Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Understanding chronic pain in Neurofibromatosis Type 1 using the Neurofibromatosis Pain Module (NFPM).

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder that can cause an individual significant chronic pain (CP). CP affects quality of life and daily functioning, yet there are limited effective treatments for CP within NF1. The current study describes the impact of CP using the Neurofibromatosis Pain Module (NFPM). The NFPM is a self-reported clinical assessment that evaluates the impact of CP across multiple domains (e.g., interference, severity, tolerance, and symptomology) and three prioritized pain regions. A cross-sectional study (N = 242) asked adults with NF1 to describe and rate their pain using the NFPM. The results indicated that they reported moderate pain severity (M = 6.6, SD = 2.0) on a 0-10 scale, that 54% (n = 131) had been in pain at least 24 days in the last 30, for 75% (n = 181) sleep was affected, and 16% reported that nothing was effective in reducing their CP for their primary pain region. The current results extend previously published work on CP within adults with NF1 and indicate that more emphasis on understanding and ameliorating CP is required. The NFPM is a sensitive clinical measure that provides qualitative and quantitative responses to inform medical providers about changes in CP.

A Serious Video Game Targeting HIV Testing and Counseling: A Randomized Controlled Trial.

PURPOSE: Adolescents are the age group that is least likely to know their HIV status and may unknowingly transmit the virus to others. A randomized controlled trial was conducted to evaluate the impact of the original video game intervention, PlayTest!, on behavioral antecedents for HIV testing and counseling (HTC). METHODS: Participants (N = 287 adolescents) were recruited between 2018 and 2020 and were 48% female, aged 14-18 years (mean age = 15.4 years), and 76% racial minorities. Participants were randomized 1:1 and assigned to either play PlayTest! or a set of control games, ∼one session per week for an hour per session over 4-6 weeks (gameplay) after school. The primary outcome measure was participants' attitudes around HTC at 6 months, with intentions, knowledge, self-efficacy, and behaviors assessed as secondary outcomes. RESULTS: Two hundred and ninety-six participants were enrolled/randomized; nine were withdrawn due to incomplete parental consent forms, leaving 287 participants: 145 were randomized to PlayTest! and 142 to the control condition. Mixed between-within subjects ANOVAs assessed the impact of the study conditions on outcomes. Improvements were seen in the PlayTest! group in HTC attitudes (p < .001), intentions (p < .001), knowledge (p < .001), and self-efficacy (p = .002) at all time-points. At 6 months, for those who had access to HTC (N = 134; prior to COVID-19) and for those who did not have access to HTC (N = 261; during COVID-19), there were no differences in self-reported HTC between the two groups (p = .289 and p = .074, respectively). DISCUSSION: PlayTest! impacted important behavioral antecedents related to HTC and has the potential to broadly increase HTC rates in adolescents.

Including Community Partners in the Development and Adaptation of Intervention Strategies to Prevent Initiation or Escalation of Opioid Misuse.

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness.

Maintaining Engagement in Adults with Neurofibromatosis Type 1 to Use the iCanCope Mobile Application (iCanCope-NF).

INTRODUCTION: Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic condition in which chronic pain is a predominant issue. Given the rarity of the disease, there are limited psychosocial treatments for individuals with NF1 suffering with chronic pain. Using mobile applications can facilitate psychosocial treatments; however, there are consistent issues with engagement. Utilizing a mixed methodology, the current study evaluated the customized iCanCope mobile application for NF1 on increasing engagement through the usage of contingency management. METHODS: A mixed methods study from a subset of data coming from a randomized clinical trial that occurred from January 2021 to August 2022 was undertaken. Two groups (iCC and iCC + CM) were exposed to the customized iCanCope mobile application in which engagement data were captured in real-time with daily check-ins for interference, sleep, mood, physical activity, energy levels, goal setting, and accessing article content (coping strategies). Additionally, semi-structured interviews were conducted to gain insight into the participants' experience at the end of the trial. RESULTS: Adults (N = 72) were recruited via NF patient advocacy groups. Significant differences were noted between the groups in total articles read (p = 0.002), goals achieved (p = 0.017), and goals created (p = 008). Additionally, there were significant differences observed between user-generated goals and those that were app recommended (p < 0.001). Both groups qualitatively reported positive feedback on the customized mobile application, indicating that continued usage and engagement of the mobile application were acceptable. CONCLUSIONS: Employing customized mobile applications for adults with NF1 along with contingency management can leverage self-managed pain treatments while providing auxiliary resources to this population.

Work readiness and barriers to employment during COVID-19 for individuals with Neurofibromatosis Type 1 (NF1).

BACKGROUND: The global COVID-19 pandemic has directly impacted individuals with rare diseases who are attempting to maintain or obtain employment. Individuals with Neurofibromatosis Type 1 are especially at risk due to their disease. OBJECTIVE: The current study compared the impact that generalized anxiety and quality of life had on work readiness and potential barriers that individuals with NF1 had in gaining and maintaining employment during the COVID-19 pandemic to a sample of healthy individuals using a moderating mediation analysis. METHODS: A total of 213 individuals (105 NF1; 108 Healthy individuals) were recruited to complete a cross-sectional study in which a series of work-related assessments were completed. RESULTS: Generalized anxiety had an indirect effect on work readiness, fully mediated by barriers, with higher anxiety associated with more barriers, in turn negatively correlating with work readiness; quality of life partially mediated the effect of barriers on work readiness and was negatively associated with the former and positively with the latter. CONCLUSION: Quality of life was a mediator of the relationship between perceived employment barriers and work readiness for the healthy individuals group only. The results imply that anxiety and quality of life are significant mediators and require consideration in terms of evaluation and facilitation of employment maintenance and acquisition.

Perspectives on adapting a mobile application for pain self-management in neurofibromatosis type 1: results of online focus group discussions with individuals living with neurofibromatosis type 1 and pain management experts.

OBJECTIVE: Neurofibromatosis type 1 (NF1) is a genetic disorder in which chronic pain commonly occurs. The study sought to understand the needs of individuals with NF1 and pain management experts when adapting a pain self-management mobile health application (app) for individuals with NF1. DESIGN: We conducted a series of online, audio-recorded focus groups that were then thematically analysed. SETTING: Online focus groups with adults currently residing in the USA. PARTICIPANTS: Two types of participants were included: individuals with NF1 (n=32 across six focus groups) and pain management experts (n=10 across three focus groups). RESULTS: Six themes across two levels were identified. The individual level included lifestyle, reasons for using the mobile app and concerns regarding its use. The app level included desired content, desired features and format considerations. Findings included recommendations to grant free access to the app and include a community support feature for individuals to relate and validate one another's experience with pain from NF1. In addition, participants noted the importance of providing clear instructions on navigating the app, the use of an upbeat, hopeful tone and appropriate visuals. CONCLUSIONS: Both participant groups endorsed the use of iCanCope (iCC) as an NF1 pain self-management mobile app. Differences between groups were noted, however. The NF1 group appeared interested in detailed and nuanced pain tracking capabilities; the expert group prioritised tracking information such as mood, nutrition and activity to identify potential associations with pain. In tailoring the existing iCC app for individuals with NF1, attention should be paid to creating a community support group feature and to tailoring content, features and format to potential users' specific needs.

An umbrella review on the use of antipsychotics in anxiety disorders: A registered report protocol.

Anxiety disorders, including panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), agoraphobia, and specific phobia, are among the most common psychiatric disorders. Although the traditional pharmacologic treatments for anxiety included barbiturates and then benzodiazepines, the introduction of tricyclic antidepressants, followed by the selective serotonin reuptake inhibitors (SSRIs), marked a tidal shift in the treatment of anxiety. Although not approved for treatment of anxiety disorders (with the exception of trifluoperazine) there is ongoing off-label, unapproved use of both first-generation "typical" antipsychotics (FGAs) and second-generation or "atypical" antipsychotics (SGAs) for anxiety. Although there have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of these reviews focused on SGAs, primarily the use of quetiapine in GAD. Given that there is little known about the potential benefits and short-and long-term risks of using antipsychotics in anxiety, there is a need for an umbrella review of systematic reviews and meta-analyses of the use of both FGAs and SGAs in anxiety disorders. The specific aims of this study are as follows: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs) and other non-antipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects; and (3) Evaluate the short- and long-term risks and side effects of prescribing antipsychotics in anxiety disorders. The review is registered on PROSPERO (CRD42021237436). Since data extraction has not begun, there is not preliminary data to share.

Development and validation of a new scale to measure chronic suicidal ideation: The Chronic Suicidal Ideation Inventory-5 (CSI-5).

OBJECTIVE: Little is known about characteristics that differentiate acute from chronic suicidal ideation. Studies have been hampered by the lack of a formal operational definition or measurement tool for chronic suicidal ideation (CSI). We sought to adapt a standardized measure of obsessive-compulsive thinking to rate chronic suicidal ideation in a mood disorder inpatient cohort. METHOD: We devised a novel self-report instrument, based on constructs related to obsessive-compulsive thinking and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), as applied to preoccupations with suicidal thoughts and their persistence over 24 months in a previously described cohort of 97 inpatients with mood disorder. Exploratory factor analysis and principal components analysis were used to establish the factor structure of the instrument, and Cronbach's alpha and McDonald's omega were calculated to determine internal consistency of the scale. RESULTS: Significant Pearson correlations with individual scale items and total CSI-5 scores were evident in relation to the 2-, 6-, 12- and 24-month periods preceding the index hospitalization. A one-factor solution explained 75% of the variance in total CSI-5 scores. Cronbach's alpha was 0.914, and McDonalds's omega was 0.916. CSI-5 scores were not significantly associated with current depression severity scores or actual past suicide attempts. CONCLUSIONS: This 5-item adaptation of Y-BOCS-type questions provides an internally consistent and reliable assessment of chronic suicidal ideation in patients with mood disorder. The integrated assessment of time occupied by suicidal thoughts, activity interference, associated distress, efforts to resist suicidal thoughts, and degree of control over suicidal thinking provides a cohesive framework for understanding chronic suicidal ideation.

Innovation in the treatment of persistent pain in adults with Neurofibromatosis Type 1 (NF1): Implementation of the iCanCope mobile application.

Neurofibromatosis Type 1 (NF1) is a genetic disorder presenting with chronic pain symptoms that has limited treatment options for addressing the pain. The utilization of a mobile application allows for greater reach and scalability when using empirically valid psychosocial self-management treatments for pain. The iCanCope mobile application has been utilized in several different populations dealing with pain symptoms and has demonstrated initial effectiveness. To address the need for this population, we have customized the iCanCope mobile application for the NF1 population and included additional tailored features. We describe the rationale and design of a pilot randomized control study with a sample of 108 adults with NF1, in which two groups will receive access to the mobile application, of which one group will be incentivized to engage in the mobile application and the third group will treatment as usual over the course of 8-week period with a six-week follow-up. Outcomes will focus on the acceptability of the iCanCope-NF mobile application within the NF1 population and the impact of pain related activity on psychometric evaluations to determine if the contingency management will impact the engagement of mobile application, as well as to identify the participants' experiences in relationship to their treatment satisfaction and perceived support.

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options.

(Appeared originally in Frontiers in Psychiatry 2020 Dec 23; 11:595584).

Intensive Dialectical Behavior Treatment for Individuals With Borderline Personality Disorder With and Without Substance Use Disorders.

Treatment of borderline personality disorder (BPD) with comorbid substance use disorder can be challenging due to symptom overlap and limited assessment methods. Preliminary evidence has shown promising effectiveness of dialectical behavioral therapy (DBT) for BPD with comorbid substance use disorders. The current study compared the benefits of a 28-day transitional DBT treatment program for individuals with BPD with and without substance use disorders through evaluating the changes in coping skills, generalized anxiety, and depression symptom scales at admission and discharge. A total of 76 patients were split into two groups: Group 1 consisted of individuals with BPD without substance use disorders (n = 41), and Group 2 involved individuals with BPD and a substance use disorder (SUD) (n = 35). A univariate general linear model showed significant differences between the two groups in improvement of coping skills and depressive symptoms. After a 28-day transitional DBT treatment program there were significant decreases from severe to moderate depression scores in both groups. Our findings support the effectiveness of DBT treatment in patients with comorbid BPD and SUD.

The mediating effects of quality of life, depression, and generalized anxiety on perceived barriers to employment success for people diagnosed with Neurofibromatosis Type 1.

BACKGROUND: Neurofibromatosis Type 1 (NF1) is a genetic disorder that presents with physical symptoms that can negatively impact numerous areas of one's life, including occupational and psychological functioning, with decreased quality of life compared to a normative population. The purpose of the current study was to explore differences in the impact of psychological factors (anxiety and depression), quality of life and employment hope on barriers to successful employment between those with NF1 and matched controls. METHODS: A total of 212 individuals were stratified into two groups (NF1 and matched controls) using a cross-sectional design that collected a one-time response. RESULTS: A mediation analysis in which total barriers to successful employment on the differences between groups with quality of life, anxiety and depression as the mediators, and levels of employment hope as the co-variates were examined. The results confirmed a direct (.001) and indirect (< .001) relationship between barriers to successful employment with NF1 to matched controls, and with quality of life, anxiety, and depression. CONCLUSIONS: The current findings indicate that the barriers to successful employment for individuals with NF1 impact their quality of life, anxiety, and depression more than that of the matched controls. Poorer barriers of employment observed amongst people with a genetic disease can impact mental health and quality of life.

Parsing the effects of comorbid adult ADHD and substance misuse on affective lability in bipolar disorder.

INTRODUCTION: Attentional deficits, substance misuse, and affective lability are all common features among adults with bipolar disorder, but little research has attempted to parse their inter-relationships. METHODS: Using standardized scales and semi-structured interviews, we evaluated adult ADHD features and affective lability in 113 dually-diagnosed mood/substance use disorder inpatients (mean age 32.6 years, 63% female) drawn from one private suburban academically affiliated inpatient treatment program. RESULTS: 24% of bipolar subjects had above-threshold ADHD screens. Affective Lability Scale (ALS) total and subscores were significantly associated with ADHD scores (univariate r's ranging from 0.38-0.63). ALS total and most subscale scores were significantly higher among bipolar subjects having above- (versus below-) threshold ADHD ratings. Linear regressions to predict affective lability revealed significant partial correlations between bipolar diagnoses and ALS total, depression, elation, and anger subscores, while controlling for significant effects from ADHD comorbidity. Inclusion of current substances of abuse did not change goodness-of-fit. LIMITATIONS: Subjects were drawn from a single private institution, potentially limiting generalizability. CONCLUSIONS: Comorbid ADHD appears to moderate multiple domains of affective lability in bipolar disorder inpatients, independent of current substance misuse.

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options.

Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

Patient Requests for Discharge from Voluntary Psychiatric Hospitalization: a Chart Review.

The purpose of this study was to examine the rate of 72-hour letters (written requests for discharge, with 72 hours indicating the time the hospital has to discharge or seek retention) placed by voluntary psychiatric inpatients at a New York City hospital and determine whether there are factors contributing to the rates of discharge requests. Charts from all voluntary psychiatric hospitalizations during the calendar year 2007 were retrospectively reviewed. Included were all single voluntary admissions by adults (age 18 years and older) to the hospital. A confirmatory factor analysis (CFA) was conducted with the following factors: urine toxicology, cigarette use on admission, suicidal ideation upon presentation, employment, past inpatient psychiatric admission, and admission day. A linear regression was used to evaluate the relationship between discharge requests and these factors. Of the total sample (N = 581), 119 (20.5%) patients submitted 72-hour letters. The stepwise linear regression analysis confirmed a positive relationship between letter placement and admission day (M = 3.5, SD = 1.7), unemployment (M = 4.7, SD = 2.1), suicidal ideation (M = .5, SD = .5), positive urine toxicology (M = .47, SD = .5), previous psychiatric hospitalization (M = .7, SD = .5) and cigarette usage (M = .5, SD.5) R2 = .043, (6, 461) = 3.42, p = .003). These specific variables accounted for 55.6% of likelihood of a patient submitting a 72-hour letter. Several factors, related to substance and tobacco use, employment, and recurrent use of inpatient services, likely contribute to requests for early discharge. Addressing these factors may help improve inpatient care, reduce costs and improve patient outcomes in the long term.