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Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance. [ABSTRACT FROM AUTHOR]

Introduction: Separation anxiety disorder (SAD) comprises one aspect of attachment dysregulation or insecurity. Although SAD aggravates posttraumatic stress disorder (PTSD) risk, no clinical research has tracked how many patients with PTSD have SAD, its clinical associations, or its response to PTSD treatment. Our open trial of interpersonal psychotherapy (IPT) for veterans with PTSD assessed these SAD domains.Methods: Twenty-nine veterans diagnosed with chronic PTSD on the Clinician-Administered PTSD Scale were assessed for SAD using the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), and for Symptom-Specific Reflective Function (SSRF), another dysregulated-attachment marker capturing patients' emotional understanding of their symptoms. Patients received 14 IPT sessions for PTSD with assessments at baseline, Week 4 (SCI-SAS and SSRF), and termination for SAD, PTSD, and depression.Results: At baseline, 69% of patients met SAD criteria. Separation anxiety did not correlate with baseline PTSD severity, depressive severity, or age when traumatized; patients with and without SAD had comparable PTSD and depression severity. Patients with baseline comorbid SAD who completed IPT (N = 17) reported significantly improved adult separation anxiety (p = .009). Adult SAD improvements predicted depressive improvement (p = .049). Patients with SAD showed a stronger relationship between early SSRF gains and subsequent adult SAD improvement (p = .021) compared with patients without SAD.Discussion: This first exploration of dysregulated/insecure attachment features among patients with PTSD found high SAD comorbidity and adult SAD improvement among patients with SAD following IPT. Highly impaired attachment patients normalized attachment posttreatment: 14-session IPT improved attachment dysregulation. This small study requires replication but begins to broaden clinical understanding of separation anxiety, attachment dysregulation, and PTSD. [ABSTRACT FROM AUTHOR]

Objective: Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder.Method: In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1).Results: The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen's d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine's effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.Conclusions: Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect. [ABSTRACT FROM AUTHOR]

Objective: The Psychotherapies for Chronic PTSD randomised trial found that three 14-week psychotherapies acutely benefitted patients with chronic posttraumatic stress disorder (PTSD). Previous research has reported sustained follow-up benefits for prolonged exposure (PE) and relaxation therapy (RT), but few comparable data exist for interpersonal psychotherapy (IPT). We describe 3-month follow-up for acute responders to all 3 treatments.Method: Acute responders, defined a priori as ≥30% improved from baseline, were reevaluated after 3-month no-treatment follow-up by independent evaluators using the Clinician-Administered PTSD Scale (CAPS).Results: Fifty of 110 initial study entrants met acute responder status at week 14. Forty-three (86%) responders entered follow-up: 23 remitters (CAPS ≤20) and 20 responders. At week 26, 27 had achieved remission status, 10 remained responders, and 6 had relapsed. Of week 14 remitters, 8 of 9 PE, all 8 IPT, and 4 of 6 RT patients remained remitted. Relapse rates were 7% (1/9) for PE, 10% (2/20) for IPT, and 33% (3/9) for RT. At week 26, PE showed greater improvement on CAPS than RT ( P = 0.048) and a trend for superiority over IPT ( P = 0.098), with no significant difference between IPT and RT. Depressive symptoms remained low during follow-up.Conclusions: These are the first systematic data on follow-up responder status and persistence of acute treatment benefits in patients receiving individual IPT for chronic PTSD. Patients generally maintained gains across treatments, fluctuating most in RT. Study limitations include small sample size and brief follow-up interval. PTSD research should employ response and remission criteria. [ABSTRACT FROM AUTHOR]

Background: Separation anxiety disorder was recently recognized by fifth edition of the Diagnostic and Statistical Manual of Mental Disorders as a diagnosis in adults, but no publications to date have characterized a sample of patients seeking treatment for adult separation anxiety disorder (ASAD) or assessed treatment efficacy. We hypothesized that vilazodone, a selective serotonin reuptake inhibitor (SSRI) and serotonin 1a (5HT1a ) receptor partial agonist, would have efficacy in ASAD, because SSRIs have appeared efficacious in children with mixed diagnoses including separation anxiety disorder and in animal models of separation anxiety.Methods: In this pilot study, 24 adults (ages 18-60) with a principal diagnosis of ASAD were randomized to 12 weeks of double-blind treatment with vilazodone (n = 13) or placebo (n = 11). Outcome was assessed by an independent evaluator and self-ratings, and analyzed with mixed effect models.Results: This sample was predominantly female (67%), with comorbid psychiatric disorders (58%), and adult onset of separation anxiety disorder (62%). Response rates at week 12 did not differ significantly between groups. Across all time points, the vilazodone group evidenced greater improvement on the Structured Clinical Interview for Separation Anxiety Symptoms (P = .026) and the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .011), and trends toward greater improvement on the Adult Separation Anxiety Questionnaire (P = .054) and the Clinical Global Impression-Change Scale (P = .086), all with large between-group effect sizes.Conclusions: Findings demonstrate feasibility of a clinical trial in ASAD, and they suggest that vilazodone may have efficacy in the treatment of ASAD and warrants further study. [ABSTRACT FROM AUTHOR]

Objective: Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies.Method: Adult outpatients with major depressive disorder were randomly assigned to open or placebo-controlled citalopram treatment. Following measurement of pre- and postrandomization expectancy, participants were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the open and placebo-controlled groups, and mixed-effects models assessed group effects on Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-group differences in patient expectancy mediated the group effect on HAM-D scores.Results: Postrandomization expectancy scores were significantly higher in the open group (mean=12.1 [SD=2.1]) compared with the placebo-controlled group (mean=11.0 [SD=2.0]). Mixed-effects modeling revealed a significant week-by-group interaction, indicating that HAM-D scores for citalopram-treated participants declined at a faster rate in the open group compared with the placebo-controlled group. Patient expectations postrandomization partially mediated group effects on week 8 HAM-D.Conclusions: Patient expectancy is a significant mediator of placebo effects in antidepressant trials. Expectancy-related interventions should be investigated as a means of controlling placebo responses in antidepressant clinical trials and improving patient outcome in clinical treatment. [ABSTRACT FROM AUTHOR]

Background: To assess within and across diagnosis variability we examined fear processing in healthy controls (HC) and three diagnostic groups that share symptoms of pathological anxiety: obsessive compulsive disorder (OCD); social anxiety disorder (SAD), and anorexia nervosa (AN).Methods: Unmedicated adults (N=166) participated in a paradigm assessing associative fear acquisition, extinction, extinction recall, and fear renewal. Data were analyzed from two perspectives: comparison of each disorder to HC and exploratory latent class analysis (LCA) of the combined data.Results: The diagnosis-based analyses indicated significantly increased fear renewal in OCD and trends toward decreased extinction recall in OCD and increased renewal in SAD. The LCA indicated four Response Types, none of which were congruent with the diagnostic categories. Most participants had a normative response (50%) or a moderate extinction recall deficit (30%). The two remaining groups (8% each) had more extreme responses: one showed complete failure of extinction recall; the other persistent arousal in expectation of, but prior to, actual conditioning (threat sensitivity).Limitations: Due to small sample size (N=20) results for AN are regarded as preliminary.Conclusions: Our diagnosis-based findings are consistent with previous data suggesting an association between pathological anxiety and difficulties maintaining fear extinction. The LCA reveal substantial within-diagnosis heterogeneity in fear processing and support inclusion of empirically driven approaches as a complement to standard analyses. This heterogeneity may also have implications for treatment, particularly cognitive behavioral therapy, which relies on strengthening extinction recall and requires patients to tolerate anxious expectation in order to engage with feared situations. [ABSTRACT FROM AUTHOR]

Objective: The Aberrant Behavior Checklist (ABC) is a standardized rating scale used for assessing problematic behavior of individuals with developmental disabilities. It has five subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech. A previous study in individuals with fragile X syndrome (FXS) reported six factors, with the Social Withdrawal factor bifurcating into Socially Unresponsive and Social Avoidance factors, suggesting a different factor structure in people with FXS. Methods: We assessed the ABC's factor structure (with both exploratory and confirmatory analyses) in 797 people with FXS and we compared these findings with exploratory factors derived from an independent sample of 357 individuals with FXS. In an ancillary analysis, we compared the overlap of the traditional ABC's Social Withdrawal scores with the Social Avoidance scores from the FXS-derived newer scale to determine whether overlap between these was very high and essentially redundant. Finally, we computed norms using both the traditional and the FXS-specific algorithms. Results: In confirmatory factor analyses, the FXS-specific algorithm produced the most consistent factor structure for the sample of 797 participants, but model fit was only marginally better than that derived by the original ABC scoring algorithm. Comparisons of factor structures from separate exploratory analyses revealed no consistent advantage of the FXS algorithm over the traditional algorithm. While a Social Avoidance subscale did emerge in some analyses, in other analyses, this was accompanied by loss of coherence on other domains of interest, such as the Socially Unresponsive/Social Withdrawal subscale. Conclusion: We question whether the newer FXS scoring algorithm contributes data that are consistently helpful in evaluating behavior of people with FXS. In general, we recommend continued use of the original ABC algorithm for scoring behavior of clients with FXS. However, we acknowledge that there may be circumscribed times when the new algorithm may be appropriate for scoring, namely when anxiety and/or social avoidance constructs are the central and unequivocal domains of interest. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use.Methods: Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use.Results: Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time.Conclusion: In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation.Clinical Trial Registration: ClinicalTrials.gov (NCT02032433). [ABSTRACT FROM AUTHOR]