Objectives Functional impairment is an important driver of disability in patients with bipolar disorder (BD) and can persist even when symptomatic remission has been achieved. The objectives of this systematic literature review were to identify studies that assessed functioning in patients with BD and describe the functional scales used and their implementation. Methods A systematic literature review of English‐language articles published between 2000 and 2017 reporting peer‐reviewed, original research related to functional assessment in patients with BD was conducted. Results A total of 40 articles met inclusion criteria. Twenty‐four different functional scales were identified, including 13 clinician‐rated scales, 7 self‐reported scales, and 4 indices based on residential and vocational data. The Global Assessment of Functioning (GAF) and the Functional Assessment Short Test (FAST) were the most commonly used global and domain‐specific scales, respectively. All other scales were used in ≤2 studies. Most studies used ≥1 domain‐specific scale. The most common applications of functional scales in these studies were evaluations of the relationships between global or domain‐specific psychosocial functioning and cognitive functioning (eg, executive function, attention, language, learning, memory) or clinical variables (eg, symptoms, duration of illness, number of hospitalizations, number of episodes). Conclusions The results of this review show growing interest in the assessment of functioning in patients with BD, with an emphasis on specific domains such as work/educational, social, family, and cognitive functioning and high utilization of the GAF and FAST scales in published literature.

Background: Schizophrenia is a heterogeneous disorder with a burden that can vary greatly depending on the severity and the duration. Previous research has suggested that patients in the earlier stages of schizophrenia (typically first-episode schizophrenia) benefit from effective early treatment, however, a comprehensive review of the burden specifically in this population has not been undertaken. A systematic literature review was therefore conducted to characterize the clinical, economic, and humanistic burden, as reported in naturalistic studies of schizophrenia populations specifically at an early stage of disease in comparison with healthy controls, patients with chronic schizophrenia, and patients with other psychiatric disorders.

Purpose: Two phase 2 studies evaluated the efficacy and tolerability of centanafadine sustained-release (SR) for adults with attention-deficit/hyperactivity disorder (ADHD). Patients and Methods: In a phase 2a, flexible-dose, single-blind study, 41 male patients (aged 18-55 years) with a diagnosis of ADHD (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were titrated with centanafadine-SR 200-300, 400, or 500 mg/d for 2 weeks, and then were treated with the titrated dose for 2 weeks. In a phase 2b, randomized, double-blind, placebo-controlled, crossover study, 85 male and female patients (aged 18-60 years) with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) were titrated to target doses of centanafadine-SR 400, 500, 600, or 800 mg/d over the course of 1 week, and then received their titrated dose for 3 weeks. The primary outcome in both studies was mean total ADHD Rating Scale-IV (ADHD-RS-IV) score. Results: In the phase 2a study, mean ADHD-RS-IV total score decreased by 21.41 (standard deviation 10.74) from the start of active centanafadine-SR treatment to the end of week 4 (P<0.001). In the phase 2b study, centanafadine-SR treatment resulted in a statistically significant improvement in ADHD-RS-IV from baseline to week 3 compared with placebo (least-squares mean −16.5 vs −8.4; P<0.001; effect size 0.66), with significant efficacy demonstrated as early as week 1. Centanafadine-SR was generally well tolerated at doses ≤400 mg. Most treatmentemergent adverse events (TEAEs) were mild or moderate; decreased appetite, headache, and nausea were the most frequently reported. In the 2 studies, 13 of 120 patients discontinued centanafadine-SR due to TEAEs; however, only 1 patient who received ≤400 mg discontinued due to a TEAE. No serious TEAEs were reported at any dose. Conclusion: These results support the continued development of centanafadine-SR at doses up to 400 mg/d.

BackgroundThe long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I.MethodsThis open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive (“de novo”) patients as well as AOM 400-experienced (“rollover”) patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324–331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery–Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder–Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified.ResultsOf 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications.ConclusionAOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment.Trial registration ClinicalTrials.gov, NCT01710709Electronic supplementary materialThe online version of this article (10.1186/s40345-018-0122-z) contains supplementary material, which is available to authorized users.

Background: The single-injection start regimen for aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia requires a single intramuscular injection in the gluteal or deltoid site and 14 days of concurrent oral therapy. A simplified, single-day regimen of two injections at separate gluteal and/or deltoid injection sites, together with a single 20-mg dose of oral aripiprazole on the 1st day, was assessed. Patients and methods: A previously developed population-pharmacokinetic (popPK) model for characterizing aripiprazole PK following oral administration and gluteal intramuscular depot injection was expanded to include deltoid injection. Simulations were conducted to assess PK profiles following various (including two-injection) start regimens. Postmarketing data on patients who received higherthan-recommended AOM doses were used to assess overall safety/tolerability. Results: The two-injection start regimen with a single concurrent oral dose displayed a comparable PK profile to the single-injection start regimen with concurrent 14-day oral administration in simulations. The safety assessment indicated the two-injection start regimen was unlikely to be associated with safety concerns beyond those expected with a single-injection start regimen. Conclusion: These data support use of the two-injection start regimen in clinical practice to reduce reliance on daily oral administration and optimize the therapeutic benefits of AOM 400 in patients with schizophrenia.