An open-label extension study (NCT02873208) evaluated the long-term tolerability, safety, and efficacy of combination olanzapine/samidorphan (OLZ/SAM) treatment in patients with schizophrenia. This qualitative sub study explored perceptions of benefit, burden, and satisfaction with previous medications and OLZ/SAM.

Semi-structured interviews (60 minutes; audio-recorded) were conducted. Interviewer sensitivity training, senior interviewer oversight, and a list of common medications to aid recall supported data collection. Interview transcripts were content coded and analyzed (NVivo v11.0).

All 41 patients reported a lifetime burden with schizophrenia adversely impacting employment, relationships, emotional health, social activities, and daily tasks. Hospitalization for schizophrenia management was another reported aspect of disease burden. Although most (n=32) patients reported previous medication benefits, side effects affecting physical, emotional/behavioral, and cognitive functioning were reported by all (n=41). Following OLZ/SAM treatment, 39/41 patients (95%) reported improvements in symptoms including hallucinations, paranoia, depression, sleep, and concentration. Furthermore, patients described improvements in self-esteem, social activities, relationships, and daily activities. Twenty-three patients (56%) reported side effects attributed to OLZ/SAM; lack of energy (n=12 [29%]) and dry mouth (n= 5 [12%]) were most common. Twenty-four (59%) patients were “very satisfied” with OLZ/SAM; most (n=35 [85%]) preferred to continue OLZ/SAM vs switching to another medication. As most substudy patients (n=40; 98%) completed the extension study, satisfied patients may be overrepresented in this analysis.

This qualitative interview approach provided valuable insight into patients’ experiences with previous medications and OLZ/SAM. Overall, most patients reported treatment satisfaction and improvements in symptoms, function, and health-related quality of life with OLZ/SAM.

Alkermes, Inc.

The randomized, controlled, phase 3b ALPINE study evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) initiated with a 1-day regimen during hospitalization for an acute exacerbation of schizophrenia; paliperidone palmitate (PP) was included as an active control. The primary efficacy outcome, within-group change from baseline in PANSS total score at 4 weeks, was previously reported. Here we report additional exploratory PANSS subscale endpoints and patient-reported outcomes (PROs).

Adults aged 18–65 years were enrolled as inpatients and randomized to AL 1064 mg q8wk or PP 156 mg q4wk and discharged after 2 weeks of study treatment if clinically stable. Patients were followed as outpatients through week 25. Exploratory efficacy endpoints were PANSS subscale (Positive, Negative, and General) and Clinical Global Impression-Severity (CGI-S) scores. The Burden Assessment Scale was administered to patients’ nonprofessional caregivers (family member or friend). Exploratory PROs (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form [Q-LES-Q-SF] and Medication Satisfaction Questionnaire) were assessed during the outpatient period. Within-group changes in PANSS subscales and CGI-S scores from baseline through week 25 were analyzed for AL and PP using mixed models with repeated measures. PROs were summarized based on observed data.

In total, 200 patients were randomized (AL, n=99; PP, n=101); 99 (AL, n=56; PP, n=43) completed the 25-week study. PANSS Positive, Negative, and General subscale scores improved with AL treatment as measured by change from baseline to week 25 (least squares [LS] mean [95% CI]: Positive, −7.0 [−8.1, −6.0]; Negative, −3.7 [−4.7, −2.8]; General, −11.1 [−12.7, −9.5]), as did CGI-S scores (LS mean [95% CI] change at week 25: –1.2 [–1.4 –1.0]). Caregiver burden decreased over the treatment period, with the largest decline noted at week 9 for AL patients’ caregivers (mean change from baseline at week 9: −8.4; week 25: −8.9). Over weeks 5, 9, and 17, 70.8%−74.7% of AL-treated patients were somewhat or very satisfied with treatment. Mean Q-LES-Q-SF total scores were stable. With PP, PANSS subscale and CGI-S scores improved from baseline to study end (LS mean [95% CI] changes at week 25: Positive, −7.1 [−8.2, −5.9]; Negative, −3.5 [−4.6, −2.5]; General, −10.4 [−12.1, −8.6]; CGI-S, −1.2 [−1.5, −1.0]). Mean caregiver burden decreased (week 9: −8.8; week 25: −9.2). Most PP patients were satisfied or very satisfied with treatment (64.7%−69.3% at weeks 5, 9, and 17), and mean Q-LES-Q-SF total scores were stable.

In ALPINE, patients who initiated AL or PP in the hospital and continued treatment during outpatient care experienced improvement in schizophrenia symptoms and reported satisfaction with medication, decreased caregiver burden, and stable quality of life.

Alkermes, Inc.

Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2).

Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis.

In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3–7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI.

Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.

Evaluate efficacy and safety of a 2-month dose of aripiprazole lauroxil (AL) with a 1-day initiation regimen during hospitalization for an acute exacerbation of schizophrenia.

In the phase 3b double-blind ALPINE study, adults with schizophrenia were randomized to AL (AL NanoCrystal® Dispersion + oral aripiprazole 30 mg day 1; AL 1064 mg day 8 and every 8 weeks) or paliperidone palmitate (PP 234 mg day 1; PP 156 mg day 8 and every 4 weeks). Patients were discharged after 2 weeks of hospitalization and followed through week 25. Primary endpoint was within-group changes in PANSS total score from baseline to week 4 (observed cases). Secondary analyses included within-group changes at weeks 9 and 25 (observed) and between-group comparisons at weeks 4, 9, and 25 (MMRM). Adverse events (AEs) were monitored throughout the study.

200 patients were randomized (AL, n=99; PP, n=101); 56.6% and 42.6%, respectively, completed the study. Within-group changes from baseline in PANSS were −17.4 for AL and −20.1 for PP at week 4 (both groups, P<0.001) and continued to decline at weeks 9 (AL, −19.8; PP, −22.5) and 25 (AL, −23.3; PP, −21.7). The change in PANSS over time was similar between groups. AEs occurring in ≥10% of patients in either group were injection site pain (AL, 17.2%; PP, 24.8%), akathisia (AL, 9.1%; PP, 10.9%), and weight increased (AL, 9.1%; PP, 16.8%).

AL and PP were effective and well-tolerated for initiating treatment of schizophrenia in the hospital and continuing in the outpatient setting.

This study was funded by Alkermes, Inc.

Asenapine is a 2nd-generation antipsychotic currently marketed as a sublingual (SL) tablet in the US for the treatment of schizophrenia. HP-3070, asenapine transdermal system, is a patch for treatment of schizophrenia in adults. Low- and high- HP-3070 doses deliver asenapine concentrations that are similar to SL asenapine 5 mg BID and 10 mg BID, respectively, but with fewer peak and trough fluctuations.

In this Phase 3, randomized, double-blind, placebo (PBO)-controlled, 6-week inpatient study, adults with schizophrenia having baseline Positive and Negative Syndrome Scale (PANSS) total score ≥80 and Clinical Global Impression–Severity of Illness Scale (CGI-S) score ≥4 were randomized 1:1:1 to HP 3070 high-dose, HP-3070 low-dose, or PBO.

The primary efficacy objective was Week 6 PANSS score change from baseline (CFB) vs PBO.

The key secondary objective was Week 6 CGI-S CFB vs PBO. Safety assessments included treatment-emergent adverse events (TEAEs), laboratory results, vital signs, dermal safety, and extrapyramidal symptoms (EPS) assessments.

A total of 616 patients were randomized, with 486 patients completing the study. Discontinuation rates were 23.3%, 18.6%, and 21.4% for HP-3070 high-dose, HP-3070 low-dose, and PBO, respectively; withdrawal of consent and AEs were the most common reasons for discontinuation. Demographics and baseline characteristics were well-balanced among treatment groups.

For PANSS total score, least squares mean (LSM) (standard error [SE]) estimates of the treatment comparison (HP-3070 vs PBO) for CFB at Week 6 were -4.8 (1.634; 95% CI: -8.06, -1.64; p=0.003) and -6.6 (1.630; 95% CI: 9.81, 3.40; p<0.001) for HP-3070 high- and low-dose, respectively. For CGI-S CFB at Week 6, LSM (SE) for the treatment comparison were 0.4 (0.100; 95% CI: 0.55, 0.16; p<0.001) for HP 3070 high-dose and 0.4 (0.099; 95% CI: 0.64, 0.25; p<0.001) for low-dose.

No deaths or serious TEAEs related to study treatment occurred. The HP-3070 safety profile was consistent with SL asenapine. Incidence of TEAEs at the patch application site was higher for HP-3070 (14.2% high-dose, 15.2% low-dose) than for PBO (4.4%); most of these events were mild or moderate in severity. PBO patients had higher rates of psychiatric disorders (24.3% vs 15.7% and 17.6% for HP-3070 high- and low-dose, respectively), with insomnia and anxiety as most common. Study treatment discontinuations due to application site reactions or skin disorders were low (≤0.5%) across treatment groups. There was no marked mean CFB for vital signs or electrocardiogram parameters, nor treatment differences observed on EPS assessments.

In this study, HP-3070 was efficacious, safe, and well-tolerated for treating schizophrenia in adults; both doses met primary and key secondary endpoints. As the first transdermal antipsychotic patch in the US, HP-3070 will provide patients a novel treatment option.

Funded by Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical Co.

There is a paucity of long-term prospective disaster studies of the psychological sequelae among survivors.

At 1½ and 25 years after the Spitak earthquake, 142 early adolescents from two cities were assessed: Gumri (moderate–severe exposure) and Spitak (very severe exposure). The Gumri group included treated and not-treated subjects, while the Spitak group included not-treated subjects. Instruments included: DSM-III-R PTSD-Reaction Index (PTSD-RI); DSM-5 PTSD-Checklist (PCL); Depression Self-Rating Scale (DSRS); and Center for Epidemiological Studies-Depression Scale (CES-D).

(1) Between 1½ and 25 years, PTSD rates and mean scores decreased significantly in the three groups (over 50%). However, at 25 years 9.1–22.4% met DSM-5 PTSD criteria. (2) At 1½ years, the Spitak group had higher PTSD-RI (p < 0.001) and DSRS scores (p < 0.001) compared to the Gumri-not-treated group. At 25 years, the Spitak group that had experienced fewer post-earthquake adversities (p < 0.03), had a greater decrease in PTSD-RI scores (p < 0.02), and lower CES-D scores (p < 0.01). (3) Before treatment, PTSD-RI and DSRS scores did not differ between the Gumri-treated and not-treated groups. At 25-years, the Gumri-treated group showed a greater decrease in PTSD-RI scores (p < 0.03), and lower mean PTSD-RI (p < 0.02), PCL (p < 0.02), and CES-D (p < 0.01) scores. (4) Predictors of PTSD symptom severity at 25-years included: home destruction, treatment, social support, post-earthquake adversities, and chronic medical illnesses.

Post-disaster PTSD and depressive symptoms can persist for decades. Trauma-focused treatment, alleviation of post-disaster adversities, improving the social ecology, and monitoring for chronic medical illnesses are essential components of recovery programs.

Prevention of Clostridioides difficile infection (CDI) is a national priority and may be facilitated by deployment of the Targeted Assessment for Prevention (TAP) Strategy, a quality improvement framework providing a focused approach to infection prevention. This article describes the process and outcomes of TAP Strategy implementation for CDI prevention in a healthcare system.

Hospital A was identified based on CDI surveillance data indicating an excess burden of infections above the national goal; hospitals B and C participated as part of systemwide deployment. TAP facility assessments were administered to staff to identify infection control gaps and inform CDI prevention interventions. Retrospective analysis was performed using negative-binomial, interrupted time series (ITS) regression to assess overall effect of targeted CDI prevention efforts. Analysis included hospital-onset, laboratory-identified C. difficile event data for 18 months before and after implementation of the TAP facility assessments.

The systemwide monthly CDI rate significantly decreased at the intervention (β2, −44%; P = .017), and the postintervention CDI rate trend showed a sustained decrease (β1 + β3; −12% per month; P = .008). At an individual hospital level, the CDI rate trend significantly decreased in the postintervention period at hospital A only (β1 + β3, −26% per month; P = .003).

This project demonstrates TAP Strategy implementation in a healthcare system, yielding significant decrease in the laboratory-identified C. difficile rate trend in the postintervention period at the system level and in hospital A. This project highlights the potential benefit of directing prevention efforts to facilities with the highest burden of excess infections to more efficiently reduce CDI rates.

The Tower Hamlets Crisis House (voluntary sector), in partnership with the local home treatment team, offers a brief residential alternative to psychiatric hospital admission. Here, we review clinician-reported (Health of the Nation Outcome Scales; HoNOS) and patient-reported (DIALOG) outcome scores collected from successive admissions between June 2015 and December 2016, to assess the effectiveness of the service model. We identified 153 successive admissions, and of these, 85 (55.6%) and 91 (59.5%) patients completed both admission and discharge DIALOG and HoNOS questionnaires, respectively. We analysed ten out of twelve HoNOS domains and eight patient-reported outcome measure DIALOG domains.

We found a statistically significant improvement in nine out of ten domains of HoNOS and three out of eight domains of DIALOG.

A partnership between a home treatment team and crisis house can result in positive outcomes for patients, as determined by both clinicians and patients.

None.