Efficacy of sofpironium bromide gel on clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia: double-blind, controlled crossover study.

BACKGROUND: Hypersalivation is a major side-effect of clozapine in patients with treatment-resistant schizophrenia. AIMS: We investigated the efficacy of topical anticholinergic formulation sofpironium bromide gel for improving hypersalivation in patients with treatment-resistant schizophrenia receiving clozapine. METHOD: A double-blind, controlled crossover study was conducted with sofpironium bromide gel and a placebo gel to treat clozapine-induced hypersalivation in 16 patients with treatment-resistant schizophrenia. Patients were randomly divided between groups A and B (each n = 8). Group A was treated with sofpironium bromide gel for 6 weeks, followed by a 2-week washout period and 6 weeks of placebo gel, after which they were observed for another 2 weeks. In contrast, group B was treated with placebo gel for 6 weeks, followed by a 2-week washout period, 6 weeks of sofpironium bromide gel and a 2-week observation period. One-minute saliva volume, objective salivation ratings (Drooling Severity and Frequency Scale and Nocturnal Hypersalivation Rating Scale) and subjective salivation ratings (Visual Analogue Scale) were assessed every 2 weeks. RESULTS: All patients completed the trials. Three patients reported mild, spontaneously resolved skin itching. Compared with baseline values, the 1-min saliva volumes of both groups were significantly decreased by approximately 30% at the second week of sofpironium bromide gel treatment (P < 0.001), and significantly decreased by >40% at the fourth and sixth weeks of treatment (P < 0.001). The effects were maintained for over 2 weeks even after the treatment was discontinued. CONCLUSIONS: We suggest that sofpironium bromide gel is effective in treating clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia.

Effects of electrical stimulation-induced resistance exercise training on white and brown adipose tissues and plasma meteorin-like concentration in rats.

Chronic endurance exercise training induces morphological and metabolic alterations including mitochondrial biogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT) in rodents. A myokine called meteorin-like (Metrnl) is associated with morphological and metabolic adaptation and increased in blood after acute resistance exercise. However, the effects of chronic resistance exercise training (RT), which aims to increase muscle mass and strength, on WAT and BAT are unclear. Therefore, we aimed to clarify the effects of RT on morphological and metabolic parameters in WAT and BAT and on plasma Metrnl concentrations. We applied electrical stimulation to both legs of rats as RT three times a week for 4 weeks. RT reduced adipocyte size in subcutaneous WAT but induced no changes in mitochondrial and thermogenesis proteins. In BAT, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protein levels and mitochondrial content markers were significantly higher in the RT group compared with the control group. A significant positive correlation was found between the expression of PGC-1α in BAT and plasma Metrnl concentrations. These results suggest that plasma Metrnl is associated with PGC-1α and mitochondrial biogenesis in BAT. This study describes a potential role of RT in preventing metabolic diseases via altering WAT and BAT and increasing plasma Mertnl concentrations.

A Questionnaire-based Study of the Views of Schizophrenia Patients and Psychiatric Healthcare Professionals in Japan about the Side Effects of Clozapine.

OBJECTIVE: It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. METHODS: Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. RESULTS: Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. CONCLUSION: Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan.

[Alteration of cerebral blood flow by modified electroconvulsive therapy in major depression].

BACKGROUND: Modified electroconvulsive therapy (mECT) aims to improve major depression, giving an electronic stimulation to a patient in order to make tonic-clonic convulsion. Elevation of regional cerebral oxygen saturation (rSO2) was reported just after stimulation. Increase of oxygen consumption in brain is compensated by increase of cerebral blood flow. Oxygenation and blood flow over the entire brain are evaluated by measuring rSO2 at forehead. We followed alteration of rSO2 at each mECT. METHODS: rSO2 was measured by INVOS 5100 (Edwards Lifesciences). Patients had Somasensor placed at the right and left forehead, rSO2 was measured from before and after mECT. After general anesthesia induction, patients were stimulated by Tymatron SYSTEM IV (Somatics, America). Intensity of stimulation was decided by a single psychiatrist. We showed rSO2 values as follows: before stimulation (before), minimum value after stimulation (mini) and maximum value after stimulation (max). Hamilton depression scale (HAM-D) was used for severity of depression. RESULTS: All patients showed improved HAM-D. The values of (max-before)/before of rSO2 increased at the end of the therapy. CONCLUSIONS: We suggested that the response of cerebral vasculatures for electroconvulsive stimulation was improved as depression was improved.

[A case of meningeal carcinomatosis due to the ethmoid sinus mucoepidermoid carcinoma].

We report here a 65-year-old man with ptosis, diplopia, and progressive lower limb muscle weakness without nasal symptoms. CA19-9 and CEA were elevated in the serum and cerebrospinal fluid (CSF), but Squamous Cell Carcinoma Antigen (SCC) was not. CA19-9-positive atypical cells were found in the CSF. A right ethmoidal tumor was discovered by paranasal CT and 18F-Deoxyglucose Positron Emission Tomography (FDG-PET) studies. The ethmoidal tumor invaded to the orbits and disseminated into the CSF space through the cribriform plate. Biopsy demonstrated that the paranasal tumor consisted of mucoepidermoid carcinoma. We report here the first case of meningeal carcinomatosis due to mucoepidermoid carcinoma in the ethmoid sinus.