Adjunctive Pimavanserin in Patients with Major Depressive Disorder: Combined Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies.

Objective: In a phase 2 study, pimavanserin demonstrated efficacy as adjunctive treatment for major depressive disorder (MDD). Subsequently, two phase 3 studies (NCT03968159 in the US; NCT03999918 in Europe) were initiated to examine the efficacy and safety of adjunctive pimavanserin in subjects with MDD and inadequate response to antidepressant treatment. Studies were combined with a prespecified statistical analysis plan owing to recruitment challenges related to the COVID-19 pandemic. Experimental design: The randomized, double-blind studies enrolled 298 patients with MDD and inadequate response to current antidepressants. Patients were randomly assigned 1:1 to pimavanserin or placebo added to current antidepressant for 6 weeks. Primary endpoint was change from baseline to week 5 in the Hamilton Rating Scale for Depression, 17-item version (HAM-D-17). Principal observations: There was no effect of pimavanserin in change from baseline to week 5 in the HAM-D-17 (pimavanserin [n = 138]: least-squares mean [LSM] [standard error {SE}], -9.0 [0.58]; placebo [n = 135]: -8.1 [0.58]; mixed-effects model for repeated measures LSM [SE] difference, -0.9 [0.82], P = 0.2956). Nominal improvement with pimavanserin was observed on 2 secondary endpoints: Clinical Global Impressions-Severity scale, Karolinska Sleepiness Scale. Treatment-emergent adverse events occurred in 58.1% of pimavanserin-treated and 54.7% of placebo-treated patients. Conclusions: Adjunctive pimavanserin did not significantly improve depressive symptoms, although pimavanserin was well tolerated.

Enhancing person-centred care in inpatient mental health settings through supported person-side handover: a multi method study.

BACKGROUND: Many nursing contexts have introduced bedside handover, where the person in care participates in the transfer of clinical information, with benefits for person, carers, and clinicians. This type of handover has been implemented across a number of mental health settings, but there is limited evidence regarding implementation approaches or of practice change. This study reports the development and evaluation of a co-produced education and support package. AIM: To evaluate changes in nurses' practice regarding bedside (person-side) handover following implementation of a structured education and support package. DESIGN: Multi-method design incorporating nurse surveys and chart audit. METHODS: The survey and audit were conducted in 2019-2020 on two inpatient mental health units in a metropolitan health service immediately prior to, and 6 months after, implementation, with 70 survey responses and 52 files audited. Non-parametric tests assessed change, and text comments were reported. RESULTS: Significant improvements were observed in nurses' reports of confidence, the ability to maintain privacy, identified benefits for the person and in information transfer. In contrast, the chart audit identified no change in documentation of this practice. CONCLUSIONS: The implementation of a co-produced education and support package demonstrated positive practice change in engaging people receiving care in handover. This approach to handover provides increased opportunity for nurses to work in partnership with people receiving mental healthcare, facilitating collaborative person-centred care and shared decision making.

Extending the role of nursing assistants in mental health inpatient settings: A multi-method study.

With continued growth in the demand for nursing care, many organizations have incorporated nursing assistants into the acute care workforce. However, role descriptions are often generic and do not provide clarity in specialist areas such as mental health inpatient settings. Issues have been noted regarding the role of assistants, delegation, and their integration with the nursing team. This study extended an existing set of care activities and explored the perceptions of nursing assistants and registered nurses regarding these activities. A modified Delphi approach added 14 new care activities for nursing assistants. A follow-up survey found significant differences between nursing assistants and registered nurses regarding utilization of the activities, delegation, teamwork, and role clarity. Future research must incorporate the perspectives of those with lived experience of mental health issues, and develop an understanding of the interactions between nursing assistant care activities and other factors such as local supports, skillmix, and the practice environment, as these may impact how an organization can introduce nursing assistants to specialty areas while maintaining consumer and staff safety.

Direct care activities for assistants in nursing in inpatient mental health settings in Australia: A modified Delphi study.

This paper describes a modified Delphi approach to developing a set of direct care activities for assistants in nursing (AIN) working in mental health settings within a metropolitan local health district (LHD). Although AIN have been employed in a range of health care settings in recent years, they have not routinely been placed in the mental health context. A modified Delphi method was utilised as it has a proven history of application in the health sector, particularly in circumstances where new guidelines, policies or practice frameworks were required. A set of direct care activities for working in mental health settings was developed from an initial set of baseline descriptors and then two rounds of consensus conferencing with a panel of experts. This paper will detail that process and discuss the resulting implications for the consensus reached on the set of direct care activities.

Assistants' in nursing perceptions of their social place within mental health-care settings.

An international nurse shortage, tightening fiscal constraints, and increased service demands have seen health systems increasingly turn to employing assistants in nursing (AIN) as a cost-effective means to meet demand. This paper describes social positioning from the perspective of 11 AIN who were employed to work in specialist mental health settings in a metropolitan health service in Sydney. Data was collected by means of semistructured interviews. Interview questions encouraged AIN to explore their experience with reference to positioning within the service, role perception, role development, staff relationship, and role satisfaction. Thematic analysis was utilized to generate themes and explore meaning within the data. The following themes emerged: role definition and clarity; socialization and adaptation; and enhancing education. Analysis suggests that whilst AIN were integrated into mainstream service, the scope of activities or role remains geographically variable and inconsistent. Encouragingly, as AIN became familiar with their work environments and teams, they considered themselves to be of value and were able to play a meaningful role. A desire for learning and a need for continuing education also emerged as a primary theme. Findings from the data suggest that AIN in the mental health setting remain a novel and, to some extent, poorly utilized resource.

A randomized, double-blind study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder.

This study evaluated once-daily, extended-release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 10-week (8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase), double-blind, randomized, placebo-controlled study (D1448C00009). Primary end point was change from randomization at week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Overall, 951 patients with GAD were randomized (quetiapine XR: 50 mg/d, n = 234; 150 mg/d, n = 241; 300 mg/d, n = 241; placebo, n = 235). At week 8, HAM-A total scores significantly (P < 0.001) improved versus placebo (-11.10) with quetiapine XR 50 mg/d (-13.31) and 150 mg/d (-13.54), but not 300 mg/d (-11.87; P = 0.240). At week 1, HAM-A total scores significantly improved versus placebo (-5.94) with quetiapine XR 50 mg/d (-7.47; P < 0.01), 150 mg/d (-8.19; P < 0.001), and 300 mg/d (-7.23; P < 0.01). Versus placebo at week 8, quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic (P < 0.01 and P < 0.001, respectively) and somatic (P < 0.001; P < 0.01, respectively) cluster scores, HAM-A response (≥ 50% total score reduction; P < 0.05), and Clinical Global Impression-Improvement categorical changes (P < 0.05). For quetiapine XR 150 mg/d, significant (P < 0.05) improvements were seen for HAM-A remission (total score, ≤ 7) and Clinical Global Impression-Severity of Illness scores. For quetiapine XR 300 mg/d, improvements in these secondary variables were not significantly different versus placebo. Pittsburgh Sleep Quality Index global scores improved with all 3 doses (quetiapine: XR 50 mg/d, -4.07 [P < 0.05]; 150 mg/d, -4.38 [P < 0.05]; 300 mg/d, -3.97 [P < 0.05], versus -3.31 with placebo). Adverse events (>10% with quetiapine XR) were dry mouth, somnolence, sedation, dizziness, headache, and fatigue. Quetiapine XR (50/150 mg/d) monotherapy was effective at week 8 in patients with GAD; symptom improvement was seen at week 1 for all doses (50/150/300 mg/d). Safety and tolerability were consistent with the known profile of quetiapine.

Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study.

This study evaluated once-daily extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, MADRS total scores significantly improved with quetiapine XR 300 mg/d vs. placebo (-14.7 vs. -11.7, p<0.01). Quetiapine XR 300 mg/d showed significant improvements vs. placebo for: MADRS total score from week 1 onwards; MADRS response [(> or = 50% total score reduction) 58.9% vs. 46.2%, p<0.05] and remission [(total score < or = 8) 42.5% vs. 24.5%, p<0.01] rates; Hamilton Depression Rating Scale (HAMD) (-13.53 vs. -10.80, p<0.01) and Clinical Global Impression-Severity of illness (CGI-S) change (-1.52 vs. -1.23, p<0.05) at week 6. For quetiapine XR 150 mg/d, improvements were not significantly different vs. placebo, except for MADRS (weeks 1 and 2) and HAMD (week 6) total scores. Withdrawal rates due to adverse events (AEs) were: quetiapine XR 150 mg/d 11.5%, 300 mg/d 19.5%, and placebo 0.7%. The most common AEs (>10%) with quetiapine XR were dry mouth, somnolence, sedation, dizziness, constipation, nausea, insomnia, headache, and fatigue. In this study, quetiapine XR 300 mg/d as adjunctive therapy in patients with MDD with an inadequate response to ongoing antidepressant treatment was effective at week 6. However, the difference from placebo for quetiapine XR 150 mg/d at week 6 was not statistically significant. Both doses studied (150 and 300 mg/d) were effective at week 1 and generally well tolerated.

Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study.

INTRODUCTION: Once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy was evaluated in major depressive disorder (MDD). METHOD: This was an 8-week (6-week randomized-phase; 2-week drug-discontinuation/tapering phase), double-blind, parallel-group, placebo-controlled study. The primary outcome measure was Montgomery-Asberg Depression Rating Scale (MADRS) total score randomization-to-Week 6 change. Other assessments included the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and adverse events (AEs). RESULTS: 723 patients were randomized: 182, 178, 179, and 184 to quetiapine XR 50, 150, 300 mg/day, and placebo, respectively. At Week 6, significant reductions occurred in MADRS score with quetiapine XR 50 mg/day (-13.56; P<.05), 150 mg/day (-14.50; P<.01) and 300 mg/day (-14.18; P<.01) versus placebo (-11.07); at Day 4, reductions for quetiapine XR (titrated to 50 or 150 mg/day according to dose group) versus placebo (-2.9) were: -4.7 (P<.01), -5.2 (P<.001), and -5.1 (P<.001), respectively. At endpoint, MADRS response (>or=50% reduction in score) was 42.7% (P<.01), 51.2% (P<.001), and 44.9% (P