Facilitation of performance on a picture fragment completion test: Data-driven potentiation in perception

A technique commonly used to study the structure of memory entails preceding a task by a brief masked presentation of a potentially relevant stimulus. In two experiments, I examined the type of facilitation obtained on a picture fragment completion task by prior presentation of either the name of the completed object, a complete picture of the object, or the fragment itself. In Experiment 1a significantly more ambiguous picture fragments (i.e. fragments supporting a number of interpretations) were identified after exposure to pictures than to picture names or picture fragments. Experiment 1b verified that the information in the masked primes was not available to conscious awareness. These results suggest that under limited encoding conditions only bottom-up activation provided by prior presentation of the fragments aids shape recognition under degraded conditions. Implications for the structures and processes involved in shape recognition are discussed

Development of a self-report measure of drug craving

The construct of craving is frequently invoked as a causal factor in on going substance use or in relapse after a period of abstinence. The aim of the present study is to develop a general self-report questionnaire of craving that can be used to assess craving at any point in addiction and recovery. The study was conducted in two phases. In the first phase of the study a sample of 23 addicts were interviewed about their subjective experience of craving. The purpose of this phase of the study was to develop a theory of the subjective experience of craving that could be used to guide the development of the self-report questionnaire. Analysis of the text of these interviews revealed nine dimensions of the subjective experience of craving: specificity, strength, positive outcomes, behavioral intention, physical symptoms, affect, internal cues, situations, and drug availability. The first six dimensions were hypothesized to load on a general craving factor, and the last three dimensions were hypothesized to load on a cue reactivity factor. Questionnaire items were generated to broadly sample each of these dimensions. In the second phase the questionnaire was administered to a heterogenous sample of 205 addicts. Confirmatory factor analytic procedures were used to assess the present theory of craving and the psychometric properties of the instrument. The two factor model of craving fit the data well based on practical fit indices (Robust CFI =.95) and the discriminant validity of the two factors was supported. These analyses supported the theory of craving underlying the development of the questionnaire and indicated that the questionnaire has acceptable psychometric properties. The theoretical, psychometric, and clinical implications of the results are discussed

Assessing the Relationship between Performance on the University of California Performance Skills Assessment (UPSA) and Outcomes in Schizophrenia: A Systematic Review and Evidence Synthesis

Objective. To perform a systematic review of the published literature to evaluate how functional capacity, as measured by the University of California at San Diego (UCSD) Performance-based Skills Assessment (UPSA), relates to other functional measures and real-world outcomes among individuals with schizophrenia. Methods. The MEDLINE® and Embase® databases were searched to identify joint evaluations with UPSA and key functional outcomes (functional scale measures; generic or disease-specific, health-related quality of life [HRQoL]; or real-world outcomes [residential status; employment status]) in patients with schizophrenia. Pearson correlations were estimated between UPSA scores, HRQoL, other functional scale measures, and real-world outcomes, for outcomes described in at least six studies. Results. The synthesis included 76 studies that provided 73 unique data sets. Quantitative assessment between the Specific Level of Function (SLOF) (n=18) scores and UPSA scores demonstrated a moderate borderline-significant correlation (0.45, p=0.06). Quantitative analysis of the relationship between the Global Assessment of Functioning (GAF) (n=11) and the Multidimensional Scale of Independent Functioning (MSIF) (n=6) scales revealed moderate and small nonsignificant Pearson correlations of -0.34 (p=0.31) and 0.12 (p=0.83), respectively. There was a small borderline-significant correlation between UPSA score and residential status (n=36; 0.31; p=0.08), while no correlation was found between UPSA score and employment status (n=19; 0.04; p=0.88). Conclusion. The SLOF was the most often used functional measure and had the strongest observed correlation with the UPSA. Although knowledge gaps remain, evidence from this review indicates that there is a quantitative relationship between functional capacity and real-world outcomes in individuals with schizophrenia

Treatment patterns, healthcare resource utilization, and costs following first-line antidepressant treatment in major depressive disorder: a retrospective US claims database analysis

Abstract Background Although the symptoms of major depressive disorder (MDD) are often manageable with pharmacotherapy, response to first-line antidepressant treatment is often less than optimal. This study describes long-term treatment patterns in MDD patients in the United States and quantifies the economic burden associated with different treatment patterns following first-line antidepressant therapy. Methods MDD patients starting first-line antidepressant monotherapy and having continuous enrollment ≥12 months before and ≥24 months following the index date (i.e., the first documented prescription fill) were selected from the Truven Health Analytics MarketScan (2003–2014) database. Based on the type of first treatment change following initiation, six treatment cohorts were defined a priori (“persistence”; “discontinuation”; “switch”; “dose escalation”; “augmentation”; and “combination”). Treatment patterns through the fourth line of therapy within each cohort, healthcare resource utilization (HCRU), and cost analyses were restricted to patients with adequate treatment duration (defined as ≥42 days) in each line (analysis sub-sample, N = 21,088). HCRU and costs were described at the cohort and pattern levels. Treatment cohorts representing <5% of the analysis sub-sample were decided a priori not to be analyzed due to limited sample size. Results 39,557 patients were included. Mean age was 42.1 years, 61.1% of patients were female, and mean follow-up was 4.1 years. Among the analysis sub-sample, the discontinuation (49.1%), dose escalation (37.4%), and switch (6.6%) cohorts were the most common of all treatment cohorts. First-line antidepressant discontinuation without subsequent MDD pharmacotherapy (22.9%) and cycling between discontinuation and resumption (11.2%) were the two most common treatment patterns. Median time to discontinuation was 23 weeks. The switch cohort exhibited the highest HCRU (18.9 days with medical visits per-patient-per-year) and greatest healthcare costs ($11,107 per-patient-per-year) following the index date. Treatment patterns representing a cycling on and off treatment in the switch cohort were associated with the greatest healthcare costs overall. Conclusion A high proportion of patients discontinue first-line antidepressant shortly after initiation. Patterns representing a cycling on and off treatment in the switch cohort were associated with the highest healthcare costs. These findings underscore challenges in effectively treating patients with MDD and a need for personalized patient management

Determination of a clinically important difference and definition of a responder threshold for the UCSD performance-based skills assessment (UPSA) in patients with major depressive disorder

This article reports an evaluation of the psychometric properties and clinically important difference (CID) threshold of the UCSD Performance-Based Skills Assessment (UPSA) in major depressive disorder (MDD), using data from a large-scale study of the effects of vortioxetine on cognitive functioning and functional capacity in MDD patients. Adults with moderate-to-severe recurrent MDD and self-reported cognitive dysfunction were randomized to 8 weeks of double-blind treatment with vortioxetine 10/20mg QD (flexible), duloxetine 60mg QD, or placebo. Pearson correlation coefficients were calculated between UPSA composite score and demographic/disease characteristics at baseline to examine construct validity. Two methods (distribution-based and anchor-based) were used to establish a CID threshold. A total of 602 patients were randomized; 528 comprised the full analysis set. For the entire sample mean UPSA composite scores were 77.8 at baseline and 83.9 at week 8 (mean change, +6.1). As hypothesized, at baseline, the UPSA composite score correlated with cognitive functioning (Digit Symbol Substitution Test: r=0.36, P<0.001) and workplace productivity (Work Limitations Questionnaire: r=–0.17, P=0.008), but not depressive symptoms (Montgomery-Åsberg Depression Rating Scale: r=0.02, P=0.707) or subjective cognitive dysfunction (Perceived Deficits Questionnaire: r=–0.02, P=0.698). Two versions of the UPSA were used and no inclusion/exclusion criteria were based on the UPSA. These results support the construct validity of UPSA for assessing functional capacity independent of mood symptoms. The estimated CID for changes in UPSA scores was quite consistent at +6.4 points and +6.7 based on distribution-based and anchor-based methods, respectively. •UPSA was developed for schizophrenia patients and can predict real-world functioning.•We evaluated the psychometric properties of the UPSA in patients with MDD.•We also used two methods to determine a CID and CIR threshold for this population.•Construct validity was established in patients with moderate-to-severe MDD.•The CID and CIR methods support an UPSA increase of 6–7 points as meaningful

The Effect of Vortioxetine on Overall Patient Functioning in Patients with Major Depressive Disorder

Background: The objectives of this meta-analysis of data from randomized, placebo-controlled studies were to assess the effect of vortioxetine on overall functioning (primary) and functional remission (secondary) using the Sheehan Disability Scale (SDS) in adults with major depressive disorder (MDD). Methods: Data from nine short-term (6/8 weeks) pivotal studies that included patient functioning assessments were included in this random-effects meta-analysis, which used aggregated study-level data for all therapeutic vortioxetine doses and a mixed-effect model for repeated measures using the full analysis set. Results: A total of 4,216 patients received ≥1 dose of study treatment (1,522 placebo, 2,694 vortioxetine 5–20 mg/day). At study end, the meta-analysis showed improvement for vortioxetine versus placebo (n = 911) in SDS total score (vortioxetine 5 mg, n = 564, change from baseline versus placebo [Δ] −0.24, p = NS; 10 mg, n = 445, Δ −1.68, p ≤ .001; 15 mg, n = 204, Δ −0.91, p = NS; 20 mg, n = 340, Δ −1.94, p ≤ .01). Functional remission (SDS total score ≤6) was observed with vortioxetine 10 mg (n = 170/573; odds ratio [OR] relative to placebo 1.7, p \u3c .001) and 20 mg (n = 144/447; OR 1.6, p \u3c .05), but not 5 mg (n = 207/757; OR 1.1, p = NS) or 15 mg (n = 92/295; OR 1.3, p = NS). Conclusion: Vortioxetine 5–20 mg for 6/8 weeks improved overall patient functioning in patients with MDD. Relative to placebo, vortioxetine 10 and 20 mg demonstrated significant improvement in SDS total score and functional remission

The Effect of Vortioxetine on Overall Patient Functioning in Patients with Major Depressive Disorder

Background: The objectives of this meta-analysis of data from randomized, placebo-controlled studies were to assess the effect of vortioxetine on overall functioning (primary) and functional remission (secondary) using the Sheehan Disability Scale (SDS) in adults with major depressive disorder (MDD). Methods: Data from nine short-term (6/8 weeks) pivotal studies that included patient functioning assessments were included in this random-effects meta-analysis, which used aggregated study-level data for all therapeutic vortioxetine doses and a mixed-effect model for repeated measures using the full analysis set. Results: A total of 4,216 patients received ≥1 dose of study treatment (1,522 placebo, 2,694 vortioxetine 5–20 mg/day). At study end, the meta-analysis showed improvement for vortioxetine versus placebo (n = 911) in SDS total score (vortioxetine 5 mg, n = 564, change from baseline versus placebo [Δ] −0.24, p = NS; 10 mg, n = 445, Δ −1.68, p ≤ .001; 15 mg, n = 204, Δ −0.91, p = NS; 20 mg, n = 340, Δ −1.94, p ≤ .01). Functional remission (SDS total score ≤6) was observed with vortioxetine 10 mg (n = 170/573; odds ratio [OR] relative to placebo 1.7, p \u3c .001) and 20 mg (n = 144/447; OR 1.6, p \u3c .05), but not 5 mg (n = 207/757; OR 1.1, p = NS) or 15 mg (n = 92/295; OR 1.3, p = NS). Conclusion: Vortioxetine 5–20 mg for 6/8 weeks improved overall patient functioning in patients with MDD. Relative to placebo, vortioxetine 10 and 20 mg demonstrated significant improvement in SDS total score and functional remission

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).

BackgroundFragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy.DesignCONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS.MethodsPatients were randomized to 12&nbsp;weeks of ZYN002 (250&nbsp;mg or 500&nbsp;mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist-Community Edition FXS (ABC-CFXS) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely.ResultsA total of 212 patients, mean age 9.7&nbsp;years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%).ConclusionsIn CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe.Trial registrationThe CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663)