Journal of Affective Disorders
May 1, 2026
Michel Danon, Gabriela Ostronoff, Anne-Cécile Petit et al.
Regulatory approvals for intranasal esketamine in treatment-resistant depression differ on its indication for suicidal ideation. In a two-center observational study of 261 adults with moderate-to-severe treatment-resistant depression, eight esketamine sessions over four weeks improved both depressive symptoms and suicidal ideation. However, after statistically adjusting for the antidepressant effect, the reduction in suicidal ideation was no longer significant. The findings suggest that esketamine's anti-suicidal effect does not persist independently of its antidepressant effect.
Journal of Affective Disorders
April 15, 2026
Jen-Ping Chen, Chih-Wei Hsu, Yi-Ting Chen et al.
Among adults with treatment-resistant depression, repetitive transcranial magnetic stimulation (rTMS) was associated with fewer medical complications than esketamine over the first year, including lower risks of hospitalization, arrhythmia, and any injury. Suicide-related outcomes were broadly comparable overall, though esketamine showed a protective advantage during the 30-90-day interval and among patients aged 45-65 years. The analysis used target trial emulation with propensity score matching on 50 covariates, drawing on electronic health records of 1,690 matched patients per treatment group. The findings suggest rTMS has a more favorable overall medical safety profile, while suicide risks were similar except for specific subgroups and time periods.
Journal of Affective Disorders
April 1, 2026
Kayla M Teopiz, Gia Han Le, Sabrina Wong et al.
A systematic review of 13 preclinical studies and 1 human study found that dextromethorphan (DXM), a glutamatergic modulator with antidepressant properties, attenuates reward-seeking behavior in rats, as measured by conditioned place preference and behavioral sensitization. In the single human study involving 20 healthy participants, self-reported drug-liking for DXM (400 mg/70 kg) was significantly lower compared to psilocybin (20 mg and 30 mg) 7 hours after dosing. The review highlights a paucity of human studies and suggests that future research should investigate DXM's effects on reward function using validated paradigms in people with anhedonia.
Journal of Affective Disorders
February 12, 2026
Erica Kaczmarek, Nelson Rodriguez, Noah Chisamore et al.
Anhedonia, a core symptom of depression that often resists standard treatments, may be reduced by psilocybin-assisted psychotherapy (PAP). In a secondary analysis of a randomized, waitlist-controlled trial, 30 adults with treatment-resistant depression (major depressive disorder or bipolar II disorder) received one 25 mg dose of oral psilocybin plus psychotherapy. Anhedonia severity, measured by the Snaith-Hamilton Pleasure Scale, decreased significantly at the 2-week primary endpoint, with clinically meaningful improvements persisting at 3 and 6 months. The analysis adjusted for sex and age. These preliminary results suggest PAP could be a promising intervention for anhedonia in treatment-resistant depression, though larger placebo-controlled trials are needed to confirm the findings and clarify underlying mechanisms.
Journal of Affective Disorders
February 4, 2026
Raquel Kosted, Alli Waddell, Ken Adolph et al.
Depression symptoms improved over time in patients receiving five ketamine infusions, with faster initial improvement that slowed later. Higher scores on the Adverse Childhood Experiences (ACE) survey were linked to greater symptom reduction, regardless of whether patients received ketamine-assisted therapy or infusions alone. Younger adults showed a stronger response to infusions alone compared to ketamine-assisted therapy, while older adults showed the opposite pattern. The association between higher ACE scores and greater symptom reduction was particularly pronounced in younger adults and reversed in older adults. These findings suggest ketamine may offer a targeted benefit for people with early life stress, especially younger adults.
Journal of Affective Disorders
February 2, 2026
Alene Sze Jing Yong, Aimee Freeburn, Suzie Bratuskins et al.
Australia became the first country to allow authorized prescribing of MDMA for PTSD outside clinical trials. Interviews with 21 clinicians, researchers, and patients who had direct experience with MDMA-assisted psychotherapy or PTSD revealed eleven themes, including the importance of expectation management, comprehensive baseline screening, shared decision-making, flexible treatment protocols, ongoing consent, strong therapeutic alliance, and post-treatment continuity of care. The findings emphasize the need for safeguards, provider training, and integration of care as MDMA-assisted psychotherapy enters clinical practice.
Journal of Affective Disorders
January 30, 2026
Yao-Zu Li, Cai-Qun Zhao, Mu-Yan Zuo et al.
A multimodal therapy combining esketamine with dexmedetomidine patient-controlled sleep (PCSL) was associated with sustained improvements in depressive symptoms and sleep quality over 6 months in 233 patients with treatment-resistant depression. Antidepressant response rates were 62% at 1 month, 59.73% at 3 months, and 58.49% at 6 months. Use of PCSL was linked to response at all time points, while additional esketamine during follow-up was associated with response at 3 months but not statistically significantly at 6 months. Age and disease duration also influenced response. No serious adverse events occurred.
Journal of Affective Disorders
January 23, 2026
Reinhard Janssen-Aguilar, Jithin Joseph, Huda Al-Shamali et al.
In a retrospective chart review of 209 adults with treatment-resistant depression treated with intravenous ketamine, depressive and anxiety symptoms improved significantly over four or six infusions, but the improvements were modest and highly variable across individuals. Anxiety symptoms improved more slowly and less robustly than depressive symptoms. End-of-treatment response and remission rates were numerically higher after six infusions than after four, but the difference was not statistically significant. Four distinct patterns of symptom change emerged for both depression and anxiety, highlighting the heterogeneity of treatment response. Durability after six infusions could not be assessed because follow-up data were available only for the four-infusion group.
Journal of Affective Disorders
January 20, 2026
Laura Mills, Susan L. Rossell, Sean Carruthers
Psilocybin use among people with bipolar disorder is associated with both benefits and risks. Analysis of 354 Reddit posts and comments revealed four themes: mania, depression, mixed experiences, and broader perspectives. Some users reported reduced depression symptoms and shifts in perspective, but others described increased or new mania, psychosis, and worsened depression. The findings suggest that while psilocybin may help some individuals with bipolar disorder, it also carries potential for adverse mental health effects.
Journal of Affective Disorders
January 19, 2026
Maria Garcia Garcia, Dahbia Belahda, Carine Graux et al.
In psilocybin-assisted psychotherapy, participants who responded to treatment described their experience as an inner dialogue and used adaptive coping strategies, while non-responders focused on sensory and affective details and relied on suppressive coping. The presence of inner dialogue may represent a unique therapeutic mechanism, underscoring the value of preparation and integration in such therapy.
Journal of Affective Disorders
June 18, 2025
Julia Myerson, Katrina A Rufino, Sanjay J. Mathew et al.
Electroconvulsive therapy (ECT) shows stronger antidepressant effects than intravenous ketamine for severe depression. In a retrospective chart review of 146 patients aged 18 to 74 with major depressive episodes, 94 received ketamine infusions twice weekly and 52 received ECT two to three times weekly. Overall, 45.2% of participants showed clinical symptom change on the Montgomery-Asberg Depression Rating Scale. ECT had a response rate of 67.3% and remission rate of 60.0%, compared to 45.7% and 46.1% for ketamine. Chi-square tests indicated a significant association between treatment type and symptom improvement, favoring ECT.
Journal of Affective Disorders
December 15, 2024
Rodrigo Machado‐Vieira, Gregory H Jones, Alan C. Courtes et al.
Fatigue, a multidimensional condition that often overlaps with depression, responds only modestly to standard antidepressants and mood stabilizers but has shown positive response to intravenous ketamine, which is limited by cost and access. This study evaluated a single 50 mg dose of intranasal ketamine in 28 individuals with major depressive disorder or bipolar depression, about 60% of whom also had alcohol use disorder. The group by time interaction for the NIH-Brief Fatigue Inventory score was significant, favoring intranasal ketamine over placebo at 4, 24, and 48 hours post-treatment. Intranasal ketamine was well-tolerated with minimal adverse effects. The findings suggest intranasal ketamine induces rapid anti-fatigue effects and may serve as an alternative rapid-acting option for fatigue across different medical conditions.
Journal of Affective Disorders
October 1, 2023
Olivier Brown
A letter to the editor raises methodological concerns about a published study on psilocybin therapy for depression. The original study reported increased low-frequency brain responses to music after treatment, but the letter questions the ANOVA region-of-interest analysis, noting that potential confounds such as age and biological sex may have influenced the reported variance attributed to psilocybin treatment. The letter does not present new data but critiques the statistical approach and suggests the findings may be less robust than claimed.
Journal of Affective Disorders
December 29, 2020
Nelson B Rodrigues, R. Mcintyre, Orly Lipsitz et al.
A 6-item short form of the Clinician-Administered Dissociative States Scale (CADSS-6) strongly correlates with the full 23-item version in patients with treatment-resistant depression receiving IV ketamine. Using retrospective data from 260 patients split into two groups, the CADSS-6 was derived from items most sensitive to ketamine-induced dissociation. Correlations between the short and full scale ranged from 0.91 to 0.95 across four infusions. The CADSS-6 offers a brief clinical assessment for dissociation, though it remains unvalidated in this population and requires prospective validation.
Journal of Affective Disorders
November 1, 2026
Cengiz Taşkaya, Leyla Sezgin, Necmettin Çiftci
An 8-week mindfulness-based stress reduction (MBSR) program for mothers of children with physical disabilities significantly reduced parental stress and increased mindfulness compared with no intervention. Significant improvements were observed in the psychological and environmental domains of quality of life, but not in the physical or social domains. The findings suggest MBSR can be a supportive approach in family-centered rehabilitation for these mothers.
Journal of Affective Disorders
November 1, 2026
Veronica L O'Brien, Nicolette P. Rickert
People with higher anxiety may find it harder to develop mindfulness through practice. A four-week online mindfulness course with 274 participants showed that previous mindfulness experience predicted higher starting state mindfulness, while baseline anxiety predicted higher starting state mindfulness but slower growth in state mindfulness over time. Growth in state mindfulness during the course predicted higher final levels of trait mindfulness. The findings suggest that anxiety can interfere with the benefits of mindfulness training.
Journal of Affective Disorders
July 16, 2026
Sara Massetti, Sanne Y Smith-Apeldoorn, Jolien K E Veraart et al.
Ketamine and its enantiomer esketamine are effective in only 30-35% of patients with treatment-resistant depression. Increased serum brain-derived neurotrophic factor (BDNF) after a single intravenous dose has been proposed as a biomarker of antidepressant response, but effects under different treatment schedules are unclear. In a randomized, placebo-controlled trial of six-week, low-dose, oral esketamine (90 mg/day, three 30 mg intakes), depression severity and serum BDNF were measured in 54 patients at baseline, end of treatment, and after a four-week washout. BDNF levels did not significantly differ between esketamine and placebo groups during treatment or washout. An increase in BDNF occurred regardless of treatment condition.
Journal of Affective Disorders
March 15, 2026
Patrícia Cavalcanti-Ribeiro, Lara Carvalho Araújo Melo De Souza, Vagner Deuel O de Tavares et al.
In a small open-label trial of 22 patients with treatment-resistant depression who received seven weekly subcutaneous doses of esketamine, those with elevated baseline C-reactive protein (CRP > 1 mg/L) showed significant reductions in CRP by week 4 and week 8, while patients without inflammation showed no change. By week 8, CRP levels in both groups were comparable. Although the inflammation group had a greater average reduction in depression severity (15.88 points on the MADRS scale versus 11.14 points), this difference was not statistically significant, and changes in CRP did not predict symptom improvement. Larger controlled studies are needed.
Journal of Affective Disorders
February 15, 2026
Tomas Lindegaard, Anton Käll
Psychedelic-assisted psychotherapy (PAP) shows large to very large effects on symptoms of depression and anxiety at post-treatment and follow-up, with Hedge's g values ranging from 0.98 to 1.83. A meta-analysis of 23 clinical trials found some evidence that two dosing sessions produce larger between-group effects than one session, though this finding was not robust across all analyses and needs replication. Only three studies used evidence-based psychotherapy protocols, limiting analysis of that moderator. The field would benefit from more thorough reporting of psychotherapy protocols to enable comparison between studies.
Journal of Affective Disorders
February 14, 2026
H. Xue, Xu Yang, Shihui Kuai et al.
Repeated exposure to the general anesthetic sevoflurane during mid-gestation induces depression-like behaviors in postpartum rats. Pregnant rats exposed to 3% sevoflurane for two hours on gestational days 13-15 showed increased immobility in the forced swim test, prolonged feeding latency, reduced food consumption, and decreased movement in the open field test on postpartum day 1. These behaviors were accompanied by decreased AMPK/SIRT1 expression, activation of the NLRP3 inflammasome, microglial activation, and increased inflammatory cytokines in the hippocampus. Treatment with AICAR (an AMPK agonist), MCC950 (an NLRP3 antagonist), minocycline (a microglial activation inhibitor), or ketamine alleviated these effects, while dorsomorphin (an AMPK antagonist) reversed ketamine's antidepressant effects. The findings indicate that ketamine alleviates postpartum depression-like behaviors by reducing microglial neuroinflammation and NLRP3 inflammasome activation via the AMPK/SIRT1 signaling pathway.
Journal of Affective Disorders
February 1, 2026
Richard Lawrence Blake
Six weekly 90-minute online group sessions of Conscious Connected Breathwork (CCB) reduced anxiety symptoms substantially more than a waitlist control condition. Among 107 adults (80% women, mean age 41, 79% white) randomly assigned to CCB or a waitlist, the breathwork group's anxiety scores dropped from an average of 43.87 to 33.31 on the SAS, a mean reduction of 10.56 points, whereas the control group declined from 43.00 to 41.11, a reduction of only 1.89. The difference between groups was statistically significant with a large effect size. CCB shows promise as a low-cost, accessible online intervention for anxiety.
Journal of Affective Disorders
February 1, 2026
Kayla M Teopiz, Sabrina Wong, Gia Han Le et al.
Reward processing disruptions in major depressive disorder (MDD) may relate to altered frontostriatal brain activity. Glutamatergic modulators might improve reward function. This systematic review examined 11 fMRI studies testing glutamatergic agents—ketamine (9 studies), nitrous oxide (1), and memantine (1)—on frontostriatal activity in people with MDD or healthy controls. Preliminary evidence suggests intravenous ketamine may alter functional connectivity in striatal regions, potentially relevant to improved reward function in treatment-resistant depression. More research is needed on how these modulators affect reward-related brain structures, the timing of effects, and baseline characteristics predicting antidepressant response.
Journal of Affective Disorders
June 15, 2025
Guangzheng Tang, Bijun Chen, Manhua Wu et al.
Mindfulness-based cognitive therapy (MBCT) reduced worry severity more than online psychoeducation in people with generalized anxiety disorder, but both interventions reduced anxiety to a similar degree overall. Among those who experienced childhood emotional abuse, MBCT was more effective at reducing anxiety than psychoeducation, and also more effective for anxiety in that subgroup compared to those without such abuse. The findings suggest MBCT's effect on anxiety depends on a history of childhood maltreatment, especially emotional abuse.
Journal of Affective Disorders
January 15, 2024
Yong Yang, Akifumi Eguchi, Xiayun Wan et al.
Mice with hepatic ischemia/reperfusion (HI/R) injury showed depression-like behaviors, splenomegaly, systemic inflammation, reduced synaptic proteins in the prefrontal cortex, altered gut microbiota, and changed blood metabolites and lipids. Cutting the subdiaphragmatic vagus nerve blocked these changes, suggesting the gut-microbiota-liver-brain axis via the vagus nerve underlies the link between liver injury and depression. A single injection of arketamine alleviated the depression-like phenotypes in these mice, indicating potential for treating depression in chronic liver disease patients.
Journal of Affective Disorders
June 1, 2023
Gustavo C. Leal, Breno Souza-Marques, Rodrigo P Mello et al.
In a small pilot trial, the antidepressant arketamine was compared with placebo for treatment-resistant depression. Ten participants received both arketamine (0.5 mg/kg) and saline one week apart in a randomized, double-blind, crossover design. Depression improved over time, but there was no significant difference between arketamine and placebo. Dissociation and other adverse events were minimal. The study was underpowered, and the authors conclude that arketamine was not superior to placebo but was extremely safe, recommending larger trials with different dosing strategies.