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Impulse control disorders are common in Parkinson's disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a 'Sure' choice and a 'Gamble' choice of moderate risk. To commence each trial, in the 'Gain' condition, individuals started at $0 and in the 'Loss' condition individuals started at -$50 below the 'Sure' amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk ('Gamble Risk'). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the 'Gain' relative to the 'Loss' condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal. Objectives: To evaluate the feasibility, safety, and tolerability of lofexidine for facilitating induction onto ER-NTX in the management of OUD. Methods: In an open-label, uncontrolled, 10-week outpatient clinical trial, 20 adults (four women) with OUD were treated with a fixed-flexible dosing strategy (maximum 0.54 mg 4×/daily) of lofexidine for up to 10 days to manage opioid withdrawal prior to receiving ER-NTX. The COVID-19 pandemic resulted in a modification of the study methods after enrolling 10 participants who attended all visits in person. The second group of 10 participants attended most induction period visits remotely. Results: Overall, 10 of the 20 participants (50%) achieved the primary outcome by receiving the first ER-NTX injection. Rates of induction success did not differ by the presence of fentanyl or remote visit attendance, although the small sample size provided limited statistical power. Six out of 20 participants (30%) initiated on lofexidine required dose adjustments. There were no study-related serious adverse events. Conclusions: This study provides preliminary evidence supporting the feasibility of inducting individuals with OUD onto ER-NTX using lofexidine.

Background: Prescription digital therapeutics are software-based disease treatments that are regulated by the US Food and Drug Administration; the reSET-O prescription digital therapeutic was authorized in 2018 and delivers behavioral treatment for individuals receiving buprenorphine for opioid use disorder. Although reSET-O improves outcomes for individuals with opioid use disorder, most of the therapeutic content is delivered as narrative text. PEAR-008 is an investigational device based on reSET-O that uses an interactive, game-based platform to deliver similar therapeutic content designed to enhance patient engagement, which may further improve treatment outcomes., Objective: We aim to investigate how participants interact with the prescription digital therapeutic's new content delivery format. Secondary objectives include evaluating treatment success, symptoms of co-occurring mental health disorders, recovery capital, and skill development., Methods: Due to the COVID-19 pandemic, this study was redesigned using a decentralized model because it was not possible to conduct medication initiation and study visits in person, as initially intended. A decentralized, randomized controlled trial design will be utilized to compare patient engagement with PEAR-008 and that with reSET-O using both subjective and objective assessments. The study population will consist of approximately 130 individuals with opioid use disorder (based on Diagnostic and Statistical Manual of Mental Disorders 5 criteria) who have recently started buprenorphine treatment for opioid use disorder. Participants will be virtually recruited and randomly assigned to receive either PEAR-008 or reSET-O. All study sessions will be virtual, and the duration of the study is 12 weeks. The primary outcome measure of engagement is operationalized as the number of active sessions per week with either PEAR-008 or reSET-O. (An active session is any session that contains some active participation in the app, such as navigating to a different screen, engaging with a learning module, or responding to a notification.) Subjective dimensions of engagement will be assessed with participant surveys. The hypothesis is that PEAR-008 will have significantly greater participant engagement than reSET-O., Results: As of February 2021, participant enrollment is ongoing., Conclusions: This randomized controlled trial will investigate if changing the delivery format and enhancing the content of a prescription digital therapeutic for opioid use disorder will affect how participants use and interact with the prescription digital therapeutic. The study design may serve as a useful model for conducting decentralized studies in this patient population., Trial Registration: ClinicalTrials.gov NCT04542642; https://clinicaltrials.gov/ct2/show/NCT04542642., International Registered Report Identifier (irrid): DERR1-10.2196/32759., (©Hilary Luderer, Lisa Chiodo, Amanda Wilson, Christina Brezing, Suky Martinez, Xiaorui Xiong, Robert Gerwien, Bruce Imbert, Mark Deeg, Yuri Maricich, Aimee Campbell. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.01.2022.)

Background and Objectives: Fentanyl and other highly potent synthetic opioids are the leading cause of opioid overdose deaths in the United States., Methods: This study was an open-label, uncontrolled 12-week outpatient clinical trial to test the feasibility of a single-day induction onto extended-release buprenorphine (BXR) injection treatment for five adults (N = 5) with opioid use disorder using heroin-containing fentanyl. Participants were planned to receive three monthly BXR injections (300, 300, and 100 mg)., Results: After receiving 24 mg sublingual buprenorphine (SL-BUP), all five participants received the BXR 300 mg injection on the first day of induction. All five participants were retained for the full 3-month study period postinduction and received all three scheduled BXR injections., Discussion and Conclusion: This study provides preliminary evidence supporting the feasibility of inducting users of heroin-containing fentanyl onto BXR 300 mg in a single day., Scientific Significance: The ability to administer a long-acting injection of BXR that assures therapeutic serum levels for a month on the first day of treatment contact is a promising development for the treatment of OUD., (© 2021 American Academy of Addiction Psychiatry.)

Background : There is a need for alcohol use disorder (AUD) pharmacotherapy that can be administered to actively drinking outpatients. Pregabalin, a gabapentoid anticonvulsant, has preliminary evidence supporting effects on alcohol withdrawal and AUD. Objectives : To evaluate the safety, tolerability, and optimal dosing of pregabalin for treating AUD. Methods : In an open-label, 8-week, outpatient trial of eighteen adults (nine women) with AUD, participants were titrated to 600 mg/day (or the maximum tolerated dose) over 3 weeks and then maintained for 5 weeks. Results : The majority (11/14, 78.6%) of participants with at least one-week of medication exposure achieved a maximum dose of 600 mg/day. Mean retention was 6.8 weeks (SD = 2.6). Eighty percent (12/15) of participants with post-enrollment data reported any adverse effects during the trial; and for those reporting adverse effects the most common were drowsiness (33.3%, 4/12), and fogginess (25%, 3/12), dizziness (25%, 3/12), and insomnia (25%, 3/12). Two participants discontinued study medication due to adverse effects and one had a dose reduction. Mean Heavy Drinking Days (HDD)/week decreased significantly by 3.43 days (SD = 2.47; median (IQR) = 4.00 (1.00 to 5.50)); Wilcoxon signed rank test statistic ((S) = 49.5, p = .0006). Mean proportion of HDD significantly decreased on average by 48.7% (SD = 35.1%; median (IQR) = 57.1% (14.3% to 78.6%)). The proportion of abstinent days increased significantly on average by 36.1% (SD = 35.0%; median (IQR) = 17.9% (14.3% to 75.0%); S = 49.5, p = .0005). Conclusions : Pregabalin treatment of AUD appears to be safe and well tolerated in doses up to 600 mg per day. Trial Registration : clinicaltrials.gov identifier: NCT03256253.

While the detrimental effects of concurrent substance use disorders (SUDs) are now being well documented, very few studies have examined this comorbidity among women with posttraumatic stress disorder (PTSD). Data for these analyses were derived from the "Women and Trauma" study conducted within the National Drug Abuse Treatment Clinical Trials Network. Women with full or subthreshold PTSD and co-occurring cannabis use disorder (CUD) and cocaine use disorder (COD; N=99) were compared to their counterparts with co-occurring CUD only (N=26) and co-occurring COD only (N=161) on rates of trauma exposure, psychiatric disorders, psychosocial problems, and other substance use utilizing a set of multivariate logistic regressions. In models adjusted for age and race/ethnicity, women with PTSD and COD only were significantly older than their counterparts with CUD only and concurrent CUD+COD. Relative to those with CUD only, women with concurrent CUD+COD had higher odds of adult sexual assault. Relative to those with COD only, women with concurrent CUD+COD had higher odds of alcohol use disorder in the past 12months. Finally, relative to those with CUD only, women with COD only had higher odds of ever being arrested/convicted and adult sexual assault. The higher rates of adult sexual assault and alcohol use disorder among those with concurrent CUD+COD suggest the need for trauma-informed approaches that can respond to the needs of this dually-diagnosed population. Moreover, the causal link between repeated traumatic stress exposure and polysubstance use requires further examination., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: People living with HIV infection are disproportionately burdened by trauma and the resultant negative health consequences, making the combination of HIV infection and trauma a syndemic illness. Despite the high co-occurrence and negative influence on health, trauma and posttraumatic sequelae in people living with HIV infection often go unrecognized and untreated because of the current gaps in medical training and lack of practice guidelines., Objective: We set out to review the current literature on HIV infection and trauma and propose a trauma-informed model of care to target this syndemic illness., Methods: We searched PubMed, PsycINFO, and Cochrane review databases for articles that contained the following search terms: HIV AND either trauma (specifically violent trauma), PTSD, intimate partner violence (IPV), abuse, or trauma-informed care. Articles were limited to primary clinical research or metanalyses published in English. Articles were excluded if they referred to HIV-associated posttraumatic stress disorder or HIV-associated posttraumatic growth., Results: We confirm high, but variable, rates of trauma in people living with HIV infection demonstrated in multiple studies, ranging from 10%-90%. Trauma is associated with (1) increased HIV-risk behavior, contributing to transmission and acquisition of the virus; (2) negative internal and external mediators also associated with poor health and high-risk HIV behavior; (3) poor adherence to treatment; (4) poor HIV-related and other health outcomes; and (5) particularly vulnerable special populations., Conclusions: Clinicians should consider using a model of trauma-informed care in the treatment of people living with HIV infection. Its adoption in different settings needs to be matched to available resources., (Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation., (Copyright © 2011 Movement Disorder Society.)

Adolescence is characterized by participation in multiple novel and potentially risky behaviors. Amongst these behaviors are gambling and use of the Internet, and excessive engagement in these activities (as seen in pathological gambling and problematic Internet use) may be accompanied by serious impairments in school, mental health, and social functioning. This article reviews the potential impact of pathological gambling and problematic Internet use in youth, the relevance of subsyndromal levels of participation, and how prevention and treatment strategies may be considered and tested within a developmental framework., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Pathological behaviors such as problem gambling or shopping are characterized by compulsive choice despite alternative options and negative costs. Reinforcement learning algorithms allow a computation of prediction error, a comparison of actual and expected outcomes, which updates our predictions and influences our subsequent choices. Using a reinforcement learning model, we show data consistent with the idea that dopamine agonists in susceptible individuals with Parkinson's disease increase the rate of learning from gain outcomes. Dopamine agonists also increase striatal prediction error activity, thus signifying a "better than expected" outcome. Thus, our findings are consistent with a model whereby a distorted estimation of the gain cue underpins a choice bias toward gains.

Rationale: Dopaminergic medication-related impulse control disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson's disease (PD)., Hypothesis: We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice or greater discounting of delayed rewards in PD patients with ICDs (PDI)., Methods: Fourteen PDI patients, 14 PD controls without ICDs, and 16 medication-free matched normal controls were tested on the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, spatial working memory, and attentional set shifting. The EDT was used to assess choice impulsivity (hyperbolic K value), reaction time (RT), and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA., Results: On the EDT, there was a group by medication interaction effect [F(1,26) = 5.62; p = 0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p = 0.02) but not in PD controls (p = 0.37). PDI patients also had faster RT compared to PD controls [F(1,26) = 7.51, p = 0.01]. DA status was associated with shorter RT [F(3,24) = 8.39, p = 0.001] and decision conflict RT [F(1,26) = 6.16, p = 0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t = 2.13, df = 26, p = 0.04)., Conclusion: Greater impulsive choice, faster RT, faster decision conflict RT, and executive dysfunction may contribute to ICDs in PD.