All Shades of Anxiety: A Review of Therapeutic and Psychotropic Considerations for Child and Adolescent Youth of Color.

The literature on anxiety in Black, Indigenous, and other persons of color youth is a developing area. This article highlights distinct areas for the clinician to consider in working with these populations. We highlight prevalence and incidence, race-related stress, social media, substance use, spirituality, the impact of social determinants of health (including COVID-19 and the Syndemic), as well as treatment considerations. Our aim is to contribute to the readers' developing cultural humility.

A Multicenter Double-Blind, Placebo-Controlled Trial of Escitalopram in Children and Adolescents with Generalized Anxiety Disorder.

Objective: Generalized anxiety disorder (GAD) in children and adolescents is associated with substantial morbidity and increases the risk of future psychopathology. However, relatively few psychopharmacologic studies have examined treatments for GAD in pediatric populations, especially in prepubertal youth. Methods: Children and adolescents aged 7-17 years of age with a primary diagnosis of GAD were treated with flexibly dosed escitalopram (10-20 mg daily, n = 138) or placebo (n = 137) for 8 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS) for GAD, Clinical Global Impression of Severity (CGI-S) scale, Children's Global Assessment Scale (CGAS); safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as adverse events (AEs), vital signs, and electrocardiographic and laboratory monitoring. Results: Escitalopram was superior to placebo in reducing anxiety symptoms of GAD, as seen in the difference in mean change from baseline to week 8 on the PARS severity for GAD score (least squares mean difference = -1.42; p = 0.028). Functional improvement, as reflected by CGAS score, was numerically greater in escitalopram-treated patients compared with those receiving placebo (p = 0.286), and discontinuation owing to AEs did not differ between the two groups. Vital signs, weight, laboratory, and electrocardiographic results were consistent with previous pediatric studies of escitalopram. Conclusions: Escitalopram reduced anxiety symptoms and was well tolerated in pediatric patients with GAD. These findings confirm earlier reports of escitalopram efficacy in adolescents aged 12-17 years and extend the safety and tolerability data to children with GAD aged 7-11 years. ClinicalTrials.gov Identifier: NCT03924323.

Interventions for generalized anxiety disorder.

PURPOSE OF REVIEW: To provide an overview of recently published work on anxiety, focusing on generalized anxiety disorder (GAD) and its treatment. RECENT FINDINGS: Self-reported anxiety symptoms were highly prevalent during the COVID-19 global pandemic in both the general population and in selected groups. There remains divided opinion about whether internet-based cognitive behavioural therapy (CBT) is noninferior to face-to-face CBT for GAD. A systematic review of drug treatment for GAD showed efficacy for selective serotonin reuptake inhibitors (SNRIs), agomelatine, and quetiapine. There may be a place for repetitive transcranial magnetic stimulation in the treatment of GAD. There was some evidence of efficacy for complementary therapies, including physical exercise, yoga, acupuncture, and Withania somnifera (ashwagandha). However, a systematic review of cannabidiol and tetrahydrocannabinol found insufficient evidence of efficacy in anxiety disorders. SUMMARY: Antidepressants and quetiapine show efficacy in the treatment of GAD. Internet-based psychological interventions have a place in the treatment of GAD when face-to-face treatment is inaccessible. There is increasing evidence for the use of physical exercise in the management of GAD. Some other complementary therapies, including cannabinoids, require further, methodologically sound, research.

Pharmacological Treatment for Pediatric Anxiety Disorders.

Pediatric anxiety disorders (PADs) occur in up to 20% of youth and can cause impairment across the lifespan. Coronavirus disease 2019 (COVID-19) added unique pressures on those with PADs, as children and adolescents endured the longest pandemic restrictions, stymieing their ability to develop socially, emotionally, and cognitively. Although first-line treatment for PADs is psychotherapy, those with severe anxiety symptoms will require pharmacological interventions. Selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor (SNRI) medications are effective in treating PADs, yet only duloxetine (a SNRI) is approved by the U.S. Food and Drug Administration for children aged >7 years with generalized anxiety disorder. Treatment of children and adolescents with benzodiazepines for PADs presents unique challenges with potential paradoxical reactions. Caution must be observed as well due to risk for misuse related to long-term use of benzodiazepines with PADs. [Journal of Psychosocial Nursing and Mental Health Services, 60(9), 6-9.].

Dysfunctional Heteroreceptor Complexes as Novel Targets for the Treatment of Major Depressive and Anxiety Disorders.

Among mental diseases, major depressive disorder (MDD) and anxiety deserve a special place due to their high prevalence and their negative impact both on society and patients suffering from these disorders. Consequently, the development of novel strategies designed to treat them quickly and efficiently, without or at least having limited side effects, is considered a highly important goal. Growing evidence indicates that emerging properties are developed on recognition, trafficking, and signaling of G-protein coupled receptors (GPCRs) upon their heteromerization with other types of GPCRs, receptor tyrosine kinases, and ionotropic receptors such as N-methyl-D-aspartate (NMDA) receptors. Therefore, to develop new treatments for MDD and anxiety, it will be important to identify the most vulnerable heteroreceptor complexes involved in MDD and anxiety. This review focuses on how GPCRs, especially serotonin, dopamine, galanin, and opioid heteroreceptor complexes, modulate synaptic and volume transmission in the limbic networks of the brain. We attempt to provide information showing how these emerging concepts can contribute to finding new ways to treat both MDD and anxiety disorders.

Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders.

The word "psychedelic" (psyche (i.e., the mind or soul) and delos (i.e., to show)) has Greek origin and was first coined by psychiatrist Humphry Osmond in 1956, who had been conducting research on lysergic acid diethylamide (LSD) at the time. Psychedelic drugs such as N,N-DMT/DMT (N,N-dimethyltryptamine), 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxymethamphetamine) and psilocybin have had significant value as an entheogen in spiritual, religious (shamanic) and sociocultural rituals in Central and South American cultures for thousands of years. In the 1960s, the globalization of these drugs and their subsequent spread outside of their indigenous, old-world cultures, led to the subsequent implementation of strict drug control laws in many Western countries. Even today, psychedelics are still classified as Schedule I drugs, resulting in a still lingering negative stigmatization/perception, vilification, and ultimate criminalization of psychedelics. This controversy still lingers and still limits scientific research and full medical acceptance. For many years up until recently, the spiritual, religious and medicinal value of these drugs could not be explored in a scientific context. More recently, a second wave of psychedelic research is now focusing on psychedelics as neuropharmaceuticals to treat alcohol and tobacco addiction, general mood and anxiety disorders and cancer-related depression. There is now a vast array of promising evidence-based data to confirm the years of anecdotal evidence of the medicinal values of psychedelics. Natural therapeutic alternatives such as psychedelic drugs may provide a safe and efficacious alternate to conventional drugs used to treat mood and anxiety disorders. In a Western context in particular, psychedelic drugs as therapeutic agents for mood and anxiety disorders are becoming increasingly of interest amidst increasing rates of such disorders globally, changing social constructions, the implementation of government regulations and increasing investment opportunities, that ultimately allow for the scientific study to generate evidenced-based data. Alternative psychotherapeutic interventions are gaining interest also, because of their low physiological toxicity, relatively low abuse potential, safe psychological effects, and no associated persisting adverse physiological or psychological effects during and after use. On the other hand, conventional psychotic drugs and anti-depressants are becoming less favorable because of their adverse side effects. Psychedelic neuropharmaceutical interventions may with medical oversight be the solution to conventional psychiatric disorders such as depression and anxiety, and an alternative to conventional psychiatric treatment options. This paper will review the therapeutic potential of psychedelic drugs as alternative therapeutic options for mood and anxiety disorders in a controlled, clinical setting, where the chances of adverse psychological episodes occurring are mitigated.

Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders.

Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.

Safety and efficacy of aviandr in patients with generalized anxiety disorder: A multicenter, randomized, double-blind, placebo-controlled, dose-finding, pilot study.

Generalized anxiety disorder (GAD) is associated with an imbalance in the functioning of the stimulating neurotransmitter systems in human's brain. We studied the safety and therapeutic efficacy of aviandr, the new noradrenergic and specific serotonergic antidepressant, for GAD patients in the phase II, double-blind, placebo-controlled, randomized, multicenter, pilot trial at 17 clinical sites of the Russian Federation. 129 eligible patients were 18 years and older and met the criteria for GAD diagnosis. The patients were randomly assigned (1:1:1) to receive oral aviandr at daily dose of 40 mg (cohort 1, n = 41) or 60 mg (cohort 2, n = 43) or placebo (cohort 3, n = 43) for 8 weeks. The patients were assessed by the Hamilton anxiety scale (HAM-A), Hamilton Depression Scale (HAM-D), Clinical Global Impression Scale (CGI-S), Visual Analogue Scale and vital signs. At week 8, the decreases of the HAM-A score were achieved in 53∙7%, 47∙7% and 16∙3% in cohorts 1, 2 and 3, respectively. Changes of HAM-A, HAM-D, CGI-S, and CGI-I scores in aviandr-treated patients were superior to placebo (p < 0∙001). The psychic components of anxiety decreased on the first day, throughout the 8 weeks of treatment and on a follow-up week after aviandr discontinuation. Aviandr (40 mg daily dose) reduced drowsiness compared to baseline, was safe, well-tolerated and did not cause serious or severe adverse events or signs of withdrawal syndrome within one week after treatment completion. Aviandr at both 40 and 60 mg daily doses demonstrated therapeutic efficacy in GAD patients over placebo.

Systematic review of benzodiazepines for anxiety disorders in late life.

BACKGROUND: Benzodiazepines are currently the most commonly prescribed medication for the treatment of anxiety in older adults, although there is a dearth of good-quality data on this subject. The aim of this review was to systematically review studies examining the efficacy and tolerability of benzodiazepines for the treatment of anxiety disorders among older adults. METHODS: The authors conducted a systematic review, searching PubMed, Ovid MEDLINE, Ovid Embase, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. All searches were limited to English-language articles. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine for randomized controlled trials. RESULTS: A total of 8,785 citations were retrieved and pooled in EndNote and de-duplicated to 3,753. This set was uploaded to Covidence for screening. Two separate screeners (AG and SAF) evaluated the titles, abstracts, and full text of the eligible articles. Five studies met the inclusion criteria. Across all studies, benzodiazepines were associated with decreased anxiety at the end of the study period. The limited tolerability data show mild adverse effects from the benzodiazepines studied. Limitations of the trials included limited data on the long-term use of benzodiazepines for anxiety and a preponderance of trials examining generalized anxiety disorder, with relatively less data on other anxiety disorders. CONCLUSIONS: Benzodiazepines are effective for treating anxiety disorders in late life, at least in the short term, but more data is needed to establish tolerability and their long-term benefits.

[Astenic disorders within the framework of post-covid syndrome]. / Astenicheskie rasstroistva v ramkakh postkovidnogo sindroma.

The direct neurotropic and neurotoxic effect of the SARS-CoV-2 virus on the central nervous system, as well as the stressful effect of various factors of the COVID-19 pandemic, contribute to the development of the so-called post-COVID syndrome. The clinical picture of the syndrome includes asthenic, anxiety-asthenic, and depressive manifestations. When prescribing psychopharmacotherapy to patients who have undergone COVID-19, it is recommended to assess the potential benefits and risks in the aspect of using drugs not only with therapeutic antiasthenic and anxiolytic properties, but with minimally expressed undesirable effects and adverse drug interactions.

[Panic and pandemic: Review of the literature on the links between panic disorder and the SARS-CoV-2 epidemic]. / Panique et pandémie : revue de la littérature sur les liens entre le trouble panique et l'épidémie à SARS-CoV-2.

Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence given that some etiological and maintenance factors associated with panic disorder - i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities - are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 epidemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe, thus caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety reduction. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19).

Brief psychotic disorder associated with quarantine and mild COVID-19.

A 30-year-old man with no significant previous or family psychiatric history became severely anxious about his health after a positive COVID-19 test. Physical symptoms of COVID-19 were mild, with no evidence of hypoxia or pneumonia, throughout his illness. He was admitted to a quarantine facility. He remained highly anxious, and 1 week later, he developed paranoid delusions and auditory hallucinations (his first psychotic episode). He was treated with lorazepam 1 mg four times a day, mirtazapine 30 mg nocte and risperidone 1 mg two times a day. His psychotic symptoms lasted 1 week. He stopped psychiatric medication after 4 weeks and had remained well when reviewed 3 months later. A Diagnostic and Statistical Manual of Mental Disorders fifth edition diagnosis of brief psychotic disorder with marked stressor (brief reactive psychosis) was made. Anxiety about his health and social isolation appeared the main aetiological factors but an inflammatory component cannot be excluded. The case highlights that first episode psychosis can be associated with mild COVID-19.

Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?

Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), a chemical isolated from Cannabis sativa with reported anxiolytic properties, could be a therapeutic option for the treatment of COVID-19-related anxiety disorders. In the global over-the-counter CBD market, anxiety, stress, depression, and sleep disorders are consistently the top reasons people use CBD. In small randomized controlled clinical trials, CBD (300-800 mg) reduces anxiety in healthy volunteers, patients with social anxiety disorder, those at clinical high risk of psychosis, in patients with Parkinson's disease, and in individuals with heroin use disorder. Observational studies and case reports support these findings, extending to patients with anxiety and sleep disorders, Crohn's disease, depression, and in PTSD. Larger ongoing trials in this area continue to add to this evidence base with relevant patient cohorts, sample sizes, and clinical end-points. Pre-clinical studies reveal the molecular targets of CBD in these indications as the cannabinoid receptor type 1 and cannabinoid receptor type 2 (mainly in fear memory processing), serotonin 1A receptor (mainly in anxiolysis) and peroxisome proliferator-activated receptor gamma (mainly in the underpinning anti-inflammatory/antioxidant effects). Observational and pre-clinical data also support CBD's therapeutic value in improving sleep (increased sleep duration/quality and reduction in nightmares) and depression, which are often comorbid with anxiety. Together these features of CBD make it an attractive novel therapeutic option in COVID-related PTSS that merits investigation and testing through appropriately designed randomized controlled trials.

Impact of the coronavirus 2019 (COVID-19) pandemic on anxiety diagnosis in general practices in Germany.

Little is known about the effects of the coronavirus disease-2019 (COVID-19) pandemic on the diagnosis of anxiety disorder. Therefore, the goal of this study was to compare the number of adults with a diagnosis of anxiety disorder and the number of adults newly diagnosed with anxiety disorder in Germany between January-June 2019 and January-June 2020, and to identify potential differences in terms of sociodemographic characteristics, prescriptions and comorbidities between these patients. The study included patients with at least one consultation in one of 1140 general practices in Germany in January-June 2019 and January-June 2020. Sociodemographic characteristics included age and sex, while there were three families of drugs and nine common comorbidities available for the analysis. An increase in the number of patients with anxiety disorder was observed in 2020 compared with 2019 (January: +4%, p = 0.643; February: +4%, p = 0.825; March: +34%, p < 0.001; April: +8%, p = 0.542; May: +2%, p = 0.382; June: +19%, p = 0.043; and March-June: + 19%, p < 0.001). There was also an increase in the number of patients newly diagnosed with anxiety disorder between March-June 2020 and March-June 2019 (11,502 versus 9506; +21%, p-value<0.001). Antidepressants, anxiolytics and herbal sedatives were less frequently prescribed in patients newly diagnosed with anxiety disorder in 2020 than in 2019 (30.4% versus 35.6%, p-value<0.001). Finally, COPD (9.4% versus 7.9%, p-value<0.001) and asthma (11.3% versus 9.7%, p-value<0.001) were more frequent in 2020 than in 2019. Taken these findings together, public health measures are urgently needed to mitigate the negative impact of the COVID-19 pandemic on anxiety disorder.