Journal of Psychiatric Research
May 1, 2022
Yazen Alnefeesi, D. Chen-Li, Ella Krane et al.
177 citations
Ketamine shows substantial real-world antidepressant effects in treatment-resistant depression, with about 45% of patients responding and 30% achieving remission, based on a systematic review and meta-analysis of 79 studies involving 2665 patients. The effect varies considerably among individuals; more treatment-resistant cases remit less often, but response rates do not differ. The therapeutic benefit does not significantly decline with repeated treatments, indicating that even the most treatment-resistant patients may benefit and that mid-to-long term treatment is effective for many.
Journal of Psychiatric Research
December 11, 2020
Jiaqi Xiong, Orly Lipsitz, D. Chen-Li et al.
122 citations
A meta-analysis of nine randomized controlled trials (197 participants) found that a single dose of intravenous ketamine or intranasal esketamine is associated with large reductions in suicidal thoughts at 2, 4, and 24 hours after administration. The pooled effect size for intravenous racemic ketamine at 24 hours was 1.035, and for intranasal esketamine it was 1.309. No trials of intramuscular, oral, or sublingual ketamine reported anti-suicidal ideation effects suitable for quantitative analysis. The authors suggest that further studies are needed to evaluate these other routes of delivery and to compare formulations.
Journal of Psychiatric Research
May 1, 2022
Tuyen T. Le, Isabel Pazos Cordero, Muhammad Youshay Jawad et al.
82 citations
Ketamine and its enantiomers show different abuse liability. Preclinical evidence indicates that (R,S)-ketamine and (S)-ketamine carry greater risk for abuse than (R)-ketamine, which at antidepressant-relevant doses in rodents appears safe with minimal liability. In clinical settings, limited studies suggest that single or repeated ketamine administrations under professional control did not lead to misuse, dependence, diversion, or gateway activity in patients with treatment-resistant depression. However, most clinical studies were retrospective and lacked systematic evaluation with validated scales. The review identified 65 eligible studies (55 preclinical, 10 clinical), with only 4 preclinical studies evaluating enantiomer abuse liability.
Journal of Psychiatric Research
December 24, 2014
Ke Xu, J. Krystal, Y. Ning et al.
65 citations
Ketamine, a drug that blocks NMDA glutamate receptors, produces symptoms resembling schizophrenia. Analyzing the Positive and Negative Syndrome Scale (PANSS) in four groups—135 healthy people given ketamine or saline, 187 chronic ketamine abusers, 154 early-course schizophrenia patients, and 522 chronic schizophrenia patients—revealed five similar symptom dimensions (positive, negative, cognitive, depressed, excitement/dissociation) across all groups. The chronic ketamine group's symptom structure more closely matched the schizophrenia groups than the acute ketamine group did. Symptoms were milder in ketamine users than in schizophrenia patients (Cohen's d = 0.7). The findings suggest ketamine-induced psychosis shares symptom dimensions with schizophrenia, though confounding factors warrant caution.
Journal of Psychiatric Research
March 1, 2021
Joshua D. Di Vincenzo, Ashley N. Siegel, Orly Lipsitz et al.
59 citations
Most antidepressant medication trials have focused on adults aged 18-65, leaving gaps in knowledge about older and younger populations. Ketamine shows promise for treatment-resistant depression, but its effects in adolescents and older adults are not well understood. This systematic review of 13 studies found that ketamine produced rapid antidepressant effects (within two weeks) in ten studies, with better results from larger, repeated doses and in open-label rather than blinded settings. Two case reports in adolescents noted rapid anti-suicidal effects. Ketamine appeared safe and well-tolerated in these age groups. However, the small number of studies, high heterogeneity, and generally low quality prevent firm conclusions, and rigorous randomized controlled trials are still needed.
Journal of Psychiatric Research
February 10, 2018
Andrew P. Allen, Maura Naughton, J. Dowling et al.
53 citations
Current first-line antidepressants often take weeks to improve symptoms, but low-dose ketamine may work faster, even in treatment-resistant depression. This study compared the effects of ketamine infusion and electroconvulsive therapy (ECT) on biological markers related to stress and inflammation in patients with treatment-resistant depression versus healthy controls. Both treatments improved depressive symptoms. At baseline, patients showed differences in cortisol and kynurenine pathway metabolites compared to controls, though inflammatory markers were similar. After ECT, the cortisol awakening response decreased in responders. Ketamine showed a trend toward reduced kynurenine in responders but did not significantly alter any measured biomarkers.
Journal of Psychiatric Research
September 1, 2018
Li Ren, Jie Deng, S. Min et al.
48 citations
Electroconvulsive therapy (ECT) is highly effective for depression, and ketamine at sub-anesthetic doses also produces rapid antidepressant effects. This systematic review and meta-analysis of 16 randomized controlled trials involving 928 patients examined whether adding ketamine to ECT improves outcomes. At the end of the ECT course, depressive symptoms were not significantly lower in the ketamine group compared to controls. However, depressive scores were lower after the first and after the third through sixth ECT sessions, particularly when ketamine was used as an add-on anesthetic. Ketamine did not improve overall response or remission rates and increased adverse events, especially cardiovascular and psychiatric side effects. Ketamine may accelerate antidepressant effects during ECT but should be used cautiously due to added risks.
Journal of Psychiatric Research
May 8, 2021
R. Mello, Mariana V F Echegaray, A. P. Jesus-Nunes et al.
22 citations
Dissociative symptoms are common side effects of ketamine and esketamine used for depression. In adults with treatment-resistant depression randomly assigned to a single 40-minute infusion of either esketamine 0.25 mg/kg or ketamine 0.5 mg/kg, those with higher trait dissociation (measured by the Dissociative Experience Scale) had a greater risk of experiencing induced dissociation (measured by the Clinician-Administered Dissociative States Scale). Every 5-point increase in trait dissociation was associated with a 10.9% increase in induced dissociation. Subjects with high trait dissociation had a 1.41 times higher risk of induced dissociation and a 3.05 times higher risk of very high induced dissociation. Induced dissociation was not a serious adverse effect. The findings suggest screening for trait dissociation and counseling patients on risks.
Journal of Psychiatric Research
July 1, 2023
Mu-Hong Chen, Wei-Chen Lin, Cheng-Ta Li et al.
8 citations
In patients with treatment-resistant depression and strong suicidal thoughts, a single low-dose infusion of ketamine did not change blood levels of two proteins—VEGF and MMP-9—compared to a control drug, midazolam. However, patients who had higher VEGF levels before treatment showed greater improvements in depression and suicidal ideation after ketamine. This suggests that baseline VEGF might help predict who will benefit from ketamine, but the drug itself does not alter these protein levels.
Journal of Psychiatric Research
November 27, 2025
Tor-Morten Kvam, Ivar W Goksøyr, Joanna Róg et al.
3 citations
In a small long-term follow-up of twelve people with major depressive disorder, MDMA-assisted therapy—two MDMA dosing sessions combined with nine psychotherapy sessions—led to sustained reductions in depression severity and disability seven months after baseline. Depression scores on the Montgomery-Asberg Depression Rating Scale and disability scores on the Sheehan Disability Scale remained significantly lower than before treatment, with no significant changes from the immediate post-treatment visit. Suicidal ideation did not exceed pre-study levels. The results suggest lasting treatment effects and safety, though the authors call for larger controlled trials to confirm these preliminary findings.
Journal of Psychiatric Research
May 26, 2025
Bjørn Holmøy, Tor-Morten Kvam, Kristoffer Andreas Aamodt Andersen et al.
3 citations
A Norwegian translation of the Challenging Experience Questionnaire (CEQ) shows strong reliability and validity for assessing adverse psychedelic experiences. An online survey of 729 Norwegian recreational psychedelic users, mostly male (73%) and aged 26–35 (41%), with 90% having used LSD or psilocybin, confirmed the original 7-factor structure. The translated CEQ demonstrated excellent internal consistency (alpha = 0.94) and good overall model fit. The tool also showed factorial invariance across gender and psychiatric status, and convergent validity through relationships between reported difficulty and factors like fear, grief, insanity, and death. This provides Norwegian researchers with a culturally adapted, psychometrically valid tool for evaluating complex adverse reactions to psychedelic use.
Journal of Psychiatric Research
October 30, 2025
Isabella S Ji, M Cheng, Kayla M. Teopiz et al.
2 citations
Ketamine and esketamine, NMDA receptor antagonists, are effective for depressive symptoms in major depressive disorder (MDD) and treatment-resistant depression (TRD), but functional impairments in work, social, and family life often persist even when mood improves. This systematic review of randomized controlled trials found no controlled studies on ketamine's effect on functional outcomes, highlighting a major gap. For esketamine, nine studies showed significant improvements: Sheehan Disability Scale scores dropped by an average of 13.6 points versus 9.4 for placebo, and workplace productivity loss, presenteeism, and activity impairment all significantly decreased. Esketamine thus improves both depressive symptoms and daily functioning, especially at work.
Journal of Psychiatric Research
January 19, 2026
Gwynnevere Suter, Ian Apperly, L. Zhang et al.
1 citation
Reality monitoring—the ability to remember whether information came from one's own mind or from the outside world—is often impaired in clinical conditions, but no prior review had compared this ability across dissociation and psychosis. A systematic review of four high-quality papers (482 participants) found a small but significant negative association between reality monitoring and dissociation, indicating slight impairment. A narrative review of psychosis showed that clinical psychosis is robustly linked to impaired reality monitoring and an externalizing bias (attributing internal information to an external source), while results for non-clinical psychotic-like experiences were mixed. Comparing the two fields suggests a shared cognitive basis, but no studies have examined clinical dissociation or source-attribution biases, leaving the comparison incomplete.
Journal of Psychiatric Research
June 23, 2026
Júlio César Claudino Dos Santos, Sofia Januário Bolan, Guilherme Lodetti da Silva et al.
Psychedelic compounds such as psilocybin, LSD, MDMA, and ketamine are being explored as potential treatments for autism spectrum disorder (ASD), a condition marked by social communication deficits, repetitive behaviors, and sensory differences, often with anxiety and emotional dysregulation. These drugs may modulate serotonin and glutamate signaling, enhance neuroplasticity, and reorganize brain networks. Current evidence does not support treating core ASD symptoms like social communication deficits or repetitive behaviors, but psychedelics may help with associated issues such as social anxiety, emotional dysregulation, cognitive rigidity, and co-occurring mood symptoms. Direct clinical studies in ASD remain scarce, and ethical and safety concerns, especially for pediatric and neurodivergent populations, are noted.