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Journal of Addiction Medicine 2018: Alprazolam is one of the most widely prescribed benzodiazepines for the treatment of generalized anxiety disorder and panic disorder. Its clinical use has been a point... (Review)
Review
: Alprazolam is one of the most widely prescribed benzodiazepines for the treatment of generalized anxiety disorder and panic disorder. Its clinical use has been a point of contention as most addiction specialists consider it to be highly addictive, given its unique psychodynamic properties which limit its clinical usefulness, whereas many primary care physicians continue to prescribe it for longer periods than recommended. Clinical research data has not fully shed light on its "abuse liability," yet it is one of the most frequently prescribed benzodiazepines. "Abuse liability" is the degree to which a psychoactive drug has properties that facilitate people misusing it, or becoming addicted to it, and is commonly used in the literature. We have replaced it in our manuscript with "misuse liability" as it reflects a more updated terminology consistent with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In this paper, we have reviewed alprazolam's indications for use, its effect on pregnant women, misuse liability, withdrawal syndrome, pharmacodynamic properties, and suggest better clinical prescription practice of alprazolam by presenting an indepth theory of its clinical effects with use and withdrawal.
Topics: Alprazolam; Anxiety Disorders; Benzodiazepines; Female; Humans; Panic Disorder; Pregnancy; Prescription Drug Misuse; Substance Withdrawal Syndrome
PubMed: 28777203
DOI: 10.1097/ADM.0000000000000350 -
The Cochrane Database of Systematic... Jul 2012The 'off-label' effect of alprazolam on depression has not been systematically evaluated. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 'off-label' effect of alprazolam on depression has not been systematically evaluated.
OBJECTIVES
To determine the antidepressant effect, including tolerability and acceptability, of alprazolam as monotherapy for major depression, when compared to placebo and conventional antidepressants in outpatients and patients in primary care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register, which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to February 2012); EMBASE (1970 to February 2012); MEDLINE (1950 to February 2012) and PsycINFO (1960 to February 2012). Two review authors identified relevant trials by assessing the abstracts of all possible studies. We applied no language restrictions.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) of alprazolam versus placebo or conventional antidepressants for depression in adults, excluding studies with inpatients only.
DATA COLLECTION AND ANALYSIS
Two review authors performed the data extraction and 'Risk of bias' assessment independently with disagreements resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of depression on a continuous measure of depression symptoms, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CI).
MAIN RESULTS
We identified 21 alprazolam studies (22 reports) with a total of 2693 participants. Seven studies used a placebo (n = 771) and 20 used cyclic antidepressants (n = 1765). The typical duration of the studies was four to six weeks. We considered six studies to have a high risk of bias.When alprazolam was compared with placebo for reduction in symptoms all estimates indicated a positive effect for alprazolam. Pooled estimates of efficacy data showed a moderately large continuous mean difference (MD) at the end of trial (-5.34, 95% CI -7.48 to -3.20; I(2) = 68%). The risk difference (RD) for the dichotomous measure of clinical response (50% improvement) was 0.32 in favour of alprazolam (95% CI 0.22 to 0.42; I(2) = 0%), with a number needed to treat to benefit (NNTB) of 3 (95% CI 2 to 5). The RD of all-cause withdrawals did not differ between alprazolam and placebo.When depression severity was measured as a continuum the effect of alprazolam did not differ statistically or clinically from the effects of any of the conventional antidepressants combined (MD 0.25, 95% CI -0.93 to 1.43; I(2) = 55%). However, for dichotomised depression severity, alprazolam had less effect than antidepressants (RR 0.86, 95% CI 0.75 to 0.99; I(2) = 37%; RD -0.11, 95% CI -0.24 to 0.01; I(2) = 58%; NNTB 9, 95% CI 4 to 100). The RD of all-cause withdrawals was -0.04 (95% CI -0.07 to 0.00; I(2) = 35%), in favour of alprazolam.
AUTHORS' CONCLUSIONS
Alprazolam appears to reduce depressive symptoms more effectively than placebo and as effectively as tricyclic antidepressants. However, the studies included in the review were heterogeneous, of poor quality and only addressed short-term effects, thus limiting our confidence in the findings. Whilst the rate of all-cause withdrawals did not appear to differ between alprazolam and placebo, and withdrawals were less frequent in the alprazolam group than in any of the conventional antidepressants combined group, these findings should be interpreted with caution, given the dependency properties of benzodiazepines.
Topics: Adult; Aged; Alprazolam; Antidepressive Agents; Depression; Humans; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 22786504
DOI: 10.1002/14651858.CD007139.pub2 -
The Annals of Pharmacotherapy Mar 1995There is insufficient evidence to support the use of alprazolam in the treatment of tinnitus. The Johnson trial is the only study to date assessing the role of... (Review)
Review
There is insufficient evidence to support the use of alprazolam in the treatment of tinnitus. The Johnson trial is the only study to date assessing the role of alprazolam, and at best it is an open-label trial demonstrating activity. There is a need for definitive double-blind, controlled, crossover studies of sufficient statistical power to resolve the issue. Furthermore, once efficacy is demonstrated, further studies are needed to determine the appropriate length of therapy, the necessity for maintenance therapy, the role of "drug holidays," appropriate dose tapering schedules, and a more careful delineation of which populations of patients are more likely to respond to alprazolam.
Topics: Alprazolam; Clinical Trials as Topic; Humans; Research Design; Tinnitus
PubMed: 7606078
DOI: 10.1177/106002809502900313 -
The Cochrane Database of Systematic... Dec 2015Essential tremor (ET) is one of the most common movement disorders. Treatment is based primarily on pharmacological agents. On this basis, although primidone and... (Review)
Review
BACKGROUND
Essential tremor (ET) is one of the most common movement disorders. Treatment is based primarily on pharmacological agents. On this basis, although primidone and propranolol are well-established treatments in clinical practice, they could be ineffective in 25% to 55% of patients and can produce serious adverse events (AEs) in a large percentage of individuals. For these reasons, evaluating treatment alternatives for ET may be a worthwhile pursuit. Alprazolam has been suggested as a potentially useful agent for treatment of individuals with ET, but its efficacy and safety are uncertain.
OBJECTIVES
PrimaryTo assess the efficacy and safety of alprazolam in the treatment of individuals with ET. SecondaryTo examine effects of alprazolam treatment on the quality of life of people with ET.
SEARCH METHODS
We carried out a systematic search without language restrictions to identify all relevant trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to September 2015), EMBASE (January 1988 to September 2015), the National Institute for Health and Care Excellence (NICE) (1999 to September 2015), ClinicalTrials.gov (1997 to September 2015) and the World Health Organiza tion (WHO) International Clinical Trials Registry Platform (ICTRP) (2004 to September 2015). We handsearched grey literature and examined the reference lists of identified studies and reviews.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of alprazolam versus placebo or any other treatment. We included studies in which ET was diagnosed according to accepted and validated diagnostic criteria. We excluded studies that included patients presenting with secondary forms of tremor or reporting only neurophysiological parameters for the pur p ose of assessing outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected and extracted data using a data collection form. We assessed risk of bias and the body of evidence. We used inverse variance methods for continuous outcomes and measurement scales. We compared differences between treatment groups as mean differences. We used Review Manager software for management and analysis of data.
MAIN RESULTS
We included in this review one trial that compared alprazolam versus placebo (24 participants). It was judged to have high overall risk of bias. We graded the overall quality of evidence as very low. Compared with those given placebo, participants treated with alprazolam showed a significant reduction in tremor severity (mean difference (MD) -0.75, 95% confidence interval (CI) -0.83 to -0.67). Nine alprazolam-treated participants (75%) developed AEs, mainly represented by sedation (50%), constipation (17%) and dry mouth (9%). No participants in the alprazolam group and no p articipants in the placebo group discontinued treatment and dropped out of the study.
AUTHORS' CONCLUSIONS
Currently available data reveal evidence insufficient for assessment of the efficacy and safety of alprazolam treatment for individuals with ET.
Topics: Adult; Aged; Alprazolam; Anticonvulsants; Constipation; Essential Tremor; Humans; Middle Aged; Randomized Controlled Trials as Topic; Xerostomia
PubMed: 26638213
DOI: 10.1002/14651858.CD009681.pub2 -
The Journal of Clinical Psychiatry Oct 1993The triazolobenzodiazepine alprazolam is biotransformed by hepatic microsomal oxidation, yielding two hydroxylated metabolites (4-hydroxy- and a-hydroxy-alprazolam) as... (Review)
Review
The triazolobenzodiazepine alprazolam is biotransformed by hepatic microsomal oxidation, yielding two hydroxylated metabolites (4-hydroxy- and a-hydroxy-alprazolam) as the principal metabolic products. Both metabolites have lower benzodiazepine receptor affinity than the parent compound and at steady state appear in plasma at concentrations considerably lower than intact alprazolam. Thus, clinical activity during treatment with alprazolam is essentially entirely attributable to intact alprazolam. The cytochrome P450 IIIA subfamily appears to mediate alprazolam metabolism in humans. This cytochrome subfamily is not subject to variation due to genetic polymorphism. Ketoconazole, cimetidine, macrolide antibiotics, and serotonin-reuptake-inhibitor antidepressants impair alprazolam biotransformation in vitro. Reduced clearance of alprazolam in vivo has been demonstrated for drugs in this group that have been studied in humans; for those not yet studied, impaired alprazolam clearance should be anticipated during coadministration. Studies of plasma alprazolam concentration versus clinical response during short-term treatment of panic disorder indicate that therapeutic response at steady-state plasma levels of 20 to 40 ng/mL is significantly greater than at levels less than 20 ng/mL. Substantial additional benefit from plasma levels greater than 40 ng/mL is not consistently demonstrated. However, side effects attributable to benzodiazepine agonist activity (e.g., drowsiness, sedation) increase in frequency with increasing steady-state plasma levels. Concentration-response data indicate that monitoring of alprazolam plasma levels can be of considerable clinical value during treatment of panic disorder.
Topics: Alprazolam; Anxiety Disorders; Biotransformation; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Drug Monitoring; Humans; Panic Disorder
PubMed: 8262889
DOI: No ID Found -
Journal of Substance Abuse Treatment 1991Alprazolam and diazepam, the two most prescribed benzodiazepine anxiolytics in the United States, have potential for addictive use. The Drug Abuse Warning Network (DAWN)... (Review)
Review
Alprazolam and diazepam, the two most prescribed benzodiazepine anxiolytics in the United States, have potential for addictive use. The Drug Abuse Warning Network (DAWN) indicates they are the most mentioned benzodiazepines, and the National Household Survey indicates significant abuse of tranquilizers. Both drugs are rapidly absorbed and enter the brain tissue rapidly, leading to reinforcement. Alprazolam has a shorter half-life, which may lead to more withdrawal symptoms than diazepam. In experimental conditions, they are among the most reinforcing benzodiazepines. Each causes a withdrawal syndrome, but alprazolam withdrawal may be more severe and may occur after a shorter period of use. Adverse effects from their use are said to be rare, yet subtle negative consequences may be seen with some regularity. Alprazolam deserves special caution because of its relative newness, great popularity, reinforcing capabilities, relatively severe withdrawal syndrome, and reports of addiction and negative consequences of use.
Topics: Alprazolam; Diazepam; Humans; Risk Factors; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 2051498
DOI: 10.1016/0740-5472(91)90026-7 -
Clinical Therapeutics 1991Alprazolam is the product of the incorporation of the triazolo ring into the benzodiazepine structure. More than 90% of alprazolam is absorbed after an oral dose; the... (Review)
Review
Alprazolam is the product of the incorporation of the triazolo ring into the benzodiazepine structure. More than 90% of alprazolam is absorbed after an oral dose; the absorption rate is dose independent. After a single oral dose of 0.5 to 3 mg of alprazolam, peak plasma concentrations of 7 to 40 ng/ml are reached at 0.7 to 2.1 hours after administration. Factors such as liver and kidney disease, smoking, age, sex, and obesity have minimal effects on alprazolam pharmacokinetics. A review of alprazolam-drug interactions revealed few that were clinically significant, except that cimetidine and oral contraceptives reduce alprazolam clearance and increase its half-life. The mechanisms of action of alprazolam are reviewed. Its anxiolytic effect is similar to that of other benzodiazepines, but the basis of its other effects is less clear. Like other benzodiazepines, it has a good ratio of efficacy to side effects; its most common side effect, mild sedation, occurs early in treatment. The potential of dependence to and abuse of alprazolam and its toxicity are similar to that of other benzodiazepines. Finally, alprazolam's therapeutic role as an anxiolytic and anti-depressant and its use in the management of panic attacks, agoraphobia, schizophrenia, cancer, the premenstrual syndrome, and anxiety and as a cardioprotective agent are assessed.
Topics: Agoraphobia; Alprazolam; Antidepressive Agents; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Platelet Activating Factor; Substance-Related Disorders
PubMed: 2029716
DOI: No ID Found -
The Australian and New Zealand Journal... Aug 1996There are reports of alprazolam-induced hypomania/mania. Here is a case report of a patient who developed hypomania during treatment with alprazolam, but not with...
OBJECTIVE
There are reports of alprazolam-induced hypomania/mania. Here is a case report of a patient who developed hypomania during treatment with alprazolam, but not with diazepam, another benzodiazepine derivative.
CLINICAL PICTURE
The illness was of 2 months' duration and the patient received a diagnosis of anxious depression. Following treatment with alprazolam, the patient developed hypomania characterised by euphoria, overactivity, overtalkactivity, racing thoughts, oversocialisation, enhanced self-confidence and disturbed sleep.
TREATMENT
Hypomania subsided when alprazolam was withdrawn. There was no recurrence with fluoxetine or diazepam that ameliorated the primary condition.
OUTCOME
The patient was symptom-free on follow-up.
CONCLUSIONS
Alprazolam can induce hypomania/mania and, perhaps, it differs from other benzodiazepines in its mode of action. Clinicians have to be alert to the possibility of their patients developing hypomania/mania while on alprazolam.
Topics: Adult; Alprazolam; Anxiety Disorders; Bipolar Disorder; Depressive Disorder; Female; Humans; Psychiatric Status Rating Scales; Somatoform Disorders
PubMed: 8887708
DOI: 10.3109/00048679609065031 -
The Journal of Clinical Psychiatry Oct 1993Therapeutic efficacy for depression and panic disorder has been demonstrated with the triazolobenzodiazepine alprazolam. However, potentially serious adverse events,... (Review)
Review
Therapeutic efficacy for depression and panic disorder has been demonstrated with the triazolobenzodiazepine alprazolam. However, potentially serious adverse events, including depression and suicide attempts, have been reported in patients taking this medication. In this paper, reports addressing the association between each of these two events and benzodiazepine use in general and, more specifically, alprazolam use, are reviewed. We conclude that while these adverse events do occur in patients taking alprazolam, the causal relationship remains unclear and requires further study. Fortunately, these events are observed only rarely, so the prudent clinician may continue to safely prescribe this useful medication.
Topics: Adolescent; Adult; Aged; Alprazolam; Benzodiazepines; Clinical Trials as Topic; Depressive Disorder; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Panic Disorder; Suicide; Suicide, Attempted
PubMed: 8262892
DOI: No ID Found -
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