Impact of changes in social anxiety on social functioning and quality of life in outpatients with schizophrenia: A naturalistic longitudinal study.

The prevalence of comorbid social anxiety disorder among patients with schizophrenia is currently attracting attention, and symptoms of social anxiety are reportedly associated with various clinical features. However, the contribution of social anxiety to social functioning and quality of life (QOL) over time remains obscure. The aim of this study was to examine the impact of changes in social anxiety symptoms on social functioning and QOL among outpatients with schizophrenia. Of the 207 outpatients who were eligible at baseline, 118 patients agreed with and completed a follow-up investigation at least 1 year (695.8 days on average) after the baseline study. Stepwise multiple regressions examining the change in social functioning using demographic data and changes in clinical variables as explanatory variables demonstrated that the changes in social anxiety and general psychopathology contributed to the change in the Social Functioning Scale, while the changes in clinical severity and negative symptoms contributed to the change in the Global Assessment of Functioning scale. Stepwise multiple regressions for the change in QOL demonstrated that the changes in social anxiety and depression contributed to the change in the World Health Organization QOL scale, Brief version, and the changes in social anxiety and positive symptoms contributed to the Subjective Well-being Under Neuroleptic Drug Treatment, Short Form. The results revealed that the changes in social anxiety symptoms were significantly associated with the change in functional outcome among patients with schizophrenia. Treatments targeting social anxiety seem to be key to achieving a full recovery in patients with schizophrenia.

Post-hoc analysis investigating the safety and efficacy of brexpiprazole in Japanese patients with schizophrenia who were switched from other antipsychotics in a long-term study (Secondary Publication).

A post hoc analysis was performed using data obtained over eight weeks from 200 Japanese patients with schizophrenia who were switched to brexpiprazole monotherapy in a long-term treatment study. The 8-week period comprised of a 4-week switching phase and a 4-week post-switch phase. For the antipsychotic switching schedule, brexpiprazole was first administered at 1 mg/day and increased to 2 mg/day by the end of week 4. Concurrently, the previous antipsychotic(s) was/were tapered gradually from the start of week 3 and discontinued by the end of week 4. Brexpiprazole could then be increased up to 4 mg/day according to the CGI-I criteria. At week 8, 1.8%, 23.2%, 25.0%, and 50% of patients were administered daily brexpiprazole doses of 1, 2, 3, and 4 mg, respectively. The discontinuation rate at week 8 was 17.0%. The major reasons for discontinuation were consent withdrawal (9.5%), occurrence of adverse events (5.5%), and physician's decision (2.0%). Commonly reported adverse events were nasopharyngitis (13.5%), schizophrenia (9.0%), insomnia (6.5%), headache (5.5%), and akathisia (5.5%). The discontinuation rate was 4.9% for patients who were switched from aripiprazole as the primary antipsychotic and 25.4% for those who were switched from other antipsychotics. Owing to the serious adverse events that led to treatment discontinuation, careful switching to brexpiprazole is necessary in patients who previously used olanzapine as their primary antipsychotic.

[Preclinical pharmacological profiles and clinical efficacy of the novel antipsychotic drug brexpiprazole (REXULTI® Tablets 1†mg, 2†mg)].

Brexpiprazole (Rexulti®) is the second antipsychotic agent in the world with dopamine D2 receptor partial agonist which was developed by Otsuka Pharmaceutical Co. Ltd. It is categorized as 〝Serotonin- dopamine Activity Modulator (SDAM)〟 that regulates both serotoninergic and dopaminergic systems by acting as a partial agonist for serotonin 5-HT1A receptors and D2 receptors and as an antagonist for 5-HT2A receptors. In preclinical pharmacological studies, brexpiprazole showed the equivalent antipsychotic-like effects to those of other atypical antipsychotics. And it was suggested that brexpiprazole has the low potentials to induce extrapyramidal symptoms, hyperprolactinemia and tardive dyskinesia, with improvement effects on cognitive dysfunction. Furthermore, brexpiprazole has the weak effects on histamine H1 receptors which are associated with sedation and weight gain in clinical. In the clinical trials in patients with schizophrenia in both acute and maintenance phase, brexpiprazole showed improvement of antipsychotic effects against placebo, and low incidence of adverse events, e.g., extrapyramidal symptoms, hyperprolactinemia, and weight gain, as suggested in preclinical studies. Furthermore, brexpiprazole showed low incidence of metabolic abnormalities. In particular, brexpiprazole showed relatively low incidences of akathisia, insomnia and agitation which has been commonly reported with aripiprazole. This would be based on the pharmacological features of brexpiprazole that is more potent antagonism at 5-HT2A receptors and D2 receptors partial agonism with lower intrinsic activity compared to those of aripiprazole. In conclusion, brexpiprazole could be one of the antipsychotics with the most rational mechanism of action, and the better efficacy and safety/tolerability profiles would contribute to the treatment of patients with schizophrenia.