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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 -
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 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
The Cochrane Database of Systematic... Dec 2020Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods.
OBJECTIVES
To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines.
SEARCH METHODS
We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform.
SELECTION CRITERIA
We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia.
DATA COLLECTION AND ANALYSIS
One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures.
MAIN RESULTS
We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines.
AUTHORS' CONCLUSIONS
When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.
Topics: Adult; Aged; Aged, 80 and over; Alprazolam; Anti-Anxiety Agents; Anxiety; Bias; Clonidine; Drug Administration Schedule; Humans; Melatonin; Midazolam; Middle Aged; Oxazepam; Postoperative Care; Postoperative Complications; Preoperative Care; Publication Bias; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 33319916
DOI: 10.1002/14651858.CD009861.pub3