Drug-related deaths: practical responses to a growing problem

This review discusses the reasons behind the ever-growing number of drug-related deaths (DRDs) due to misuse in the UK, the principal types of drug involved, and practical ways in which prescribers can support patients to help reduce the risks.

In 2018, drug-related deaths (DRDs) were at their highest recorded levels in England, Wales and Scotland. While non-prescribed opioid misuse remains the major contributor to these deaths, other drugs have started to emerge as problematic. In this article, I will explore the current DRD milieu primarily in England and Wales with some reference to Scotland; what drugs and other substances are involved; the risk factors for DRDs; and what prescribers can do to help reduce DRDs.

What is the current picture for DRDs in the UK?

In 2018, there were 4359 deaths relating to drug poisoning in England and Wales, the highest number and the highest annual increase (16%) since records began in 1993. Two-thirds of DRDs were related to drug misuse (2917 deaths) and the majority were accidental (80% in males and 67% in females). The mortality rate of males continued to be over twice the rate of females (105.4 vs 47.5 deaths per million) but the female rate increased for the ninth consecutive year. Individuals aged between 40 and 49 years had the highest age-specific drug misuse rate at 125.7 deaths per million, with increases in all age groups except those 70 years and older (see Figure 1).1     


Figure 1. Age-specific mortality rates for deaths related to drug misuse, by age group, England and Wales, registered between 1993 and 2018. Source: Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2018 registrations. August 20191

A wide variation is also seen in the different regions of England and Wales. The North East continues to have a significantly higher rate of deaths relating to drug misuse than all other English regions while London has a significantly lower rate (see Figure 2).1 Public Health England (PHE) has reported a correlation between economic and health inequalities, deprivation and DRDs, observing the highest rates and sharpest rises in the North East and North West of England, although they also note the high rate of drug use in these areas, which may also account for some of the correlation.2    


Figure 2. Age-standardised mortality rate for deaths related to drug misuse, by country and region, registered in 2018. Source: Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2018 registrations. August 20191

Deaths involving fentanyl remained stable at 74 in 2018 compared to 75 in 2017 in England and Wales while deaths related to cocaine were at their highest levels in 2018 at 637, almost double the number registered in 2015 (320 deaths).1 Deaths involving heroin and morphine increased to their highest ever rate in 2018 at 1336 or 20.4 deaths per million; a 14% increase compared to 2017. One reason highlighted for this is that heroin purities remain “consistently high”.3    

In Scotland there were 1187 deaths related to drug poisoning registered in 2018, an increase of 27% compared to 2017, which represents the largest number ever recorded and more than double the number recorded a decade ago.4

Drugs involved in DRDs

Opioids

Opioids represent the most prevalent group of drugs mentioned in DRDs in 2018. In England and Wales, 2644 deaths or 60.7% of all DRDs mentioned opioids. Figure 3 shows a breakdown of the contribution of different types of opioids to DRDs in 2018.1    


Figure 3. Drug-related deaths in 2018 for different types of opioid drugs in England and Wales. (% increase/decrease vs 2017 figures in brackets). Source: Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2018 registrations. August 20191

Opioids can lead to DRD mainly through respiratory depression. Combining opioids with other drugs or substances, for example, antidepressants and/or alcohol, increases the risk of respiratory depression and death. Deaths involving heroin are becoming more polysubstance use in nature with alcohol being the most common other substance used, but there have also been increases in use of other substances including benzodiazepines.5 A study in Scotland demonstrated that 97% of DRDs were the result of multiple drugs present in the body at death, with more than one drug implicated in 68% of DRDs.6    

In the UK since October 2015, people working in drug treatment services have been permitted to supply the opioid antagonist naloxone without a prescription to individuals who may come into contact with people at risk of opioid overdose, for use in an emergency. The licensed intramuscular naloxone formulation in the UK (Prenoxad) will completely reverse the effects of an opioid overdose in the majority of cases if administered in time. In September 2018, an intranasal formulation of naloxone (Nyxoid) was introduced to the market, and this can now also be supplied without a prescription for use in an emergency following a change in the legislation in February 2019.

Benzodiazepines and Z-drugs

In 2018, benzodiazepines were involved in 420 deaths in England and Wales, an increase of 29 (7.4%) on 2017. Z-drugs (zopiclone and zolpidem) were involved in 143 deaths, an increase of 13.5% on 2017 and the highest level since records began in 1993. Benzodiazepines rarely cause DRDs as a sole agent, although cases have been reported. However, when combined with other drugs, particularly opioids, and when used at supra-therapeutic doses, they can demonstrate significant interactions:6

  • Pharmacokinetic – At very high doses, benzodiazepines can increase opioid and other drug blood concentrations. This is primarily as a result of competition at the CYP3A4 metabolic pathway, which can result in reduced clearance of one or more drugs and increase the risk of DRD. The same mechanism occurs for z-drugs. Drugs metabolised through this pathway include methadone, buprenorphine, tricyclic antidepressants, SSRIs, trazadone, alcohol and antipsychotics
  • Pharmacodynamic – Benzodiazepines can have a synergistic CNS depressive effect in the presence of opioids, alcohol and/or other CNS depressants. This is particularly relevant for buprenorphine, as supra-therapeutic doses of benzodiazepines have been shown to reduce or inhibit the protective respiratory depression ‘ceiling effect’ of buprenorphine.

Cocaine

Cocaine is the second most commonly used illicit drug in the UK and purity levels are at a historical high.1 It is not possible to distinguish between the use of powdered cocaine or crack cocaine in these DRDs, but deaths mentioning cocaine have shown a rising trend in England and Wales since 2011.    

Deaths involving cocaine are usually cardiovascular in nature. These include arrhythmias, myocardial infarction and stroke. Reports of death through excited delirium syndrome, characterised by hyperthermia, delirium and agitation, have also been reported. Serotonin syndrome may be a significant component, which may be compounded by the use of other substances including, for example, SSRI prescription drugs. Clinicians should be aware of the risks of serotonin syndrome when discussing the harms of using any substances that may increase the levels of serotonin. Table 1 summarises the signs and symptoms of mild, moderate and severe serotonin syndrome.7


Table 1. Signs and symptoms of serotonin syndrome. Reproduced with permission of American Association of Critical-Care Nurses from: Cooper BE, Sejnowski CA, 20137

New psychoactive substances

New psychoactive substances (NPS; previously known as ‘legal highs’) represent a diverse range of drugs. In 2017, over 560 substances were being monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) with 100 new agents identified in 2015.8 NPS can be stimulant-like, cannabinoid-like, hallucinogenic, depressant-like or opioid-like. The nature of the NPS will also reflect its action and mortality risk.    

In 2018, NPS deaths in England and Wales returned to 2016 levels (125 vs 123 deaths), having dipped to 61 deaths in 2017.1 The Home Office has concluded that, due to the lack of evidence on the extent to which NPS users have substituted with other substances, it is not possible to identify whether the introduction of the Psychoactive Substances Act (2016) has led to an overall reduction in drug-related harm.

Gabapentinoids

The CNS depressant effect of the gabapentinoids (gabapentin and pregabalin), particularly when combined with opioids and usually at high doses, is a significant risk factor that has been implicated in DRDs. Pregabalin has represented a growing concern in the health community and, together with gabapentin, was classified as a Schedule 3 controlled drug from April 2019. In 2018 there were 187 deaths involving pregabalin in England and Wales – a doubling in the DRD rate compared to 2015 (90 deaths). The increase in DRDs for pregabalin has also correlated closely with an increase in prescribing.9 A similar increase has also been seen with gabapentin with 93 deaths recorded in 2018, against a figure of 49 in 2015.

What are the risk factors for DRDs?

There are a number of factors that can impact on the risk of a DRD. A report produced by PHE in 2016 outlined the multifactorial nature of DRDs and highlighted a number of risk factors.2 These included:

  • The availability of heroin and its purity
  • The ageing cohort of heroin users who are now experiencing cumulative physical and mental health conditions that make them more susceptible to overdose
  • Non-engagement in drug treatment
  • Polydrug and alcohol use
  • Increasing suicides
  • Increasing deaths among women
  • Improved reporting
  • Increased prescribing of some medicines.

A further PHE-commissioned ‘deep-dive’ study in 2017 also identified some common characteristics in a cohort of 115 drug misuse deaths.10 These are highlighted in Table 2. The findings of this study point to a vulnerable, at-risk population engaging in unsafe drug-taking practices such as consuming multiple drugs alongside alcohol. Other risk factors include:

  • Injecting drug use
  • Taking drugs alone
  • High-dose opioid use
  • Low tolerance due to recent discharge from prison or after completion of an opioid detoxification.


Table 2. Common characteristics of people at increased risk of drug misuse deaths10

What can prescribers do to help reduce DRDs?

There are a number of practical ways in which prescribers can try to help reduce the incidence of DRDs, as outlined below.

Harm-reduction advice

Prescribers should actively promote harm-reduction messages to patients. This would include, for example, promotion of safer methods of drug taking such as oral use or smoking in preference to injecting. Prescribers should always provide advice on the risks of polysubstance use, including alcohol, for patients prescribed medication and for those using non-prescribed drugs.

Low-volume (quantity) prescribing

Where there is a risk of potential misuse and/or diversion then prescribers should adopt a pragmatic approach to the quantity of medication prescribed. This would also include a risk assessment on self-harm. For example, a patient who has a recent history of self-harm involving medication and a current substance use disorder should not receive large quantities of a drug with a potential for harm, eg a tricyclic antidepressant. A prescription for 7 to 14 days’ treatment with a regular review period may be appropriate.

Naloxone distribution and training on managing opioid overdoses

Drug treatment services across the UK are now familiar with naloxone and are able to distribute it for use in an emergency in people at risk of an opioid overdose. Prescribers need to be aware of the availability of both the intramuscular and intranasal formulations, and either supply under the current legislation or prescribe to those patients at risk of an opioid overdose. Prescribers can work with the local drug and alcohol service to understand current supply, and where supply through the primary care network would be an advantage. This could include, for example, where prescribers are supplying high-dose opioid prescriptions especially to patients who have had a recent history of overdose.

Patients supplied naloxone in primary care should, as a minimum, be provided with information and support on:

  • How to recognise an opioid overdose
  • How to administer the formulation and
  • How to administer basic life support.

The manufacturers of both the intramuscular and intranasal formulations of naloxone provide websites to support both professionals who prescribe and patients who are supplied with naloxone. These are available at:

Management of physical and mental health needs in the older population

Meeting the general health needs of this ageing cohort of drug users is an essential component of reducing DRDs, as recognised by PHE in 2016.2 There is a role for a whole-system approach here, which includes innovative commissioning, but primary care prescribers should be mindful to deliver effective services for this group. This would also include the promotion of smoking cessation services.

Referral to structured treatment

There is now robust evidence that people in structured treatment and receiving evidence-based drug interventions are at lower risk of a DRD compared to those not in treatment, especially those who use heroin.2 Prompt access to structured treatment with careful induction and dose optimisation can therefore support a reduction in the risk of DRDs. Prescribers should be aware of the process for referring patients to structured treatment, and follow up these referrals to check that individuals have engaged with treatment.

Supervised consumption and safe storage of medication

Supervision of consumption of medication by an appropriate professional (usually a community pharmacist) provides the best guarantee that a medicine is being taken as prescribed. While an essential component of recovery is allowing an individual to take home their medication, where appropriate, a patient prescribed an opioid substitution treatment (OST) should receive this initially under a supervised consumption arrangement.    

Safe storage is an essential component of medicines management for all healthcare professionals. Patients prescribed medication should be provided with information about the risks of the medicine and healthcare professionals should check that safe-storage arrangements are in place at home.

Conclusion

Reducing DRDs is every healthcare professional’s responsibility. This article highlights the current high levels of DRDs in the UK and provides suggestions on the reasons behind this significant problem and which drugs are involved. Prescribers can adopt a number of simple, practical steps to support individuals and try to reduce this trend. From simple harm reduction advice to supporting patients to engage with structured treatment and the supply of naloxone, it remains the responsibility of all healthcare professionals to support a reversal in the increasing DRD trend.

Declaration of interests

Graham Parsons has received funding from Martindale Pharma to provide educational talks at conferences and from Indivior to attend a conference.

Graham Parsons is Chief Pharmacist and Pharmacist Independent Prescriber at Turning Point, London

References

  1. Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2018 registrations. August 2019. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/
    birthsdeathsandmarriages/deaths/bulletins/
    deathsrelatedtodrugpoisoninginenglandandwales/2018registrations
  2. Public Health England. Understanding and preventing drug-related deaths. The report of a national expert working group to investigate drug-related deaths in England. September 2016. Available from: https://assets.publishing.service.gov.uk/government/uploads/
    system/uploads/attachment_data/file/669308/Understanding_and_preventing_drug_related_deaths_report.pdf
  3. National Crime Agency. National strategic assessment of serious and organised crime. 2019. Available from: https://nationalcrimeagency.gov.uk/who-we-are/publications/296-national-strategic-assessment-
    of-serious-organised-crime-2019/file
  4. National Records of Scotland. Drug-related deaths in Scotland in 2018. July 2019. Available from: https://www.nrscotland.gov.uk/files//statistics/drug-related-deaths/2018/drug-related-deaths-18-pub.pdf
  5. Barnsdale L, et al; National Services Scotland. The National Drug-Related Deaths Database (Scotland) report: analysis of deaths occurring in 2015 and 2016. Available from: https://www.isdscotland.org/Health-Topics/Drugs-and-Alcohol-Misuse/Publications/2018-06-12/2018-06-12-NDRDD-Report.pdf?20693606139
  6. Johnson CF, et al. Investigating the role of benzodiazepines in drug-
    related mortality. A systematic review undertaken on behalf of The Scottish National Forum on Drug-Related Deaths.
    NHS Health Scotland, 2016. Available from: https://www.scotpho.org.uk/media/1159/
    scotpho160209-investigating-the-role-of-benzodiazepines-in-drug-
    related-mortality.pdf
  7. Cooper BE, Sejnowski CA. Drug update: Serotonin Syndrome: recognition and treatment. AACN Adv Crit Care 2013;24(1):15–20. Permission conveyed through Copyright Clearance Center, Inc.
  8. Tracy DK, et al. Novel psychoactive substances: types, mechanisms of action, and effects. BMJ 2017;356:i6848.
  9. Lyndon A, et al. Risk to heroin users of polydrug use of pregabalin or gabapentin. Addiction 2017;112(9):1580–9.
  10. Office for National Statistics. Drug-related deaths “deep dive” into coroners’ records. August 2018. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/drugrelateddeathsdeepdiveintocoronersrecords/2018-08-06

Drug-related deaths: practical responses to a growing problem.

Add yours ↓
Web design and marketing agency Leamington Spa