金原 信久

22q11.2欠失症候群(以下,本疾患)は先天性心疾患や特徴的顔貌,そして精神疾患の合併が多いことで知られている。今回我々は,神経発達症や統合失調症として治療が行われ,先天性心疾患の既往や特徴的顔貌を欠くも後に本疾患と診断された症例を経験したので報告する。症例は20代前半女性。薬物療法を行うも,精神病症状,特に爆発性や衝動性を伴う滅裂な言動は改善せず,治療に難渋した。本疾患を疑い遺伝子診療科にコンサルトしたが,先天性心疾患の既往と特徴的顔貌を欠き疑いにくいとされた。翌年再度コンサルトを行い,遺伝子検査で本疾患との診断が確定した。本疾患は先天奇形の既往がないと診断されにくいとの報告があり,本邦で本症例のような経過での報告は,管見の限り初出である。先天奇形の既往が無くとも,神経発達症と精神病症状が存在し,特に爆発性や衝動性を伴う精神運動興奮が前景に立つ場合には,本疾患を鑑別することが望ましい。(著者抄録)

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 two 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 three agents: -4.10, -2.80 and -1.65 mg in diazepam-equivalent dose in the SUV, LEM and RMT groups, respectively. Dose reduction was significantly greater in the DORA than the RMT group (F=15.053, P<0.001). Within the DORA group, dose reduction was significantly greater in patients taking SUV than those taking LEM (F=4.337, P=0.043). 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 one 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.

Background: Several studies have reported that a switch to the dopamine partial agonist (DPA) aripiprazole (ARP), especially when the switch is abrupt, is likely to fail and sometimes worsen psychosis in schizophrenia patients already under high-dose antipsychotic treatment. Such a switching failure is speculated to be related to be the dopamine supersensitivity state. The risks of switching to the DPA brexpiprazole (BREX) have not been reported. Aims and Methods: We retrospectively analyzed the cases of 106 patients with schizophrenia to identify any factors related to the success or failure of switching to BREX. Results: The comparison between the patients with dopamine supersensitivity psychosis ( n = 44) and those without ( n = 62) revealed no significant difference in the switching failure judged at the sixth week. A comparison of the patients with successful switching ( n = 80) and those who failed ( n = 26) revealed that patients with treatment-resistant schizophrenia (TRS) were significantly more likely to fail. A logistic regression analysis also revealed that patients with past failure of switching to ARP are likely to succeed in switching to BREX. The 2-year follow-up of the patients with successful switching to BREX suggested that the patients who were treated with BREX, even temporarily, experienced some improvement in their Global Assessment of Functioning and Clinical Global Impression-Severity scores. Conclusions: Overall, the results indicate that patients with schizophrenia can be switched more safely to BREX compared to ARP. However, the failure of switching to BREX could be higher in patients with TRS, and thus, starting BREX treatment in refractory patients warrants careful monitoring.