Journal of Affective Disorders
June 15, 2024
Gia Han Le, Sabrina Wong, Sebastian Badulescu et al.
25 citations
A systematic review examined how serotonergic psychedelics (psilocybin, LSD) and ketamine affect brain wave patterns measured by EEG and MEG in people with major depressive disorder, treatment-resistant depression, and healthy controls. Ketamine and psychedelics both increase theta power in depressed individuals. In healthy controls and depressed persons, both drug classes decrease alpha, beta, and delta power. Ketamine also increases gamma power in both groups. Theta power specifically rises in those with major depressive disorder when given psychedelics. The studies varied in patient populations, dosing, and measurement devices. The findings support disease models involving altered network connectivity and may guide future treatment discovery.
Journal of Affective Disorders
March 1, 2023
Debora de A. Simoes Moreira, Luís Eduardo Gauer, Guilherme Teixeira et al.
25 citations
A systematic review and meta-analysis of eight randomized controlled trials or cohort studies comparing ketamine with electroconvulsive therapy (ECT) for treatment-resistant depression found no evidence that ketamine is superior to ECT in reducing depressive symptom severity or in achieving response to therapy. Among side effects, patients treated with ketamine had a statistically significant lower risk of muscle pain compared with those receiving ECT. The analysis also noted trends toward more dissociative symptoms with ketamine and less nausea and headache, but these differences were not statistically significant. The authors caution that the small number of eligible studies, high heterogeneity, and risk of bias limit the strength of these conclusions.
Journal of Affective Disorders
February 15, 2023
Priel Meir, Leslie Taylor, Jair C Soares et al.
25 citations
Most psychologists are willing to inform eligible patients about psilocybin-assisted therapy if it becomes FDA-approved, but over 90% would still recommend non-psilocybin psychotherapies first. Among 119 surveyed psychologists, 77.4% agreed they would inform patients about PAT, yet 91.6% would prioritize other therapies. Three-quarters endorsed that more knowledge about psilocybin would increase their likelihood of informing patients. Greater openness to engaging patients with PAT was associated with more positive attitudes and beliefs about psilocybin, greater self-reported knowledge, personal psychedelic use, and positive attitudes toward medical cannabis. Attitudes toward medical cannabis and beliefs about psilocybin were the only significant predictors of openness in regression analysis.
Journal of Affective Disorders
March 15, 2025
Polymnia Georgiou, Cristan A Farmer, Gustavo C Medeiros et al.
24 citations
Baseline levels of stress-related hormones (CRF, ACTH, and cortisol) did not significantly influence how well ketamine worked as an antidepressant in people with treatment-resistant depression. However, higher levels of ACTH and CRF were associated with longer overall duration of depressive episodes, suggesting these hormones might serve as biomarkers for chronic depression. Additionally, people who developed depression at a younger age tended to have more severe depressive symptoms, indicating that earlier onset may lead to greater cumulative stress on the brain and body. The study involved 42 participants in a randomized, placebo-controlled, crossover trial.
Journal of Affective Disorders
January 6, 2023
G. Ahmed, Y. Elserogy, G. M. A. Elfadl et al.
24 citations
Ketamine infusions reduce suicidal ideation and depression in people with treatment-resistant depression, regardless of other psychiatric or personality disorders. In a randomized double-blind trial with 36 patients, those receiving two weekly ketamine infusions showed significantly greater decreases on the Hamilton Depression Rating Scale and Suicide Probability Scale than those given a placebo. The presence of other psychiatric symptoms did not influence the magnitude of improvement. Receiving ketamine was the only significant factor predicting better suicide and depression scores. The study lacked data on quality of life and cognition and had a small sample size.
Journal of Affective Disorders
January 15, 2025
Sara Ellis, Catherine Bostian, Wendy Feng et al.
23 citations
In a small, uncontrolled trial, 15 veterans with severe treatment-resistant depression received a single 25 mg dose of psilocybin. At three weeks, 60% met criteria for response and 53% for remission. By twelve weeks, 47% maintained response and 40% remission. Co-occurring PTSD did not affect outcomes, and the intensity of the psychedelic experience did not correlate with depression improvement. Four participants who needed to restart antidepressants were counted as non-responders from that point. No unexpected adverse events occurred. The authors note limitations including the small sample and lack of a control group, and call for further study.
Journal of Affective Disorders
September 15, 2024
David S. Mathai, Thomas D Hull, Leonardo Vando et al.
22 citations
In a large longitudinal study of 11,441 moderately-to-severely depressed patients who received four doses of sublingual ketamine at home over four weeks within a supportive digital health context, treatment was associated with improvement in depression symptoms. A modal antidepressant response occurred in both non-severe (55.8%) and severe (18.1%) baseline depression levels. Adverse events were detected in 3.0-4.8% of participants, predominantly neurologic or psychiatric. A second course of treatment extended improvements in those who responded favorably. Improvement was most strongly predicted by lower baseline depression scores and younger age. Symptoms of depressed mood and anhedonia persisted despite treatment. The study lacked a control group and fixed-dose procedure. At-home, telehealth-supported ketamine administration was largely safe, well-tolerated, and associated with improvement.
Journal of Affective Disorders
December 15, 2024
Dan Xu, Guilin Liu, Mingming Zhao et al.
21 citations
A single dose of arketamine (10 mg/kg) improved both depression-like behaviors and demyelination in the corpus callosum of mice exposed to chronic restraint stress. Correlations linked depression-like behaviors with demyelination in that brain region. Blocking the transforming growth factor β1 (TGF-β1) receptor with RepSox prevented arketamine's beneficial effects, while a single intranasal dose of TGF-β1 alone also ameliorated both depression-like behaviors and demyelination. The precise mechanisms remain unclear, but the findings suggest that stress-induced demyelination in the corpus callosum may contribute to depression-like behaviors, and arketamine may act through a TGF-β1-dependent pathway.
Journal of Affective Disorders
November 15, 2024
Abigail E. Calder, Gregor Hasler
20 citations
A new standardized tool, the Swiss Psychedelic Side Effects Inventory (SPSI), was developed to systematically record clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. The SPSI was constructed from previous research and pilot tested in 145 participants across three studies, with expert panel feedback improving its validity. The final version contains 32 side effects with standardized follow-up questions, compatible with any study design and administrable as interview or self-report. It omits less important side effects but includes space for additional symptoms. The SPSI is available in English and German to improve clinical decisions, informed consent, and patient safety.
Journal of Affective Disorders
March 15, 2025
Kevin H. Yang, Wayne Kepner, Charles M Cleland et al.
19 citations
Ketamine use among US adults increased significantly from 2015 to 2019 and again from 2021 to 2022. From 2015 to 2019, use rose among both adults with and without depression, but from 2021 to 2022, an increase occurred only among those without depression. Depression was linked to higher odds of ketamine use in 2015–2019 but not in later years. New correlates emerged in 2021–2022, including adults aged 26–34 and college graduates. Use of other drugs, especially ecstasy/MDMA and gamma-hydroxybutyrate, was consistently associated with higher odds of ketamine use. These shifts may reflect changes in the ketamine landscape or survey methodology.
Journal of Affective Disorders
April 1, 2024
Sabrina Wong, Angela T H Kwan, Kayla M Teopiz et al.
19 citations
A systematic review of randomized controlled trials compared the clinical efficacy of psilocybin and esketamine in adults with treatment-resistant depression. 25 mg of psilocybin significantly reduced depressive symptoms at 21 days post-dose, with a number needed to treat (NNT) of 5. Psilocybin-induced nausea had a number needed to harm (NNH) of 5. Fixed doses of esketamine (56 mg and 84 mg) showed significant effects at 28 days post-dose, with NNTs of 7. Esketamine-induced headache, nausea, dizziness, and dissociation had NNHs below 10. The preliminary results may reflect only a small portion of the patient population and require replication and longer-term studies. Both agents showed clinically meaningful NNT estimates and acceptable NNH profiles, underscoring their clinical relevance for treatment-resistant depression.
Journal of Affective Disorders
January 1, 2020
Roman M Dale, Kelly A. Bryant, Nora Finnegan et al.
17 citations
In people with treatment-resistant depression who had previously failed electroconvulsive therapy, higher openness to experience—a personality trait reflecting curiosity and willingness to try new things—was the only factor among the Big Five personality domains that significantly predicted a sustained response to repeated intravenous ketamine infusions. The study of 125 participants confirmed that, regardless of treatment response, the group as a whole showed elevated neuroticism, low conscientiousness, and low extraversion. The authors suggest that assessing openness could help identify patients most likely to benefit from long-term ketamine therapy and reduce unnecessary exposure to its unknown risks, though they note limitations including the lack of a placebo control, small sample, and non-standardized infusion schedules.
Journal of Affective Disorders
January 1, 2025
Xiangyang Zang, Jingting Zhang, Jingping Hu et al.
16 citations
Combining esketamine with electroconvulsive therapy (ECT) improves depression symptoms more than ECT alone. In a small human trial, patients receiving propofol plus esketamine before ECT had lower depression scores on the 24-item Hamilton Depression Rating Scale after the fifth and sixth treatments than those receiving propofol alone. In a rat model of depression, the combination reduced depression-like behaviors and lowered brain glutamate levels. Both esketamine and ECT activated the PI3K/Akt/GLT-1 pathway, which helps clear excess glutamate. Blocking this pathway with inhibitors eliminated the antidepressant effects, suggesting that activation of PI3K/Akt/GLT-1 is a key mechanism.
Journal of Affective Disorders
May 1, 2024
Chuntana Reangsing, Sasinun Punsuwun, Sarah Oerther
16 citations
A meta-analysis of 19 studies involving 1,480 pregnant women found that mindfulness-based interventions reduced depression compared to control groups, with a moderate effect size (g = 0.457). Mindfulness-based cognitive therapy showed a larger effect (g = 1.13) than mindfulness-based stress reduction (g = 0.64) or adapted interventions (g = 0.31). The findings suggest these programs, especially MBCT, are effective complementary treatments for depression during pregnancy.
Journal of Affective Disorders
April 1, 2023
A. Zavaliangos-Petropulu, S. Mcclintock, Jacqueline Khalil et al.
16 citations
Ketamine treatment improves cognitive function in people with treatment-resistant depression, and these improvements last at least five weeks. In a study of 66 patients receiving four ketamine infusions, significant gains occurred in inhibition, working memory, processing speed, and overall fluid cognition after the first and fourth infusions. Processing speed and overall fluid cognition remained improved at a five-week follow-up, even though depressive symptoms had largely returned to baseline by then. Baseline working memory and changes in inhibition were moderately linked to antidepressant response, but cognitive improvements were statistically independent of mood changes, suggesting ketamine acts on overlapping but distinct brain systems.
Journal of Affective Disorders
September 1, 2022
David S. Mathai, Scott M Lee, Victoria Mora et al.
16 citations
Informed consent documents from 23 American ketamine clinics for psychiatric treatment cover most required elements but vary greatly in detail. Key gaps include poor communication about long-term side effects, alternative treatments, pre-treatment evaluations, support during treatment, psychological interventions, and dissociative effects. All forms are written at a readability level too high for many patients. The findings suggest that both patients and providers would benefit from more deliberate, evidence-informed consent processes to support shared decision-making as off-label ketamine use expands.
Journal of Affective Disorders
April 15, 2024
Jinjun Liu, Wei Duan, Zeping Xiao et al.
15 citations
Online group Mindfulness-based Cognitive Therapy (MBCT) reduced clinician-rated depression and anxiety symptoms in Chinese outpatients with depression, regardless of whether they were taking medication. After a 10-week program, scores on the Hamilton Depression Scale and Hamilton Anxiety Scale dropped significantly, with more than half of patients showing at least a 50% reduction in depression scores. However, self-reported depression, mindfulness, and self-acceptance did not change significantly. Attendance was high, with 85% of participants completing more than four sessions. The findings suggest that shifting MBCT from an in-person to an online format can be effective for treating depression in this population.
Journal of Affective Disorders
December 15, 2024
Ethan Faries, Landon A Mabe, Ronald L Franzen et al.
13 citations
Repetitive transcranial magnetic stimulation (rTMS) produced significantly larger reductions in depression scores than electroconvulsive therapy (ECT) in adolescents with treatment-resistant depression, and potentially larger reductions than ketamine. A meta-analysis of 10 observational studies examined standardized mean differences in depression scores for youth aged 10-24 treated with ECT, rTMS, or ketamine. ECT had a significantly lower standardized mean difference of 1.99. No significant difference was found between ECT and ketamine. The comparison of ketamine versus rTMS suggested a potential difference favoring rTMS. rTMS shows promise as a first-line treatment for pediatric treatment-resistant depression due to its favorable side effect profile compared to ECT.
Journal of Affective Disorders
October 15, 2024
Angela T H Kwan, Joshua D. Rosenblat, Rodrigo B. Mansur et al.
13 citations
Ketamine and esketamine are increasingly prescribed for treatment-resistant mood disorders and suicide risk, but ketamine is also misused. Analyzing reports in the World Health Organization pharmacovigilance database up to January 2024, ketamine showed elevated reporting odds ratios for alcohol abuse (3.24), substance dependence (12.48), substance use disorder (170.44), substance abuse (2.94), drug dependence (2.88), drug use disorder (11.54), and drug abuse (2.85). Esketamine had reduced odds for substance abuse (0.41), drug dependence (0.083), and drug abuse (0.052), and no increased odds for any alcohol or substance misuse parameter. These associations do not establish causation.
Journal of Affective Disorders
May 1, 2023
Guy M. Goodwin, Megan Croal, Lindsey Marwood et al.
13 citations
Blinding in psychiatric clinical trials is considered ideal, but unblinding due to subjective drug effects raises concerns about demand characteristics undermining research findings. For conventional antidepressants, the strong link between dose and subjective effects does not correspond to a strong relationship with efficacy in randomized controlled trials, disproving the idea that unblinding primarily drives trial outcomes. Instead, early changes in brain function predict treatment outcomes and align with neuroscience. For psychedelic treatment of depression, unblinding is inevitable, but the therapeutic effect stems directly from serotonin receptor activation and altered brain connectivity, not just expectancy. A dose-response relationship is expected with novel mechanisms. Unblinding does not invalidate genuine recovery.
Journal of Affective Disorders
August 1, 2025
Morgan C H Cheng, Christine E. Dri, Hana Ballum et al.
12 citations
Ketamine and esketamine produce rapid antidepressant effects in major depressive disorder and treatment-resistant depression, but their impact on patient-reported quality of life has been unclear. A systematic review of five studies found that both agents improve quality of life measures on scales such as the WHOQOL-BREF, Assessment of Quality of Life 8D, and EuroQol-5 Dimension-5 Layers, with statistically significant results. However, the studies had an overall moderate risk of bias and varied in the quality-of-life scales used and study duration. Further research should examine effects on specific quality-of-life domains.
Journal of Affective Disorders
July 18, 2025
Mary E. Kittur, Mingyao Liu, Brett D. M. Jones et al.
12 citations
Psilocybin therapy shows promise for rapid and lasting clinical benefits when paired with psychological support, but the field lacks standardized therapeutic guidelines. A systematic review of 22 recent trials across conditions like depression, substance use, and obsessive-compulsive disorders found broad consistency in the structure of therapy sessions—before, during, and after psilocybin administration. However, trials varied widely in therapeutic intensity, diagnostic adaptations, and use of evidence-based psychotherapies. Fewer than half reported standardization measures such as manualized procedures, specific training, or adherence monitoring. These gaps undermine replicability and generalizability, and until support protocols are clearly defined, mechanistic understanding and clinical adoption will remain limited.
Journal of Affective Disorders
March 1, 2025
Xiang Liu, Zhipeng Wei, Lifeng Li et al.
12 citations
People with major depressive disorder show widespread damage to the brain's white matter, particularly in fibers connecting different regions. A two-week treatment with intravenous esketamine (0.25 mg/kg) effectively reduced depression, anxiety, and suicidal thoughts and improved cognitive function in 20 patients compared to 20 healthy controls. However, brain scans revealed that the damaged white matter did not recover during this short treatment period. The degree of damage in certain projection fibers was linked to the severity of anxiety and suicidal ideation. The study lacked a placebo control and many patients also took sertraline, making it difficult to isolate esketamine's specific effects on the brain.
Journal of Affective Disorders
February 1, 2025
Grant Jones, Matthew X. Lowe, Sandeep M. Nayak et al.
12 citations
Psilocybin, the psychoactive compound in magic mushrooms, is linked to improved mental wellbeing on average, but few studies examine how effects differ by race. In a large online longitudinal study of 2,833 people planning naturalistic psilocybin use, race/ethnicity moderated changes in spiritual wellbeing, cognitive flexibility, and emotion regulation (expressive suppression) at 2–3 months post-experience, but not at 2–4 weeks. Participants of Color reported minor differences in context and subjective effects, such as being more likely to set an intention before use. Both groups showed comparable reductions in anxiety and depression, with no significant moderation by race.
Journal of Affective Disorders
January 1, 2025
Qing-Bin Zeng, De-Cheng Zou, Xing-Bing Huang et al.
12 citations
For people with treatment-resistant depression, electroconvulsive therapy (ECT) is a common option. Esketamine, a fast-acting antidepressant, had not been tested as an anesthetic for ECT. In a double-blind randomized trial, 40 patients received either esketamine or propofol anesthesia for eight ECT sessions. Esketamine-ECT was non-inferior to propofol-ECT for reducing depressive symptoms after eight sessions. Response rates were 80% for esketamine versus 70% for propofol, and remission rates were 65% versus 55%, but non-inferiority was not confirmed for these outcomes. Cognitive function was similar between groups. Results for anxiety, suicidal ideation, and adverse events were inconclusive. Larger replication studies are needed.