Fast and reliable analysis of veterinary metomidate and etomidate in human blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a postmortem case.

Metomidate and etomidate belong to the non-barbiturate imidazole family of sedative-hypnotics and elicit little analgesic action when used alone. Metomidate, in particular, has little analgesic activity in humans and is, therefore, used for veterinary purposes. In 2019, a Korean woman in her twenties was found unconscious in a motel bath and eventually died. Etomidate, alprazolam, escitalopram, and metomidate were detected in the postmortem specimens. To our knowledge, this is the first case of human metomidate abuse reported in the Republic of Korea. In this research, a simple and reliable method was developed for the analysis of metomidate and etomidate in human blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Blood samples were deproteinized with acetonitrile, filtered, and analyzed by LC-MS/MS. Linear calibration curves were obtained with six concentrations ranging from 1 to 50 ng/ml for metomidate and 10 to 500 ng/ml for etomidate. The method was validated by assessing the selectivity, linearity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precision and accuracy, matrix effect, and stability and successfully applied to the analysis of metomidate and etomidate in human blood samples. In a postmortem case, the concentrations of metomidate and etomidate were found to be 8 and 110 ng/ml in femoral blood and 6 and 210 ng/ml in cardiac blood, respectively.

The Risk of Overdose With Concomitant Use of Z-Drugs and Prescription Opioids: A Population-Based Cohort Study.

OBJECTIVE: The Z-drugs (zolpidem, zopiclone, zaleplon) are widely used to treat insomnia in patients receiving prescription opioids, and the risk of overdose resulting from this coprescription has not been explored. The authors compared the rates of overdose among patients using opioids plus Z-drugs and patients using opioids alone. METHODS: All individuals 15 to 85 years of age receiving prescription opioids, regardless of underlying indication and without evidence of cancer, were identified in the IBM MarketScan database (2004-2017). Patients with concomitant exposure to Z-drugs were matched 1:1 to patients with exposure to prescription opioids alone based on opioid prescribed, morphine equivalents, number of days' supply, and hospitalization within the past 30 days. The primary outcome was any hospitalization or emergency department visit due to an overdose within 30 days, using an intention-to-treat approach. Fine stratification on the propensity score was used to control for confounding. RESULTS: A total of 510,529 exposed patients and an equal number of matched reference patients were analyzed. There were 217 overdose events among the exposed patients (52.5 events per 10,000 person-years) and 57 events among the reference patients (14.4 events per 10,000 person-years), corresponding to an unadjusted hazard ratio of 3.67 (95% CI=2.75, 4.90). Using fine stratification on the propensity score (c-statistic: 0.66), the adjusted hazard ratio was 2.29 (95% CI=1.79, 2.91). Results were consistent across sensitivity analyses. CONCLUSIONS: Among patients receiving prescription opioids, after controlling for all confounding factors, concomitant treatment with Z-drugs was associated with a substantial relative increase in the risk of overdose. The potential implications are significant given the large number of opioid-treated patients receiving Z-drugs.

Association Between Benzodiazepine or Z-Drug Prescriptions and Drug-Related Poisonings Among Patients Receiving Buprenorphine Maintenance: A Case-Crossover Analysis.

OBJECTIVE: Persons with opioid use disorder who take benzodiazepines are at high risk for overdose. The objective of this study was to evaluate the association of benzodiazepine and Z-drug use with drug-related poisonings among patients receiving buprenorphine maintenance treatment. METHODS: A case-crossover study design was used to analyze prescription claims among persons ages 12-64 with opioid use disorder who had buprenorphine prescriptions and had claims data in the IBM MarketScan databases (2006-2016), encompassing 14,213,075 person-days of observation time for 23,036 individuals who experienced drug-related poisoning. The exposures were buprenorphine prescriptions and benzodiazepine or Z-drug prescriptions, standardized as daily diazepam-equivalent milligram doses and separated by pharmacologic properties (short-acting or long-acting benzodiazepines, Z-drugs). The outcome of interest was nonfatal drug-related poisoning. Conditional logistic regression was used to evaluate variation in benzodiazepine or Z-drug and buprenorphine use between poisoning and nonpoisoning days. RESULTS: Buprenorphine treatment days were associated with a nearly 40% reduction in the risk of poisoning events (odds ratio=0.63, 95% CI=0.60, 0.66) compared with nontreatment days, whereas benzodiazepine or Z-drug treatment days were associated with an 88% increase in the risk of such events (95% CI=1.78, 1.98). In stratified analyses by dose, we observed a 78% (95% CI=1.67, 1.88) and 122% (95% CI=2.03, 2.43) increase in poisonings associated with low-dose and high-dose benzodiazepine or Z-drug treatment days, respectively. High-dose, but not low-dose, benzodiazepine or Z-drug treatment was associated with increased poisonings in combination with buprenorphine cotreatment (odds ratio=1.64, 95% CI=1.39, 1.93), but this was lower than the odds risk associated with benzodiazepine or Z-drug treatment in the absence of buprenorphine (low-dose: odds ratio=1.69, 95% CI=1.60, 1.79; high-dose: odds ratio=2.23, 95% CI=2.04, 2.45). CONCLUSIONS: Increased risk of nonfatal drug-related poisoning is associated with benzodiazepine or Z-drug treatment in patients with opioid use disorder, but this risk is partially mitigated by buprenorphine treatment. Dose reduction of benzodiazepines or Z-drugs while maintaining buprenorphine treatment may provide the advantage of lowering drug-related poisoning risk.

[Diffuse cerebral atrophy and reversible polyneuropathy in a patient with chronic Bromvalerylurea intoxication: a case report].

A 37-year-old man who had been on bromvalerylurea (BU) medication for 11 years at a maximum dose of 2,400 mg per day for headache therapy was admitted to our hospital due to gait disturbance. He had weight loss and exanthema all over his body. Cognitive dysfunction, intellectual deterioration, attention disturbance, decreased muscle strength, and decreased vibratory sense in the lower limbs were observed. Brain MRI showed diffuse brain atrophy, and a peripheral nerve conduction examination revealed decreased nerve conduction velocity and action potential amplitude in the extremities. We diagnosed him with chronic BU intoxication based on pseudohyperchloremia, BU detected in the blood, and bromide elevation. By discontinuing BU and performing intravenous infusion, neurological symptoms and exanthema were improved, and peripheral nerve conduction examination findings also improved. There are few reports of peripheral neuropathy cases of chronic BU intoxication; herein we report one such case along with previously reported cases.

Accidental poisoning, intentional self-harm and event of undetermined intent mortality over 20 years in Iceland: a population-based cohort study.

OBJECTIVES: The aim was to study mortality due to suicide, accidental poisoning, event of undetermined intent and drug-related deaths through 20 years in Iceland. DESIGN: A population-based register study. PARTICIPANTS: Individuals who died due to road traffic injury, suicide, accidental poisoning, event of undetermined intent and drug-related deaths in the population of Iceland during the years 1996-2015. Annual age-standardised rates were calculated, and the trend analysed by Pearson correlation and joinpoint regression. SETTING: The population of Iceland framed the study material, and the data were obtained from nationwide registries for information on number of deaths and age-specific mean population in each year by gender. RESULTS: The crude overall suicide rate during the last 10 years was 12.2 per 100 000 persons per year (95% CI 7.4 to 18.1), while the crude overall rate due to road traffic injuries was 4.6 per 100 000 persons per year (95% CI 2.0 to 8.3). Among men, suicide rates decreased, however not significantly (r(19)=-0.22, p=0.36), and for overdose by narcotics the rates increased significantly (r(19)=0.72, p<0.001) during the study period. Among women, the suicide rates increased, however not significantly (r(19)=0.35, p=0.13), for accidental poisoning, suicide and event of undetermined intent combined the rates increased significantly (r(19)=0.60, p=0.006); and the rates for overdose by sedative and overdose by narcotics both increased significantly r(19)=0.49, p=0.03, and r(19)=0.67, p=0.001, respectively. CONCLUSION: The suicide rates have not changed during 1996 to 2015; however, the rates for the combined accidental poisoning, suicide and event of undetermined intent increased significantly for women. The rise of the overdose rates for sedative among women and for narcotics among both genders are consistent with reports elsewhere.

Clonazolam a new designer benzodiazepine intoxication confirmed by blood concentration.

BACKGROUND: Recently the number of new psychoactive substances have significantly increased, becoming popular among experienced users of designer drugs. A significant group includes benzodiazepine derivatives, which have not been introduced as medications but are abused by people experimenting with new and classical psychoactive substances. CASE PRESENTATION: The aim of this paper was to present the case of a clonazolam ingestion by a person who was not habituated to benzodiazepines. The intake caused only prolonged coma, decreased muscle tone, and deep tendon reflexes without any other concomitant toxicity and cardio-respiratory failure. CONCLUSIONS: Clonazolam concentrations in patient's blood, measured three times were 0.077 mg/L, 0.015 mg/L, 0.009 mg/L after 4, 8 and 12 h, respectively. Clonazolam's human toxicity has not been well established, so any case of poisoning should be closely monitored.

Clinical predictors of adverse cardiovascular events for acute pediatric drug exposures.

Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures.Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20 mEq/L; QTc ≥500 ms), for the primary/secondary outcomes.Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20 mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ≥ 500 ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE.Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

Trends in gabapentin and baclofen exposures reported to U.S. poison centers.

Context: Prescriptions for nonopioid pharmacological therapies such as gabapentin and baclofen have been increasing. While gabapentin and baclofen are less likely than opioids to result in fatal overdose, they are each associated with dependence, misuse and adverse effects.Objective: The objective of this study is to evaluate and describe trends in adult exposures to gabapentin and baclofen reported to U.S. Poison Centers.Methods: This was a retrospective review of data collected by U.S. Poison Centers and entered in the National Poison Data System. We identified all cases of exposures to gabapentin (2013-2017) and baclofen (2014-2017) in patients aged 18 years and over. We then analyzed demographics, common co-ingestions, medical outcomes, and geographic distribution.Results: During the five-year period (2013-2017), there were 74,175 gabapentin exposures. All gabapentin exposures increased by 72.3%; isolated exposures increased by 67.1%; and isolated abuse/misuse exposures increased by 119.9%. During the four-year period (2014-2017), there were 15,397 baclofen exposures. All baclofen exposures increased by 36.2%; isolated exposures increased by 35.0%; and isolated abuse/misuse exposures increased by 31.7%. Co-ingestions of sedatives and opioids were common for both medications. Admissions to a health care facility were required in 16.7% of isolated gabapentin exposures, and 52.1% of isolated baclofen exposures. Intentional suspected suicide attempts with isolated gabapentin exposures increased by 80.5% over a five-year period; and increased by 43% for isolated baclofen exposures over a four-year period. All states saw increases in gabapentin exposures and most states saw increases in baclofen exposures, gabapentin misuse/abuse, and baclofen misuse/abuse.Conclusion: Gabapentin and baclofen misuse, toxicity, use in suicide attempts, and associated healthcare utilization among adults in the United States have significantly increased since 2013. Careful consideration and risk-benefit analysis should be employed when prescribing these medications.

End-tidal capnography provides reliable ventilatory monitoring for non-intubated patients presenting after sedative overdose to the emergency department.

OBJECTIVE: To assess the ability of end-tidal capnography to provide continuous ventilatory monitoring in sedated, non-intubated ED patients following sedative overdose. METHODS: Observational study undertaken in a tertiary hospital ED. Patient ventilation was assessed using capnography over 60 min. RESULTS: Capnography provided uninterrupted monitoring for 99% of total study time. Capnography detected all episodes of hypoxia detected by SpO2 monitoring. Changes in capnography preceded 70% of hypoxic episodes detected by SpO2 . There were no major adverse events or incidents of device failure. CONCLUSION: Capnography provided reliable measurement of ventilatory function in sedated non-intubated, poisoned ED patients.

Nonopioid Overdose Death Rates Rose Almost As Fast As Those Involving Opioids, 1999-2016.

The number of Americans dying from drug overdoses has risen rapidly, but the contribution of nonopioid drugs to this growth is not well understood. Using vital statistics data from the universe of deaths among US residents in the period 1999-2016, I calculated levels of and increases in overall nonopioid fatal overdose rates and those for subgroups stratified by manner of death, sex, race/ethnicity, and age. Mortality rates were also calculated separately for sedatives, stimulants, antidepressants, and cocaine. Recently developed methods were used to correct for the incomplete reporting of drug involvement on death certificates. From 1999 to 2016 the number of nonopioid drug deaths rose 274 percent, and deaths per 100,000 population rose by 223 percent. Over the same period, opioid-involved fatality counts and rates grew by 371 percent and 307 percent, respectively. Fatal overdose rates involving stimulants increased more than tenfold, with slower growth but higher rates for deaths involving sedatives and cocaine. Midlife non-Hispanic whites generally experienced the highest levels and rise in nonopioid death rates, but cocaine fatality rates were particularly common among nonwhite or Hispanic males ages 40-59. Policies designed to curb the opioid epidemic are probably helpful in reducing nonopioid deaths, but targeted interventions may also be needed.

Successful use of the two-tube approach for the treatment of phenobarbital poisoning without hemodialysis.

Half-life of the antipsychotic vegetamin is very long, partially due to the presence of phenobarbital, and mortality due to phenobarbital poisoning is high. Here, we present the case of a 22-year-old female admitted to the emergency department with disturbed consciousness due to vegetamin overdose. Her blood phenobarbital level was elevated to 123 µg/ml. Phenobarbital undergoes enterohepatic circulation, and its retention in the intestine causes its blood levels to remain sustained. The utility of hemodialysis for drug poisoning has been previously reported; however, its efficiency is not yet established and its efficacy is low for drugs with long half-lives such as phenobarbital. Therefore, we performed a two-tube approach to adsorb phenobarbital in the intestines with activated charcoal delivered via a gastric tube and to remove the phenobarbital-adsorbed activated charcoal using whole bowel irrigation via an ileus tube 2 h later. The patient successfully eliminated the charcoal via stool, the blood phenobarbital level decreased drastically without hemodialysis, and the clinical course improved. We propose that this two-tube approach is suitable for treatment of poisoning with drugs that undergo enterohepatic circulation and have long half-lives.

A retrospective observational study on patients intoxicated by drugs and other xenobiotics.

OBJECTIVES: Many research studies conducted in various toxicology centers point to drugs as the most common cause of intoxication. Long-term observations make it possible to clarify the nature of these poisonings. The aim of this study was to examine the trends and reasons of intoxication in patients hospitalized over a 10-year observation period (2005-2015), as well as to compare the number of patients poisoned with nonsteroidal anti-inflammatory drugs (NSAIDs), mainly over-the-counter (OTC) drugs. MATERIAL AND METHODS: A retrospective observational study examined the medical documentation of patients hospitalized in the Department of Toxicology and Internal Diseases of the T. Marciniak Lower Silesian Specialist Hospital in Wroclaw in 2005-2015, including the analysis of the causes of intoxication as well as total poisoning-related death statistics. Quarterly and annual analyses of the numerical data, and comparisons of the frequency of poisonings were included. The patient population from the area of Lower Silesia, Poland, was examined. RESULTS: The number of hospitalized patients has increased, with attempted suicide being the leading cause of death. Male intoxication and mortality have been found to predominate. Drugs are the most common cause of poisoning, and among these the most common are sedatives and psychotropic drugs. Intoxication due to NSAIDs, especially OTC drugs, increased significantly in the observation period. In 2005 no fatal cases were reported as a result of NSAID intoxication, while in 2015 mortality significantly increased to 43%. CONCLUSIONS: The lack of a common trend in poisonings is observed but the number of hospitalized patients has increased, especially among young people, which is consistent with global trends. Drugs are the most common cause of mortality, and a significant increase in NSAID (mainly OTC) poisonings in particular indicates the growing prevalence of an uncontrolled use of these drugs. Int J Occup Med Environ Health. 2019;32(4):489-501.

A quasi-experimental evaluation of partnerships for success's impact on community-level ethanol and prescription drug poisoning rates.

The emerging dual threats of underaged drinking (UAD) and prescription drug misuse (PDM) require sustained prevention efforts across multiple levels of interventions. In response to the continuing proliferation of UAD and PDM among youth and young adults, the Substance Abuse and Mental Health Services Administration (SAMHSA) developed the Partnerships for Success (PFS) program. Across five cohorts funded from 2012 to 2016, PFS created linkages between health care providers, treatment and prevention services providers, government agencies, and nonprofit organizations for the delivery of multiple sets of services (e.g., prevention education, community activities, screening) targeted toward UAD and PDM. This paper reports on the impact of the PFS program on reductions in ethanol and prescription drug poisoning exposures as reported from data in the National Poisoning Data System (NPDS). Across 35 States, communities targeted by PFS interventions were compared to non-targeted communities using a non-equivalent comparison groups design and propensity score weighting. Using propensity-weighted, multilevel latent growth modeling, steeper reductions in ethanol and prescription drug poisoning exposure call rates were observed in States which had a higher proportion of communities participating in PFS. Grantee-level longitudinal analogs to Cohen's d effect sizes ranged from -0.24 to -0.97, whereas PFS' effects on individual communities (net of Statewide effects) were negligible. The study serves as a unique exemplar of using the NPDS to extract community-level intervention effects that might otherwise be "hidden" within epidemiological data while underscoring the cumulative effects of PFS' community-level efforts in stemming the tide on underaged drinking and prescription drug misuse.

Somnophilia and Sexual Abuse through the Administration of GHB and GBL.

Somnophilia, the desire to have sex with an unconscious, sleeping, or comatose person who is unable to respond, is a sexual paraphilia that is seldom reported. The underlying desire is often overshadowed by the act of sexual violation and when using GHB or GBL to induce unconsciousness, as in the case presented here, the victim might not even be able to recall, for certain, that they have been sexually violated. A case study is offered of a somnophile who adulterated drinks to render young men unconscious, so he could rape them in that state, before progressing to administering drugs anally on the pretext of applying lubrication to the anus to facilitate sexual intercourse. The offender's fetishistic compulsion to have sex with unconscious men propelled him to experiment with the means by which he surreptitiously administered drugs to his victims in order to deepen their comatose state.

Suicide by Fatal Pentobarbital Intoxication in Ontario, Canada, from 2012 to 2015.

A fatal concentration of pentobarbital found in a coroner's case where the history had not indicated use of this drug prompted a review of fatalities in Ontario from 2012 to 2015. Coroner's case files, including police and toxicology reports, were reviewed in twenty deaths, in which pentobarbital was identified as the primary cause of death. In all of the deaths (11 females, 9 males), the blood concentration of pentobarbital was greater than 10 mg/L. There were three to eight deaths per year and each was classified as suicide. In 11 cases, there was clear evidence that the drug was purchased over the internet from Mexico or China and imported into Canada. In four cases, it appears that the pentobarbital was labeled as a different, innocuous chemical to facilitate crossing the border without scrutiny. The findings underscore the value of a thorough scene investigation, including details of evidence that may be considered unrelated.

Fatal zolpidem poisoning due to its intravenous self-injection: Postmortem distribution/redistribution of zolpidem and its predominant metabolite zolpidem phenyl-4-carboxylic acid in body fluids and solid tissues in an autopsy case.

We experienced a curious fatal case, in which a male in his 20s self-administered zolpidem intravenously. The victim was found dead lying on floor of his apartment room, with a tourniquet band and new injection marks on his right forearm. Nearby the body, a medical disposal syringe containing small-volume solution dissolving crushed zolpidem tablets was found. The postmortem interval was estimated at about two days. The direct cause of his death was judged as asphyxia due to the aspiration of stomach contents into the trachea and bronchi. The specimens dealt with were body fluids and solid tissues including femoral vein blood, right and left heart blood, pericardial fluid, urine, bile, stomach contents, the brain, lung, heart muscle, liver, spleen, kidney, pancreas and skeletal muscle. For the extractions of zolpidem, zolpidem phenyl-4-carboxylic acid, deuterated internal standards zolpidem-d7 and zolpidem phenyl-4-carboxylic acid-d4, a modified QuEChERS method was used, followed by the analysis by liquid chromatography-tandem mass spectrometry. Because this study included various kinds of human matrices with quite different properties, the standard addition method was most preferable to overcome the matrix effects and recovery rates, and also did not need to use blank human matrices for validation experiments. The concentration of zolpidem and its phenyl-4-carboxylic acid metabolite in various specimens tested were generally extreme higher than those of reported fatal cases, supporting that the victim had died of intravenous zolpidem injection. The concentrations of zolpidem in femoral vein blood and right and left heart blood specimens in the present case were 9.55, 28.5 and 46.9µg/mL, respectively, which far exceeded estimated fatal levels. The present study also showed the postmortem distribution/redistribution of zolpidem and its phenyl-4-carboxylic acid metabolite in 15 body fluid and solid tissue specimens including stomach contents. Although a number of published literatures dealt with zolpidem poisoning cases due to oral ingestion of the drug, this is the first report on fatal intravenous zolpidem injection case and postmortem distribution of zolpidem and its predominant metabolite.

Characteristics of Drugs Ingested for Suicide Attempts in the Elderly.

BACKGROUND: Suicide is a significant public health problem worldwide. Suicide rates among elderly persons (≥ 65 years of age) are three times higher than those of younger people in Korea. The emergency department is an important entry of drug-related suicide attempt patients. In this study, we compared the frequency of drug types by age subgroup. Furthermore, we provide suggestions for preventing suicide attempts in the elderly. METHODS: We investigated 433 patients who were admitted to the emergency department for drug-related suicide attempts between 1 May 2015 and 30 April 2017. RESULTS: The proportion of patients who overdosed on antidepressants was 32.5% in the non-elderly age group and 8.0% in the elderly group (≥ 65 years of age) (P < 0.001). Among the elderly, the most commonly ingested agent was hypnotics (59.1%) (P < 0.001). Compared with the non-elderly, the results showed that the elderly used fewer antidepressants (P < 0.001) and analgesics (P < 0.001). Meanwhile, the elderly used more hypnotics (P < 0.001). Over-the-counter drugs and other medications showed similar usage trends in both age groups (P = 0.664, P = 0.193). CONCLUSION: The categories of drugs ingested for suicide attempts vary widely between different age groups. Younger people used antidepressants more frequently in suicide attempts, while the elderly used hypnotics more frequently. And the elderly required longer hospital stays. Suicide ideation and depressive mood in older patients who are prescribed hypnotics for various reasons should not be neglected. Further prevention efforts are needed to prevent suicide among the elderly.

Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality.

The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005-2012. Data on suicide by self-poisoning were obtained from the Office for National Statistics, information on intentional non-fatal self-poisoning was derived from the Multicentre Study of Self-harm in England and data on prescriptions in general practice from the Clinical Practice Research Datalink. We used two indices of relative toxicity: fatal toxicity (the number of fatal self-poisonings relative to the number of individuals prescribed each drug) and case fatality (the number of fatal relative to non-fatal self-poisonings). Diazepam was the reference drug in all analyses. Temazepam was 10 times (95% confidence interval 5.48-18.99) and zopiclone/zolpidem nine times (95% confidence interval 5.01-16.65) more toxic in overdose than diazepam (fatal-toxicity index). Temazepam and zopiclone/zolpidem were 13 (95% confidence interval 6.97-24.41) and 12 (95% confidence interval 6.62-22.17) times more toxic than diazepam, respectively (case-fatality index). Differences in alcohol involvement between the drugs were unlikely to account for the findings. Overdoses of temazepam and zopiclone/zolpidem are considerably more likely to result in death than overdoses of diazepam. Practitioners need to exercise caution when prescribing these drugs, especially for individuals who may be at risk of self-harm, and also consider non-pharmacological options.

Suicide by Medication Overdose in Prison: A Study of Three Cases.

Suicide is one of the principal causes of mortality in a prison environment. Although suicide by medication overdose is less frequent than suicide by hanging, self-strangulation, or vein cutting, it raises questions as to how the medications are obtained, particularly in view of the specific organization of the medication circuit in prisons. We present three cases of suicide by medication overdose involving different therapeutic classes with different distribution circuits and review the regulatory requirements and the measures that could be taken to prevent such suicides.