Nine out of ten overdose deaths involve prescribed or OTC medicines, writes Dr Des Corrigan
The number of poisoning or overdose deaths in Ireland was down by almost 20 per cent – to 354 – in 2021, compared to the previous year, according to the bulletin on drug-related deaths published in September by the Health Research Board (HRB) team responsible for compiling the National Drug Related Deaths Index (NDRDI).
However, almost nine in 10 such deaths involved one or more prescribed drugs such as opioids, benzodiazepines (BZD), Zed drugs, anti-depressants, anti-psychotics, anti-epileptics, and surprisingly, anti-histamines.
For the most part it is a case of “round up the usual suspects” because the majority of deaths involved methadone, cocaine, BZD, and alcohol – often in combination, with the bulletin noting that in 81 per cent of cases polydrug use was implicated.
Not surprisingly, there was much media attention on the trebling of cocaine-related deaths between 2012 and 2021, which is the most recent year for which figures are available, but little attention given to the elephant in the room, which was an even bigger rise in deaths attributable to one or more pharmaceuticals.
For example, there was a five-fold increase in deaths due to alprazolam, from 18 in 2012 to 107 in 2021. Deaths in which gabapentinoids were implicated rose by 410 per cent between 2013, when there were 14 fatalities, and 2021 when there were 83 deaths linked to pregabalin as well as another 14 fatalities where gabapentin was detected.
In fact, between 2013 and 2021 there were a staggering 514 deaths in which pregabalin was implicated, in comparison to 677 deaths for cocaine and 905 deaths for heroin. I have expressed my concern about pregabalin on many previous occasions, most recently in March of this year. That article had already gone to press when the Irish Times editorial on 28 February called for the inclusion of gabapentinoids within the Misuse of Drugs Acts. I could not have agreed more when it roundly condemned the inaction of the Department of Health and the Health Products Regulatory Authority (HPRA), and asked how much more evidence did they need in order to act. In my view all the evidence needed is contained in this recent NDRDI data – and regulatory action will save many lives.
An unpleasant surprise in the HRB bulletin was that one or more anti-depressants were detected in 124 deaths. The main drug listed was mirtazapine followed by sertraline, but amitriptyline, venlafaxine, and fluoxetine also featured. However, although 16 deaths were linked to citalopram in 2016 it is not linked to any deaths this time.
It is not possible to know if these anti-depressant-related deaths were deliberate or accidental. The bulletin notes that at least 48 per cent of those who died had a history of mental health issues and were in contact with medical services. It puts a spotlight on the delicate balancing act needed when prescribing for a patient with a dual diagnosis of depression and opioid use disorder so that both can be adequately treated while avoiding dangerous polydrug interactions.
The most surprising aspect of the report was the detection of promethazine and diphenhydramine in post-mortem samples. Again, it is not possible to know for sure if the use of either anti-histamine was accidental or deliberate as most of the fatalities also involved several other drugs.
One possibility regarding promethazine is that it was being deliberately abused for its intoxicating effect in the form of a drink called ‘Lean’ or ‘Purple Drank’ which is made from promethazine and codeine syrup (or, if this is unavailable a dextromethorphan-containing syrup can replace the codeine), mixed with a soft drink and sweets to mask the bitter taste.
Drinking Lean has been associated with elements of hip-hop and rap culture in the US. Here, it has been mentioned as being occasionally used in the Blanchardstown area according to the Drug and Alcohol Trends Monitoring System developed on behalf of the Local Drug and Alcohol Task Force.
This suggests that Lean could be an issue in other areas and highlights the need for pharmacists to be vigilant about unusual patterns of requests for promethazine products, especially those that are over-the-counter (OTC). It is worth noting that the Summaries of Product Characteristics (SPC) draws attention to case reports of drug abuse particularly in patients with a history of such abuse, and to the ability of promethazine to potentiate the effects of alcohol and other CNS depressants. The same applies to the many OTC forms of diphenhydramine with the SPC typically referring to abuse/dependence in teenagers and young adults resulting from recreational use.
An unpleasant surprise in the HRB bulletin was that one or more antidepressants were detected in 124 deaths
It is probable that OTC products also contributed significantly to the 198 deaths involving codeine in the period from 2013 to 2021. I say this as some 80 per cent of respondents to the Irish National Drug and Alcohol Survey who reported using codeine in the month prior to the survey indicated OTC use compared to 14 per cent who stated that prescribed codeine was involved.
Whether the 27 deaths in 2021 prompts Ireland to make codeine a prescription-only medicine (POM) as is the case in many other countries remains to seen. It seems unlikely given the slowness of the authorities to reclassify pregabalin or control the even more toxic nitazenes.
However, the profession must be seen to react to the stark findings of this bulletin. Both the Pharmaceutical Society of Ireland (PSI) and the Irish Pharmacy Union (IPU) need to become proactive in reducing the effects of pharmaceutical drug misuse.
Firstly, the next National Drugs Strategy must fully identify and explicitly endorse the key role of pharmacists in the prevention and treatment of problematic drug use. Secondly, the profession needs to enter into discussions on a collegiate basis with the various representative medical bodies to facilitate meaningful changes in the prescribing and dispensing of opioids, BZDs, and other psychotropics that meet the needs of patients while reducing harms up to and including death.
For example, in cases where opioids and BZDs absolutely have to be co-prescribed, then consideration should be given to the simultaneous provision of take-home naloxone to such high-risk patients.
“Where there’s a will, there’s a way” and it is vital to reduce the number of deaths from pharmaceutical drug poisonings.
Dr Des Corrigan, Best Contribution in Pharmacy Award (winner), GSK Medical Media Awards 2014, is an Adjunct Associate Professor at the School of Pharmacy and Pharmaceutical Sciences at TCD where he was previously Director and won the Lifetime Achievement Award at the 2009 Pharmacist Awards. He was chair of the Government’s National Advisory Committee on Drugs from 2000 to 2011, having previously chaired the Scientific and Risk Assessment Committees at the EU’s Drugs Agency in Lisbon. He chaired the Advisory Subcommittee on Herbal Medicines and was a member of the Advisory Committee on Human Medicines at the HPRA from 2007 to 2024. He has been a National Expert
on Committee 13B (Phytochemistry) at the European Pharmacopoeia in Strasbourg and served on the editorial boards of a number of scientific journals on herbal medicine.
