A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Maintenance Treatment in Adults with Schizophrenia.

Background: Brexpiprazole is a serotonin-dopamine activity modulator with efficacy in acute schizophrenia and relapse prevention. The aim of this Phase 3, multicenter study was to assess the long-term safety, tolerability, and efficacy of treatment with brexpiprazole flexible-dose 1-4 mg/d. Methods: Patients rolled over into this 52-week open-label study (amended to 26 weeks towards the end) from 3 randomized, double-blind, placebo-controlled Phase 3 studies. De novo patients, not part of the previous studies, were also enrolled. The primary outcome variable was the frequency and severity of treatment-emergent adverse events. Efficacy was assessed as a secondary objective using the Positive and Negative Syndrome Scale and the Personal and Social Performance scale. Results: A total of 1072 patients was enrolled (952 for 52 weeks and 120 for 26 weeks), 47.4% of whom completed the study. Among patients who took at least one dose of brexpiprazole, 14.6% discontinued due to treatment-emergent adverse events, most commonly schizophrenia (8.8%) and psychotic disorder (1.5%). Treatment-emergent adverse events with an incidence of ≥5% were schizophrenia (11.6%), insomnia (8.6%), weight increased (7.8%), headache (6.4%), and agitation (5.4%). Most treatment-emergent adverse events were mild or moderate in severity. The mean increase in body weight from baseline to week 26 was 1.3 kg and to week 52 was 2.1 kg. There were no clinically relevant findings related to prolactin, lipids, and glucose, or QT prolongation. On average, patients' symptoms and functioning showed continual improvement. Conclusions: Treatment with brexpiprazole 1-4 mg/d was generally well tolerated for up to 52 weeks in patients with schizophrenia. ClinicalTrials.gov identifier: NCT01397786 (https://clinicaltrials.gov/show/NCT01397786).

Brexpiprazole in patients with schizophrenia: overview of short- and long-term phase 3 controlled studies.

OBJECTIVE: Review efficacy, safety, and tolerability of brexpiprazole in patients with schizophrenia in short- and long-term phase 3 studies. METHODS: Patients experiencing a current exacerbation of schizophrenia received brexpiprazole in two fixed-dose (2 and 4 mg), 6-week, placebo-controlled studies, one flexible-dose (2-4 mg), 6-week, placebo-control and active reference study, and one fixed-dose (1-4 mg), 52-week, placebo-controlled maintenance study. RESULTS: The efficacy of brexpiprazole was demonstrated in the two short-term fixed-dose studies with statistically significant improvements from baseline in Positive and Negative Syndrome Scale (PANSS) total score compared with placebo. In the flexible-dose short-term study, treatment with brexpiprazole resulted in numerically greater improvements in PANSS total score than with placebo that approached statistical significance (p=0.056). A meta-analysis of these short-term studies showed a mean change in PANSS total score of -20.1, reflecting a clinically meaningful reduction in symptoms. In the maintenance study, brexpiprazole had a beneficial effect relative to placebo on time to exacerbation of psychotic symptoms/impending relapse (p<0.0001). For all studies, brexpiprazole demonstrated clinically meaningful treatment effects on the Personal and Social Performance scale. Brexpiprazole had a favourable safety profile, with a relatively low prevalence of activating and sedating side effects. Weight gain in the short-term studies was ~1 kg greater than placebo. No safety concerns were observed with brexpiprazole in laboratory values, electrocardiogram, or vital signs. CONCLUSIONS: Overall, the results indicate brexpiprazole, used either short-term or as part of a long-term maintenance treatment programme, is an efficacious therapy option in adults with schizophrenia and has a favourable safety/tolerability profile.

Hospitalisation Utilisation and Costs in Schizophrenia Patients in Finland before and after Initiation of Risperidone Long-Acting Injection.

Objectives. Quantify changes in hospital resource use in Finland following initiation of risperidone long-acting injection (RLAI). Materials and Methods. A retrospective multi-center chart review (naturalistic setting) was used to compare annual hospital bed-days and hospital episodes for 177 schizophrenia patients (mean age 47.1 years, 52% female, 72% hospitalized) before and after initiation of RLAI (between January 2004 and June 2005) using the within-patient "mirror-image" study design. The base case analytical approach allocated hospital episodes overlapping the start date entirely to the preinitiation period. In order to investigate the impact of inpatient care ongoing at baseline, the change in bed-days was also estimated using an alternative analytical approached related to economic modelling. Results. In the conventional analysis, the mean annual hospitalisation costs declined by €11,900 and the number of bed-days was reduced by 40%, corresponding to 0.19 fewer hospital episodes per year. The reductions in bed-days per patient-year were similar for patients switched to RLAI as inpatients and as outpatients. In the modelling-based analysis, an 8% reduction in bed-days per year was observed. Conclusion. Despite uncertainty in the choice of analytic approach for allocating inpatient episodes that overlapping this initiation, consistent reductions in resource use are associated with the initiation of RLAI in Finland.

Onset of neuropsychiatric symptoms after psychological trauma may result in erroneous diagnostic bias.

We report a case of neuroacanthocytosis, which was misdiagnosed as conversion disorder. Because the onset was after a psychologically stressful physical trauma, the patient's symptoms were interpreted in terms of psychological regression. The case clearly points out the defects of descriptive psychiatric diagnosis, especially in the area of somatoformal disorders. It also reminds the clinicians to keep in mind rare neurological disorders as possible causes for psychiatric symptoms.

Brain glucose metabolism and temperament in relation to severe somatization.

Little is known about the pathophysiology of somatization. The authors' aim was to explore associated factors with somatoform disorders. The authors studied 10 female patients with a diagnosis of somatization disorder or undifferentiated somatoform disorder with no comorbid current Diagnostic and Statistical Manual of Mental Disorders (4th edn) Axis I disorder and 12 healthy female volunteers. The predicting variables were temperament factors of the 240-item Temperament and Character Inventory instrument and regional brain glucose metabolism. Low novelty-seeking and high harm avoidance temperament traits and low caudate and low putamen glucose metabolism were statistically significantly associated with severe somatization (P < 0.05). In the present study, severe somatization associates with both altered brain glucose metabolism and temperament factors. No other studies on association of somatization with brain glucose metabolism and temperament have been published. The results are still considered exploratory due to the small number of subjects.

Volumes of the caudate nuclei in women with somatization disorder and healthy women.

Very little is known about the pathophysiology of somatization disorder. This study was designed to analyze the volumes of some brain structures possibly involved in somatization based on the observation of glucose metabolism of the brain in these patients. We studied 10 female patients with a diagnosis of somatization disorder or undifferentiated somatoform disorder with no comorbid current DSM-IV Axis I disorder and compared them to 16 healthy female volunteers using brain MRI (1.5 T instrument). The patients had bilateral enlargement of caudate nuclei volumes compared with healthy volunteers. These volume differences in the caudate nuclei could be associated with the pathophysiology of somatization.