The Effect of Pharmacist-led Psychiatric Pharmacotherapy Conferences on the Appropriate Use of Antipsychotics.

The Hakodate Watanabe Hospital has held pharmacist-led multidisciplinary psychiatric pharmacotherapy conferences since September 2013 in order to optimize pharmacotherapy. The effects of holding regular conferences on the correction of high-dose antipsychotic polypharmacy, prevention and reduction of adverse reactions to antipsychotics, and reduction of the drug costs were investigated in psychiatric inpatients prescribed 4 or more antipsychotics. The results revealed that the number of antipsychotics and number of all drugs were significantly reduced by 1, the chlorpromazine (CP)-equivalent dose was significantly reduced by approximately 350 mg, and the drug costs were significantly reduced by 176.5 yen/d. In regard to the effects on the laboratory test data, the blood glucose and hemoglobin A1c (HbA1c) levels were significantly reduced. In addition, 84.8% of the patients were assessed as "unchanged" using the Clinical Global Impression of Change (CGI-C), indicating the absence of any significant changes in the severity of the clinical psychiatric symptoms. The results confirm that psychiatric pharmacotherapy conferences are effective for promoting appropriate use of antipsychotics, reducing the incidence of metabolic adverse reactions, such as elevation of the blood glucose, and also reducing the drug costs. The above results suggest that psychiatric pharmacotherapy conferences encourage psychiatric medical teams to adjust prescriptions while sharing information, and are effective for optimizing pharmacotherapy.

Use of psychotropics and the risk of falls in hospitalized psychiatric patients.

As hospitalized patients in psychiatry departments are often prescribed multiple psychotropics depending on their psychiatric symptoms, psychotropics are considered as important factors potentially associated with a high risk of falls. In this study, we attempted to investigate, from the aspect of drug prescription, to what degree the number and doses of psychotropics must be adjusted in order to reduce risk of falls in hospitalized psychiatric patients. The subjects were 526 patients, consisting of a fall group of 313 patients, who had experienced 1 to 5 falls (510 events) and a control group of 213 patients who had never experienced falls. Multiple logistic regression analysis was performed to determine the correlations between the occurrence of falls and the number and doses of psychotropics. The results showed that the risk of falls increased with increasing number of antipsychotics and anxiolytics/hypnotics prescribed, with the risk increasing, by 3.75-fold with the increase in the dose of chlorpromazine (CP)-equivalents to more than 600 mg, by 2.08-fold when the dose of diazepam (DAP)-equivalents to more than 15 mg, and by 7.80-fold with increase in CP-equivalents to more than 600 mg concomitantly with an increase in DAP-equivalents to more than 15 mg. In addition, a tendency towards increase in the frequency of falls was observed when more than 5 psychotropics were prescribed concomitantly. The above results suggested that the risk of falls may be reduced by appropriately adjusting the number of drugs and the doses of psychotropics used in the treatment of psychiatric disorders.

Differential effects of familial parkinson mutations in LRRK2 revealed by a systematic analysis of autophosphorylation.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified in pedigrees of autosomal-dominant familial Parkinson's disease (PARK8). It has been shown that the kinase activity of LRRK2 is required for its neuronal toxicity, although how familial Parkinson mutations affect the function of LRRK2 has not been well characterized. In the present study, we systematically characterized the autophosphorylation of LRRK2 by phosphopeptide mapping and identified Thr1348, Thr1349, and Thr1357 as the major autophosphorylation sites. We found that the autophosphorylation at Thr1357 is downregulated by the Y1699C mutation, possibly through a conformational alteration of the ROC domain. We also found that I2020T mutant LRRK2 undergoes excessive autophosphorylation in cell lysates in vitro at a low concentration of ATP. These results highlight the differential effects of familial mutations in LRRK2 on its conformation and enzymatic properties.

Genetic and chemical comparison of Boi (Sinomeni Caulis et Rhizoma) and Seifuto (Caulis Sinomenii).

Boi and its original plant Sinomenium acutum from Japan were compared with Seifuto and its botanical origins from China in terms of their internal transcribed spacer (ITS) sequences and major chemical components. Boi, Seifuto, and their botanical origins overall showed seven variable sites in the ITS sequence and six genotypes. Japanese S. acutum and Boi had one nucleotide variation at position 593 to show two genotypes (J1 and J2) and their heterozygote (J3). Seifuto samples and their botanical origins, S. acutum and S. acutum var. cinereum from China, showed three genotypes (C1, C2, and C3), which did not agree with the botanical classification, indicating that they cannot be distinguished according to their ITS sequences. All Seifuto samples from Henan market showed the same ITS genotype (C1). The Japanese and Chinese genotypes differed in the nucleotide position 424, which can be used to distinguish the country of origin of these materials. In the HPLC analysis of six major components, sinomenine (1), magnoflorine (2), menisperine (3), 6-O-methyllaudanosoline glucoside (4), liriodendrin (5), and menisdaurin (6), all were detected in Boi, whereas five (all except for menisdaurin) were detected in Seifuto. The main component in the rhizome of Seifuto was sinomenine, whereas magnoflorine was the main component in the rhizome and the climbing stem of Boi. The content of sinomenine in Seifuto was almost twice that in Boi. Although the individual content of alkaloids 1-4 differed between Boi and Seifuto, the total contents of these alkaloids were comparable between them both in the climbing stem and rhizome.