No abstract

Background This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. Methods Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. Results Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M − PP3M) in the percentages of patients who remained relapse free was −2.9% (−6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of −10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged. Conclusions The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M. Trial Registration Clinical Trials.gov identifier: NCT03345342

Background Half of Americans experience mental illness during their lifetime. Significant opportunity exists for community pharmacists to deliver services to these patients; however, personal and practice-related barriers may prevent full engagement. Objective To assess the demographics, practice characteristics, service provision, stigma, attitudes and beliefs of a national sample of community pharmacists towards individuals with mental illness. Setting National random sample of 3008 community pharmacists in the USA. Method 101-item cross-sectional mailed survey questionnaire on: (1) demographics, (2) knowledge and practice characteristics, (3) provision of clinical pharmacy services, and (4) comparative opinions. Main outcome measure Scaled measures of service provision (comfort, confidence, willingness and interest) and comparative opinions (stigma, attitudes and beliefs) of mental illness, four linear regression models to predict service provision. Results A total of 239 responses were received (response rate 7.95%). Across pharmacy services, ratings for willingness/interest were higher than those for comfort/confidence. Pharmacists who reported providing medication therapy management (MTM) services for patients reported higher comfort (18.36 vs. 17.46, p < 0.05), confidence (17.73 vs. 16.01, p < 0.05), willingness (20.0 vs. 18.62, p < 0.05) and interest (19.13 vs. 17.66, p < 0.05). Pharmacists with personal experience with mental illness also resulted in higher scores across all four domains of service provision, lower levels of stigma (18.28 vs. 20.76, p < 0.05) and more positive attitudes (52.24 vs. 50.53, p < 0.01). Regression analyses demonstrated increased frequency of MTM service delivery and more positive attitudes as significantly predictive across all four models for comfort, confidence, willingness and interest. Increased delivery of pharmacy services was significantly associated with both willingness and interest to provide mental illness-specific services. Conclusion Despite willingness/interest to provide services to patients with mental illness, decreased levels of comfort/confidence remain service-related barriers for community pharmacists.

Injection site reactions and pain were low and similar between both treatments, regardless of administration site and dose.

With more long-acting injectable (LAI) antipsychotics available for treating schizophrenia, each with variable durations of action (2 weeks to 3 months), it is important to have clear management strategies for patients developing breakthrough psychotic symptoms or experiencing symptomatic worsening on LAIs. However, no treatment guidelines or clinical practice pathways exist; health-care providers must rely on their own clinical judgment to manage these patients. This article provides practical recommendations—based on a framework of clinical, pharmacokinetic, and dosing considerations—to guide clinicians’ decisions regarding management of breakthrough psychotic symptoms. Management options include ruling out/addressing medical illness or substance abuse/misuse as a contributing factor, addressing stressors, optimizing nonpharmacologic treatments, treating medical/psychiatric comorbidities, ensuring proper LAI administration technique, addressing missed LAI doses or lack of steady-state attainment, and increasing LAI dose directly or indirectly by shortening the injection interval (off-label). If these strategies do not work sufficiently with frequent monitoring, the LAI could be supplemented with a low dose of the corresponding oral formulation for fast symptom control (off-label). However, caution should be exercised with this strategy, because data on the safety of concomitant use of LAI and oral antipsychotics (OAPs) are limited, especially over extended periods. If symptoms abate, therapy optimization could be continued and slow discontinuation of the OAP could be considered. For persistent/worsening symptoms, the OAP should be increased to optimum effective dose while intensifying the initial steps used before it was added. If this fails, switching the OAP or LAI could be considered. We believe that these strategies will help clinicians manage breakthrough psychotic symptoms during LAI treatment and improve overall outcomes among those who can benefit from LAIs.