橘 真澄

STUDY OBJECTIVES: Although novel hypnotics have recently emerged, there are currently no data comparing the clinical potency of benzodiazepine receptor agonists (BZRAs) and novel hypnotics, or the effectiveness of different methods of switching between them. This study examined how novel hypnotics might help reduce BZRA use in real-world practice. METHODS: 289 patients with psychiatric disorders who took BZRAs for over 1 year before switching to either of 2 dual-orexin receptor antagonists (DORAs; suvorexant [SUV] or lemborexant [LEM]) or a melatonin receptor agonist (ramelteon [RMT]) were enrolled. We collected data on BZRAs at baseline and 3 months after commencement of SUV/LEM/RMT. RESULTS: Significant reductions in BZRAs were observed for all 3 agents: -4.10, -2.80, and -1.65 mg in diazepam-equivalent doses in the SUV, LEM, and RMT groups, respectively. Dose reduction was significantly greater in the DORA than the RMT group (F = 15.053, P < .001). Within the DORA group, dose reduction was significantly greater in patients taking SUV than those taking LEM (F = 4.337, P = .043). The switching success rate did not differ among the switching methods for any of the hypnotics. CONCLUSIONS: The reduction rate of BZRAs achieved by the switch fell into their equivalent-potency range estimated from clinical trials. The results suggest that DORAs can replace approximately 1 tablet of a BZRA. The difference in dose reduction between DORAs and RMT reflected the greater sleeping potency of the DORAs, whereas that between SUV and LEM might have reflected patient backgrounds: patients taking LEM may have been more strongly dependent on BZRAs. CITATION: Tachibana M, Kanahara N, Oda Y, Hasegawa T, Kimura A, Iyo M. A retrospective clinical practice study comparing the usefulness of dual-orexin receptor antagonists and a melatonin receptor agonist in patients switching from long-term benzodiazepine receptor agonists. J Clin Sleep Med. 2024;20(4):603-613.

AIM: The spread of the novel coronavirus infection (coronavirus disease 2019 [COVID-19]) has caused behavioral changes and mental illness in patients and their attendants during its early phase. The present study aimed to examine the association between precautionary behaviors against COVID-19 and psychosocial factors in outpatients with pre-existing disease and their attendants. METHODS: We conducted a cross-sectional paper-based questionnaire survey in Chiba University Hospital on 1019 patients and 513 attendants, and a web-based questionnaire survey in Japan on 3981 individuals from the general population. We evaluated the participants' anxiety about COVID-19, depression, health anxiety, and precautionary behaviors. RESULTS: Regarding knowledge and anxiety about COVID-19, the protective factors for the high precautionary behaviors group were knowledge of COVID-19 (odds ratio [OR] = 1.178, 95% confidence interval [CI]: 1.099-1.263), anxiety about the spread of COVID-19 (OR = 1.348, 95% CI: 1.243-1.461), and anxiety about infecting someone with COVID-19 (OR = 1.135, 95% CI: 1.039-0.239). Regarding psychosocial factors, the protective factors for the high precautionary behaviors group were patients (OR = 1.759, 95% CI: 1.056-2.929), their attendants (OR = 3.892, 95% CI: 1.416-10.700), health anxiety (OR = 2.005, 95% CI: 1.451-2.772), and nondepression states (OR = 1.368, 95% CI: 1.004-1.864). CONCLUSION: Our findings suggest that patients and their attendants may perform high precautionary behaviors. Health anxiety and nondepression states may be associated with high precautionary behaviors.

BACKGROUND: Accumulating evidence has shown that valproate has the greatest teratogenic potential for increasing the risk of major congenital malformations, such as neural tube defects, cleft palate, and neurodevelopmental disability. Although valproate is a pharmacological option for acute mania and is used as a stabilization drug for patients with bipolar disorder, some global guidelines state that valproate should not be used for girls or women of childbearing age with bipolar disorder. We investigated patterns in psychiatrists' prescription of valproate for bipolar female patients of childbearing age in Japan. METHODS: From March to May 2018, we conducted a questionnaire survey among psychiatrists from all prefectures in Japan on psychiatric practice as it relates to major depression and bipolar disorder throughout women's life. The questionnaire had two parts: (1) assessment of participating psychiatrists' backgrounds and attitudes toward patients and (2) their patterns of prescription of psychotropics for female patients with mood disorders across generations and periods of pregnancy. Each question item had four response options: "not at all," "rarely," "sometimes," and "frequently." We examined patterns of prescription for childbearing-aged women (late adolescence/young adulthood aged 18-24 years, childbearing-age, older adults aged 25-49 years) and pregnant women. RESULTS: In total, 571 psychiatrists (427 males, 123 females, and 21 unknowns) responded appropriately to the questionnaire, including 320 who examined at least one or more late adolescence/young adulthood bipolar women. Approximately 70% of psychiatrists answered that they frequently or sometimes prescribed valproate for bipolar women of childbearing age [late adolescence/young adulthood: not at all, n = 23 (7.5%); rarely, n = 69 (22.5%); sometimes, n =116 (37.8%); and frequently, n = 99 (32.2%); childbearing-age, older adults: not at all, n = 13 (2.7%); rarely, n = 67 (13.8%); sometimes, n = 185 (38.1%); and frequently, n = 220 (45.4%)]. The proportion of general hospital psychiatrists who answered "not at all" or "rarely" to the frequency of their valproate prescriptions was higher than that of psychiatrists working in other medical facilities (χ 2(3) = 18.2, p < 0.001). CONCLUSION: Most psychiatrists frequently or sometimes prescribe valproate for women of childbearing age in Japan.

BACKGROUND: Pregnant and postpartum women with psychosocial problems are prone to face limited or absent perinatal functional support from biological grandmothers due to familial dysfunction. The study aimed to investigate whether the involvement and presence of biological maternal grandmothers providing practical support for their pre/postnatal daughters (ie, pregnant women) during the perinatal period may influence the number of support services provided by multidisciplinary agencies, including child consultation centers and municipal offices. PARTICIPANTS AND METHODS: This is a retrospective cohort study based on the medical records of all pregnant women with psychosocial problems that visited, gave birth, and received intervention from the hospital-based child protection unit at the Chiba University Hospital between February 2018 to March 2019. The primary outcome was to identify whether there was a difference in the number of multidisciplinary agencies providing perinatal support between pregnant women with and without the presence of functional support from biological maternal grandmothers during the perinatal period. RESULTS: We identified 114 pregnant and postpartum women with psychosocial problems. Seventy-six of these participants (66.7%) had functional support from their biological maternal grandmothers during the perinatal period, and 38 participants (33.3%) did not. The number of agencies involved with participants who lacked functional support was significantly higher than participants with functional support (t(55.14) = 2.98, p < 0.01). This finding was consistent among pregnant and postpartum primipara participants (n = 70) (t(68) = 3.87, p < 0.001), but not multipara (n = 44). CONCLUSION: The findings indicate that the presence and functional support of biological maternal grandmothers influence the support that is needed from multidisciplinary perinatal support systems by pregnant and postpartum women with psychosocial problems. Primipara mothers without support from their own mothers may need greater multidisciplinary support.

BACKGROUND: Child abuse and/or neglect is a serious issue, and in many cases, parents are the perpetrators. Hospital-based child protection teams (CPTs) play pivotal roles in the management of not only abused and/or neglected children but also of their parents; this is generally conducted through multidisciplinary practice. The aim of this study is to survey hospital-based CPT members to determine the professions they perceive to be most applicable to participation in CPTs. PARTICIPANTS AND METHODS: The participants were members of CPTs affiliated with hospitals that had pediatric emergency departments and which were located in Chiba Prefecture; specifically, 114 CPT members from 23 hospitals responded to this survey. The two main questionnaire items concerned are as follows: 1) each respondent's evaluation of conducting assessments, providing support, and implementing multidisciplinary collaborative practice in the treatment of abusive and negligent parents, and 2) each CPT member's opinion on the professions that are most important for CPT activities. An exploratory factor analysis (EFA) was performed to explore the factor structure of the data, and a correlation analysis was performed using the result obtained. RESULTS: The EFA returned two factors: multidisciplinary collaborative practice (α = 0.84) and assessment and support (α = 0.89). A correlational analysis showed that multidisciplinary collaborative practice had a positive correlation for obstetricians (r = 0.315, p = 0.001), neonatologists (r = 0.261, p = 0.007), midwives (r = 0.248, p = 0.011), and psychiatrists (r = 0.194, p = 0.048); however, assessment and support was only significantly correlated with midwives (r = 0.208, p = 0.039). CONCLUSION: This study showed that hospital-based CPT members highly evaluate multidisciplinary collaborative practice for the management of abusive and/or negligent parents, and they believe that, in addition to pediatric physicians and nurses, perinatal care and mental health professionals are the most important participants in advanced CPT activities.

OBJECTIVE: Dopamine supersensitivity psychosis (DSP) is one of the key factors contributing to the development of antipsychotic treatment-resistant schizophrenia (TRS). We investigated the efficacy of blonanserin, an atypical antipsychotic, for patients with TRS and DSP. METHODS: In this 12-month retrospective follow-up study, we investigated the cases of eight consecutive patients with unstable TRS and DSP treated with blonanserin as an add-on therapy. We examined changes in scores for the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-Severity of Illness (CGI-S) scale and the Global Assessment of Functioning scale (GAF) during the 12 months after the administration of blonanserin. RESULTS: The patients' total scores on the BPRS and GAF scores were significantly improved by 3 months at the latest. Positive BPRS and CGI-S scores were also improved by 6 months at the latest. The total chlorpromazine-equivalent doses of antipsychotics were significantly reduced from 1462.3±499.6mg to 794.1±642.8mg (p=0.001) after 12 months of blonanserin treatment, with a favorable safety and tolerability profile. CONCLUSIONS: Blonanserin may be a promising antipsychotic for the treatment of TRS and DSP.

BACKGROUND: This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. METHODS: We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24. RESULTS: Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P < 0.001; and 12.5 vs. 81.8 %, P = 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased (χ2 = 8.5, df = 3, P = 0.036) and serum mature BDNF levels were temporarily significantly decreased (F = 3.5, df = 2.4, P = 0.027) in the responders of both groups at week 24. CONCLUSION: This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.

BACKGROUND: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD. SUBJECTS AND METHODS: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0) received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS), Japanese version, and the Das-Naglieri Cognitive Assessment System (DN-CAS), Japanese version. RESULTS: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores) improved significantly (P<0.001). Furthermore, a comparison of baseline DN-CAS total scores and 4-week end-point scores showed a mild trend of improvement (P=0.093). Tipepidine was well tolerated, with no patients discontinuing medication because of side effects. CONCLUSION: Our pilot study suggests that tipepidine therapy may prove to be an effective alternative treatment for pediatric patients with ADHD. Nonetheless, more detailed randomized, double-blind trials are needed to confirm tipepidine's efficacy.