The antidepressant effect of zuranolone appears to be sustained beyond the treatment period in postpartum depression, whereas in major depressive disorder it may not persist after treatment discontinuation.
The antidepressant effect of zuranolone appears to be sustained beyond the treatment period in postpartum depression, whereas in major depressive disorder it may not persist after treatment discontinuation.
Aim: Recent neuropathological studies suggest that the accumulation of neurodegenerative disease-associated proteins in subcortical structures may contribute to mood symptoms. Animal models have highlighted the role of the paraventricular thalamic nucleus (PVT) in bipolar disorder (BD) pathophysiology. However, neuropathological investigations in the thalamus in BD remain limited. This study aimed to examine neurodegenerative pathology in the thalamus and medial temporal region including the hippocampus in patients with BD.
Methods: Postmortem brain tissues of the thalamus and medial temporal region of nine patients with BD and nine age-matched controls were obtained from Matsuzawa Hospital, with additional medial temporal samples of 14 BD cases acquired from the Stanley Foundation Brain Bank. Immunohistochemical analyses were performed using antibodies against phosphorylated tau, amyloid-β, α-synuclein, TDP-43, and granulovacuolar degeneration (GVD) markers including CHMP2B and CK-1δ.
Results: The 23 BD cases exhibited a significantly greater burden of tau pathologies, including higher neurofibrillary tangle Braak stages (P = 0.015) and more severe argyrophilic grain Saito stage (P = 0.029), compared with the nine controls. Notably, CHMP2B-positive GVD was significantly more frequently observed in the PVT of BD cases than in the controls (five of nine vs. zero of nine, P = 0.029).
Conclusions: These findings suggest that neurodegenerative processes, particularly tau pathology and CHMP2B-positive GVD in the PVT may play a role in BD pathophysiology.
Aim: This study aimed to evaluate the likelihood of discontinuing dual orexin receptor antagonists in patients continuously prescribed hypnotics using a large-scale claims database in Japan.
Methods: The cohort comprised 4422 patients identified from insurance claims data, who were newly prescribed a single hypnotic with more than three consecutive prescriptions over 3 months. The outcome was defined as the absence of a hypnotic prescription for 90 consecutive days after the final prescription. Kaplan-Meier and Cox proportional hazards analyses were used to compare the hazards of discontinuing hypnotics among four classes: benzodiazepines, non-benzodiazepines, dual orexin receptor antagonists, and melatonin receptor agonists, adjusting for age, sex, and the number of diagnostic categories based on the International Statistical Classification of Diseases, Tenth Revision.
Results: Kaplan-Meier analysis revealed significant differences among the hypnotic classes (P < 0.001), with dual orexin receptor antagonists demonstrating the highest rate of discontinuation. Multivariable Cox regression indicated a significantly higher likelihood of discontinuing dual orexin receptor antagonists than that of benzodiazepines (hazard ratio = 1.40; P < 0.001). Older age (hazard ratio = 0.995; P < 0.001) and a higher number of International Statistical Classification of Diseases, Tenth Revision diagnostic categories (hazard ratio = 0.975; P < 0.001) were significantly associated with a lower likelihood of discontinuation.
Conclusion: Dual orexin receptor antagonists are more likely to be discontinued than benzodiazepines after continuous hypnotic prescription, highlighting their potential clinical utility in insomnia treatment.
Aim: The aim was to explore the preventive effects of smartphone cognitive behavioral therapy (CBT) in addressing depression and anxiety in patients with recurrent pregnancy loss (RPL) due to lack of such previous studies.
Methods: This was an exploratory decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. A total of 432 patients with RPL were randomized and patients who completed the psychoeducation component of the app within 2 weeks of consent were included. Five CBT components-namely, self-monitoring, behavioral activation, cognitive restructuring, assertion training, and problem solving-were randomly assigned as present or absent, resulting in 25 = 32 combinations. The primary outcomes were changes in Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scores at weeks 8 and 12 from baseline.
Results: A total of 419 patients were analyzed. The presence or absence of specific CBT components did not significantly affect patient outcomes. However, patients experienced a statistically significant overall reduction in depressive symptoms from baseline to weeks 8 and 12. Pre-post effect sizes for overall improvement ranged from -0.30 to -0.38 at week 8 and from -0.22 to -0.33 at week 12. No significant overall reduction in anxiety symptoms was observed.
Conclusion: The CBT application significantly reduced depressive symptoms in patients with RPL; however, no specific CBT component showed superior effects. The findings did not indicate efficacy in comparison to the pure treatment-as-usual group. Further research is required to enhance its impact on anxiety and refine the selection and delivery of individual CBT components.

