Masahiro Takeshima

Total sleep deprivation followed by sleep phase advance and bright light therapy in drug-resistant mood disorders

BACKGROUND Drug-resistant depression is a major therapeutic issue in psychiatry and the development of non-drug therapies that treat drug-resistant depression is required. Sleep deprivation (SD) is a non-drug treatment classified as a form of chronotherapy in addition to bright light therapy (BLT) and sleep phase advance (SPA). Combined chronotherapy is hypothesized to improve drug-resistant depression. In this study, we investigated the benefits of total sleep deprivation (TSD) followed by SPA and BLT in drug-resistant depression alongside ongoing antidepressant medication and observed the added effectiveness of the combined chronotherapy. METHODS Thirteen drug-resistant inpatients affected by a major depressive episode were studied. They were treated by TSD followed by SPA (three days) and BLT (five days) with ongoing drug treatment. Effectiveness was rated using the Hamilton Rating Scale for Depression (HAM-D), the Zung Self-Rating Depression Scale (SDS), and the Visual Analogue Scale (VAS) over 3 weeks. RESULTS Significant improvements of depressive symptoms were observed in both objective mood ratings (HAM-D) and subjective mood ratings (SDS and VAS). Eight out of 13 patients maintained this responsiveness (50% or greater changes in HAM-D) across the study period. Moreover, no patients dropped out of the combined chronotherapy procedure. LIMITATIONS The study did not have a placebo group, and more subjects may be needed. CONCLUSION The trial of combined chronotherapy successfully induced rapid improvement in depressive symptoms in drug-resistant patients without early relapse or obvious side effects.

Lamotrigine-Induced Disseminated Intravascular Coagulation With Anticonvulsant Hypersensitivity Syndrome: A Case Report

Received January 15, 2016; revised February 24, 2016; accepted February 26, 2016. From Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan (MT, HI, TS); Department of Dermatology and Plastic Surgery, Akita University Graduate School of Medicine, Akita, Japan (AT, MM). Send correspondence and reprint requests to Masahiro Takeshima, M.D., Ph.D., Department of Neuropsychiatry, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita-shi, Akita 010-8543, Japan; e-mail: m. takeshima@med.akita-u.ac.jp & 2016TheAcademy of PsychosomaticMedicine. Published by Elsevier Inc. All rights reserved. Dr Shimizu has received research support from KAKEN (15K09821). Dr Manabe has received research support from KAKEN (26461679). Case Report

Core body temperature rhythms in circadian rhythm sleep disorder, irregular sleep-wake type

JAPAN HAS A relatively high prevalence rate of death due to suicide, with more than 30 000 suicides every year since 1998. According to Nagasaki prefecture health office, in the last decade, there has been a high prevalence of suicide among middle-aged men, with debt and/or losing one’s job being listed as one of the major causes. Previous studies have suggested several ways of relieving stress among Japanese people, but effective approaches to increase resilience as a means of preventing suicide among Japanese middle-aged men are yet to be established. The authors conducted this study to determine to what extent bars and izakaya pubs can contribute to mitigating stress among middle-aged Japanese men by providing a place for them to de-stress. A self-administered questionnaire was posted to masters of a total of 260 bars and izakaya pubs registered in Ohmura-city, Nagasaki prefecture, in December 2009. The questionnaire collected information on demographic characteristics, years of experience of working in bars and izakaya pubs, experience of being asked for advice on personal matters by their customers 40 years old, and the kinds of matters on which they were asked to advise. In total, 84 returned the completed questionnaires. A further 19 participated in telephone interviews using the same questionnaire, which was conducted with those who did not initially respond. In total, 103 respondents were included in the analysis. Half of the respondents from bars were 60 years old, and 43 (68.3%) had 10 years of experience working in bars. The most frequent matters that they were asked to listen to and give advice on were those related to work (56.3%). Regardless of respondent sex and age, those respondents with longer working histories in bars and izakaya pubs had a higher likelihood of experience of customers consulting them about debts/loans (adjusted odds ratio: 5.48, P < 0.05). Having a place to complain and to receive counseling could potentially mitigate stress in critical situations. Bars and izakaya pubs with masters with more years of experience may function as one possible avenue of stress mitigation by providing such a place where middle-aged men could consult on various issues such as debts/loans, and thereby potentially play the role of gate-keeper to prevent suicide.

Orexin/hypocretin levels in the cerebrospinal fluid and characteristics of patients with myotonic dystrophy type 1 with excessive daytime sleepiness

Purpose Myotonic dystrophy type 1 (DM1) is often characterized by excessive daytime sleepiness (EDS) and sleep-onset rapid eye movement periods caused by muscleblind-like protein 2. The EDS tends to persist even after treatment of sleep apnea. We measured the cerebrospinal fluid (CSF) orexin levels in DM1 patients with EDS and compared the clinical characteristics with narcolepsy type 1 and idiopathic hypersomnia (IHS) patients. Patients and methods We measured the CSF orexin levels in 17 DM1 patients with EDS and evaluated subjective sleepiness using the Epworth Sleepiness Scale (ESS), objective sleepiness using mean sleep latency (MSL), and sleep apnea using apnea-hypopnea index (AHI). We compared the ESS scores and MSL between decreased (≤200 pg/mL) and normal (>200 pg/mL) CSF orexin group in DM1 patients. Furthermore, we compared the CSF orexin levels, ESS scores, MSL, and AHI among patients with DM1, narcolepsy type 1 (n=46), and IHS (n=30). Results Seven DM1 patients showed decreased CSF orexin levels. There were significant differences in the ESS scores and MSL between decreased and normal CSF orexin groups in DM1 patients. The ESS scores showed no significant difference among patients with DM1, narcolepsy type 1, and IHS. The MSL in DM1 and IHS patients were significantly higher than narcolepsy type 1 patients (p=0.01, p<0.001). The AHI in DM1 patients was significantly higher than narcolepsy type 1 patients (p=0.042) and was insignificantly different from IHS patients. The CSF orexin levels in DM1 patients were significantly lower than IHS patients and higher than narcolepsy type 1 patients (p<0.001, p<0.001). Conclusion The CSF orexin levels of DM1 patients moderately decreased compared to those of IHS patients as the control group. However, the EDS of DM1 patients may not be explained by only orexin deficiency.

A case of perampanel-induced delirium in a patient with symptomatic epilepsy

Perampanel (PER) is a new antiepileptic drug that suppresses neuronal hyperexcitability by selectively and non-competitively inhibiting AMPA receptors. Previous reports have indicated that antiepileptic drugs place patients at risk for the onset of delirium [1]; however, to date, there have been no reported cases of delirium associated with PER use. In the present report, we discuss a case of symptomatic epilepsy in which delirium appeared following administration of PER and completely resolved following discontinuation of PER. Written consent has been obtained from the patient for the publication of this case report.

Low dose of aripiprazole advanced sleep rhythm and reduced nocturnal sleep time in the patients with delayed sleep phase syndrome: an open-labeled clinical observation

Objectives Delayed sleep phase syndrome (DSPS) is a chronic dysfunction of circadian rhythm of the subject that impairs functioning in social, occupational, or other spheres. High rate of depression is found among DSPS patients. Aripiprazole (APZ), a second-generation antipsychotic, is effective in treatment of depression as well as schizophrenia. Recently, few case reports show the effectiveness of APZ in treating DSPS and non-24-hour sleep–wake rhythm disorder. Therefore, we tried to treat DSPS with depression using APZ. Methods Twelve subjects (including four women) aged 19–64 years were included. The subjects were prescribed initially 0.5–3 mg of APZ once a day with subsequent dose adjustments. Results Sleep onset, midpoint of sleep, and sleep offset were significantly advanced by 1.1, 1.8, and 2.5 hours, respectively. Unexpectedly, sleep duration became significantly shorter by 1.3 hours after treatment. Their depressive moods showed an unremarkable change. Conclusion Low dose of APZ advanced the sleep rhythm and reduced nocturnal sleep time in the subjects with DSPS. Since it is not easy for physicians to treat prolonged sleep duration often associated with DSPS, this medication would become a new therapeutic option for these patients.

Inpatient phase-advance therapy for delayed sleep–wake phase disorder: a retrospective study

Purpose The efficacy of inpatient phase-advance therapy among patients with delayed sleep–wake phase disorder (DSWPD) has not been adequately investigated because response rates are considered low. We aimed to examine the efficacy of such treatment in this patient population. Patients and methods: The present retrospective study included data from 66 patients with DSWPD who had been admitted to Akita University Hospital for inpatient phase-advance therapy between September 1, 2005, and April 30, 2018. DSWPD was diagnosed based on the International Classification of Sleep Disorders, 3rd edition, criteria using electronic medical records. We examined remission rates during inpatient therapy as well as relapse rates at the time of the first outpatient examination following discharge. Univariate analysis was performed to investigate predictive factors for postinpatient therapy relapse. Results The rate of DSWPD remission over the course of inpatient phase-advance therapy was 100% (95% CI: 95.6%–100%), with a median duration of 1 day (IQR: 1–2 days; range: 1–9 days) until remission. The rate of relapse following discharge was 45.8% (95% CI: 32.7%–59.2%). Univariate analysis indicated that the rate of relapse was significantly higher for minors (under 18) than adults (18 and over), for those whose age at onset was below 16 years than for those whose age at onset was 16 or above, and for those with relatively low motivation for their occupation (P=0.0339, P=0.0136, and P<0.001, respectively). Conclusion The rate of DSWPD remission under inpatient phase-advance therapy was remarkably high (100%), while the rate of relapse after discharge was ~50%. Further studies are required to determine the long-term prognosis of inpatient therapy, risk factors for relapse, and the types of treatment most effective for preventing relapse.

Successful Management of Clozapine-induced Akathisia with Gabapentin Enacarbil: A Case Report

The management of clozapine (CLZ)-induced adverse events affects patient prognoses. Akathisia is a relatively rare adverse event related to CLZ administration and thus the management of this syndrome is not well established. Here, we report a case of treatment-resistant schizophrenia wherein CLZ-induced akathisia was successfully managed with gabapentin enacarbil (GE). The patient was a 39-year-old woman who had been treated with atypical antipsychotics other than CLZ for three years with poor tolerability. Initiation of CLZ (400 mg/day) attenuated her psychotic symptoms, but was followed by moderate akathisia. Neither benzodiazepines nor biperiden improved the akathisia; however, akathisia was finally diminished with co-administration of GE. GE facilitated a dosage increase in CLZ (450 mg/day) for the improved management of pyschotic symptoms, and thus indirectly contributed to treatment of the patient’s schizophrenia. We suggest that GE is a useful candidate for the management of CLZ-induced akathisia. The improved management of treatment-induced akathisia and other adverse events can extend the potential application of CLZ for treatment-resistant schizophrenia.