Factors associated with high‐dose antipsychotic prescriptions in outpatients with schizophrenia: An analysis of claims data from a Japanese prefecture

Abstract Background Antipsychotics are commonly prescribed in high doses in combination with multiple psychotropic drugs. This study focused on the high‐dose antipsychotic prescriptions in patients with schizophrenia, while aiming to identify their associations with patients’ characteristics and concurrent psychotropic prescriptions. Methods This cross‐sectional study used claims data from a prefecture in Japan, between October 2014 and March 2015, to investigate antipsychotic prescriptions in adult outpatients with schizophrenia. The objective variable was the presence/absence of a high‐dose prescription. The explanatory variables included sex, age (category), presence of comorbid conditions, and the use of psychiatrist's therapy. Results After exclusion, a total of 13 471 patients with schizophrenia were analyzed. The frequency of high‐dose prescriptions was higher in men, with chlorpromazine‐equivalent values highest in the age ranges of 45‐54 and 35‐44 years for men and women, respectively. Patients aged below 65 years with cerebrovascular diseases showed a decrease in high‐dose prescriptions. There was a high frequency of polypharmacy psychotropic drug use in combination with a high‐dose antipsychotic prescription in patients aged below 65 years. Conclusion High‐dose antipsychotics are often used in combination with several psychotropic agents in patients with schizophrenia. Our findings emphasize the need to evaluate the prescribing behavior of physicians to avoid high‐dose antipsychotic prescriptions for improved patient care

JNJ-56136379, an HBV capsid assembly modulator, is well-tolerated and has antiviral activity in a phase 1 study of patients with chronic infection

JNJ-56136379 (JNJ-6379), a capsid assembly modulator that blocks hepatitis B virus (HBV) replication, was well tolerated and demonstrated dose-proportional pharmacokinetics in healthy participants in part 1 of its first clinical trial. In part 2, we have evaluated the safety, pharmacokinetics, and antiviral activity of multiple doses of JNJ-6379 in patients with chronic HBV infection. We performed a double-blind study of 57 treatment-naïve patients with HB e antigen-positive or -negative (74%) chronic HBV infection without cirrhosis. Patients were randomly assigned to groups given JNJ-6379 at 25 mg (100 mg loading dose), 75 mg, 150 mg, or 250 mg or placebo daily for 4 weeks with an 8-week follow-up period. Twenty-three (56%) of 41 patients given JNJ-6379 had at least 1 adverse event (AE) during treatment, compared with 10 (63%) of 16 patients given placebo. No serious AEs were reported during the treatment period. Three patients (7%) given JNJ-6379 vs none given placebo had grade 3 AEs; of these, 1 patient (150 mg) also had an isolated grade 4 increase in the level of alanine aminotransferase that led to treatment discontinuation. JNJ-6379 exposure increased with dose, with time-linear pharmacokinetics. HBV-DNA and HBV-RNA decreased from baseline in patients receiving all doses of JNJ-6379, independently of viral genotype and HB e antigen status. On day 29, 13 (32%) of 41 patients had levels of HBV DNA below the lower limit of quantification. No clinically significant changes in levels of HB surface antigen were observed. In a phase 1 study of treatment-naïve patients with chronic HBV infection, all doses tested of JNJ-6379 were well tolerated, showed dose-dependent pharmacokinetics, and had potent antiviral activity in patients with CHB. The findings support a phase 2a study to evaluate JNJ-6379 ± nucleos(t)ide analogs in patients with chronic HBV infection, which is under way. ClinicalTrials.gov identifier: NCT02662712