Pharmacopsychiatry
January 19, 2022
Hitoshi Sakurai, Kengo Yonezawa, Hideaki Tani et al.
35 citations
Nine antidepressant compounds with mechanisms beyond the monoaminergic hypothesis have shown positive results in phase II or III trials. AXS-05 (dextromethorphan and bupropion) and ansofaxine hydrochloride outperformed placebo in phase III trials for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, botulinum toxin A facial injection, prasterone, and casopitant each showed at least one positive phase II result. Ayahuasca produced a greater response rate than placebo at one week, suggesting rapid antidepressant effects. These novel compounds may expand treatment options if preliminary findings are confirmed.
Psychiatry and clinical neurosciences
December 1, 2024
Yohei Ohtani, Hideaki Tani, Kie Nomoto-Takahashi et al.
13 citations
In a double-blind randomized placebo-controlled trial with 34 Japanese patients suffering from treatment-resistant depression, intravenous ketamine (0.5 mg/kg) given twice a week for two weeks did not show a statistically significant advantage over placebo in reducing depression scores when all participants were analyzed together. However, among those who completed the full treatment protocol, ketamine led to a significantly greater reduction in depressive symptoms than placebo. Higher baseline depression severity and body mass index were linked to greater symptom improvement with ketamine. Adverse events were more common with ketamine but no serious events occurred. These results suggest ketamine may be effective for treatment-resistant depression across diverse ethnic groups.
Pharmacopsychiatry
July 30, 2023
Kengo Yonezawa, H. Uchida, T. Yatomi et al.
8 citations
Later age of depression onset is linked to a better treatment response three days after intravenous ketamine in adults with treatment-resistant depression. In a placebo-controlled, double-blind, randomized trial of 31 patients (13 women; average age 48.4 years), logistic regression showed that older age at onset positively correlated with response after three days. No associations were found between response and age, sex, baseline depression severity, or dissociative symptoms. Multiple regression found no factors significantly correlated with change in depression scores. The authors suggest that earlier onset may impair glutamatergic signaling and neuroplasticity, reducing ketamine's effectiveness.
Neuropsychopharmacology Reports
March 13, 2024
Kengo Yonezawa, Hideaki Tani, Shinichiro Nakajima et al.
5 citations
A Japanese version of the Mystical Experiences Questionnaire (MEQ30) has been developed to assess mystical experiences induced by psychedelics, which are being studied as potential treatments for mental illness. Two Japanese psychiatrists independently translated the original English questionnaire into Japanese, then reconciled the translations into a unified version. This version was back-translated into English and reviewed by the original authors through an iterative process until they approved the final back-translated version. The authorized Japanese MEQ30 is now available for use in psychedelic-assisted therapy research with Japanese speakers, though further studies are needed to evaluate its reliability and validity.
Journal of affective disorders
August 15, 2025
Yohei Ohtani, Hideaki Tani, Shiori Honda et al.
3 citations
About 30% of people with treatment-resistant depression respond to ketamine, but reliable predictors of response have been lacking. This study examined whether the ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex (dACC) could predict ketamine's effectiveness. In a double-blind randomized trial with an open-label extension involving 30 participants, a higher baseline Glx/GABA ratio in the dACC correlated with greater improvement in depression scores (measured by the HDRS-17). After ketamine treatment, a reduction in this ratio also correlated with symptom improvement. The findings suggest that an excitatory-inhibitory imbalance in the dACC may help predict which patients will benefit from ketamine therapy.
Neuropsychopharmacology Reports
March 13, 2024
Keisuke Kusudo, Hideaki Tani, Kengo Yonezawa et al.
2 citations
A Japanese version of the Ego-Dissolution Inventory (EDI) was developed through a translation and back-translation process following international guidelines. Two Japanese psychiatrists independently translated the original English EDI, reconciled differences, and had the resulting version back-translated into English. The original authors reviewed and approved the back-translated version after iterative revisions. The final Japanese EDI is intended to help assess ego-dissolution experiences during psychedelic-assisted therapy in Japanese-speaking populations. Further research is needed to test the reliability and validity of this new instrument.
Psychiatry and Clinical Neurosciences
February 26, 2026
Kengo Yonezawa, M. Hirata, Hiroaki Takano et al.
1 citation
Psilocybin, a classic psychedelic compound, is being reexamined as a treatment for psychiatric disorders after decades of legal restrictions. Clinical trials report therapeutic effects for major depressive disorder, depressive symptoms in life-threatening illnesses, and some substance use disorders, with phase III trials for depression underway. Short-term side effects are generally mild and transient, but long-term effects need investigation. Neuroimaging research, mainly using MRI and EEG, is limited and focused on MDD, though ongoing trials include broader studies. Regulatory frameworks vary; controlled use is permitted in Switzerland, parts of the US, Canada, and Australia. Challenges remain, including the need for larger blinded trials and standardized protocols.
Neuropsychopharmacology Reports
November 8, 2024
Hideaki Tani, Kengo Yonezawa, Keisuke Kusudo et al.
1 citation
A Japanese version of the Challenging Experience Questionnaire (CEQ) was developed to assess difficult aspects of psychedelic experiences in Japanese speakers. Following international guidelines for translation and cultural adaptation, two psychiatrists independently translated the original English CEQ into Japanese, reconciled the versions, and had them back-translated into English. The original authors reviewed the back-translation and approved the final version after revisions. The resulting questionnaire enables evaluation of challenging experiences during psychedelic-assisted therapy for Japanese-speaking populations, though further studies are needed to confirm its reliability and validity.
Psychiatry research. Neuroimaging
August 1, 2026
Kengo Yonezawa, Shinichiro Nakajima, Shuhei Shibukawa et al.
In patients with treatment-resistant depression, higher baseline levels of magnetic substances in the right nucleus accumbens and the left amygdala, measured by brain imaging, predicted a greater reduction in specific depressive symptoms after repeated ketamine infusions. The study included 17 Japanese patients and used a double-blind, randomized placebo-controlled design followed by an open-label phase. Baseline magnetic susceptibility in the right nucleus accumbens correlated with improvement in retardation symptoms, while baseline R2* in the left amygdala correlated with improvement in vegetative symptoms. These brain markers may help predict which patients will benefit from ketamine treatment.
Pharmacopsychiatry
July 7, 2026
Kie Nomoto, Yohei Ohtani, Taisuke Yatomi et al.
In a double-blind, randomized, placebo-controlled trial, 34 Japanese patients with treatment-resistant depression received four intravenous doses of either ketamine (0.5 mg/kg) or saline. No significant differences emerged between the groups on objective or subjective cognitive function measures. Among ketamine-treated patients, those who responded to treatment (at least 50% reduction on the Montgomery-Åsberg Depression Rating Scale) showed greater improvement in subjective cognitive function than non-responders. Participants with weaker inhibitory control at baseline experienced larger reductions in depressive symptoms after ketamine. Repeated ketamine administration did not worsen cognitive function compared to placebo, suggesting cognitive safety, and baseline cognitive control deficits may predict better treatment response.