Increased non-fatal overdose risk associated with involuntary drug treatment in a longitudinal study with people who inject drugs.

AIM: To assess the effect of involuntary drug treatment (IDT) on non-fatal overdose among people who inject drugs (PWID). DESIGN: Longitudinal study. SETTING: Tijuana, Mexico. PARTICIPANTS: Baseline sample of 671 PWID included 258 (38.4%) women and 413 (61.6%) men. MEASUREMENTS: Primary independent variables were reported recent (i.e. past 6 months) non-fatal overdose event (dependent variable) and IDT. Substance use the day of the non-fatal overdose was also examined. FINDINGS: From 2011 to 2017, 213 participants (31.7%) reported a recent non-fatal overdose and 103 (15.4%) reported recent IDT. Heroin, in combination with methamphetamine and tranquilizers, were the drugs most reported at the day of the event. IDT significantly increased the odds of reporting a non-fatal overdose event [adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI) = 1.04-2.96]. Odds of non-fatal overdose also increased independently for each additional injection per day (aOR = 1.05; 95% CI = 1.02-1.08), recent tranquilizer use (aOR = 1.92; 95% CI = 1.41-2.61) and using hit doctors (aOR = 1.68; 95% CI = 1.29-2.18) and decreased with age (aOR = 0.97 per year, 95% CI = 0.95-0.99). CONCLUSIONS: Recent involuntary drug treatment in Mexico is a risk factor for non-fatal drug overdose.

Factors associated with history of non-fatal overdose among young nonmedical users of prescription drugs.

OBJECTIVES: The current study examines the prevalence and correlates of lifetime non-fatal overdose (OD) involving the nonmedical use of prescription opioids and tranquilizers among a sample of high-risk young adults in New York, NY and Los Angeles, CA. METHODS: Data were derived from a cross-sectional study of 16-25 year old nonmedical users of prescription drugs (n=596). Unadjusted associations between OD history and socio-demographic and drug use variables were investigated in bivariate logistic regression models. Multivariate logistic regression models identified correlates of non-fatal OD. RESULTS: Lifetime prevalence of non-fatal overdose involving prescription opioids and/or tranquilizers was 23.6%. Factors associated with increased risk of non-fatal overdose included lower social class while growing up (OR: 1.81, 95% CI: [1.15, 2.83], p<0.01), having ever received care at a psychiatric hospital (OR: 1.79, 95% CI: [1.12, 2.85], p<0.05), ever witnessing a family member OD on drugs (OR: 1.59, 95% CI: [1.02, 2.50], p<0.05), being prescribed tranquilizers (OR: 2.07, 95% CI: [1.29, 4.27], p<0.01), ever snorting or sniffing opioids (OR: 2.51, 95% CI: [1.48, 4.27], p<0.001), injecting tranquilizers (OR: 3.09, 95% CI: [1.61, 5.93], p<0.001), and past 90-day injection drug use (OR: 1.68, 95% CI: [1.03, 2.74], p<0.05). Participants who reported past 90-day stimulant misuse had lower odds of reporting OD compared to those who were not recent stimulant users (OR: 0.60, 95% CI: [0.38-0.96], p<0.05). CONCLUSIONS: This study documents the high prevalence of experiencing non-fatal overdose among young nonmedical users of prescription drugs. Results could inform overdose prevention efforts throughout the U.S.

[Comparison of four immunoassay screening devices for detection of benzodiazepine and its metabolites in urine: mainly detection of etizolam, thienodiazepine and its metabolites].

The immunoassay screening of benzodiazepines in urine is one of the most important methods of drug analysis in clinical and forensic laboratories. We experienced an unusual case of poisoning wherein the result of Triage DOA immunoassay screening was negative, although Depas (etizolam) was detected in the blood of the victim who had been suspected to prescribe Depas by gas chromatography-mass spectrometry. Depas has been widely used for the treatment of anxiety in Japan. Three immunoassay screening devices (AccuSign BZO, Monitect-3, and Fastect II) were evaluated for their specificity for etizolam, its 2 major metabolites M-III and M-VI, and other metabolites of benzodiazepines in urine. With AccuSign BZO, etizolam, M-III, and M-VI could be detected at concentrations of 1,000 ng/mL in urine; however, they could not be detected even at concentrations of 25,000 ng/mL with the other kits. In the case of etizolam poisoning, the result of AccuSign BZO was positive; however, Triage DOA, which is mainly used for the detection of drugs in urine at intensive care units (ICUs) or forensic laboratories, showed negative result for benzodiazepines. The concentrations of etizolam and its metabolites in urine were measured by the established high-performance liquid chromatographic method. The concentrations of M-III and M-V were 700 and 1,600 ng/mL, respectively. AccuSign BZO demonstrated higher specificity-than the other screening kits for the detection of etizolam and its metabolites in urine. Therefore, the types of drugs detected would be increased by combining Triage DOA with AccuSign BZO in ICUs or forensic laboratories.

Case report: Etizolam and its major metabolites in two unnatural death cases.

A simultaneous analytical method for etizolam and its main metabolites (alpha-hydroxyetizolam and 8-hydroxyetizolam) in whole blood was developed using solid-phase extraction, TMS derivatization and ion trap gas chromatography tandem mass spectrometry (GC-MS/MS). Separation of etizolam, TMS derivatives of alpha-hydroxyetizolam and 8-hydroxyetizolam and fludiazepam as internal standard was performed within about 17 min. The inter-day precision evaluated at the concentration of 50 ng/mL etizolam, alpha-hydroxyetizolam and 8-hydroxyetizolam was evaluated 8.6, 6.4 and 8.0% respectively. Linearity occurred over the range in 5-50 ng/mL. This method is satisfactory for clinical and forensic purposes. This method was applied to two unnatural death cases suspected to involve etizolam. Etizolam and its two metabolites were detected in these cases.

Accidental etizolam ingestion in a child.

Etizolam (ETZ) is an antidepressive thienodiazepine drug that is used worldwide. The most frequent adverse effects in adults are drowsiness and muscle weakness, and this can rarely cause paradoxical excitation; however, no information exists on intoxication in children. Furthermore, evidence bearing on its safety in children is not available. We present a case of a child who accidentally took a single dose of ETZ, approximately the same as a therapeutic dose for adults, and who showed paradoxical excitation and muscle weakness. The case presented here suggests that pediatricians and emergency physicians should be aware of the possible adverse effects in children and therapeutic approaches in intoxication of ETZ and the necessity of further investigations on a specific therapeutic guideline for overdose management especially in children.

[A case of fluvoxamine overdose].

Selective serotonin reuptake inhibitors (SSRI) are newly developed-antidepressants authorized in 1999 in Japan. We experienced a case of drug poisoning including fluvoxamine, one of SSRI. A comatose nineteen-year-old girl was transported to our ER in the morning on July 25, 2000. There remained many empty packages of fluvoxamine and several sorts of tranquilizers in the room. Her consciousness became alert over the next morning. HPLC analysis revealed fluvoxamine, chlorpromazine, promethazine, biperiden, phenobarbital, and zopiclone in her blood and that serum concentrations of the first three were above the therapeutic ranges. The peak values of fluvoxamine, chlorpromazine, and promethazine were 1,343 ng/ml (6.7 times of the upper limit), 861 ng/ml (2 times), and 529 ng/ml (1.3 times), respectively. Fluvoxamine must be a main cause of her toxic symptoms although other CNS-depressing drugs might work jointly.

Substances used in deliberate self-poisoning 1985-1997: trends and associations with age, gender, repetition and suicide intent.

BACKGROUND: Rates of deliberate self-poisoning have increased in recent years. While over-the-counter availability and prescribing patterns may influence trends in substances used in overdose, these may also be related to clinical characteristics of patients. We investigate trends in substances used for self-poisoning and the influence of age, gender, suicidal intent and repetition status on the substances used. METHOD: Data collected by the Oxford Monitoring System for Attempted Suicide were used to review trends and patterns of self-poisoning between 1985 and 1997. RESULTS: There were substantial increases in self-poisoning with paracetamol and antidepressants. While the increase in antidepressant self-poisoning closely paralleled local prescribing figures during 1995-97, SSRI antidepressant overdoses occurred somewhat more often than expected compared with tricyclic overdoses. Paracetamol overdoses were more common in first-timers and young people, whereas overdoses of antidepressants and tranquillizers were more common in repeaters and older people. Self-poisoning with gas and non-ingestible poisons was associated with high suicidal intent. CONCLUSIONS: There have been marked changes in the substances used for self-poisoning, which seem primarily to reflect availability, as do the influences of age and repeater status on choice of substances used. Degree of suicidal intent may also influence choice of method of self-poisoning.

Severe intoxication with the veterinary tranquilizer xylazine in humans.

Xylazine (Rompun, Proxylaz) is a veterinary tranquilizing agent. A case of self-injection of 1.5 g xylazine by a 27-year-old farmer is reported. He subsequently became comatose, hypotensive, bradycardic, and mildly glycemic. An intensive supportive therapy including intubation and ventilation was required. The patient made a full recovery over the next 30 h. The largest concentrations measured were 4.6 mg/L in plasma, 446 mg/L in gastric fluid, and 194 mg/L in urine. The calculated plasma half-life was 4.9 h. Kinetic data correlated with clinical symptoms. Qualitative and quantitative analyses of xylazine were done by thin-layer chromatography, gas chromatography-mass spectrometry, and high-performance liquid chromatography. These methods allow the detection of small amounts substance in stomach, plasma, and urine. Liquid-liquid extraction was used for the isolation of drug. The sensitvity is high, and with these methods, a rapid analysis is possible. Xylazine intoxications in humans are rare. We describe the management of acute poisoning and present a review of xylazine toxicity in humans.

Poisoning caused by the combined ingestion of nifedipine and metoprolol.

Poisonings due to ingestion of a calcium channel or beta-adrenergic blocker have been the subject of several previous reports, but reports of poisoning due to combined ingestion of these drugs are infrequent. This is a report of suicidal ingestion of nifedipine 600 mg, metoprolol 200 mg, and etizolam 20 mg. Intravenous dopamine, norepinephrine, and calcium chloride had little effect but the administration of methylprednisolone and glucagon were associated with an increase in systolic blood pressure above 100 mm Hg.

Adult respiratory distress syndrome from overdose of tricyclic antidepressants.

Adult respiratory distress syndrome (ARDS) from overdose of tricyclic antidepressants (TCA) has been reported but is not well known. During a 1-year period, 81 patients with serious overdose from tranquilizers and other psychotropic drugs were examined. TCA alone induced overdose in 30 patients or were combined with other drugs in 26 patients. Twenty-five (31%) patients had overdose from drugs other than TCA. Chest radiography revealed that 30 (54%) patients with TCA overdose and six (24%) patients with non-TCA overdose had abnormalities. Clinical and radiographic findings consistent with ARDS were noted in five (9%) patients with TCA overdose and none of the patients with non-TCA overdose. Five patients with TCA overdose and one (4%) patient with non-TCA overdose had interstitial edema that never progressed to ARDS. TCA should be added to the list of drugs associated with the development of ARDS.