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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 Canadian Veterinary Journal = La... Sep 2021This review focuses on pre-appointment medications used to decrease fear and anxiety in dogs and cats related to veterinary visits. A review of the literature revealed... (Review)
Review
This review focuses on pre-appointment medications used to decrease fear and anxiety in dogs and cats related to veterinary visits. A review of the literature revealed data on 4 medications from 4 medication classes that have been used to ameliorate acute situational fear and anxiety in dogs and cats: gabapentin, trazodone, oral transmucosal dexmedetomidine, and alprazolam. The available information on use, mechanism of action, and pharmacokinetics is reviewed.
Topics: Animals; Anxiety; Cat Diseases; Cats; Dog Diseases; Dogs; Fear; Gabapentin
PubMed: 34475580
DOI: No ID Found -
Psychotherapy and Psychosomatics 2020Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to... (Review)
Review
Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to illustrate withdrawal after decrease, discontinuation, or switch of psychotropic medications based on the drug class (i.e., benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, antidepressants, ketamine, antipsychotics, lithium, mood stabilizers) according to the diagnostic criteria of Chouinard and Chouinard [Psychother Psychosom. 2015;84(2):63-71], which encompass new withdrawal symptoms, rebound symptoms, and persistent post-withdrawal disorders. All these drugs may induce withdrawal syndromes and rebound upon discontinuation, even with slow tapering. However, only selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, and antipsychotics were consistently also associated with persistent post-withdrawal disorders and potential high severity of symptoms, including alterations of clinical course, whereas the distress associated with benzodiazepines discontinuation appears to be short-lived. As a result, the common belief that benzodiazepines should be substituted by medications that cause less dependence such as antidepressants and antipsychotics runs counter the available literature. Ketamine, and probably its derivatives, may be classified as at high risk for dependence and addiction. Because of the lag phase that has taken place between the introduction of a drug into the market and the description of withdrawal symptoms, caution is needed with the use of newer antidepressants and antipsychotics. Within medication classes, alprazolam, lorazepam, triazolam, paroxetine, venlafaxine, fluphenazine, perphenazine, clozapine, and quetiapine are more likely to induce withdrawal. The likelihood of withdrawal manifestations that may be severe and persistent should thus be taken into account in clinical practice and also in children and adolescents.
Topics: Humans; Mental Disorders; Psychotropic Drugs; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 32259826
DOI: 10.1159/000506868 -
Frontiers in Psychiatry 2020Stress in general, and early life stress in particular, has been associated with the development of anxiety and mood disorders. The molecular, biological and... (Review)
Review
Stress in general, and early life stress in particular, has been associated with the development of anxiety and mood disorders. The molecular, biological and psychological links between stress exposure and the pathogenesis of anxiety and mood disorders have been extensively studied, resulting in the search of novel psychopharmacological strategies aimed at targets of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperactivity of the HPA axis has been observed in certain subgroups of patients with anxiety and mood disorders. In addition, the effects of different anti-anxiety agents on various components of the HPA axis has been investigated, including benzodiazepines, tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs). For example, benzodiazepines, including clonazepam and alprazolam, have been demonstrated to reduce the activity of corticotrophin releasing factor (CRF) neurons in the hypothalamus. TCAs and SSRIs are also effective anti-anxiety agents and these may act, in part, by modulating the HPA axis. In this regard, the SSRI escitalopram inhibits CRF release in the central nucleus of the amygdala, while increasing glucocorticoid receptor (GRs) density in the hippocampus and hypothalamus. The molecular effects of these anti-anxiety agents in the regulation of the HPA axis, taken together with their clinical efficacy, may provide further understanding about the role of the HPA axis in the pathophysiology of mood and anxiety disorders, paving the way for the development of novel therapeutic strategies.
PubMed: 32499732
DOI: 10.3389/fpsyt.2020.00443 -
Nature Jan 2019Type-A γ-aminobutyric (GABA) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general...
Type-A γ-aminobutyric (GABA) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABA receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (γ-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes and mechanistic effects of these ligands, the closed and desensitized states of the GABA receptor gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding region and the transmembrane, pore-forming region. This work provides a structural framework in which to integrate previous physiology and pharmacology research and a rational basis for the development of GABA receptor modulators.
Topics: Allosteric Regulation; Alprazolam; Benzodiazepines; Bicuculline; Binding, Competitive; Cryoelectron Microscopy; Diazepam; GABA Modulators; Humans; Ligands; Models, Molecular; Nanostructures; Picrotoxin; Receptors, GABA-A; Signal Transduction
PubMed: 30602790
DOI: 10.1038/s41586-018-0832-5 -
The Journal of Clinical Investigation Dec 2023Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the...
Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.
Topics: Mice; Animals; Corticotropin-Releasing Hormone; Neurons; Anxiety; Brain; Neoplasms
PubMed: 37847562
DOI: 10.1172/JCI167725 -
British Journal of Pharmacology Mar 2020The first clinically relevant reports of preparations of St. John's wort (SJW), a herbal medicine with anti-depressant effects, interacting with other drugs, altering... (Review)
Review
The first clinically relevant reports of preparations of St. John's wort (SJW), a herbal medicine with anti-depressant effects, interacting with other drugs, altering their bioavailability and efficacy, were published about 20 years ago. In 2000, a pharmacokinetic interaction between SJW and cyclosporine caused acute rejection in two heart transplant patients. Since then, subsequent research has shown that SJW altered the pharmacokinetics of drugs such as digoxin, tacrolimus, indinavir, warfarin, alprazolam, simvastatin, or oral contraceptives. These interactions were caused by pregnane-X-receptor (PXR) activation. Preparations of SJW are potent activators of PXR and hence inducers of cytochrome P450 enzymes (most importantly CYP3A4) and P-glycoprotein. The degree of CYP3A4 induction correlates significantly with the hyperforin content in the preparation. Twenty years after the first occurrence of clinically relevant pharmacokinetic drug interactions with SJW, this review revisits the current knowledge of the mechanisms of action and on how pharmacokinetic drug interactions with SJW could be avoided. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.
Topics: Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Herb-Drug Interactions; Humans; Hypericum; Phytotherapy; Plant Preparations
PubMed: 31742659
DOI: 10.1111/bph.14936