Frontiers in psychiatry
January 1, 2025
Dimitri Perivoliotis, Kayla Knopp, Shannon Remick et al.
2 citations
Set and setting—the mindset a person brings to therapy and the environment in which it occurs—are foundational to MDMA-assisted therapy for PTSD and critically influence its efficacy. Drawing on experience conducting clinical trials in the Veterans Health Administration, this article describes advantages and challenges of implementing this intervention in large healthcare systems. Specific, practical suggestions are offered for optimizing set and setting from both participant and clinician perspectives, aiming to leverage opportunities and adapt to challenges. These recommendations are intended to inform future research and potential clinical implementation efforts in traditional healthcare settings.
Frontiers in psychiatry
January 1, 2025
Qijing Liu, Ying Liu, Qian Fu et al.
2 citations
Postoperative sleep disturbance (PSD) is a common complication after surgery, caused by personal, intraoperative, postoperative, and environmental factors, and it impairs recovery and long-term prognosis. Esketamine, a non-competitive NMDA receptor antagonist and the dextrorotatory isomer of ketamine, has stronger receptor affinity, more significant analgesic effects, and better safety than ketamine. Beyond its sedative, analgesic, and antidepressant properties, emerging evidence suggests esketamine may improve PSD through various mechanisms, though existing research results remain controversial. This article reviews the latest research progress on esketamine for improving PSD, discussing its clinical efficacy and potential mechanisms to guide perioperative anesthesia management and postoperative rehabilitation.
Frontiers in psychiatry
January 1, 2024
Claudia Calciu, Rob Macpherson, Sui Yung Chen et al.
2 citations
No existing research directly links dissociation and recovery from psychosis. A systematic review of 2110 articles found only 19 that met inclusion criteria, and none of those conceptualized or hypothesized a relationship between dissociation and recovery from a psychotic episode. This gap indicates the topic remains unstudied. The review synthesizes international research on the phenomenology of dissociation, psychosis, and recovery separately, charting a direction for future investigation.
Frontiers in psychiatry
January 1, 2024
Tigran Makunts, Ruben Abagyan
2 citations
MDMA, currently being studied as a treatment for PTSD, is extensively metabolized by the liver, raising concerns about rare but serious drug-induced liver injury (DILI). While clinical trials have not measured liver injury markers or observed DILI symptoms, analysis of over 1,500 reports from the FDA Adverse Event Reporting System identified 23 cases of hepatic injury or failure where MDMA was taken with other substances. Twenty-two of those cases involved other drugs with known DILI concern, and only one report listed MDMA as the primary suspect. Given nearly 20 million annual doses of MDMA, this single report is insufficient to establish a significant association with DILI.
Frontiers in psychiatry
January 1, 2026
Sivert Drange, Jacob Cohen, Sys Stybe Johansen et al.
1 citation
In identical twins discordant for obsessive-compulsive disorder, the affected twin self-administered low doses of psilocybin (1–5 mg every third day) while the unaffected twin did not. The affected twin reported notable reductions in OCD symptoms, improved emotional regulation, and better well-being. However, cognitive flexibility, measured with a set-shift task, remained impaired compared to the unaffected twin. Low-dose psilocybin may alleviate some OCD symptoms but does not fully address underlying cognitive deficits.
Frontiers in psychiatry
January 1, 2026
Haihua Tian, Zongfeng Zhang, Yan He et al.
1 citation
A 19-year-old woman with treatment-resistant depression and multiple suicide attempts received two courses of intranasal esketamine. During the first course, she experienced transient dissociative symptoms lasting about 55 minutes, including depersonalization and a 'drunken gait.' Patient-selected music reduced anxiety and disorientation, and prophylactic oxazepam prevented later mild dissociative episodes. By the end of treatment, suicidal ideation had resolved. The case suggests that dissociative reactions to esketamine are typically self-limiting and manageable, and that music intervention may help by modulating prefrontal-amygdala circuits and autonomic regulation.
Frontiers in psychiatry
January 1, 2025
Alexandre Fraichot, Sophie Favre, Hélène Richard-Lepouriel
1 citation
A 37-year-old patient with treatment-resistant depression received intranasal Esketamine (84 mg) and used ChatGPT-4 to generate images and interpretations of his dissociative experiences, supported by a nurse. Depression severity was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). The patient achieved remission, with MADRS scores declining by 50% by the third session and indicating mild depression or euthymia in the eight subsequent sessions. The patient reported that the artificial intelligence-generated images and interpretations helped him create a timeline of his experiences. The case report suggests combining intranasal Esketamine with generative artificial intelligence may be effective, but further research is needed.
Frontiers in psychiatry
January 1, 2025
Zhan-Ming Shi, Xing-Bing Huang, Yan-Ling Zhou et al.
1 citation
China's National Health Commission prioritizes early diagnosis and standardized treatment of major depressive disorder (MDD). Rapid treatment centers across the country use electroconvulsive therapy (ECT), intravenous ketamine/esketamine, esketamine nasal spray, magnetic seizure therapy (MST), and Stanford Neuromodulation Therapy (SNT). This policy and practice review examines the strengths and shortcomings of these techniques in China, noting their potential to accelerate recovery. The findings offer insights for other countries and regions adopting rapid antidepressant strategies.
Frontiers in psychiatry
January 1, 2025
Scott Matthews, Antonino Greco, Clara Rastelli et al.
1 citation
Virtual reality simulations of psychedelic phenomenology can replicate neurophysiological and behavioral markers of classic serotonergic psychedelics in healthy subjects, suggesting they may serve as an adjunct or replacement for aspects of psychedelic-assisted therapy for alcohol use disorder. The authors propose four clinical applications: preparing patients for psychedelics, extending their efficacy, facilitating integration after dosing, and standardizing the therapeutic set and setting. Virtual reality may also function as a placebo in clinical research and as a tool to study subjective psychedelic experiences. Integrating virtual reality into psychedelic therapy and research could enable new treatment possibilities and implementation pathways.
Frontiers in psychiatry
January 1, 2025
Zixuan Zeng, Fei Liu, Chenyi Zhu et al.
1 citation
Chronic insomnia disorder affects many people and is usually treated with cognitive behavioral therapy (CBT-I), but about 20% of patients do not respond well. Mindfulness may improve CBT-I outcomes, and mindfulness-based cognitive therapy (MBCT) has shown effectiveness for insomnia. This protocol describes a planned two-armed, parallel-group randomized controlled trial with 80 Chinese adults who have chronic insomnia. Participants will be randomly assigned to either a therapist-guided internet-based MBCT for insomnia (iMBCT-I) program or a sleep hygiene education program. Assessments occur at baseline, week 8 (end of intervention), and week 20 follow-up, with insomnia severity at week 8 as the primary outcome. This is the first test of therapist-guided iMBCT-I for chronic insomnia.
Frontiers in psychiatry
January 1, 2025
Aleksandra Jeličić, Maja Drobnič Radobuljac, Louis Sass et al.
1 citation
People with autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD) often show similar social difficulties, leading to misdiagnosis. This study used in-depth phenomenological interviews with 42 participants aged 15 to 26, all with at least average intelligence and no acute psychiatric symptoms, to compare their subjective experiences. The SSD group showed higher levels of minimal self-disorder, demarcation phenomena, paranoid anxiety, short-term memory disorder, and magical thinking. Both groups overlapped in obsessive thinking, attention problems, diminished presence in the world, social anxiety, and hyper-reflectivity. The findings suggest that a disorder of ipseity (the sense of self) is central to SSD, while a disorder of primary intersubjectivity is central to ASD.
Frontiers in psychiatry
January 1, 2025
Baozhou Zhang, Yifan Liu, Jinwei Zheng et al.
1 citation
Research on esketamine for depression has surged from 2015 to 2024, totaling 925 articles, with 286 published in 2024 alone. The United States contributed the most publications (308), followed by China (260) and Canada (114). Leading journals include the Journal of Affective Disorders, Frontiers in Psychiatry, and the International Journal of Neuropsychopharmacology. Key authors are McIntyre, Roger S (52 publications), Hashimoto, Kenji (49), and Rosenblat, Joshua D (41). Prominent research keywords over the last decade are "treatment-resistant depression," "efficacy," "antidepressant," and "suicidal ideation." Current focus remains on assessing long-term safety, while a large disparity in research resources persists between developed and low- and middle-income countries.
Frontiers in psychiatry
January 1, 2024
Magdalena Więdłocha, Piotr Marcinowicz, Jan Komarnicki et al.
1 citation
correction
No Summary
Frontiers in psychiatry
January 1, 2023
Simon G D Ruffell, Nige Netzband, WaiFung Tsang et al.
1 citation
correction
This is a correction notice for a previously published article. It provides no new findings, arguments, or data.
Frontiers in psychiatry
January 1, 2022
Marianthi Lousiana Deligianni, Joseph Studer, Gerhard Gmel et al.
1 citation
Among 2,796 young Swiss men who had used substances, 32.2% reported at least one type of substance-induced consciousness alteration: 20.5% experienced ego dissolution, 16.7% visual pseudo-hallucinations, and 14.6% anxiety or paranoia. Former and current use of psychedelics and ketamine was linked to all three types and to a positive perceived influence on life. Associations with other substances were less consistent and not statistically significant. Sociability was negatively associated with all three alterations; anxiety-neuroticism was positively associated with ego dissolution and anxiety/paranoia; aggression-hostility with anxiety/paranoia; and sensation seeking with ego dissolution and visual pseudo-hallucinations. The findings suggest psychedelics can induce consciousness alterations perceived as beneficial, even in street-drug users.
Frontiers in psychiatry
January 1, 2026
Rong Zhou, Jingjing Lu, Yunxiang Ling et al.
Burst firing in the lateral habenula (LHb) is linked to depression, and ketamine blocks this firing to produce rapid antidepressant effects. This study investigated whether NMDA receptors (NMDARs) are necessary for burst firing in LHb neurons. Using brain slices from adult male mice, researchers recorded spontaneous and rebound burst firing while applying NMDAR antagonists D-AP5 and MK-801. Neither antagonist altered spontaneous or rebound burst firing: the percentage of neurons showing burst firing, burst frequency, and spikes per burst remained unchanged. The results indicate that NMDARs are not required for generating burst firing in LHb neurons, though they may modulate it under certain conditions.
Frontiers in psychiatry
January 1, 2026
Sofia Abramsky-Sze, Elliot Marseille, Richard Matzopoulos et al.
correction
This is a correction notice for a previously published article. It does not present new findings, arguments, or data.
Frontiers in psychiatry
January 1, 2026
Hang Yu, Yuqiong Zhu, Jie Wang et al.
In a mouse model of depression induced by chronic social defeat stress, susceptible mice showed reduced social interaction, lower sucrose preference, decreased NRG1 protein expression in the prefrontal cortex, and increased immobility time compared to controls. A subanesthetic dose of esketamine increased NRG1 expression in the prefrontal cortex within 30 minutes and improved social interaction and reduced immobility at both 30 minutes and 24 hours post-injection. No significant changes were observed in GAD67 or ErbB4 expression. Esketamine may rapidly improve depressive-like behavior by regulating the NRG1-ErbB4 signaling pathway.
Frontiers in psychiatry
January 1, 2026
Ngo Cheung
Four patients with hard-to-treat trauma-spectrum disorders—somatic PTSD, acute bereavement-related PTSD, trauma-linked adolescent depression, and complex PTSD with bipolar II, ADHD, and borderline features—showed clinically meaningful symptom improvement within days to weeks after starting an inexpensive oral protocol centered on dextromethorphan potentiated by fluoxetine, with optional piracetam or bupropion. Reductions in intrusive memories, rumination, somatic pain, and functional disability were noted; no episodes of dissociation, hypertension, or mania were clinically documented during follow-up, though structured screening for hypomania and serotonergic toxicity was not performed. The findings are hypothesis-generating and suggest further controlled investigation of oral NMDA-AMPA modulators for trauma-related conditions.
Frontiers in psychiatry
January 1, 2026
Gláucio Silva Camargos, Geraldo Magela De Faria Júnior, Marcelo Lourenço et al.
Over six months, depressive symptoms decreased significantly in 280 adults with depressive, anxiety, or substance use disorders after ritualistic ayahuasca use combined with psychotherapeutic support. Scores on the Montgomery-Åsberg Depression Rating Scale dropped shortly after the intervention and remained lower for up to 180 days, though individual responses varied. The findings suggest that ayahuasca-assisted therapy can reduce depression and anxiety and may help treat substance dependence. Variability in outcomes indicates that psychodynamic factors, including integration of the psychedelic experience and ongoing therapeutic support, are crucial for effectiveness. The work supports developing personalized psychedelic-assisted treatment protocols for complex psychiatric conditions.
Frontiers in psychiatry
January 1, 2026
Ahmad H Almadani, Ayedh H Alghamdi, Gosay M Almazyad et al.
Among 223 psychiatrists surveyed in Saudi Arabia, fewer than 20% had prescribed esketamine for treatment-resistant depression, and most of those had treated only 1-2 patients. The most frequently perceived side effects were dissociation, delusions, or hallucinations (66.82%) and dizziness or vertigo (59.19%). Older age, consultant-level practice, practice in the Western Region, lower concern about misuse, easier perceived access, and fewer concerns about the administration process were significantly linked to having prescribed esketamine. Senior registrars, registrars, and residents were less likely to prescribe than consultants. The main barriers were the administration process (66.37%) and cost (65.02%). Actual adoption remains low despite interest.
Frontiers in psychiatry
January 1, 2026
Jean Jacque Lovely, Hiedi Yardley, Reverdi Darda et al.
A collaborative pilot program between Siksika Health Services and ATMA CENA designed and delivered a culturally responsive ketamine-assisted therapy (KAT) program within the Siksika First Nation in Alberta, Canada. Six participants (3 Indigenous, 3 non-Indigenous) completed care. Notable improvements in symptoms of depression, anxiety, and PTSD were observed, with participants reporting increased emotional regulation and stronger cultural connections. Cultural elements such as shared meals, traditional decor, and a mid-program break for cultural events were central to participant safety, trust, and meaning making. Indigenous and non-Indigenous participants treated together reported comparable gains, suggesting the model may reduce inequities in group KAT delivery. Challenges included stigma, systemic barriers, and logistical obstacles in a rural First Nation setting.
Frontiers in psychiatry
January 1, 2026
Søren Esben Rytter Heilskov, Julie Nordgaard, Unn Kristin Haukvik et al.
Delusions are often used as key evidence of psychosis in insanity assessments because they are verbalized and express faulty reality judgments. However, psychosis can also involve disturbances that are enacted rather than spoken. This paper revisits Klaus Conrad's concept of "senseless actions"—unintelligible behaviors seen in early schizophrenia—and illustrates its forensic relevance through a historical case study from Karl Wilmanns. These actions reflect a global disruption in how a person finds relevance, meaning, and constraint in the world, and may signal the transition from prodromal to manifest psychosis. The authors argue that evaluating such actions requires contextual and biographical information, and that the concept, though imperfect, can help identify reality disturbances overlooked in current forensic practice.
Frontiers in psychiatry
January 1, 2026
C M Diendorfer, C Bum, A Weidenauer et al.
Ketamine, a drug used for treatment-resistant depression, may offer benefits for negative and depressive symptoms in schizophrenia, though no randomized controlled trials have tested it in psychotic disorders. Negative symptoms like apathy and anhedonia are hard to treat and often overlap with depression. Case reports show ketamine can improve mood without triggering psychosis, and its dissociative effects usually fade within one to two hours. This review examines ketamine's potential advantages and risks for schizophrenia patients, focusing on negative and depressive symptoms.
Frontiers in psychiatry
January 1, 2025
Meng-Han Zhang, Yi-Fan Wang, Juan Li et al.
A 55-year-old woman with depressive catatonia, who had a poor response to initial treatment with benzodiazepines and aripiprazole and could not receive modified electroconvulsive therapy due to deep vein thrombosis, was given a single sub-anesthetic dose of intravenous esketamine (0.2 mg/Kg) combined with desvenlafaxine. Catatonia symptoms, measured by the Bush-Francis Catatonia Rating Scale, dropped from 19 to 0 within 4 hours. Depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale, fell from 46 to 9 at 48 hours, and the improvement remained stable over 20 weeks. Esketamine may offer a rapid and safe option for catatonic patients who cannot undergo electroconvulsive therapy or do not respond to conventional treatment.