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Background: The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment. Case presentation: A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary. Interpretation: The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.

Recurrent malignant ventricular arrhythmias and paresthesia-a mystery revealed as aconitine poisoning: a case report.

BACKGROUND: We report a case of a clinical challenge lasting for 12 months, with severe and unresolved clinical features involving several medical disciplines. CASE PRESENTATION: A 53-year-old Caucasian male, who had been previously healthy apart from a moderate renal impairment, was hospitalized 12 times during a 1-year period for a recurrent complex of neurological, cardiovascular, and gastrointestinal symptoms and signs, without any apparent etiology. On two occasions, he suffered a cardiac arrest and was successfully resuscitated. Following the first cardiac arrest, a cardiac defibrillator was inserted. During the 12th admission to our hospital, aconitine poisoning was suspected after a comprehensive multidisciplinary evaluation and confirmed by serum and urine analyses. Later, aconitine was also detected in a hair segment, indicating exposure within the symptomatic period. After the diagnosis was made, no further episodes occurred. His cardiac defibrillator was later removed, and he returned to work. A former diagnosis of epilepsy was also abandoned. Criminal intent was suspected, and his wife was sentenced to 11 years in prison for attempted murder. To make standardized assessments of the probability for aconitine poisoning as the cause of the eleven prior admissions, an "aconitine score" was established. The score is based on neurological, cardiovascular, gastrointestinal, and other clinical features reported in the literature. We also make a case for the use of hair analysis to confirm suspected poisoning cases evaluated after the resolution of clinical features. CONCLUSION: This report illustrates the medical challenge raised by cases of covert poisoning. In patients presenting with symptoms and signs from several organ systems without apparent cause, poisoning should always be suspected. To solve such cases, insight into the effects of specific toxic agents is needed. We present an "aconitine score" that may be useful in cases of suspected aconitine poisoning.

Quantifying Alcohol Consumption in the General Population by Analysing Phosphatidylethanol Concentrations in Whole Blood: Results from 24,574 Subjects Included in the HUNT4 Study.

AIMS: To evaluate the association between self-reported alcohol consumption and phosphatidylethanol (PEth) concentrations in blood in a large general population study, and discuss optimal cut-off PEth concentrations for defined levels of alcohol consumption. METHODS: Population based, longitudinal cohort study including 24,574 adults from The Trøndelag Health Study 4 (HUNT4) conducted in Trøndelag County, Norway. Data included PEth concentration, self-reported alcohol consumption and CAGE score. RESULTS: PEth levels in whole blood increased with the number of alcohol units consumed, the frequency of alcohol consumption, the frequency of binge drinking and the CAGE score (lifetime, i.e. 'have you ever'). The cut-off concentrations with highest combined sensitivity and specificity were 0.057 µmol/l (40 ng/ml) for identification of those consuming >1 alcohol unit per day (sensitivity 86%, specificity 76%), 0.087 µmol/l (61 ng/ml) for consuming >2 units per day (sensitivity 87%, specificity 81%) and 0.122 µmol/l (86 ng/ml) for consuming >3 alcohol units per day (sensitivity 80%, specificity 86%). By defining a CAGE score ≥ 2 as potentially harmful consumption, a cut-off of 0.100 µmol/l (70 ng/ml) identified 52% of all those subjects. CONCLUSIONS: Cut-off limits of PEth concentrations should take into account the indication for sampling. Using cut-offs for the PEth concentrations of about 0.05 µmol/l (35 ng/ml) and 0.08 µmol/l (56 ng/ml) would identify about 90% of the subjects consuming more than 1 and 2 alcohol units per day, respectively. Concentrations above these cut-offs should lead to a more detailed interview related to alcohol use.

Identification of unhealthy alcohol use by self-report and phosphatidylethanol (PEth) blood concentrations in an acute psychiatric department.

BACKGROUND: The use of standard screening methods could improve the detection rate of unhealthy alcohol use in patients admitted to psychiatric acute and emergency departments. The aim of the present study was to investigate the ability of the alcohol biomarker phosphatidylethanol (PEth) to identify patients with high levels of alcohol consumption prior to admission. METHODS: The data were prospectively collected at admittance to an acute psychiatric department in the period January 2016 to June 2017. A blood sample for the analysis of PEth was available from 177 patients. We compared the PEth concentrations with the Alcohol Use Disorders Identification Test (AUDIT) scores during the hospital stay, and psychiatric diagnoses at discharge. RESULTS: A total of 45.8% of the patients had a PEth concentration ≥ 0.03 µmol/L, indicating significant alcohol consumption. AUDIT scores consistent with unhealthy alcohol use were present in 51.7%. There was a significant positive correlation between PEth concentrations and AUDIT scores (r = 0.631, p < 0.001). PEth was above the detection limit of 0.03 µmol/L in 19% of those reporting an average daily intake of zero alcohol units per day during the last week before admission. PEth concentrations were significantly higher among those with an alcohol diagnosis than among those without such a diagnosis (0.82 µmol/L vs. 0.09 µmol/L, p = 0.001). CONCLUSION: PEth provides supplementary information on recent alcohol consumption in a psychiatric population and would be particularly helpful in patients unable or unwilling to give such information at admission.

Stability of Phosphatidylethanol 16:0/18:1 in Freshly Drawn, Authentic Samples from Healthy Volunteers.

Due to its specificity, phosphatidylethanol (PEth) 16:0/18:1 has gained increased popularity as a marker for high alcohol consumption in recent years. As conflicting results regarding the stability of PEth 16:0/18:1 in whole blood have been published, there are still uncertainties related to optimum handling, transport and storage of blood samples for the analysis of PEth 16:0/18:1. A stability study where whole blood samples were drawn from healthy volunteers, who had ingested alcohol, is presented. The samples were collected in tubes with ethylenediamine tetraacetic acid (EDTA) and heparin as additives and stored under standardized conditions within 1 h of blood sampling. Storage times were 28 days in ambient temperature and at 4-8°C, and 90 days at -20°C and -80°C. All samples were analyzed regularly during the storage periods. PEth 16:0/18:1 concentrations were stable (defined as < 15% decrease compared with baseline values) at all temperatures up to 28 days, independent of additive. After 90 days of storage at -20°C, the mean concentrations had decreased by 18.8% in EDTA tubes and by 13.8% in heparin tubes. At -80°C, the concentrations were stable throughout the 90-day period. The present study shows that in samples containing PEth formed in vivo, PEth 16:0/18:1 is stable for 28 days irrespective of storage temperature. During long-term storage, samples should be stored at -80°C.

A woman in her forties who used addictive drugs in very high doses. / En kvinne i 40-årene som brukte vanedannende legemidler i svært høye doser.

BACKGROUND: Following a surgical procedure, a female patient in her forties was prescribed opioids (oxycodone). The prescription escalated into doses that were extremely high, and at a level beyond any experienced previously, either at the various hospital units that were involved in the treatment or in the medical literature. CASE PRESENTATION: The patient had no known history of substance abuse. After the surgical procedure, her general practitioner continued to prescribe the drug. The prescriptions escalated over the course of a couple of years, and at the time of our first contact with her, the doses had reached 11 000 mg oxycodone per day. INTERPRETATION: The high doses were tapered down over the course of around nine months. The spiralling prescriptions had several causes: the oxycodone treatment was initiated without a set plan for withdrawal; the patient had a change of general practitioner during the early stage; and she was a patient without any history of substance abuse. The costs escalated to the extent that the Norwegian Health Economics Administration eventually refused further payments. In such cases there is a need for close cooperation between the inpatient drug rehabilitation care unit and medical and pharmacological units.

[Drug screening among patients aged 17-40 admitted with psychosis]. / Rusmiddelscreening av pasienter i alderen 17--40 år innlagt med psykose.

BACKGROUND: High frequency of co-occurring substance use disorders and psychiatric disorders is reported in several studies. An important issue is whether we can rely on patient reports only. The purpose of this investigation was to find the prevalence of substance use among younger psychotic inpatients in Norway and to compare patients' self reports with the results of screening for drugs. MATERIAL AND METHODS: 65 patients aged 17 to 40, consecutively admitted to Blakstad Psychiatric Hospital in 2001 with psychosis were interviewed with regard to substance use 30 days prior to admittance. The Addiction Severity Index (EuropASI) was used for interviews. Blood and urine samples for drug analysis were taken at admittance. RESULTS: 54% of the patients reported having used one or more substances for intoxication during the month prior to admittance. 40% of the included patients had used illegal drugs. Laboratory analyses revealed use of illegal drugs, mostly cannabis and amphetamine, in 34% of the patients. Only one patient tested positively for a drug not reported in the interview. INTERPRETATION: The investigation shows that 54% of the younger psychotic inpatients intoxicate themselves with legal or illegal substances. This fact is important for the total medical management of these patients in psychiatric hospitals. We also found that this group of patients were reliable in reporting their substance use when a standardised interview was used.

Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes.

BACKGROUND: The aims of the study were to quantify the drug exposure in breastfed infants of antidepressant-treated mothers, to identify possible adverse events, and to correlate these variables to maternal and infant drug metabolism-relevant genotypes and milk triglyceride content. METHOD: The study included 25 lactating women treated with citalopram (N = 9), sertraline (N = 6), paroxetine (N = 6), fluoxetine (N = 1), or venlafaxine (N = 3) and their 26 breastfed infants. Drug concentrations in maternal and infant serum and milk were analyzed using liquid chromotography mass spectrometry methods; milk triglyceride levels were measured with a commercial kit. Cytochrome P450 (CYP) 2D6 and CYP2C19 activity was determined by polymerase chain reaction-based genotyping of the mothers and infants. An infant adverse event questionnaire was completed by the medication-treated mothers as well as by a control group of medication-free breastfeeding mothers of 68 infants. RESULTS: Sertraline and paroxetine were not detected in any of the drug-exposed infants. The infant serum level of citalopram was either undetectable (N = 4) or low (N = 6). All venlafaxine-exposed infants had measurable drug concentrations. We identified a paroxetine-treated mother and her infant who were both CYP2D6 poor metabolizers, as well as a citalopram-treated mother with CYP2C19 poor metabolizer status, but the serum drug levels of their infants were still either undetectable (paroxetine) or low (citalopram). There was no evidence of adverse events in the drug-exposed infants. CONCLUSION: Serum drug levels in breastfed infants of antidepressant-treated mothers were undetectable or low. This study adds further evidence to previously published data indicating that breastfeeding should not be generally discouraged in women using serotonin reuptake inhibitor anti-depressants.