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Psychiatry research

ISSN 1872-7123

57 papers in the library · 711 citations · publishing 1995-2026

Papers

Low-dose ketamine improved brain network integrity among patients with treatment-resistant depression and suicidal ideation.

Psychiatry research March 1, 2025 Tung-Ping Su, Li-Kai Cheng, Pei-Chi Tu et al. 6 citations

A single low-dose infusion of ketamine (0.5 mg/kg) reduced depressive and suicidal symptoms more than a low-dose midazolam infusion in 43 patients with treatment-resistant depression and suicidal ideation. Brain scans showed that ketamine increased network integrity, specifically degree centrality and clustering coefficient in the angular gyrus and degree centrality in the right thalamus. These changes in the thalamus and default-mode network may underlie ketamine's antidepressant effect.

Safety outcomes of ketamine for treatment-resistant depression in clinical settings and development of the ketamine side effect tool-revised (KSET-R).

Psychiatry research February 1, 2025 Adam Bayes, Thanh Vinh Cao, Ana Rita Barreiros et al. 6 citations

Ketamine and its derivatives are increasingly used for treatment-resistant depression, but they can cause side effects during and between treatment sessions. The Ketamine Side Effect Tool (KSET) was designed to monitor these effects, but its length limited its use in clinics. Using retrospective data from three outpatient services, researchers calculated how often side effects occurred within sessions, between sessions, and at follow-up. They then developed a shorter version, the KSET-Revised (KSET-R), which showed good construct and concurrent validity for specific items and an overall tolerability rating. The revised tool is more feasible for clinical practice and is recommended for monitoring side effects in patients receiving ketamine treatment.

Effect of intravenous ketamine on suicidality in adults with treatment-resistant depression: A real world effectiveness study.

Psychiatry research January 1, 2025 David C J Chen-Li, Rodrigo B Mansur, Joshua D Di Vincenzo et al. 6 citations

In a real-world clinic setting, a single ketamine infusion significantly reduced suicidal ideation among 96 adults with treatment-resistant depression, as measured by the Columbia Suicide Severity Rating Scale. The reduction shifted the group average from active toward passive suicidal thoughts. A mediation analysis showed that ketamine's antisuicidal effects are partially independent of its antidepressant effects, suggesting a direct benefit on suicidality beyond mood improvement. The findings support ketamine's effectiveness for suicidal ideation outside controlled clinical trials.

Lessons learned from the regulatory alignment in ketamine, esketamine and arketamine clinical trials: A cross-sectional analysis of protocols from ClinicalTrials.gov.

Psychiatry research August 1, 2025 Damian Swieczkowski, Aleksander Kwaśny, Krzysztof Sadko et al. 5 citations

A cross-sectional evaluation of 40 clinical trials on ketamine and its enantiomers, esketamine and arketamine, for treatment-resistant depression reveals significant methodological inconsistencies. Key issues include inadequate blinding due to ketamine's dissociative effects, poor management of expectancy bias, and insufficient safety monitoring. Placebo response, accounting for a large portion of treatment effects, was inconsistently handled, and long-term follow-up was lacking in most trials, limiting understanding of extended safety. The findings call for harmonized, rigorous frameworks to improve regulatory approval and therapeutic success, with lessons applicable to other psychedelics under investigation for mental health disorders.

Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial.

Psychiatry research December 1, 2024 Shampa Maji, Archana Mishra, Debadatta Mohapatra et al. 5 citations

Adding 30 mg of dextromethorphan daily to standard SSRI treatment for eight weeks led to significantly greater reductions in depression severity, higher response and remission rates, and better clinical global improvement in patients with mild to moderate major depressive disorder, compared to adding a placebo. The combination was well-tolerated, with adverse events comparable between groups. No significant difference in serum BDNF levels was observed. These results suggest that early augmentation of SSRIs with dextromethorphan may improve clinical outcomes.

Effects of mindfulness-based interventions (MBIs) on psychotic symptoms and psychological outcomes in patients with schizophrenia spectrum disorders: A systematic review and meta-analysis.

Psychiatry research December 1, 2024 Chuntana Reangsing, Sathit Wongsuraprakit, Sasinun Punsuwun et al. 5 citations

A meta-analysis of 24 studies with 1,632 participants found that mindfulness-based interventions reduced psychotic symptoms, improved global functioning, insight, and mindfulness in people with schizophrenia spectrum disorders compared to control groups. Effects were large for functioning and insight but varied substantially across studies. Older age was linked to worse psychotic symptoms, while more days of practice improved symptoms, functioning, and insight. Mixed-format interventions (individual plus group) and those including home assignments yielded greater improvements in insight. No adverse effects were reported. The findings suggest mindfulness-based interventions may be a useful complementary treatment for schizophrenia.

Efficacy and Safety of LSD in the treatment of mental and substance use disorders: A systematic review of randomized controlled trials.

Psychiatry research July 5, 2025 Maria Helha Fernandes-Nascimento, Priscila Weber, André Brooking Negrão 4 citations

A systematic review and meta-analysis of 11 double-blind randomized controlled trials involving 682 adults with substance use disorders, anxiety, or depression found that LSD produced a small but statistically significant reduction in substance use disorder symptoms (standardized mean difference = 0.19). No heterogeneity was observed for that outcome. However, 45% of the trials did not report adverse events, and serious adverse events were noted in only one study. The effectiveness of LSD varied by mental disorder, and most trials were conducted in the 1960s and 1970s, highlighting the need for more high-quality contemporary research.

The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies.

Psychiatry research June 1, 2025 Jeremy Weleff, Alejandra Pulido-Saavedra, Ardavan Mohammad Aghaei et al. 4 citations

A systematic review of clinical studies on psychedelics for opioid use disorder found few completed trials using serotonergic psychedelics; most investigated ibogaine or ketamine. The evidence is limited by weak study designs focused on opioid withdrawal, few double-blind or placebo-controlled trials, and considerable methodological heterogeneity that makes comparisons across compounds difficult. Most studies had a high risk of bias, mainly due to lack of randomization, blinding, and blinded outcome assessment. The review outlines these limitations and steps to improve the quality of future research in this area.

Efficacy of addition of the anti-inflammatory, IV glutathione to standard ketamine IV therapy in major depressive disorder.

Psychiatry research July 1, 2024 Ladan Eshkevari, Michelle Sales, Christina Collins et al. 3 citations

Adding glutathione, an antioxidant, to standard ketamine infusion does not improve outcomes for people with major depressive disorder compared to ketamine alone. In a double-blind study with 30 patients split into two groups of 15, both groups showed significant drops in depression scores from day 1 to day 14, and from day 14 to day 28 for one measure, indicating the overall treatment was effective. However, there were no statistically significant differences between the groups over time. A sustained improvement in depressive symptoms lasted for 14 days after infusion in both groups.

Mechanisms of therapeutic change after psychedelic treatment in OCD.

Psychiatry research June 1, 2024 Gayle Maloney, Terence Ching, Stephen A Kichuk et al. 3 citations

About 30-50% of people with obsessive-compulsive disorder do not respond to standard treatments. Recent pilot data suggest benefit from both psilocybin-assisted psychotherapy and imagery rescripting. Both interventions appear to allow reprocessing of negative emotions and core beliefs linked to past aversive events. The authors propose that basing psilocybin-assisted psychotherapy on an imagery rescripting framework may provide synergistic benefits in reducing symptoms, modifying core beliefs, and supporting value-based living.

Attention deficit hyperactivity disorder symptoms and lifetime use of psychoactive substances among French university students: A cross-sectional study.

Psychiatry research October 1, 2023 François A M Jean, Ashlyn N Schwartz, Charline Galesne et al. 3 citations

Among 13,837 university students, those with more symptoms of attention deficit hyperactivity disorder (ADHD) were more likely to have used a wide range of illicit substances over their lifetime, including ketamine, magic mushrooms, and poppers, as well as nine other psychoactive drugs. Higher ADHD symptom levels were also linked to using a greater number of different substances. The findings suggest that ADHD symptoms are associated with both the likelihood of ever using psychoactive substances and the variety of substances tried.

Personalizing ketamine therapy: Real-world predictors of response to IV ketamine and intranasal esketamine in treatment-resistant depression.

Psychiatry research December 1, 2025 Ahmed Z Elmaadawi, Imane Naha, Shruti Prabhudesai et al. 2 citations

Both intravenous (IV) ketamine and intranasal esketamine significantly reduce depressive symptoms in adults with treatment-resistant depression (TRD). IV ketamine produced a greater reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS) than esketamine (mean difference about 5 points), especially in highly treatment-resistant patients. Comorbid psychiatric conditions strongly moderated outcomes: patients without comorbidities improved the most (MADRS change -22.0), while those with borderline personality disorder showed minimal response (MADRS change -3.7). Males improved more than females on the MADRS, but no sex difference appeared on the patient-rated PHQ-9. Age had no effect. Personalized approaches considering comorbidity profiles are critical for optimizing outcomes.

Efficacy of esketamine after cesarean section for women with symptoms of prenatal depression: A randomized controlled trial.

Psychiatry research November 16, 2025 2 citations

Perioperative esketamine reduces the incidence of postpartum depression in women with prenatal depression undergoing cesarean section. In a randomized trial, 18.8% of women receiving esketamine developed postpartum depression at 6 weeks, compared to 39.3% in the placebo group. Esketamine also lowered early postpartum anxiety, improved pain control with less opioid use, and increased sleep duration. Dizziness was more common with esketamine.

Outcomes of patients receiving interventional psychiatric procedures in a large integrated healthcare system.

Psychiatry research July 19, 2025 Kevin J Li, Natalie E Slama, Ingrid L Chen et al. 2 citations

Patients receiving electroconvulsive therapy, transcranial magnetic stimulation, or ketamine intravenous treatments for treatment-resistant depression showed greater improvement on the PHQ-9 depression questionnaire at six weeks compared to those receiving standard medication management alone. Among 22,481 patients in a large integrated healthcare system, the adjusted improvement was 2.16 points greater for ECT, 2.02 points greater for ketamine, and 1.64 points greater for TMS. Certain patient characteristics were linked to worsening symptoms, including non-white race for ECT and medication management, anxiety disorder for TMS, and personality disorder for all groups. Conversely, psychotic disorder was associated with better response to ECT, and bipolar disorder with better response to ketamine. Continuation or maintenance ketamine treatment was associated with a 75% lower risk of psychiatric hospitalization within 12 months.

Online mindfulness-based vs. cognitive-behavioural stress reduction for medical students: A randomized controlled trial.

Psychiatry research July 11, 2025 Aysegul Yay-Pence, Selcuk Aslan, Merve Coldur et al. 2 citations

Both online mindfulness-based stress reduction (MBSR) and cognitive behavioural stress reduction (CBSR) reduced depression, anxiety, and perceived stress in medical students. In an analysis of all randomized participants, MBSR showed small to moderate effects (depression d=0.50, anxiety d=0.73, stress d=0.48) and CBSR showed similar effects (depression d=0.40, anxiety d=0.52, stress d=0.42), with no significant differences between the two. Among those who completed the program, improvements were moderate to strong, and MBSR was superior to CBSR for reducing anxiety. Greater adherence to the programs enhanced outcomes, particularly for MBSR's effect on anxiety.

Can ketamine and other glutamate receptor modulators be considered entactogens?

Psychiatry research July 1, 2025 Hiroe Hu, Alaina N Tillman, Miyu Fujita et al. 2 citations

A systematic review of 30 studies suggests that ketamine and, to a lesser extent, d-cycloserine may enhance empathy and prosocial behavior. These glutamate receptor modulators appear to alter self- and other-perception by changing activity in brain regions linked to empathetic concern and mentalizing—the ability to understand one's own and others' thoughts and feelings. The findings point toward potential therapeutic applications for conditions involving impaired empathy and prosocial behavior, such as mood, neurodevelopmental, psychotic, and personality disorders.

Patient preference effects in a randomized comparative effectiveness study of electroconvulsive therapy and ketamine for treatment resistant depression: An ELEKT-D trial secondary analysis.

Psychiatry research May 1, 2025 Gerard Sanacora, Brian S Barnett, Bo Hu et al. 2 citations

Patients with treatment-resistant depression who preferred ketamine over electroconvulsive therapy (ECT) were more likely to respond to treatment, regardless of which treatment they actually received. Matching patients to their preferred treatment improved response rates for ketamine but not for ECT, and reduced adverse events for ECT-treated patients. Ketamine was the more popular choice overall. The findings suggest that aligning treatment with patient preference can influence effectiveness, safety, and possibly adherence, but these effects vary by treatment modality and context.

Investigating change in the ability to decentre and depressive symptomatology over the course of a six-month mindfulness-based intervention in patients with persistent depression.

Psychiatry research November 1, 2024 Jonathan Hamilton, Thorsten Barnhofer 2 citations

Decentering skills, the core ability cultivated in mindfulness-based interventions, continue to increase over six months of practice and drive reductions in depressive symptoms. In a blended online and in-person program, 44 adults with persistent depression provided self-reports at three time points. Thirty-one participants completed the intervention, averaging 68.6% of assigned practices. Statistical modeling showed that changes in decentering preceded and predicted later symptom improvements, suggesting that longer practice periods help move patients closer to recovery or remission.

Subcutaneous ketamine reduces suicide risk and improves functioning in depression: A proof-of-concept study.

Psychiatry research July 1, 2024 Ana Paula Anzolin, Daniel Prates Baldez, Bruno Braga Montezano et al. 2 citations

Subcutaneous ketamine substantially reduced suicidal thoughts and depressive symptoms in patients with severe depression. In a naturalistic study at a Brazilian hospital, 26 patients with a current depressive episode received adjustable ketamine doses starting at 0.5 mg/kg. After about eight sessions, most patients achieved remission of suicidal ideation, as measured by the Columbia Suicide Severity Rating Scale. Higher ketamine doses were associated with greater improvements in depression, suicidal ideation, and overall functioning. Improvements were sustained over six months of follow-up in 18 patients. Side effects were minor and short-lived. The findings suggest subcutaneous ketamine is a promising, well-tolerated, and potentially cost-effective treatment for severe depression with suicidal tendencies, warranting further controlled trials.

Psychedelics as a potential treatment for borderline personality disorder: A narrative review.

Psychiatry research July 1, 2026 Erin Artna, Guneet Sandhu, Noah Chisamore et al. 1 citation

Borderline personality disorder (BPD) is a serious mental illness with limited treatment options. Although patients with BPD are often excluded from psychedelic research due to safety concerns about suicide and substance misuse, emerging evidence suggests psychedelics may target core BPD symptoms and common co-occurring mood and anxiety disorders. This narrative review analyzed 22 studies from multiple databases examining ketamine, esketamine, and psilocybin in individuals with BPD. Preliminary evidence indicates these psychedelics may be safe and effective for improving core BPD symptoms and socio-occupational functioning, but more high-quality research focused on BPD-specific outcomes is needed to clarify their potential as a treatment modality.

Single fixed-dose intranasal racemic ketamine treatment for the treatment of acute suicidality in a transdiagnostic patient population: Results of a pilot study.

Psychiatry research March 1, 2026 Gijsbrecht H J Roelandt, Jurriaan F M Strous, Radboud M Marijnissen et al. 1 citation

A single open-label dose of 75 mg intranasal racemic ketamine was tested in 12 acutely suicidal patients in an emergency setting, regardless of underlying diagnosis. The treatment was generally feasible, well-tolerated, and safe. Scores for suicidal ideation and depression showed a downward trend one day after treatment, but this effect declined by day seven. One patient developed ketamine misuse several weeks after participation. No definitive conclusions about efficacy could be drawn from this pilot study.

Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.

Psychiatry research February 2, 2026 T Aboulafia-Brakha, A Buchard, C Mabilais et al. 1 citation

In a real-world clinical setting, a single session of psychedelic-assisted psychotherapy with either LSD or psilocybin was well tolerated and linked to significant reductions in depression and anxiety among adults with treatment-resistant disorders. Symptoms improved substantially, with large effects for depression and moderate effects for anxiety. Cognitive changes included less self-blame, rumination, and catastrophizing, along with more positive refocusing and reappraisal. Adverse effects were mild and temporary, with no serious complications. The findings suggest that both substances can be effective and safe in specialized routine care.

Neural basis of GAD improvement following a mindfulness-based intervention and antidepressant treatment: an analysis from a randomized controlled trial.

Psychiatry research July 12, 2025 Marianna de Abreu Costa, Patrícia Bado, Maiko Schneider et al. 1 citation

Symptom improvement in generalized anxiety disorder may involve enhanced functional coupling between brain regions critical for emotional regulation, self-referential processing, and stimulus selection, particularly between the left amygdala and right orbitofrontal cortex. In a randomized trial with 20 patients, those receiving mindfulness training showed improvement linked to amygdala connectivity with the default mode and salience networks, while those on fluoxetine showed improvement linked to amygdala-orbitofrontal cortex coupling. However, no significant differences between the two treatment groups were found. Larger studies are needed to clarify treatment-specific neural mechanisms.

The future of hallucination research: Can hallucinogens and psychedelic drugs teach us anything?

Psychiatry research January 1, 2023 Flavie Waters 1 citation

Hallucinations are among the least understood human experiences, recognized across cultures and in both mental illness and those not mentally unwell. Early research on hallucinogens like LSD was criticized and withdrawn, but its revival offers new opportunities to examine the mechanism of hallucinating. Studying psychedelic compounds in controlled settings with mentally healthy individuals may reveal temporal shifts in perceptual awareness, decode what influences contents, affect, meaning, and appraisals of hallucinations, and guide novel psychotherapy and drug therapy.

Ketamine and esketamine for the prevention of postpartum depression: A systematic review and network meta-analysis, with an integrated evidence synthesis.

Psychiatry research September 1, 2026 Isis Lunsky, Gilmar Gutierrez, Xena Wang et al.

Postpartum depression (PPD) is common and harmful if untreated, with few effective prevention strategies. Ketamine and esketamine are rapid-acting antidepressants showing promise for PPD. This review searched five databases for peer-reviewed randomized controlled trials, pilot studies, and observational studies examining ketamine or esketamine for PPD prevention during pregnancy or postpartum, for both cesarean and vaginal deliveries. A network meta-analysis and narrative synthesis were used. Thirty-six studies were identified; five included vaginal delivery, thirty included cesarean section, and one did not specify delivery mode. Results suggested that ketamine and esketamine were well tolerated and may reduce PPD risk. However, data quality was low to very low, so results should be interpreted cautiously. More high-quality studies are needed.