Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.

AIM: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. METHODS: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. RESULTS: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. CONCLUSION: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

Neurophysiological profiles of patients with bipolar disorders as probed with transcranial magnetic stimulation: A systematic review.

AIM: Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations, highlighting the need for a better understanding of the neurophysiology of BD for early diagnosis and novel therapeutic strategies. DESIGN: Employing a systematic review approach of the PRISMA guidelines, this study assessed the usefulness and validity of transcranial magnetic stimulation (TMS) neurophysiology in patients with BD. METHODS: Databases searched included PubMed, MEDLINE, Embase, and PsycINFO, covering studies from January 1985 to January 2024. RESULTS: Out of 6597 articles screened, nine studies met the inclusion criteria, providing neurophysiological insights into the pathophysiological basis of BD using TMS-electromyography and TMS-electroencephalography methods. Findings revealed significant neurophysiological impairments in patients with BD compared to healthy controls, specifically in cortical inhibition and excitability. In particular, short-interval cortical inhibition (SICI) was consistently diminished in BD across the studies, which suggests a fundamental impairment of cortical inhibitory function in BD. This systematic review corroborates the potential utility of TMS neurophysiology in elucidating the pathophysiological basis of BD. Specifically, the reduced cortical inhibition in the SICI paradigm observed in patients with BD suggests gamma-aminobutyric acid (GABA)-A receptor-mediated dysfunction, but results from other TMS paradigms have been inconsistent. Thus, complex neurophysiological processes may be involved in the pathological basis underlying BD. This study demonstrated that BD has a neural basis involving impaired GABAergic function, and it is highly expected that further research on TMS neurophysiology will further elucidate the pathophysiological basis of BD.

The Association between Electroencephalography with Auditory Steady-State Response and Postoperative Delirium.

Delirium is a disorder of consciousness and a risk factor for cognitive dysfunction and poor prognosis. We hypothesized that preoperative gamma activities would be linked to postoperative delirium. We enrolled 71 subjects for elective surgery and recorded auditory steady-state response (ASSR) by electroencephalography (EEG) before the surgery and examined postoperative delirium with DSM-5. The EEG data were analyzed for baseline power, and ASSR evoked power (EP) and phase-locking factor (PLF) within the gamma range. Postoperative delirium was found in 18 patients (delirium group) but not in 53 patients (non-delirium group). There were no significant differences in the 40-Hz EP or PLF between the two groups. The baseline gamma activity negatively correlated with the 40-Hz PLF in the non-delirium group (ρ = −0.444, p < 0.01). The correlation between baseline gamma activity and 40-Hz EP was not significant in either the delirium or non-delirium group. In all patients, both preoperative PLF and EP had no significant correlations with the Delirium Rating Scale Revised-98 and the Memorial Delirium Assessment Measure at the post-operation, respectively. The disruption of the neurophysiological relationship between baseline gamma activity before sound stimuli and the PLF of the 40-Hz ASSR may be one of the potential neurophysiological indicators associated with postoperative delirium.