Efficacy of a Combination Therapy for Difficulties Waking Up in Non-School-Attending Students

Abstract

School non-attendance due to difficulties waking up is increasing in Japan, and affected students are commonly diagnosed with orthostatic dysregulation (OD); however, OD-associated sleep problems are overlooked. To date, no sleep-medicine-based treatment for wake-up difficulties in non-school-attending students has been established. This study aimed to assess the efficacy of a novel combination therapy for these students. We assessed the combined effect of sleep hygiene guidance, low-dose aripiprazole administration (3 mg/day), and blue-light exposure on wake-up difficulty in 21 non-school-attending teenage patients. The patients were evaluated using sleep studies and questionnaires before and after treatment. The average subjective total sleep time calculated from sleep diaries before treatment in the patients was 10.3 h. The therapy improved wake-up difficulty by 85.7% and further improved school non-attendance by 66.7%. The subjective sleep time significantly decreased by 9.5 h after treatment (p = 0.0004). The self-rating Depression Scale and mental component summary of the 36-item Short-Form Health Survey significantly improved after treatment (p = 0.002 and p = 0.01, respectively). Wake-up difficulties were caused by the addition of a delayed sleep phase to the patients’ long sleep times. The novel combination therapy was effective in improving wake-up difficulty and mental quality of life in non-school-attending teenage students.

Aripiprazole disrupts cellular synchrony in the suprachiasmatic nucleus and enhances entrainment to environmental light–dark cycles in mice

“…Previous studies on human participants have indicated that patients diagnosed with certain psychiatric disorders accompanied by sleep disorders who received aripiprazole as part of treatment displayed improved daily sleep rhythms ( Takaki and Ujike, 2014 ; Matsui et al, 2017 ; Tashiro, 2017 ; Omori et al, 2018 ; Imanishi et al, 2021 ; Konishi et al, 2022 ). Prior to aripiprazole administration, many patients exhibited delayed sleep onset and sleep patterns similar to those of free-running rhythms ( Matsui et al, 2017 ; Tashiro, 2017 ).…”

“…Recent studies have reported that aripiprazole administration improves sleep disorder symptoms in humans, particularly those associated with rhythmic abnormalities ( Takaki and Ujike, 2014 ; Matsui et al, 2017 ; Tashiro, 2017 ; Omori et al, 2018 ; Imanishi et al, 2021 ; Konishi et al, 2022 ). In a case report, a female patient with delayed sleep-phase syndrome (DSPS) could entrain to environmental light–dark cycles following aripiprazole treatment, which improved daytime sleepiness and depressive mood ( Takaki and Ujike, 2014 ).…”

“…In a case trial involving 12 patients with DSPS who were treated with aripiprazole, sleep onset and offset as well as sleep midpoint were significantly advanced, and sleep duration was significantly shortened ( Omori et al, 2018 ). Moreover, aripiprazole, when administered in combination with blue light, has been shown to be effective in treating wake-up difficulties in young individuals, further suggesting the efficacy of the drug in improving adaptation to the external light–dark cycle ( Konishi et al, 2022 ). Taken together, these findings suggest that aripiprazole may serve as a potential therapeutic agent for sleep disorders, particularly circadian rhythm sleep disorders, such as DSPS.…”

Commentary: Aripiprazole disrupts cellular synchrony in the suprachiasmatic nucleus and enhances entrainment to environmental light–dark cycles in mice

“…Among circadian rhythm sleep-wake disorders (CRSWDs), delayed sleep-wake phase disorder (DSWPD) is particularly disabling for the youth. It has been reported that aripiprazole, a second-generation antipsychotic, advances the sleep phase in DSWPD (Takaki and Ujike, 2014;Tashiro, 2017;Omori et al, 2018;Konishi et al, 2022). Although this needs to be supported by further evidence, it may be a potent therapeutic option.…”