Novel pharmacological treatments for generalized anxiety disorder: Pediatric considerations.

BACKGROUND: Pediatric anxiety disorders such as generalized anxiety disorder (GAD) are common, impairing, and often undertreated. Moreover, many youth do not respond to standard, evidence-based psychosocial or psychopharmacologic treatment. An increased understanding of the gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems has created opportunities for novel intervention development for pediatric GAD. METHODS: This narrative review examines potential candidates for pediatric GAD: eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine. RESULTS: The pharmacology, preclinical data, clinical trial findings and known side effects of eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine, are reviewed, particularly with regard to their potential therapeutic relevance to pediatric GAD. CONCLUSION: Notwithstanding numerous challenges, some of these agents represent potential candidate drugs for pediatric GAD. Further treatment development studies of agomelatine, eszopiclone, pimavanserin and riluzole for pediatric GAD also have the prospect of informing the understanding of GABAergic and glutamatergic function across development.

A Systematic Review of Neuromodulation Treatment Effects on Suicidality.

Introduction: Neuromodulation is an important group of therapeutic modalities for neuropsychiatric disorders. Prior studies have focused on efficacy and adverse events associated with neuromodulation. Less is known regarding the influence of neuromodulation treatments on suicidality. This systematic review sought to examine the effects of various neuromodulation techniques on suicidality. Methods: A systematic review of the literature from 1940 to 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was conducted. Any reported suicide-related outcome, including suicidal ideation, suicide intent, suicide attempt, completed suicide in reports were considered as a putative measure of treatment effect on suicidality. Results: The review identified 129 relevant studies. An exploratory analysis of a randomized controlled trial comparing the effects of sertraline and transcranial direct-current stimulation (tDCS) for treating depression reported a decrease in suicidal ideation favoring tDCS vs. placebo and tDCS combined with sertraline vs. placebo. Several studies reported an association between repetitive transcranial magnetic stimulation and improvements in suicidal ideation. In 12 of the studies, suicidality was the primary outcome, ten of which showed a significant improvement in suicidal ideation. Electroconvulsive therapy (ECT) and magnetic seizure therapy was also shown to be associated with lower suicidal ideation and completed suicide rates. There were 11 studies which suicidality was the primary outcome and seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT. There was limited literature focused on the potential protective effect of vagal nerve stimulation with respect to suicidal ideation. Data were mixed regarding the potential effects of deep brain stimulation on suicidality. Conclusions: Future prospective studies of neuromodulation that focus on the primary outcome of suicidality are urgently needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125599, identifier: CRD42019125599.

An exploratory study of clinical and physiological correlates of problematic social media use in adolescents.

Prior validation studies of the Bergen Social Media Addiction Scale (BSMAS) demonstrate its utility for identifying problematic social media use in adolescents. There are knowledge gaps regarding the potential clinical and physiological underpinnings of problematic social media use in adolescents. This cross-sectional, single-visit study examined a sample of depressed (n = 30) and healthy (n = 30) adolescents who underwent clinical assessments of depressive symptom severity, bullying, cyberbullying, self-esteem, salivary measures of stress (cortisol and α-amylase) to identify correlates with adolescent and parental reports of the BSMAS. LASSO-penalized multiple linear regression models were implemented. With respect to the adolescent BSMAS scores in all subjects, the risk of problematic social media increased as depressive symptom severity increased. Depressed female adolescents appeared to have a greater risk. Based on parental BSMAS scores, depression status, depressive symptom severity, cyberbullying score, and salivary cortisol significantly predicted problematic social media use. For the depressed sample, the risk of problematic social media use increased as salivary cortisol increased. No significant predictors of problematic social media usage emerged in the healthy control sample. These preliminary results provide novel insights into clinical and physiological characteristics of problematic social media use in adolescents.

Altered markers of stress in depressed adolescents after acute social media use.

Social media use (SMU) is an inherent element in the daily life and neurodevelopment of adolescents, but broad concerns exist regarding the untoward effects of social media on adolescents. We conducted a prospective, cross-sectional study that sought to examine the acute effects of SMU on clinical measures and biomarkers of stress in healthy and depressed adolescents. After at least 24 h of abstinence from social media, depressed adolescents (n = 30) and healthy control adolescents (n = 30) underwent baseline clinical assessment of their prior SMU, depressive symptom severity, self-esteem, and exposure to bullying. Participants provided salivary samples that were analyzed for α-amylase and cortisol levels. After 20 min of unsupervised SMU, saliva analyses and clinical assessments were repeated. After 20 min of SMU, salivary cortisol and α-amylase levels were significantly higher in adolescents with depression but not in healthy control adolescents. Furthermore, small but statistically significant changes in depressive symptom severity occurred in all participants. These changes in depressive symptoms were not clinically meaningful. SMU did not significantly change self-esteem measures among participants. Adolescents with depression appeared to have more physiological reactivity after SMU compared with healthy adolescents. Further research should characterize SMU as a clinical dimension and risk factor among adolescents with depression and other psychiatric disorders.