morphine equivalents dose per day, or greater)
Patients with sleep-associated respiratory conditions such as sleep apnoea
Those prescribed benzodiazepines
Patients with a history of alcohol or non-opioid substance use disorder
Those at risk for returning to a high dose to which they have lost tolerance (e.g., patients undergoing tapering or those recently released from prison).
The HHS further recommends prescribing naloxone for patients who have a mental health disorder, and also for those who use heroin or illicit synthetic opioids, who misuse prescribed opioids, and/or who use other illicit drugs, which may be contaminated by synthetic opioids (such as fentanyl).[38] In the US, naloxone may be co-prescribed to be administered intramuscularly, intravenously, and subcutaneously.[33]
In some countries (e.g., England) naloxone has long been available without a prescription and can be obtained by a family member or friend of a heroin user at risk, for the purpose of saving life in an emergency.[39] In the US, naloxone nasal spray is approved for use without a prescription.
Note that available naloxone may be insufficient to reverse an overdose; patients, family members, and carers should be advised to call emergency services immediately upon recognition of an opioid overdose.[36]
Co-prescription of opioids and benzodiazepines should be avoided whenever possible as their concurrent use increases the risk of potentially fatal overdose.[31][40][41]
Extreme caution should be exercised when prescribing and using fentanyl patches due to the increased risk of serious and fatal overdose.[42] Reports of overdose are related to dosing errors, accidental exposure, and exposure of a patch to a heat source (including increased body temperature resulting from a fever). Children are particularly at risk of accidental exposure (e.g., a partially detached patch may be transferred from an adult to a child during sleep or a child may think the patches are stickers or tattoos).[43] Patients and carers should therefore be provided clear follow guidance on how to store, use, and dispose of patches safely.
Awareness of local trends in opioid use are also helpful with primary prevention strategies. For example, in the US, there have been shifts towards increased smoking of illegally manufactured fentanyls, versus injecting, in the Midwest, South, and West, and sniffing or snorting illegally manufactured fentanyls in the Northeast. Understanding local trends can increase effectiveness of local messaging, outreach, connecting to medical services which hopefully in turn will help to prevent overdose.[44] Fentanyl testing strips are another important strategy in overdose prevention, and can be a life saving tool in the community. However, there continues to be lot-to-lot variability and more sophisticated testing methods are needed.[45]
If clinicians suspect OUD, they should assess for this using DSM-5-TR criteria.[46] Clinicians should discuss their concerns with their patients in a non-judgmental manner, and allow the patient to disclose any related issues. OUD can co-exist with other substance use disorders; therefore, clinicians should ask about use of alcohol and other substances.[31]
Proper needle use is also an important strategy to prevent overdose in people with OUD. Patients should be counselled on avoiding opioid use while alone, and instructed on the use of clean needles or techniques to clean needles. One systematic review found that for injection drug users, supervised injection facilities may reduce the risk of overdose morbidity and mortality and improve access to care, while not increasing crime or public nuisance to the surrounding community.[47]
Secondary prevention
Secondary prevention interventions seek to identify which patients are at risk of repeat overdose through continued opioid use disorder (OUD), in order to minimise the potential negative consequences (e.g., overdose, death) as much as possible. This can be achieved by expanding access to drug treatments and other support systems.[90] The tools for secondary prevention are often also relevant to and overlap with those for primary prevention.
Drugs for OUD are generally considered to be a first-line intervention for treating patients with chronic OUD. As such, in combination with counselling and behavioural therapies, it has the potential to meaningfully improve patient future outcomes and hopefully avoid repeat unintentional overdose.[91] Initiation, especially across varied care settings (e.g., accident and emergency department, inpatient) in the health system, has been shown to significantly reduce unplanned hospital readmission rates in patients with OUD.[92] Initiation and future accessibility should be provided to patients prior to leaving the acute care setting.[93] In the US, this may be via a substance use disorder consultant or from a Substance Abuse and Mental Health Services Administration certified opioid treatment programme.[31] Detoxification alone, without drug treatments for OUD, is not recommended due to increased risks of resuming drug use, overdose, and overdose-related deaths.[31]
Awareness of the various drug types in relation to risk behaviour can be helpful for secondary prevention. One large meta-analysis study looking at the association between drug type, risk behaviours and non-fatal overdose among drug users found certain factors, including non-injection opioid use, heroin injection, incarceration, injecting drugs, duration of injecting, and concurrent use of buprenorphine and benzodiazepines, were associated with greater odds of non-fatal overdose among drug users. The findings support the need to improve suitable harm reduction strategies for drug users, such as peer-based overdose management, and improve health-related interventions.[94]
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