Review of findings in a case series of NPS benzodiazepines in UK deaths

Abstract

Review the other drugs present and circumstances in fatalities where NPS benzodiazepines have been detected in a case series from the UK. Determine the most frequent NPS benzodiazepines involved in deaths and concentrations where possible. Benzodiazepine-type New Psychoactive Substances (NPS) have been increasingly detected in toxicology casework worldwide. These NPS benzodiazepines are potentially more potent than traditional benzodiazepines and may present an increased risk to the user, especially if other CNS depressant drugs are taken. Also, concentration data are sometimes lacking that may be useful in determining additional toxicological significance to the cause of death. As part of routine post-mortem toxicology analysis, NPS benzodiazepines have been detected, and where able, measured in blood by LC-MS-MS. Data from 35 cases involving such drugs are presented, including other drug and alcohol findings as well as the context of the death (e.g. drug related death or alternative cause). The number and frequency of different NPS benzodiazepines has been compiled along with concentrations (where available) as well as other drug findings collated by drug type. Across the 35 fatalities, 7 different NPS benzodiazepines were detected. In decreasing order of frequency; flubromazolam (13 cases), bromazolam (12), etizolam (9), flualprazolam (5), flubromazepam (1), phenazepam (1) and bromazepam (1). 80% of cases had only one NPS benzodiazepine present with 20% of cases having two NPS benzodiazepines. All fatalities were either a drug related death–83% (including cases where other drugs were present that may have been more significant than the NPS benzodiazepines) or involved an alternative cause of death–17% (including hanging, hit by a train or other medical cause). Other drugs or alcohol were detected in all cases; traditional benzodiazepines (e.g. diazepam, lorazepam, clonazepam, alprazolam) were the most common (28 detections), followed by cocaine and antidepressants (21), methadone (16), heroin/morphine (15), pregabalin (14), codeine (12), other opioids (12), alcohol and cannabis (8), zopiclone (5), ibuprofen/paracetamol (4), ketamine, antipsychotics and anticonvulsants (3), antihistamines, amphetamines and erectile dysfunction drugs (2). In terms of concentrations (where measured), flualprazolam concentrations ranged 8.7-26 ng/mL (median 20 ng/mL, n = 5), flubromazolam concentrations ranged 2.9-45 ng/mL (median 13 ng/mL, n = 11) and etizolam concentrations ranged 4.6-95 ng/mL (median 37.5 ng/mL, n = 6). As drugs with CNS depressant capabilities, NPS benzodiazepines present a risk of toxicity to users, especially if other CNS depressant drugs are co-used. This risk is increased due to the availability of these drugs often as adulterants or in falsified traditional benzodiazepines (such as diazepam and alprazolam), whereby the user may not be aware of the constituent drugs in any product consumed and this was suspected to have occurred in some of the cases featured along with use of traditional benzodiazepines as well. The review shows that poly-drug use is a particular issue with these cases; principally traditional benzodiazepines, cocaine, heroin/morphine, antidepressants, methadone and other opiates and opioids. The concentrations of NPS benzodiazepines found, where measured, provide some data for toxicologists if investigating post-mortem casework and indicate a need for sensitive qualitative and quantitative techniques. The concentrations also overlap with available data for other (non-fatal) case types such as driving under the influence so “fatal” ranges do not seem to apply. NPS benzodiazepines have been detected in a number of drug related and non-drug related deaths in the UK supporting their prevalence worldwide. Toxicologists should ensure the necessary analytical capabilities to detect what could be low concentrations despite presenting potential toxicological significance to cause of death.