Published papers

症例は52歳男性で、2週間前からの微熱と10日前からの顔面の浮腫を主訴に受診し、血液学的所見と尿検査からネフローゼ症候群による急性腎障害と診断された。発熱が持続し、異型リンパ球、胸腹部CT検査で脾腫を認めた。HIVウエスタンブロット法検査、HIV-PCR法により、HIV-1感染症と診断した。腎生検は施行しなかったが、HIV感染末期腎不全(ESRD)の原因として、一元的にHIV-associated nephropathy(HIVAN)と診断した。週3回の血液透析も併用し第6病目からARTをDRV/RTV+RALのNRTI sparing regimenで開始した。HIV-1 RNA量はART開始後第5週以降では検出感度以下に抑えられ、CD4リンパ球数は200個/μL前後で安定したが、腎機能はCKD stage 5のままであった。腎移植を行うこととなり、タクロリムス併用予定に伴い、その血中濃度に影響を及ぼしにくいABC/3TC+RALへ変更したが、ABCによる過敏反応を起こしたため、DRV/RTV+RALを再度使用した。免疫抑制剤を供用して腎移植を行い、現在まで特に問題なく経過している。

Objective: Constipation is often overlooked in patients with schizophrenia. We examined their awareness of constipation and whether they reported it to their psychiatrists. Method: Five hundred three inpatients with schizophrenia (International Classification of Diseases, 10th Revision) were interviewed about their recent bowel movements and evaluated for the diagnostic criteria for functional constipation. If constipation was present, patients were asked if they were aware of it and had reported it to their psychiatrists in charge. Additionally, their global psychopathology and functioning were assessed using the Clinical Global Impression-Schizophrenia (CGI-SCH) and the Global Assessment of Functioning (GAF), respectively. Results: The criteria for constipation were met by 184 patients (36.6%); of these patients, only 56.0% (103/184) were aware of it. Moreover, only 34 of the constipated patients (18.5%) reported its presence to their psychiatrists. No significant differences were found in the CGI-SCH overall severity or subscale scores or in the GAF scores between those patients who reported and those who failed to report constipation. Conclusions: The present study demonstrated that constipation was neither recognized nor reported to psychiatrists by a significant percentage of the patients. These findings underscore the importance of greater vigilance and active evaluation of constipation in patients with schizophrenia for appropriate clinical management. © 2013 Elsevier Inc.

Investigating and characterizing the degree and correlates of patient's trust in their treating psychiatrists across a range of psychiatric disorders is of a great clinical relevance to enhance our therapeutic alliance, which has not been addressed in the literature. In this study, outpatients who visited one of the participating psychiatric clinics in Tokyo, Japan between October and November, 2010 were asked to complete the Trust in Physician Scale (TPS), an 11-item self-report questionnaire. A univariate general linear model was used to examine the effects of the following variables on the TPS total score: age, sex, diagnosis, Global Assessment of Functioning score, educational background, physician's years of practice as a psychiatrist, duration of treatment with their current psychiatrists, sex concordance between patients and their psychiatrists, and whether patients were older than their psychiatrists. Five hundred and four patients were enrolled (mean ± SD age = 42.8 ± 13.6 years; 176 men; Psychiatric diagnoses (ICD-10): F0 [N = 8], F2 [N = 72], F3 [N = 252], F4 [N = 147], F6 [N = 22]). A duration of treatment with their current psychiatrist of ≥1 year and a duration of their physician's clinical expertise as a psychiatrist for ≥10 years were associated with a greater degree of patient's trust in their psychiatrist. Furthermore, patients with a F3 diagnosis showed a significantly higher TPS total score than those with F4. These findings underscore an importance of paying close attention to patients who are relatively new and are not treated by well-experienced psychiatrists in terms of subjective trust. Furthermore, this likely holds more true for patients with neurotic disorders. © 2011 Springer-Verlag.

Patients' attitudes toward side effects of antidepressants are likely to differ according to gender, which has not yet been fully addressed in the literature. From the 228,310 registrants, 1,305 participants who had received antidepressant drugs within the past year were identified with the Yahoo Japan research monitor through four-step screening procedures. Participants were asked as to which side effect(s) they had experienced, whether they had reported those side effects to their physicians, and whether they had taken any action to counteract them. The questionnaire was completed by 1,187 participants. Side effects were reported in 73.4% of the participants; the prevalence of self-reported side effects was significantly higher in men than women (80.4% vs. 68.3%, P <0.05). The percentage of participants who reported side effects to their physicians widely differed depending on the nature of their experience, ranging from 45.7% to 89.9%; the lowest was for sexual dysfunction. The percentage of participants who had taken any action to relieve side effects varied among side effects from 26.3% for sexual dysfunction to 89.5% for dry mouth. Moreover, a lower percentage of women had reported sexual dysfunction to physicians (36.6% vs. 60.7%, P <0.05) and had taken any action to counteract the problem (19.8% vs. 36.9%, P <0.05). Given that patients experienced with antidepressants are likely to be reluctant to report sexual side effects, physicians should be cognizant of the potential presence of sexual dysfunction in patients who are taking antidepressants, especially for women. © 2010 Springer-Verlag.

© Georg Thieme Verlag KG Stuttgart - New York. Introduction Data on the knowledge about antipsychotic medications prescribed in patients with schizophrenia are very limited. Moreover, it remains unclear how patients' knowledge about prescribed antipsychotics affects medication adherence. Methods ighty-one Japanese outpatients with schizophrenia according to the International Classification of Diseases, 10th edition, were included. Patients' knowledge of the primary antipsychotics prescribed to them in terms of therapeutic effects, type, and implicated neurotransmitters was assessed with a multiple-choice questionnaire developed for this study. Medication possession ratios (MPRs) were compared between patients who answered correctly and those who did not in each category. Results The percentages of subjects who answered correctly regarding antipsychotic effects, type, and implicated neurotransmitters were low at 30.9%, 30.9%, and 7.4%, respectively. No differences were found in MPRs between subjects who answered correctly and those who did not. Discussion Our preliminary results indicate that patients lack knowledge about their antipsychotic medications. More concerning, they suggest that knowledge about prescribed antipsychotics may not directly translate into actual medication adherence in patients with schizophrenia.

Background: Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods: In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period. Results: Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8). Conclusion: Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects. © 2009 Sawada et al; licensee BioMed Central Ltd.

© 2020 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd Objectives: The aim of this study was to develop a consensus guideline by certified experts of the Japanese Society of Clinical Neuropsychopharmacology on the psychopharmacological treatment for bipolar disorders I and II (BP-I and BP-II), in order to fill the gap in the literature and provide more concrete guidance for challenging and controversial real-world situations. Methods: Experts were asked to assess treatment options regarding 19 clinical situations of bipolar disorder with a nine-point Likert scale (one = “disagree” and nine = “agree”). According to the responses from 119 experts, the options were categorized into the first-, second-, and third-line treatments. Results: For the treatment of BP-I, lithium monotherapy was categorized as a first-line treatment for manic episodes (mean ± standard deviation score, 7.0 ± 2.2), depressive episodes (7.1 ± 2.0), and the maintenance phase (7.8 ± 1.8). Combination therapy of lithium and an atypical antipsychotic was endorsed for manic episodes (7.7 ± 1.7), depressive episodes with (7.1 ± 2.0) and without mixed features (6.9 ± 2.2), and the maintenance phase (6.9 ± 2.1). Similarly, in BP-II, lithium monotherapy was categorized as a first-line treatment for hypomanic episodes (7.3 ± 2.2), depressive episodes (7.0 ± 2.2), and the maintenance phase (7.3 ± 2.3), while combination therapy of lithium and an atypical antipsychotic was recommended for hypomanic episodes (6.9 ± 2.4).No antipsychotic monotherapy or antidepressant treatment was categorized as a first-line treatment for any type of episode. Conclusions: These recommendations reflect the current evidence and represent the experts' consensus on using lithium for the treatment of bipolar disorder. Clinicians should consider the effectiveness and adverse effects of antipsychotic and antidepressant medications for the treatment of bipolar disorder.

© 2020 Background: Clinically relevant issues in the real-world treatment of depression have not always been captured by conventional treatment guidelines. Methods: Certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology were asked to evaluate treatment options regarding 23 clinical situations in the treatment of depression using a 9-point Likert scale (1=“disagree” and 9=“agree”). According to the responses of 114 experts, the options were categorized into first-, second-, and third-line treatments. Results: First-line antidepressants varied depending on predominant symptoms: escitalopram (mean ± standard deviation score, 7.8 ± 1.7) and sertraline (7.3 ± 1.7) were likely selected for anxiety; duloxetine (7.6 ± 1.9) and venlafaxine (7.2 ± 2.1) for loss of interest; mirtazapine for insomnia (8.2 ± 1.6), loss of appetite (7.9 ± 1.9), agitation and severe irritation (7.4 ± 2.0), and suicidal ideation (7.5 ± 1.9). While first-line treatment was switched to either an SNRI (7.7 ± 1.9) or mirtazapine (7.4 ± 2.0) in the case of non-response to an SSRI, switching to mirtazapine (7.1 ± 2.2) was recommended in the case of non-response to an SNRI, and vice versa (switching to an SNRI (7.0 ± 2.0) in the case of non-response to mirtazapine). Augmentation with aripiprazole was considered the first-line treatment for partial response to an SSRI (7.1 ± 2.3) or SNRI (7.0 ± 2.5). Limitations: The evidence level of expert consensus is considered low. All included experts were Japanese. Conclusions: Recommendations made by experts in the field are useful and can supplement guidelines and informed decision making in real-world clinical practice. We suggest that pharmacological strategies for depression be flexible and that each patient's situational needs as well as the pharmacotherapeutic profile of medications be considered.

© 2014 © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. Background: Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. Objective: To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Data Sources: Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Study Selection: Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Data Extraction: Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Data Synthesis: Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to -3.17 kg (95% CI: -4.44 to -1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.

© Copyright 2017 Physicians Postgraduate Press, Inc. Objective: To compare symptom trajectories between placebo and active drug responders and to examine whether early placebo improvement would be associated with subsequent placebo response in the treatment of patients with behavioral and psychological symptoms of dementia. Methods: A post hoc analysis of data from 371 patients with DSM-IV Alzheimer’s disease in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer’s disease (CATIE-AD) (April 2001 to November 2004) was conducted. Patients were randomly assigned to double-blind treatment with olanzapine, quetiapine, risperidone, or placebo. Trajectories of change in Brief Psychiatric Rating Scale (BPRS) total scores were compared between placebo and active drug responders. The predictive power of improvement at week 2 for response at week 8 was investigated, and sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in BPRS total score at week 2 were calculated. Results: There were no significant differences in symptom trajectories between placebo and active drug responders. BPRS score reduction at week 2 was significantly associated with placebo response at week 8 (odds ratio = 1.13; P< .001). Use of a cutoff of 10% showed the highest accuracy of 0.67 (sensitivity, 0.63; specificity, 0.70). Conclusions: Symptom trajectories of improvement of behavioral and psychological symptoms of dementia follow the same pattern irrespective of treatment. A 10% improvement at week 2 was the most appropriate predictor of subsequent placebo response at week 8, which may indicate utility for the placebo lead-in phase to minimize future trial failures of treatment for noncognitive symptoms of Alzheimer’s disease.

© 2016, Springer-Verlag Berlin Heidelberg. Introduction: Dopamine D2 receptor occupancy levels needed for the maintenance treatment of schizophrenia remain to be elucidated. We examined 3-year clinical outcomes of patients with schizophrenia who received long-acting injectable risperidone (LAI risperidone) at baseline and investigated their dopamine D2 receptor occupancy levels, estimated from plasma drug concentrations. Methods: A chart review of 52 outpatients with schizophrenia who participated in the original cross-sectional study was conducted to examine their 3-year clinical outcomes between April and September 2015. Patients who continued outpatient treatment with LAI risperidone without any usage of concomitant chlorpromazine equivalent antipsychotic dosage at >200 mg/day for the 3-year period were asked to participate in the follow-up assessments that included the Brief Psychiatric Rating Scale (BPRS) and estimated dopamine D2 receptor occupancy levels at trough, using plasma concentrations of risperidone plus 9-hydroxyrisperidone. Data were compared with the same patients collected 3 years earlier. Results: Among the original 52 participants, 14 participants (27 %) continued outpatient treatment with LAI risperidone. Ten participants (19 %) provided plasma samples; mean ± SD measured trough concentration of risperidone plus 9-hydroxyrisperidone significantly increased from 22.9 ± 15.6 to 31.8 ± 17.5 ng/mL (P = 0.02). Estimated dopamine D2 receptor occupancy numerically increased from 63.0 ± 10.9 to 69.0 ± 11.0 % (P = 0.12). A significant worsening was observed in the BPRS total score among these patients (mean ± SD, 34.3 ± 12.7 to 46.5 ± 16.9, P = 0.003). Conclusion: Paradoxically, the increased plasma concentration was found to be associated with a significant worsening of the clinical outcome. More investigations are indicated to shed further light on optimal levels of D2 blockade in the maintenance treatment of schizophrenia.

Aspiration pneumonia is a serious health concern in older patients with schizophrenia. In this study, we examined clinical and demographic variables that could impact the plasma substance P level, which is a useful predictive biomarker of aspiration. Thirty-four patients were included (mean age ± SD: 70.9 ± 10.8 years). A greater number of cigarettes/day and a higher antipsychotic dosage were found to be associated with a lower plasma substance P level, while age showed a trend-level effect. This finding suggests the need for intensive observation for prevention of aspiration pneumonia in heavy smokers who are receiving a higher antipsychotic dose in this senior population. © 2011 Japanese Society of Psychiatry and Neurology.

© 2015 Elsevier B.V. Coordinated bodily balance is necessary to prevent falls, where postural sway and/or body inflexibility should be relevant. We aimed to assess postural sway and flexibility in patients with schizophrenia and identify clinical characteristics. Postural sway (length and range of trunk motion, and Romberg ratio) and flexibility (anteflexion in sitting) were measured in schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Drug Induced Extrapyramidal Symptoms Scale (DIEPSS) were used for the assessment of psychopathology and extrapyramidal symptoms, respectively. Characteristics associated with postural sway and flexibility were examined with regression analysis. A total of 100 patients (68 men, mean ± S.D. age: 49.3 ± 13.8 years, PANSS score: 83.4 ± 15.1, DIEPSS score: 2.2 ± 2.2) participated in this study. The anteflexion in sitting was not significantly correlated with length of trunk motion, range of trunk motion, or Romberg ratio. Postural instability was associated with higher DIEPSS overall severity score and PANSS positive symptoms. A significant correlation was also found between less flexibility and increased PANSS negative symptoms. In conclusion, flexibility and postural stability might be regarded as separate elements of physical fitness in schizophrenia. Prospective exercise intervention would be worthy of investigation to enhance postural stability and flexibility in an effort to prevent falls.

Measuring dopamine D2 receptor occupancy levels using positron emission tomography (PET) is still widely unavailable. The objective of this study was to evaluate the accuracy of predicting D2 occupancy from the antipsychotic plasma level in patients with schizophrenia. Positron emission tomographic studies that measured plasma levels of antipsychotics and their corresponding D2 occupancy levels were identified, using MEDLINE and EMBASE (last search: March 2010). Antipsychotics that were investigated in a total of 20 subjects or more were included. All data points for each antipsychotic were fit to a one-site binding model to estimate the total plasma concentration of each antipsychotic associated with a 50% occupancy (ED50) of brain D2 receptors. The mean prediction error and the root mean squared prediction error were used to measure the predictive performance of individual D2 receptor occupancies from plasma drug levels derived from a one-site occupancy model using an ED50 value calculated for each data point. A total of 34 treatment arms from 23 studies involving 281 subjects were included. The mean (95% confidence interval) prediction errors and root squared prediction errors were as low as 0.0 (-1.8 to 1.8) and 8.9 (7.6-10.2) for risperidone (n = 98); 0.0 (-3.5 to 3.5) and 15.1 (12.9-17.3) for clozapine (n = 75); -0.1 (-1.2 to 1.2), 0.0 (-1.9 to 1.9), and 4.6 (3.5-5.8) for olanzapine (n = 42); 0.1 (-3.4 to 3.5) and 9.9 (7.3-12.5) for haloperidol (n = 35); and -0.1 (-3.3 to 3.1) and 12.3 (8.8-15.7) for ziprasidone (n = 31), respectively. These findings suggest that D2 occupancy of antipsychotics could be estimated with a high degree of accuracy using widely available plasma levels. © 2011 Lippincott Williams & Wilkins.

The present study, including50patients with schizophrenia, demonstrated that antipsychotic plasma concentrations of risperidone and its active moiety can be predicted before performing an actual dosage change, using population pharmacokinetic techniques. These findings suggest that individualized dosing with the measurement of antipsychotic plasma concentrations could become a real clinical application in the management of schizophrenia.