-
PloS One 2023Opioid overdose deaths have increased in Sweden and other developed countries in recent decades, despite increased treatment efforts and harm-reduction interventions.... (Observational Study)
Observational Study
BACKGROUND/AIM
Opioid overdose deaths have increased in Sweden and other developed countries in recent decades, despite increased treatment efforts and harm-reduction interventions. Further knowledge in this field is needed if this trend is to be reversed. Previous research suggests that mental health and patterns of prescription of opioids and other prescription drugs are associated with increased opioid-related mortality. The present study therefore aimed to investigate what drugs were prescribed during the last six months of life to individuals with a history of illicit substance use who died with opioids present in their blood, the relationship between drugs prescribed and drugs found in blood at time of death, and if prescription of specific drugs was temporally associated with death.
METHODS
This was a retrospective, register-based observational study that utilized data from the National Board of Forensic Medicine, the Prescribed Drug Registry, regional health care services, and municipal social services. We used conditional logistic regression to find temporal associations between the prescription and dispensing of drugs and time of death.
RESULTS
Prescription and dispensing of alprazolam and diazepam were temporally associated with death. The most frequently dispensed drugs were zopiclone, pregabalin, methylphenidate, diazepam and oxycodone. Methadone, alprazolam, and buprenorphine were the drugs most often found in the blood. Opioids and tranquilizers in combination were found in a vast majority of deaths, and prescription data suggested that the use of these drugs was illicit in a majority of cases.
CONCLUSION
Prescription of certain drugs, especially alprazolam and diazepam, should be made with great caution to patients with a history of illicit substance use or concurrent use of opioids.
Topics: Humans; Analgesics, Opioid; Retrospective Studies; Alprazolam; Autopsy; Drug Overdose; Drug Prescriptions; Substance-Related Disorders; Prescriptions; Diazepam; Opioid-Related Disorders
PubMed: 37256903
DOI: 10.1371/journal.pone.0285583 -
Forensic Science International. Synergy 2021The National Forensic Laboratory Information System (NFLIS) is a program of the U.S. Drug Enforcement Administration, Diversion Control Division. The NFLIS-Drug...
The National Forensic Laboratory Information System (NFLIS) is a program of the U.S. Drug Enforcement Administration, Diversion Control Division. The NFLIS-Drug component collects drug identification results and associated information from drug cases submitted to and analyzed by federal, state, and local forensic laboratories. This paper presents national annual estimates and national and regional yearly trend differences for clonazepam, diazepam, flubromazolam, clonazolam, and etizolam using annual report rates per 100,000 persons aged 15 or older between 2015 and 2018. An estimated 263,538 benzodiazepine reports were identified by state and local laboratories between 2015 and 2018. Methamphetamine, cocaine, and heroin accounted for 32% of the drugs reported in the same item as alprazolam. Depressants and tranquilizers and narcotic analgesics were the drug classes most frequently identified in the same item as etizolam. A timeline of some benzodiazepines' emergence in NFLIS-Drug is shown, as well as state- and county-level data for selected benzodiazepines.
PubMed: 33665593
DOI: 10.1016/j.fsisyn.2021.100138 -
Journal of Pharmaceutical Health Care... Apr 2022A high prevalence of mental disorders including depression, anxiety, somatoform, and dissociative disorder is reported during pregnancy, however, information on the...
BACKGROUND
A high prevalence of mental disorders including depression, anxiety, somatoform, and dissociative disorder is reported during pregnancy, however, information on the transfer of antipsychotics across the placenta and into breast milk is limited. We evaluated brotizolam, periciazine and sulpiride in cord blood, maternal serum, and breast milk, and alprazolam in breast milk.
CASE PRESENTATION
A 38-year-old woman with dissociative disorder was treated with brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and alprazolam during lactation. The drug concentration ratios for both cord blood and maternal serum were 33.3 and 61.5% for brotizolam and sulpiride, respectively, and periciazine (metabolite of propericiazine) was not detected in the cord blood. In breast milk, alprazolam (0.9 ng/mL), sulpiride (445.8 ng/mL), and periciazine (0.3 ng/mL) concentrations were noted at 7.5 h after the last dose on postpartum, whereas brotizolam was not detected. The relative infant doses via breast milk were 1.4, 2.7 and 0.02% of the maternal daily dose, respectively. The neonate had no congenital anomalies and did not experience any severe withdrawal symptoms after birth.
CONCLUSION
Use of brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and use of alprazolam during lactation were acceptable in this case.
PubMed: 35361275
DOI: 10.1186/s40780-022-00241-2 -
CNS Drug Reviews 2004Alprazolam is a benzodiazepine derivative that is currently used in the treatment of generalized anxiety, panic attacks with or without agoraphobia, and depression.... (Review)
Review
Alprazolam is a benzodiazepine derivative that is currently used in the treatment of generalized anxiety, panic attacks with or without agoraphobia, and depression. Alprazolam has a fast onset of symptom relief (within the first week); it is unlikely to produce dependency or abuse. No tolerance to its therapeutic effect has been reported. At discontinuation of alprazolam treatment, withdrawal and rebound symptoms are common. Hence, alprazolam discontinuation must be tapered. An exhaustive review of the literature showed that alprazolam is significantly superior to placebo, and is at least equally effective in the relief of symptoms as tricyclic antidepressants (TCAs), such as imipramine. However, although alprazolam and imipramine are significantly more effective than placebo in the treatment of panic attacks, Selective Serotonin Reuptake Inhibitors (SSRIs) appear to be superior to either of the two drugs. Therefore, alprazolam is recommended as a second line treatment option, when SSRIs are not effective or well tolerated. In addition to its therapeutic effects, alprazolam produces adverse effects, such as drowsiness and sedation. Since alprazolam is widely used, many clinical studies investigated its cognitive and psychomotor effects. It is evident from these studies that alprazolam may impair performance in a variety of skills in healthy volunteers as well as in patients. Since the majority of alprazolam users are outpatients, this behavioral impairment limits the safe use of alprazolam in patients routinely engaged in potentially dangerous daily activities, such as driving a car.
Topics: Alprazolam; Animals; Anti-Anxiety Agents; Anxiety Disorders; Automobile Driving; Behavior; Clinical Trials as Topic; Depression; Female; Humans; Male; Memory; Panic Disorder; Premenstrual Syndrome; Psychomotor Performance; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 14978513
DOI: 10.1111/j.1527-3458.2004.tb00003.x -
Australian Family Physician Aug 2010Recognising and dealing with patients who seek drugs for nonmedical purposes can be a difficult problem in general practice. 'Prescription shoppers' and patients with...
BACKGROUND
Recognising and dealing with patients who seek drugs for nonmedical purposes can be a difficult problem in general practice. 'Prescription shoppers' and patients with chronic nonmalignant pain problems are the main people who constitute this small but problematic group. The main drugs they seek are benzodiazepines and opioids.
OBJECTIVE
To provide data on current trends in prescription drug abuse and to discuss different strategies on how to deal with this issue in the clinic setting.
DISCUSSION
Misuse of prescription drugs can take the form of injecting oral drugs, selling them on the street, or simply overusing the prescribed amount so that patients run short before the due date and then request extra prescriptions from the doctor. Currently oxycontin and alprazolam are the most abused drugs in Australia. Adequate prescription monitoring mechanisms at the systems level are lacking so we need to rely on our clinical skills and the patient's behaviour pattern over time to detect problematic prescription drug misuse. Management strategies may include saying 'no' to patients, having a treatment plan, and adopting a universal precaution approach toward all patients prescribed drugs of addiction. Among patients with chronic nonmalignant pain, requests for increasing opioid doses need careful assessment to elucidate any nonmedical factors that may be at play.
Topics: Adult; Australia; Chronic Disease; Drug Prescriptions; Drug Users; Drug-Seeking Behavior; Female; General Practice; Humans; Inappropriate Prescribing; Male; Pain; Physicians; Practice Patterns, Physicians'; Prescription Drugs; Substance-Related Disorders
PubMed: 20877745
DOI: No ID Found -
Biosensors Oct 2022Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable...
Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L and 1 to 50 mg L), low limit of detection (1 µg L), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.
Topics: Alprazolam; Graphite; Nanocomposites; Gold; Electrodes; Electrochemical Techniques
PubMed: 36354454
DOI: 10.3390/bios12110945 -
CMAJ : Canadian Medical Association... Mar 1989Premenstrual syndrome (PMS) has become a popular self-diagnosis. Faulty research has led to confusion about the diagnosis, epidemiologic features, causes and treatment... (Review)
Review
Premenstrual syndrome (PMS) has become a popular self-diagnosis. Faulty research has led to confusion about the diagnosis, epidemiologic features, causes and treatment of this disorder. There is no proof that the premenstrual period is a time of increased violence. An association between menstrually related mood disorders and other psychiatric illness is also unproven. Despite many theories no definitive cause of PMS has been established, and controlled studies of various treatments have failed to find a universally effective approach. Conservative measures involving support, diet and exercise seem to help in most cases. The use of alprazolam and mefenamic acid may help some women. Rectal or vaginal progesterone therapy has been proven ineffective and should not be used.
Topics: Adult; Female; Humans; Mental Disorders; Mood Disorders; Premenstrual Syndrome; Recurrence; Severity of Illness Index; Violence
PubMed: 2645986
DOI: No ID Found -
Biomedicines Nov 2022Alprazolam is a triazolobenzodiazepine which is most commonly used in the short-term management of anxiety disorders, often in combination with antipsychotics. The four...
Alprazolam is a triazolobenzodiazepine which is most commonly used in the short-term management of anxiety disorders, often in combination with antipsychotics. The four human members of the CYP3A subfamily are mainly responsible for its metabolism, which yields the main metabolites 4-hydroxyalprazolam and α-hydroxyalprazolam. We performed a comparison of alprazolam metabolism by all four CYP3A enzymes upon recombinant expression in the fission yeast . CYP3A4 and CYP3A5 show the highest 4-hydroxyalprazolam production rates, while CYP3A5 alone is the major producer of α-hydroxyalprazolam. For both metabolites, CYP3A7 and CYP3A43 show lower activities. Computational simulations rationalize the difference in preferred oxidation sites observed between the exemplary enzymes CYP3A5 and CYP3A43. Investigations of the alprazolam metabolites formed by three previously described CYP3A43 mutants (L293P, T409R, and P340A) unexpectedly revealed that they produce 4-hydroxy-, but not α-hydroxyalprazolam. Instead, they all also make a different metabolite, which is 5-N-O alprazolam. With respect to 4-hydroxyalprazolam, the mutants showed fourfold (T409R) to sixfold (L293P and P340A) higher production rates compared to the wild-type (CYP3A43.1). In the case of 5-N-O alprazolam, the production rates were similar for the three mutants, while no formation of this metabolite was found in the wild-type incubation.
PubMed: 36551778
DOI: 10.3390/biomedicines10123022 -
AMIA ... Annual Symposium Proceedings.... 2020The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is...
The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is essential as drugs often have under-reported side effects. This study intends to use the power of digital media to discover the under-reported side effects of marketed drugs. We have collected tweets for 11 different Drugs (Alprazolam, Adderall, Fluoxetine, Venlafaxine, Adalimumab, Lamotrigine, Quetiapine, Trazodone, Paroxetine, Metronidazole and Miconazole). We have compiled a vast adverse drug reactions (ADRs) lexicon that is used to filter health related data. We constructed machine learning models for automatically annotating the huge amount of publicly available Twitter data. Our results show that on average 43 known ADRs are shared between Twitter and FAERS datasets. Moreover, we were able to recover on average 7 known side effects from Twitter data that are not reported on FAERS. Our results on Twitter dataset show a high concordance with FAERS, Medeffect and Drugs.com. Moreover, we manually validated some of the under-reported side effect predicted by our model using literature search. Common known and under-reported side effects can be found at https://github.com/cbrl-nuces/Leveraging-digital-media-data-for-pharmacovigilance.
Topics: Diagnostic Tests, Routine; Drug-Related Side Effects and Adverse Reactions; Humans; Internet; Machine Learning; Pharmacovigilance; Social Media
PubMed: 33936417
DOI: No ID Found -
Psychopharmacology Mar 2015Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects.
RATIONALE
Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects.
OBJECTIVES
This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route.
METHODS
Placebo, inhaled alprazolam (0.5, 1, and 2 mg), and oral alprazolam (1, 2, and 4 mg) were administered under double-blind, double-dummy conditions using a crossover design in 14 healthy participants with histories of drug abuse. Participant and observer ratings and behavioral and cognitive performance measures were assessed repeatedly during 9-h sessions.
RESULTS
Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer-lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 min after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose-response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., "drug liking") were similar across the two routes. On other measures (e.g., sedation and performance), the routes were equipotent.
CONCLUSIONS
The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.
Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Alprazolam; Cognition; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Mental Recall; Middle Aged; Neuropsychological Tests; Psychomotor Performance; Substance-Related Disorders; Surveys and Questionnaires; Young Adult
PubMed: 25199955
DOI: 10.1007/s00213-014-3721-0