-
Molecular Psychiatry Jan 2022Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade,... (Review)
Review
Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade, several of them were translated to humans with three clinically relevant goals: to assess potential efficacy of candidate treatments in healthy humans; to develop diagnostic tests or biomarkers; and to elucidate the pathophysiology of anxiety disorders. In this review, we scrutinise these promises and compare seven anxiety tests that are validated across species: five approach-avoidance conflict tests, unpredictable shock anticipation, and the social intrusion test in children. Regarding the first goal, three tests appear suitable for anxiolytic drug screening in humans. However, they have not become part of the drug development pipeline and achieving this may require independent confirmation of predictive validity and cost-effectiveness. Secondly, two tests have shown potential to measure clinically relevant individual differences, but their psychometric properties, predictive value, and clinical applicability need to be clarified. Finally, cross-species research has not yet revealed new evidence that the physiology of healthy human behaviour in anxiety tests relates to the physiology of anxiety symptoms in patients. To summarise, cross-species anxiety tests could be rendered useful for drug screening and for development of diagnostic instruments. Using these tests for aetiology research in healthy humans or animals needs to be queried and may turn out to be unrealistic.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Humans; Psychiatry; Psychometrics
PubMed: 34561614
DOI: 10.1038/s41380-021-01299-4 -
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 -
European Neuropsychopharmacology : the... Jul 2023The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for... (Meta-Analysis)
Meta-Analysis Review
The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for anxiety-reduction by compounds that facilitate endocannabinoid signaling in humans and animals. To identify areas of specific potential, effects of moderators were assessed. Literature was searched in Pubmed and Embase up to May 2021. A placebo/vehicle-control group was required and in human studies, randomization. We excluded studies that co-administered other substances. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. We conducted three-level random effects meta-analyses and explored sources of heterogeneity using Bayesian regularized meta-regression (BRMA). The systematic review yielded 134 studies. We analyzed 120 studies (114 animal, 6 human) that investigated cannabidiol (CBD, 61), URB597 (39), PF-3845 (6) and AM404 (14). Pooled effects on conditioned and unconditioned anxiety in animals (with the exception of URB597 on unconditioned anxiety) and on experimentally induced anxiety in humans favored the investigational drugs over placebo/vehicle. Publication year was negatively associated with effects of CBD on unconditioned anxiety. Compared to approach avoidance tests, tests of repetitive-compulsive behavior were associated with larger effects of CBD and URB597, and the social interaction test with smaller effects of URB597. Larger effects of CBD on unconditioned anxiety were observed when anxiety pre-existed. Studies reported few side effects at therapeutic doses. The evidence quality was low with indications of publication bias. More clinical trials are needed to translate the overall positive results to clinical applications.
Topics: Animals; Humans; Anti-Anxiety Agents; Endocannabinoids; Bayes Theorem; Anxiety; Cannabidiol
PubMed: 37094409
DOI: 10.1016/j.euroneuro.2023.04.001 -
Behavioural Neurology 2023The current study was planned to assess the neuropharmacological benefits of the seed. These seeds have been conventionally used for the nutritional as well as...
The current study was planned to assess the neuropharmacological benefits of the seed. These seeds have been conventionally used for the nutritional as well as amelioration of various diseases. However, there was a need to provide a pharmacological basis for such use. Four central nervous system-related functions, that is, anxiety, depression, memory, and motor coordination, were evaluated, and the levels of brain biogenic amines were also assessed. Anxiety was evaluated through selected experimental models, such as light and dark apparatus, elevated plus maze, head dip, and open field test. The head dip test was mainly used to assess exploratory behavior. Depression was assessed by two animal models, that is, the forced swim test and tail suspension test. Memory and learning ability were assessed by the passive avoidance test, stationary rod apparatus, and Morris's water maze test. Motor skilled learning was assessed by stationary rod and rotarod apparatus. Reversed phase high-pressure liquid chromatography was used to determine biogenic amine levels. Results reveal that exhibited anxiolytic and antidepressant effects with memory improvement. There was a reduction in the weight of the animal following chronic administration. Furthermore, no remarkable effects were observed on motor coordination. Norepinephrine was found elevated, which may be linked to its antidepressant effects. These biological effects of may be due to the presence of secondary metabolites, such as cucurbitacin, beta-sitosterol, polyphenolic compounds, citrulline, kaempferol, arginine, -carotene, quercetin, and other antioxidants. The outcomes of the present study authenticate that the chronic use of seeds reduces the intensity of neurological problems like anxiety and depression.
Topics: Animals; Depression; Cucurbita; Anxiety; Antidepressive Agents; Anti-Anxiety Agents; Biogenic Amines; Behavior, Animal; Maze Learning
PubMed: 37006627
DOI: 10.1155/2023/7509937 -
Prague Medical Report 2020Buspirone (BUS) belongs to the azapirone chemical class. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms,... (Review)
Review
Buspirone (BUS) belongs to the azapirone chemical class. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of BUS-associated movement disorders (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 25 reports containing 65 cases were assessed. The MD associated with BUS were: dyskinesia in 14 cases, 10 of akathisia, 8 of myoclonus, 6 of Parkinsonism, and 6 of dystonia. The cases not clearly defined were 7 tension, 14 incoordination, and the undefined number of dyskinesia, tics, and Parkinsonism. The mean age was 45.23 years (range: 15-74). The male was the predominant sex in 60.86% and the most common BUS-indication was anxiety disorder. The mean BUS-dose was 42.16 mg (range: 5-100). The time from the beginning of BUS administration to the MD onset was one month or less in 76%. The time from BUS withdrawal to complete recovery was within one month in 87.5%. The most common management was BUS withdrawal. In 16 patients the follow-up was reported: 14 had a full recovery, but in two (1 dyskinesia + 1 dystonia) the symptoms continued after the BUS withdrawal. MD associated with BUS were scarcely reported in the literature. Moreover, in the majority of cases, no clear description of the clinical profile, neurological examination, or the time data of the movement disorder onset and recovery were given.
Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Buspirone; Humans; Male; Middle Aged; Movement Disorders; Young Adult
PubMed: 32191616
DOI: 10.14712/23362936.2020.1 -
Biomedicine & Pharmacotherapy =... Nov 2020Parkinson's disease (PD) is a progressive neurodegenerative disease which affects millions of population worldwide. It is characterized by motor symptoms such as... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disease which affects millions of population worldwide. It is characterized by motor symptoms such as excessive tremor, bradykinesia, rigidity, postural instability and non-motor symptoms include neuropsychiatric complications like anxiety, depression, insomnia and cognitive impairment, orthostatic hypotension, sexual dysfunction and gastrointestinal complications. Treatment of anxiety in PD poses extensive challenge to global healthcare which makes it urgent to develop innovative treatment for the better management of the disease. The gold standard treatment by Levodopa provides symptomatic relief and its effect on neuropsychiatric complications like anxiety is elusive. Presence of anxiety worsens the condition and challenges therapeutic management of the PD. The in-depth analysis and understanding the molecular mechanism and pathophysiological pathways associated with the onset of anxiety in PD is essential. The disturbances in serotonergic, adrenergic and GABAergic neurons and hypothalamic pituitary adrenal axis play a significant role in the pathophysiology of anxiety. The drugs like Selective Serotonin Reuptake Inhibitors, tricyclic antidepressants and benzodiazepines are useful in the management of anxiety but due to severe side effects and progression of the disease it results in the failure of treatment. The present review imparts an insight in the management of anxiety in PD by understanding molecular mechanism and application of alternative treatment options which can enlighten the perception of researchers towards better therapeutic management of the disease.
Topics: Animals; Anti-Anxiety Agents; Antiparkinson Agents; Anxiety; Disease Progression; Humans; Levodopa; Parkinson Disease
PubMed: 33152935
DOI: 10.1016/j.biopha.2020.110776 -
Molecules (Basel, Switzerland) May 2022Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as , , and . This natural molecule exerts diverse pharmacological effects, which includes... (Review)
Review
Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as , , and . This natural molecule exerts diverse pharmacological effects, which includes antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and anti-apoptotic effects. Additionally, in brain structures, such as the hippocampus, prefrontal cortex, raphe nucleus, and striatum, involved in the physiopathology of anxiety and depression disorders, several neuropharmacological activities, including the activation of neurotransmitter systems (GABAergic, serotonergic, dopaminergic, and noradrenergic), neurotrophic factors, such as brain-derived neurotrophic factor and the nerve growth factor, and some signaling pathways are affected. The results showed that the anxiolytic and antidepressant-like effects of chrysin occurs through its interaction with specific neurotransmitter systems, principally the GABAergic and the serotonergic, and activation of other neurotrophic factors. However, it is not possible to discard the antioxidant and anti-inflammatory activities of chrysin while producing its anxiolytic- and antidepressant-like effects. Although these results have been obtained principally from pre-clinical research, they consistently demonstrate the potential therapeutic use of flavonoid chrysin as an anxiolytic and antidepressant agent. Therefore, this flavonoid could be considered as a promising novel therapy for anxiety and depression disorders.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Antioxidants; Flavonoids; Passiflora
PubMed: 35684488
DOI: 10.3390/molecules27113551 -
Neuropsychopharmacology Reports Sep 2023The development of clinical practice guidelines for social anxiety disorder began in March 2018 when the Joint Clinical Practice Guideline Development Committee for...
The development of clinical practice guidelines for social anxiety disorder began in March 2018 when the Joint Clinical Practice Guideline Development Committee for Anxiety and Obsessive-Compulsive Disorders was formed by the Japanese Society of Anxiety and Related Disorders and Japanese Society of Neuropsychopharmacology to jointly develop guidelines for anxiety and obsessive-compulsive disorders. Based on the universal concept of evidence-based medicine, three clinical questions (CQs) about pharmacotherapy and psychotherapy were developed for clinical guidelines for social anxiety disorder, panic disorders, and obsessive-compulsive disorder in accordance with the Minds "Manual for Guidelines Development 2017 by the Japan Council for Quality Health Care: CQ1-"What is the recommended pharmacotherapy for social anxiety disorder in adults?"; CQ2-"What is the recommended psychotherapy (psychological intervention) for social anxiety disorder in adults?"; and CQ3-"What are the recommendations regarding monotherapy and combination therapy for social anxiety disorder in adults in terms of pharmacotherapy and psychotherapy (psychological interventions)?" Summarized recommendations for social anxiety disorder in adults are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitor for CQ1, cognitive behavioral therapy for CQ2, and there are no recommendations regarding monotherapy and combination therapy for CQ3. These were answered by considering the balance between benefits and harms based on systematic reviews of each. The aim of this brief guideline for the standard-of-care (i.e., medical treatment) for social anxiety disorder in adults (18 years and older) was to help "shared decision making," in which medical professionals, including physicians, and patients share scientific evidence to decide on a course of treatment.
Topics: Adult; Humans; Anxiety; Anxiety Disorders; Cognitive Behavioral Therapy; East Asian People; Phobia, Social; Japan; Anti-Anxiety Agents; Combined Modality Therapy
PubMed: 37624975
DOI: 10.1002/npr2.12365 -
Clinical and Translational Science Jun 2023Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the... (Clinical Trial)
Clinical Trial
Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single-center, open-label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non-nasal pathways. Intranasal amiloride exhibited a dose-proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.
Topics: Animals; Humans; Administration, Intranasal; Amiloride; Anti-Anxiety Agents; Anxiety; Healthy Volunteers
PubMed: 36932683
DOI: 10.1111/cts.13514 -
JAMA Network Open Oct 2023Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications...
IMPORTANCE
Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking.
OBJECTIVE
To examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023.
EXPOSURES
Type 1 diabetes.
MAIN OUTCOMES AND MEASURES
The primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset.
RESULTS
Of 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts.
CONCLUSIONS AND RELEVANCE
This cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.
Topics: Male; Child; Humans; Adolescent; Diabetes Mellitus, Type 1; Anti-Anxiety Agents; Cohort Studies; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives
PubMed: 37787995
DOI: 10.1001/jamanetworkopen.2023.36621