Effect of Adenine on Clozapine-induced Neutropenia in Patients with Schizophrenia: A Preliminary Study

Ippei Takeuchi,Taro Kishi,Manako Hanya,Junji Uno,Kiyoshi Fujita,Hiroyuki Kamei 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.2

Objective: This study examined the utility of adenine for preventing clozapine-induced neutropenia. Methods: This retrospective study examined the effect of adenine on clozapine-induced neutropenia in patients with treatment- resistant schizophrenia and was conducted at Okehazama Hospital in Japan from July 2010 to June 2013. Adenine was available for use from June 2011 onwards. Twenty-one patients started receiving clozapine treatment from July 2010 to April 2011 (the pre-adenine adoption group), and 47 patients started receiving it from May 2011 to June 2013 (the post-adenine adoption group). The effects of adenine were assessed based on changes in the patients’ leukocyte counts and the frequency of treatment discontinuation due to clozapine-induced neutropenia. Results: Sixty-eight patients were treated with clozapine from July 2010 to June 2013. Of the 21 patients in the pre-adenine adoption group, 4 discontinued treatment due to clozapine-induced neutropenia, whereas only 2 of the 47 patients in the post-adenine adoption group discontinued treatment. The frequency of treatment discontinuation due to clozapine-induced neutropenia was significantly lower in post-adenine adoption group than in the pre-adenine adoption group (p=0.047). Conclusion: Adenine decreased the frequency of treatment discontinuation due to clozapine-induced neutropenia. Our data suggest that combined treatment with clozapine and adenine is a safe and effective strategy against treatment-resistant schizophrenia.

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

Ippei Takeuchi,Manako Hanya,Junji Uno,Yuhei Amano,Keiko Fukai,Kiyoshi Fujita,Hiroyuki Kamei 대한정신약물학회 2016 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.14 No.3

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.

Effect of Scopolamine Butylbromide on Clozapine-induced Hypersalivation in Schizophrenic Patients: A Case Series

Ippei Takeuchi,Tatsuyo Suzuki,Taro Kishi,Daisuke Kanamori,Manako Hanya,Junji Uno,Kiyoshi Fujita,Hiroyuki Kamei 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.1

Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0- 97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/ day) for 4 weeks. At the baseline and after 4 weeks’ treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients’ Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

Satisfaction Survey on Antipsychotic Formulations by Schizophrenia Patients in Japan

Masakazu Hatano,Ippei Takeuchi,Kanade Yamashita,Aoi Morita,Kaori Tozawa,Takashi Sakakibara,Genta Hajitsu,Manako Hanya,Shigeki Yamada,Nakao Iwata,Hiroyuki Kamei 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.4

Objective: To identify factors affecting adherence to medication, a subjective questionnaire survey was administered to schizophrenia patients regarding the prescribed antipsychotic formulations. Methods: We evaluated the patients’ satisfaction and dissatisfaction with prescribed antipsychotic formulations, and patients answered the Drug Attitude Inventory-10 Questionnaire (DAI-10). Inclusion criteria for patients are as follows: age between 20 and 75 years and taking antipsychotic agents containing the same ingredients and formulations, for at least 1 month. Results: In total, 301 patients answered the questionnaire survey. Tablets were found to be the most commonly used antipsychotic formulations among schizophrenia patients (n = 174, 57.8%), followed by long-acting injections (LAIs, n = 93, 30.9%). No significant differences in the formulation satisfaction level and DAI-10 scores were observed between all formulations. Formulations, except for LAI, were selected by physicians in more than half of the patients. Patients who answered “Decided by consultation with physicians” had significantly higher satisfaction levels and DAI-10 scores compared to those who answered “Decided by physicians” (4.11 ± 0.77 vs. 3.80 ± 1.00, p = 0.0073 and 6.20 ± 3.51 vs. 4.39 ± 4.56, p < 0.001, respectively). Satisfaction levels moderately correlated with DAI-10 scores (r = 0.48, p < 0.001). Conclusion: No formulation had a high satisfaction level in all patients, and it is important to be reflect the patients’ individual preferences in pharmacotherapy. Shared decision-making in the selection of the formulations is seen to be useful for improving medication adherence.

Acceptance of the Deltoid Muscle Injection of Aripiprazole Long-acting Injectable in the Patients with Schizophrenia

Hiroyuki Kamei,Yuki Homma,Ippei Takeuchi,Genta Hajitsu,Kaori Tozawa,Masakazu Hatano,Aiko Fukui,Manako Hanya,Shigeki Yamada,Nakao Iwata 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

Objective: To improve poor medication adherence in schizophrenic patients, long-acting injectable (LAI) antipsychotics are used. However, it has not yet become common in Japan. Recently, aripiprazole LAI was approved for alternative injection into the deltoid muscle in addition to the gluteal muscle. The acceptance for the proposal to switch from gluteal to deltoid injections of aripiprazole LAI was investigated. Methods: The subjects were 32 outpatients with schizophrenia who had continuously received aripiprazole LAI administration into the gluteal muscle for ≥ 6 months. In the patients who had continued deltoid injection for 3 months after switching, the changes in the pain and shame in comparison with gluteal injections were evaluated. Results: Switching to the deltoid injection was chosen by 17 out of 32 patients. Three months later, 9 patients were still receiving deltoid injections with highly rated satisfaction. The main reasons for switching to deltoid injections included the pain and shame associated with gluteal injections. The main reason for returning to the gluteal injection was the pain experienced from the injection in the deltoid. Conclusion: The option to select the injected area was based on the amount of pain in the deltoid and gluteal sites, leading to the widespread use of aripiprazole LAI.

Assessment of the Latent Adverse Events of Antipsychotic Treatment Using a Subjective Questionnaire in Japanese Patients with Schizophrenia

Masakazu Hatano,Hiroyuki Kamei,Azusa Kato,Ippei Takeuchi,Manako Hanya,Junji Uno,Shigeki Yamada,Kiyoshi Fujita,Nakao Iwata 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.2

Objective: The adverse effects of antipsychotic agents can have a marked influence on medication adherence. In this study, we investigated the adverse events of antipsychotics that are less likely to be reported by patients and the reasons why such symptoms remain latent. Methods: Data were collected by interviewing patients using a subjective questionnaire, and the associations between unreported symptoms and background factors were investigated. Results: A total of 306 patients with schizophrenia or schizoaffective disorder were examined. Their major symptoms were daytime sleepiness (50.0%), weight gain (42.2%), and sexual dysfunction (38.9%). Sexual dysfunction was nominal significantly more common among the patients that had been treated with antipsychotic agent polypharmacy (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.07 to 4.30), and was nominal significantly more common among outpatients (OR, 1.78; 95% CI, 1.02 to 3.13). Only approximately 30% of the patients had reported their symptoms to their physicians. Conclusion: Patients receiving antipsychotic treatment tolerate some symptoms and do not feel able to report them to their physicians. The most common reason for this is an insufficient patient-physician relationship. Sexual dysfunction is especially hard to identify because it is a delicate problem, and our findings demonstrate that subjective questionnaires are helpful for detecting such symptoms.