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The Cochrane Database of Systematic... Oct 2009Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies... (Review)
Review
BACKGROUND
Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium.
OBJECTIVES
To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources.
SELECTION CRITERIA
Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included.
MAIN RESULTS
Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion.
AUTHORS' CONCLUSIONS
No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.
Topics: Benzodiazepines; Delirium; Dexmedetomidine; Humans; Lorazepam
PubMed: 19821364
DOI: 10.1002/14651858.CD006379.pub3 -
Journal of Psychopharmacology (Oxford,... Sep 2022The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and...
BACKGROUND
The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and consumption have increased. Concern about increasing numbers of alprazolam-related fatalities started circulating in 2018. However, statistics on this issue are very limited. This study examined patterns in such mortality in Scotland.
METHODS
Statistics on deaths where alprazolam was mentioned in the 'cause of death' were obtained from official mortality registers. Anonymised Scottish case-level data were obtained. Data were examined in respect of the characteristics of decedents and deaths using descriptive statistics.
RESULTS
Scotland registered 370 deaths in 2004-2020; 366 of these occurred in 2015-2020: most involved males (77.1%); mean age 39.0 (SD 12.6) years. The principal underlying cause of death was accidental poisoning: opiates/opioids (77.9%); sedatives/hypnotics (15.0%). Two deaths involved alprazolam alone. Main drug groups implicated: opiates/opioids (94.8%), 'other benzodiazepines' (67.2%), gabapentinoids (42.9%), stimulants (30.1%), antidepressants (15.0%). Two-thirds (64.2%) involved combinations of central nervous system (CNS) depressants.
DISCUSSION
Alprazolam-related deaths are likely due to an increasing illicit supply. The fall in deaths in 2019-2020 is partially due to increased use of designer benzodiazepines. Treatment for alprazolam dependence is growing. Clinicians need to be aware of continuing recreational alprazolam use. When such consumption occurs with CNS depressants, overdose and death risks increase.
CONCLUSIONS
More awareness of alprazolam contributing to deaths, especially in conjunction with other CNS depressants, is needed by consumers and clinicians. Improved monitoring of illicit supplies could identify emerging issues of medicines' abuse.
Topics: Adult; Alprazolam; Analgesics, Opioid; Benzodiazepines; Central Nervous System Depressants; Humans; Hypnotics and Sedatives; Male; Opiate Alkaloids; Scotland; State Medicine
PubMed: 35912873
DOI: 10.1177/02698811221104065 -
Frontiers in Pharmacology 2022Alprazolam is a commonly prescribed benzodiazepine for anxiety or panic disorder, even in pregnant women. Information on the safety of alprazolam during pregnancy is...
Alprazolam is a commonly prescribed benzodiazepine for anxiety or panic disorder, even in pregnant women. Information on the safety of alprazolam during pregnancy is insufficient. We aimed to evaluate pregnancy and neonatal outcomes after exposure to alprazolam during pregnancy. A prospective study was conducted on 725 pregnancies from January 2000 to December 2019. Participants were recruited through the Korean Mother-Safe Program, a service providing information on drug-induced teratogenic risk during pregnancy and breastfeeding. Exposed (N = 96) and non-exposed (N = 629) women to alprazolam during pregnancy were selected and followed-up until delivery. Pregnancy outcomes, including spontaneous abortion, still birth, low birth weight (LBW), preterm birth, Apgar score (at 1 and 5 min), and malformations were measured and compared. Multivariable logistic regression was performed to examine the association between alprazolam exposure and outcomes. The mean age was 32.9 (SD 4.0) years in the alprazolam-exposed group and 31.8 (SD 3.8) years in the unexposed group ( = 0.008). The alprazolam exposure group demonstrated a significantly higher likelihood of pregnancy and neonatal outcomes: spontaneous abortion (OR = 2.38; 95% CI 1.20-4.69), LBW (OR = 3.65; 95% CI 1.22-11.00), and Apgar score at 1 min ≤ 7 (OR = 2.19; 95% CI 1.02-4.67). There was no significant difference in congenital abnormalities between the exposure and non-exposure groups. Our findings confirmed that alprazolam exposure during pregnancy was significantly associated with adverse pregnancy and neonatal outcomes, including spontaneous abortion, low birth weight, and Apgar score at 1 min ≤ 7. Alprazolam during pregnancy should be appropriately regulated and monitored.
PubMed: 35548333
DOI: 10.3389/fphar.2022.854562 -
Prague Medical Report 2020The post-mortem toxicological findings may be misinterpreted, if the drug undergoes substantial post-mortem redistribution. As alprazolam is one of the most frequently...
The post-mortem toxicological findings may be misinterpreted, if the drug undergoes substantial post-mortem redistribution. As alprazolam is one of the most frequently evaluated drug for legal/forensic reasons in drug-related fatalities, we studied possible changes in alprazolam distribution after death in a rat model. Rats were sacrificed 30 minutes after alprazolam administration. Blood and tissue samples from 8 animals per sampling time were collected at 0, 2, 6, and 24 h after death. The experimental samples were assayed for alprazolam using validated UHPLC-PDA method. Median blood alprazolam concentrations increased approximately 2 times compared with ante-mortem levels due to the redistribution during early post-mortem phase and then slowly decreased with a half-life of 60.7 h. The highest alprazolam tissue concentrations were found in fat and liver and the lowest levels were observed in lungs and brain. The median amount of alprazolam deposited in the lungs was relatively stable over the 24-h post-mortem period, while in heart, liver and kidney the deposited proportion of administered dose increased by 43-48% in comparison with ante-mortem values indicating continuous accumulation of alprazolam into these tissues. These results provide evidence needed for the interpretation of toxicological results in alprazolam-related fatalities and demonstrate modest alprazolam post-mortem redistribution.
Topics: Alprazolam; Animals; Hypnotics and Sedatives; Postmortem Changes; Rats
PubMed: 33270012
DOI: 10.14712/23362936.2020.21 -
BMJ Case Reports May 2022Benzodiazepines (BZDs) rarely cause respiratory depression and death. On the other hand, high-dose BZDs may lead to profound sedation and diminished brainstem functions...
Benzodiazepines (BZDs) rarely cause respiratory depression and death. On the other hand, high-dose BZDs may lead to profound sedation and diminished brainstem functions that mimic other structural brain lesions as described in our case: a 70-year-old unresponsive woman. She was hypothermic and had rapid shallow breathing. Her Glasgow Coma Scale score was E1V1M4, with pinpoint pupils and absent corneal, oculocephalic and oculovestibular reflexes. Other physical exams, laboratory testing and brain imaging were unremarkable. After two doses of 0.4 mg naloxone and intravenous thrombolytics were given, there were no significant responses, and the diagnosis remained a mystery. The cause of her unconsciousness was uncovered when her husband found empty bags of 80 tablets of alprazolam and lorazepam. Her consciousness and brainstem reflexes improved dramatically after 0.25 mg of intravenous flumazenil. The blood for BZDs concentration showed alprazolam 268 ng/mL (20-40 ng/mL), lorazepam 861 ng/mL (20-250 ng/mL) and their metabolites.
Topics: Aged; Alprazolam; Benzodiazepines; Brain Stem; Female; Humans; Lorazepam; Unconsciousness
PubMed: 35537772
DOI: 10.1136/bcr-2022-248796 -
BJPsych Open Jul 2018Sexual dysfunctions are associated with multiple medical and psychiatric disorders, as well as pharmacotherapies used to treat these disorders. Although sexual...
BACKGROUND
Sexual dysfunctions are associated with multiple medical and psychiatric disorders, as well as pharmacotherapies used to treat these disorders. Although sexual dysfunctions negatively affect both quality of life and treatment adherence, patients infrequently volunteer these symptoms and clinicians do not pose directed questions to determine their presence or severity. This issue is especially important in psychiatric patients, for whom most common psychotropics may cause sexual dysfunctions (antidepressants, antipsychotics, anxiolytics and mood-stabilising agents). There is limited literature addressing benzodiazepines, and alprazolam in particular.
AIMS
To report dose-dependent alprazolam anorgasmia.
METHOD
Case analysis with PubMed literature review.
RESULTS
A 30-year-old male psychiatric patient presented with new-onset anorgasmia in the context of asymptomatic generalised anxiety disorder, social anxiety, panic disorder with agoraphobia, obsessive-compulsive disorder, major depression in remission, and attention-deficit hyperactivity disorder treated with escitalopram 10 mg q.a.m., gabapentin 1000 mg total daily dose, lisdexamfetamine dimesylate 70 mg q.a.m., nortriptyline 60 mg q.h.s. and alprazolam extended-release 2.5 mg total daily dose. All psychotropic doses had been constant for >6 months excluding alprazolam, which was titrated from 1 mg to 2.5 mg total daily dose. The patient denied any sexual dysfunction with alprazolam at 1 mg q.d. and 1 mg b.i.d. Within 1 week of increasing alprazolam to 2.5 mg total daily dose, the patient reported anorgasmia. Anorgasmia was alprazolam dose-dependent, as anorgasmia resolved with reduced weekend dosing (1 mg b.i.d. Saturday/1.5 mg total daily dose Sunday).
CONCLUSIONS
Sexual dysfunction is an important adverse effect negatively influencing therapeutic outcome. This case reports alprazolam-induced dose-dependent anorgasmia. Clinicians/patients should be aware of this adverse effect. Routine sexual histories are indicated.
DECLARATION OF INTEREST
None.
PubMed: 30083378
DOI: 10.1192/bjo.2018.35 -
The Journal of Maternal-fetal &... Dec 2023While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy. We used a large...
While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy. We used a large administrative database to determine whether psychiatric medications are continued during pregnancy and predictors of continued medication treatment. Of 2,672,656 women included in our analysis, 86,454 (3.1%) filled a pre-pregnancy prescription for an anxiolytic or antidepressant medication within 3 months of estimated conception. Of women who filled a pre-pregnancy prescription, 49.4%, 26.1%, and 20.1% filled subsequent prescriptions in the 1st, 2nd, and 3rd trimesters. Discontinuation rates ranged by pharmaceutical agent, from 16% for fluoxetine to 71% for alprazolam. White women and women over 25 were more likely to continue anxiolytic and antidepressant treatment during pregnancy. Because untreated and under-treated mental health conditions are linked to adverse maternal outcomes, high discontinuation rates may have important implications for maternal health.
Topics: Pregnancy; Female; Humans; United States; Depression; Anti-Anxiety Agents; Antidepressive Agents; Fluoxetine; Pharmaceutical Preparations; Pregnancy Complications
PubMed: 36710395
DOI: 10.1080/14767058.2023.2171288 -
Journal of Psychopharmacology (Oxford,... Dec 2023Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population.
METHODS
In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC).
RESULTS
Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported.
CONCLUSIONS
Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines.
Topics: Humans; Female; Adult; Male; Alprazolam; Blood Alcohol Content; Hypnotics and Sedatives; Ethanol; Cognition; Double-Blind Method
PubMed: 37724443
DOI: 10.1177/02698811231200878 -
British Journal of Clinical Pharmacology Jul 2004To describe alprazolam poisoning and the relative toxicity of alprazolam compared with other benzodiazepines. (Review)
Review
AIMS
To describe alprazolam poisoning and the relative toxicity of alprazolam compared with other benzodiazepines.
METHODS
A database of consecutive poisoning admissions to a regional toxicology service was searched to identify consecutive benzodiazepine deliberate self poisonings, which were coded as alprazolam, diazepam or other benzodiazepine. Major outcomes used were length of stay (LOS), intensive care (ICU) admission, coma (GCS < 9), flumazenil administration and requirement for mechanical ventilation. Prescription data were obtained for benzodiazepines for the study period.
RESULTS
There were 2063 single benzodiazepine overdose admissions: 131 alprazolam overdoses, 823 diazepam overdoses and 1109 other benzodiazepine overdoses. The median LOS for alprazolam overdoses was 19 h which was 1.27 (95% CI 1.04, 1.54) times longer compared with other benzodiazepines by multiple linear regression. For patients with alprazolam overdoses, 22% were admitted to ICU which was 2.06 (95% CI 1.27, 3.33) times more likely compared with other benzodiazepines after multivariate analysis adjusting for age, dose, gender, time to ingestion and co-ingested drugs. Flumazenil was administered to 14% of alprazolam patients and 16% were ventilated, which was significantly more than for other benzodiazepine overdoses (8% and 11%, respectively). Twelve percent of alprazolam overdoses had a GCS < 9 compared with 10% for other benzodiazepines. From benzodiazepine prescription data, total alprazolam prescriptions in Australia increased from 0.13 million in 1992 to 0.41 million in 2001. Eighty five percent of prescriptions were for panic disorder, anxiety, depression or mixed anxiety/depression.
CONCLUSIONS
Alprazolam was significantly more toxic than other benzodiazepines. The increased prescription of alprazolam to groups with an increased risk of deliberate self poisoning is concerning and needs review.
Topics: Adolescent; Adult; Aged; Alprazolam; Anti-Anxiety Agents; Benzodiazepines; Critical Care; Diazepam; Drug Overdose; Humans; Length of Stay; Middle Aged
PubMed: 15206998
DOI: 10.1111/j.1365-2125.2004.02089.x