To explore relationships among post-traumatic stress disorder (PTSD), depressive spectrum symptoms, and intrusiveness in subjects who survived the crash of a train derailed carrying liquefied petroleum gas and exploded causing a fire.

A sample of 111 subjects was enrolled in Viareggio, Italy. AMOS version 21 (IBM Corp, 2012) was utilized for a structural equation model-path analysis to model the direct and indirect links between the exposure to the traumatic event, the occurrence of depressive symptoms, and intrusiveness. Subjects were administered with the SCID-IV (Structured Clinical Interview for DSM-IV), the Questionnaire for Mood Spectrum (MOODS-SR)-Last Month version, the Trauma and Loss Spectrum Questionnaire (TALS-SR), and the Impact of Event Scale-Revised version (IES-R).

Sixty-six (66/111; 59.4%) subjects met SCID-IV criteria for PTSD. Indices of goodness of fit were as followed: χ2/df = 0.2 P = .6; comparative fit index = 1 and root mean square error of approximation = 0.0001. A significant path coefficient for direct effect of potential traumatic events on depressive symptoms (β = 0.25; P < .04) and from depressive symptoms to intrusiveness (β = 0.34; P < .003) was found. An indirect effect was also observed: standardized value of potential traumatic events on intrusiveness was 0.86. The mediating factor of this indirect effect path was represented by depressive symptoms. Potential traumatic events explained 6.2% of the variance of depressive symptoms; 11.8% of the variance of intrusiveness was accounted for traumatic event and depressive symptoms.

Path analysis led us to speculate that depression symptoms might have mediated the relationship between the exposure to potential traumatic events and intrusiveness for the onset of PTSD.

The AtWoRC study is an interventional, open-label Canadian study that demonstrated significant improvements in cognitive function and workplace productivity in patients with major depressive disorder (MDD) treated with vortioxetine for a current major depressive episode. The objective of the present analysis was to assess the Canadian economic impact of improved workplace productivity based on the AtWoRC study results.

The economic impact of improved productivity in patients with MDD treated with vortioxetine was assessed over a 52-week period considering productivity loss due to absenteeism and presenteeism using the standard human capital approach and an employer’s perspective. Absenteeism was measured with the Work Productivity and Activity Impairment questionnaire; and presenteeism with the Work Limitation Questionnaire. Productivity gains following treatment initiation with vortioxetine were estimated using the difference from baseline.

In the AtWoRC study, patients at baseline reportedly missed, in the past 7 days, an average of 8.1 h due to absenteeism and 3.0 h due to presenteeism. Following 52 weeks of treatment with vortioxetine, patients reportedly missed an average of 4.9 h due to absenteeism and 2.0 h due to presenteeism. This improved workplace productivity translated into savings of C$110.64 for 1 week of work following 52 weeks of treatment. The cumulative 52-week economic impact showed potential savings of C$4,550 when factoring in the cost of therapy.

This study suggested that workplace productivity gain due to an improvement in symptoms of MDD following treatment with vortioxetine will lead to substantial cost savings for the Canadian economy.

The clinical phenotype of gambling disorder (GD) is suggestive of changes in brain regions involved in reward and impulse suppression, notably the striatum. Studies have yet to characterize striatal morphology (shape) in GD and whether this may be a vulnerability marker.

To characterize the morphology of the striatum in those with disordered gambling (at-risk gambling and GD) versus controls.

Individuals aged 18–29 years were classified a priori into those with some degree of GD symptoms (at-risk gambling and GD) or controls. Exclusion criteria were a current mental disorder (apart from GD), history of brain injury, or taking psychoactive medication within 6 weeks of enrollment. History of any substance use disorder was exclusionary. Participants completed an impulsivity questionnaire and structural brain scan. Group differences in volumes and morphology were characterized in subcortical regions of interest, focusing on the striatum.

Thirty-two people with GD symptoms (14 at-risk and 18 GD participants) and 22 controls completed the study. GD symptoms were significantly associated with higher impulsivity and morphological alterations in the bilateral pallidum and left putamen. Localized contraction in the right pallidum strongly correlated with trait impulsivity in those with GD symptoms.

Morphologic abnormalities of the striatum appear to exist early in the disease trajectory from subsyndromal gambling to GD and thus constitute candidate biological vulnerability markers, which may reflect differences in brain development associated with trait impulsivity. Striatal morphology and associated impulsivity might predispose to a range of problematic repetitive behaviors.

Patients treated with antipsychotics, regardless of psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a potentially debilitating drug-induced movement disorder. Valbenazine (INGREZZA; VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. Data from KINECT 4 (NCT02405091) were analyzed to evaluate the long-term effects of VBZ in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD) and moderate or severe TD.

KINECT 4 included open-label treatment (48weeks) followed by washout (4weeks). Entry requirements included: moderate or severe TD, qualitatively assessed at screening by a blinded, external reviewer; DSM diagnosis of SZD or MD; psychiatric stability (Brief Psychiatric Rating Scale score <50). Stable concomitant psychiatric medications were allowed. Dosing was initiated at 40mg, with escalation to 80mg at Wk4 if participants had a Clinical Global Impression of Change-TD score of ≥3 (minimally improved to very much worse) and tolerated 40mg. A reduction to 40mg was allowed if 80mg was not tolerated (80/40mg); participants unable to tolerate 40mg were discontinued. Safety was the primary focus, but the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) was used to evaluate changes in TD. Mean changes from baseline (BL) in AIMS total score (rated by on-site investigators) were analyzed descriptively. Safety assessments included treatment-emergent adverse events (TEAEs) and psychiatric scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Scale for Schizophrenia [CDSS], Montgomery-Åsberg Depression Rating Scale [MADRS], Young Mania Rating Scale [YMRS], and Columbia-Suicide Severity Rating Scale [C SSRS]).

Of 163 participants in the analyses, 103 completed the study. Adverse events (n=26) was the most common reason for discontinuation. Analyses included 119 participants with SZD (40mg=37; 80mg=76; 80/40mg=6) and 44 with MD (40mg=8; 80mg=31; 80/40mg=5). At Wk48, mean improvements from BL in AIMS total score were: SZD (40mg, –10.1; 80mg,–10.7); MD (40mg, 10.2; 80mg: –11.6). AIMS total scores at Wk52 (end of washout) indicated a return toward BL levels. Compared to SZD, the MD subgroup had a higher incidence of any TEAE (84% vs 61% [all doses]) but fewer TEAEs leading to discontinuation (7% vs 18%). Urinary tract infection was the most common TEAE in the MD subgroup (18%); somnolence and headache were most common in the SZD subgroup (7% each). Psychiatric status remained stable from BL to Wk48: SZD (PANSS positive, –0.7, PANSS negative, –0.6; CDSS, –0.7); MD (MADRS, –0.3; YMRS, –0.3). Most participants (95%) had no change in C-SSRS score during the study.

Sustained and clinically meaningful TD improvements were observed with VBZ, regardless of primary psychiatric diagnosis. VBZ was generally well tolerated and no notable changes in psychiatric status were observed.

Funding Acknowledgements: Supported by Neurocrine Biosciences, Inc.

In STAR*D, following non-remission with an SSRI, remission rates for second-line treatments were ~ 25%, regardless of the switch strategy employed. Antidepressants with novel mechanisms may improve outcomes in MDD. AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.

EVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥1 antidepressant in the current major depressive episode (MDE). A total of 186 patients were enrolled. Here we present the results for the directly enrolled patients (n =146).

Mean change in MADRS total score from a baseline of 32.2 were -9.1±7.64, -13.3±8.58, and -20.4±7.79 points at Weeks 1, 2, and 6, respectively (p< 0.001 for all). Remission (MADRS ≤10) was achieved by 5.7%, 16.2%, and 46.0% of patients at Weeks 1, 2, and 6, respectively. Improvement in functioning, measured by the SDS, was seen starting at Week 1 (p < 0.001). Improvements in MADRS and SDS were sustained at Month 12.

Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%).

AXS-05 improved depression and functioning in patients who failed one prior antidepressant in the current MDE.

Axsome Therapeutics

There is a burgeoning body of evidence suggesting that arginine vasopressin (AVP) acts as a neuromodulator of the stress response. AVP stimulates the release of adrenocorticotropic hormone, synergistic to corticotropin-releasing hormone, which might explain AVP’s role in resilience. Personal hardiness is the bedrock of resilience. Numerous studies have demonstrated elevated plasma levels of AVP in patients with major depressive disorder (MDD), suggesting an etiopathogenetic role as well as a novel therapeutic target.

The aim of this study was to examine the relationship between AVP and resilience in patients with MDD and to determine AVP levels in serum of patients with MDD.

Forty patients with MDD and 40 healthy control subjects were studied using the Dispositional Resilience (Hardiness) Scale by Barton, the Quality of Life Scale, the Social Readjustment Rating Scale, and the Beck Depression Inventory. Biochemical analysis of plasma levels of AVP, using the enzyme-linked immunosorbent assay (ELISA), was performed for all participants.

Levels of AVP were statistically significantly elevated in patients with MDD compared with healthy controls. Psychological hardiness was decreased in patients with MDD compared with healthy controls, a finding also statistically significant. There was a negative correlation between plasma AVP level and psychological hardiness.

AVP and psychological hardiness are negatively correlated, reflecting lower stress resilience. AVP levels are indeed higher in patients struggling with MDD.

We evaluated sexual functioning from 6 acute, randomized, placebo-controlled studies (6–10 weeks) of once-daily extended release quetiapine fumarate (quetiapine XR) 50, 150, or 300 mg/day as monotherapy (Studies 1–4) or adjunct therapy (Studies 6–7) in major depressive disorder (MDD).

We present a pre-planned, non-inferiority analysis of quetiapine XR monotherapy versus placebo using Changes in Sexual Functioning Questionnaire (CSFQ) total score change (Studies 1–4). Post hoc analyses evaluated CSFQ total and domain scores for fixed-dose monotherapy (Studies 1–2), modified fixed-dose (Studies 3–4), and adjunct therapy studies (Studies 6–7). CSFQ data for active comparators (duloxetine [Study 2], escitalopram [Study 4]) are reported.

Quetiapine XR monotherapy was non-inferior to placebo for sexual functioning (least squares mean [LSM] difference in CSFQ score change versus placebo, 0.16 [95% confidence interval: −0.59, 0.92]); LSM change in CSFQ score: 1.90, quetiapine XR (all doses) and 1.73, placebo. LSM differences versus placebo (95% confidence interval): 0.18 (−1.40, 1.75), duloxetine (Study 2); 0.16 (−1.77, 2.10), escitalopram (Study 4). LSM differences with adjunct quetiapine XR 150 mg/day (0.52; p = 0.338) or 300 mg/day (0.22; p = 0.679) were comparable with placebo plus antidepressants. Post hoc all-patient and gender-specific analyses were comparable for CSFQ total scores versus placebo with quetiapine XR 50, 150, or 300 mg/day, duloxetine, and escitalopram.

Lack of negative effects on sexual functioning in patients with MDD may improve treatment acceptability.

Quetiapine XR (monotherapy or adjunct therapy) had an impact on sexual function that was comparable with placebo.

Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.

Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.

Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.

Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.

Lisdexamfetamine dimesylate (LDX) is a prodrug stimulant approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and children 6–12 years of age. Parent surveys provide valuable information regarding the impact of ADHD treatments.

Parents of children with ADHD beginning treatment with LDX voluntarily completed surveys through an automated telephone system or the Internet before and 6 weeks after LDX treatment initiation. Prescribing physicians received individual reports of the responses for each survey completed by their patients' parents. All patients whose parents completed both baseline and 6 week surveys were included in the analyses. Subgroup analyses were conducted for those previously treated with medications to treat ADHD, including mixed amphetamine salts-extended release.

LDX treatment was associated with a significant decrease in ADHD symptom interference with school activities, family interactions, homework, and social interactions (P<.01; N= 11,576). Parents rated satisfaction with LDX as significantly higher than with their child's previous treatment (P<.01). On average, global improvement, tolerability, convenience, and satisfaction with LDX were all highly rated.

Patients treated with LDX showed significant symptom improvement and parents reported significantly greater satisfaction than with prior treatment.