European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
September 1, 2024
Aleksander Kwaśny, Julia Kwaśna, Alina Wilkowska et al.
24 citations
Ketamine, a medication used for depression, may also reduce anhedonia (loss of interest or pleasure). A systematic review of 22 studies (4 randomized-controlled trials and 18 open-label trials) found that all reported alleviation of anhedonia symptoms after ketamine or esketamine administration, regardless of the number of infusions. Neuroimaging studies showed changes in functional connectivity linked to improvement. However, limitations include few placebo-controlled trials. The review suggests a potential anti-anhedonic effect of ketamine in depressed patients, likely through neuroplastic changes.
Brain Sciences
January 13, 2023
Maria Gałuszko‐węgielnik, Zuzanna Chmielewska, Katarzyna Jakuszkowiak‐wojten et al.
20 citations
Psychotic treatment-resistant depression is a severe form of major depressive disorder involving hallucinations or delusions, often underdiagnosed and undertreated. Ketamine has shown rapid antidepressant effects, and its enantiomer esketamine was approved for treatment-resistant depression in 2019. This report describes four inpatients with treatment-resistant depression and psychotic features, including one in severe suicidal crisis, who received a single 0.5 mg/kg intravenous infusion of ketamine as an add-on to standard care. Monitoring showed no worsening of psychotic symptoms in short or long term, and all patients achieved stable remission with an immediate antisuicidal effect. Ketamine may benefit individuals with this condition.
Frontiers in psychiatry
January 1, 2024
Aleksander Kwaśny, Alina Wilkowska, Wiesław Jerzy Cubała
10 citations
A systematic review of clinical trials on 5-MeO-DMT, an atypical psychedelic being studied as a rapid-acting antidepressant, found that the drug has a good short-term safety and tolerability profile. Three trials involving 78 participants (two with healthy volunteers, one with treatment-resistant depression patients) reported no serious adverse events and no drop-outs. The authors conclude that 5-MeO-DMT administration in humans is safe in the short term, but call for larger, placebo-controlled trials with longer follow-up to assess potential chronic adverse events.
Frontiers in Psychiatry
December 8, 2023
Alina Wilkowska, Wiesław Jerzy Cubała
10 citations
Bipolar depression is a serious psychiatric condition linked to high suicide risk, treatment resistance, chronicity, and poor quality of life. Approved treatments are limited and often insufficient, creating an urgent need for new strategies. Intranasal esketamine, a ketamine enantiomer, is a rapid-acting antidepressant proven effective for treatment-resistant depression. Research on bipolar depression, though less extensive, suggests esketamine may be a safe alternative with low risk of mood polarity shifts. Reports indicate ketamine treatment may reduce suicidal thoughts, anhedonia, and anxiety. Ketamine's potential mood-stabilizing properties are hypothesized. This narrative review examines ketamine as an add-on to standard medication for acute bipolar depression.
Pharmaceuticals
January 24, 2023
Adam Włodarczyk, Alicja Dywel, Wiesław Jerzy Cubała
10 citations
In patients with treatment-resistant depression, intravenous ketamine may elevate psychotic symptoms in those with epilepsy. Among 49 inpatients with major depressive or bipolar depression treated with ketamine, the presence of epilepsy was significantly associated with an increase in Brief Psychiatric Rating Scale scores over time. For the subgroup with epilepsy (6 patients), substantial fluctuations occurred across all administrations. Psychotic symptoms for other comorbid conditions were not significant. The findings indicate that careful consideration of comorbidities and close clinical supervision are needed during ketamine treatment.
Asian journal of psychiatry
September 1, 2024
Michał Pastuszak, Wiesław Jerzy Cubała, Aleksander Kwaśny
8 citations
In patients with treatment-resistant bipolar depression receiving eight intravenous ketamine infusions while continuing their usual medications, the most common new symptoms that appeared included decreased appetite, weight gain, excessive sleep, and mood changes that varied throughout the day. Feelings of sadness, hopelessness about the future, reduced sexual interest, and physical discomfort did not emerge. However, 13.6% of patients reported new thoughts of death or suicide. Larger studies using both clinician and patient reports are needed to better understand these treatment-emergent symptoms, and clearer definitions would improve future research.
Frontiers in psychiatry
January 1, 2024
Aleksander Kwaśny, Wiesław Jerzy Cubała, Adam Włodarczyk
7 citations
Anhedonia, a reduced ability to experience pleasure, is a core depression symptom that often persists despite standard treatments. Ketamine appears to have antianhedonic effects. In a naturalistic study of 28 inpatients with treatment-resistant depression, both responders and non-responders to ketamine therapy showed significant reductions in anhedonia over time, as measured by the Snaith-Hamilton Pleasure Scale. Non-responders also reported significant improvement in self-reported depression at the seventh infusion, but not at follow-up. Changes in depressive symptoms and anhedonia did not fully overlap, suggesting ketamine may alleviate anhedonia as a separate symptom domain regardless of overall treatment response.
Brain Sciences
December 11, 2020
Jakub Słupski, Wiesław Jerzy Cubała, Natalia Górska et al.
7 citations
Serum copper concentration changes during ketamine treatment in patients with treatment-resistant depression, but no clear link between copper levels and treatment response was found. Patients with major depressive or bipolar disorder received weekly ketamine infusions, and copper levels were measured before, during, and after treatment. Copper concentration was significantly higher before treatment than after the fifth infusion, and also higher after the full course than after the fifth infusion. However, changes in copper levels did not correlate with scores on depression or mania rating scales, nor with somatic comorbidities. The findings provide data on copper's role in short-term ketamine therapy but do not support copper as a marker of treatment response.
Journal of Psychopharmacology
July 11, 2025
Aleksander Kwaśny, Patrycja Ciurkowska, Wiesław Jerzy Cubała et al.
6 citations
In interventional clinical trials of psilocybin and LSD, participants are overwhelmingly White, raising concerns about whether these therapies are safe and effective for diverse populations. A cross-sectional analysis of nine eligible trials (eight psilocybin, one LSD) registered on ClinicalTrials.gov through January 2025 found that among 501 psilocybin participants, 87.2% were White, 3.0% Black, and 5.0% Asian; ethnicity was reported in only four trials, with 13.4% identifying as Hispanic or Latino. The single LSD trial of 11 older adults reported no race or origin data. Participation-to-population ratios for U.S.-only trials confirmed underrepresentation of Black and Asian individuals. The authors conclude that broader recruitment and standardized reporting are essential to ensure equity and establish safety and efficacy across groups.
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.
Progress in neuro-psychopharmacology & biological psychiatry
June 7, 2025
Damian Swieczkowski, Aleksander Kwaśny, Wiesław Jerzy Cubała
5 citations
Treatment-resistant depression (TRD) is difficult to treat because many patients do not respond to standard antidepressants. NN-dimethyltryptamine (DMT), a fast-acting psychedelic, may offer benefits due to its rapid onset and short duration. This systematic review of five clinical trials found that DMT was generally well-tolerated, with no serious adverse events. Intravenous DMT caused temporary increases in systolic blood pressure (up to 25.7%) and heart rate at higher doses. Inhalation led to mild throat discomfort, and oral or intranasal use caused mild nausea and dizziness, all short-lived. Psychotomimetic effects like ego dissolution were dose-dependent but manageable. Larger, well-controlled studies are needed to confirm safety and efficacy in TRD patients.
Psychiatria polska
June 30, 2024
Piotr Gałecki, Katarzyna Maria Bliźniewska-Kowalska, Wiesław Jerzy Cubała et al.
5 citations
A Polish expert panel developed national treatment standards for intravenous racemic ketamine in depressive disorders, addressing the one-third of depressed patients who do not respond to standard antidepressants. The guidelines summarize research on ketamine's efficacy and safety for unipolar and bipolar depression, leveraging its action as an NMDA receptor antagonist to modulate the overactive glutamatergic system implicated in depression. The recommendations cover indications, contraindications, precautions, and treatment protocols, aiming to expand therapeutic options for practicing psychiatrists.
Pharmacological reports : PR
December 1, 2024
Julia Kwaśna, Wiesław Jerzy Cubała, Aleksander Kwaśny et al.
4 citations
Intravenous ketamine at 0.5-1.0 mg/kg based on actual body weight is effective for treatment-resistant depression. In a retrospective analysis of 28 inpatients with treatment-resistant major depressive disorder, alternative dosing formulas using lean body mass, ideal body weight, or body surface area generally led to underdosing compared to the standard 0.5 mg/kg dose. Only two participants received higher doses when using the Devine formula. The findings suggest that alternative dosing methods may reduce treatment response and complicate outcome interpretation. Future studies should incorporate direct body composition measures like bioimpedance and waist-to-hip ratio.
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
Neuropsychopharmacology Reports
July 20, 2025
Zofia Kachlik, Wiesław Jerzy Cubała, Michał Walaszek et al.
3 citations
Ketamine is a fast-acting antidepressant for treatment-resistant bipolar depression, but about 40% of patients do not respond. Among 35 patients receiving a four-week ketamine regimen, nonresponders had more psychiatric comorbidities (median 2 vs. 1) and were more likely to have any psychiatric comorbidity (78.6% vs. 33.3%) and prior benzodiazepine use (64.3% vs. 23.8%). Individual comorbidities and baseline suicidality were not linked to response. Ketamine remains safe and well-tolerated for short-term use, but a heavier comorbidity burden and benzodiazepine use may predict nonresponse.
Pharmacological reports : PR
April 30, 2025
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik et al.
3 citations
Among inpatients with treatment-resistant depression receiving ketamine over four weeks, 75% did not respond. Non-responders had lower rates of prior substance use disorder (53.3% vs. 100%) and fewer psychiatric comorbidities. The findings suggest that a higher burden of traditional risk factors for treatment-resistant depression may not limit ketamine's effectiveness and could even enhance response compared to 'pure' major depressive disorder. Early identification of potential non-responders could optimize treatment decisions and reduce ineffective exposure.
Drugs - real world outcomes
December 1, 2024
Michał Pastuszak, Wiesław Jerzy Cubała, Aleksander Kwaśny
3 citations
After a course of ketamine infusions, many patients with bipolar depression still experience residual symptoms, even when their overall depression scores improve. In a real-world analysis of 22 patients receiving ketamine while continuing their usual medications, 14 responded to treatment. The most common lingering symptoms were sad mood (85.7% of responders), a pessimistic view of the future (78.6%), difficulty falling asleep, and low physical energy (both 71.4%). Difficulty falling asleep and sad mood were also rated as the most severe. These findings highlight that functional recovery may require targeting specific residual symptoms beyond overall mood improvement.
Pharmacopsychiatry
April 17, 2025
Aleksander Kwaśny, Zuzanna Gaca, Damian Świeczkowski et al.
2 citations
Regulatory compliance in clinical trials of psilocybin for major depressive disorder and treatment-resistant depression shows gaps. A review of four trial protocols from ClinicalTrials.gov found that while they superficially met regulatory requirements, they inadequately addressed drug interactions, concurrent antidepressant use, and prohibited medications. Functional unblinding and expectancy bias were not fully accounted for. Risk mitigation relied on external criteria. Patients with bipolar or schizoaffective disorders were excluded. The most common psilocybin dose studied was 25 mg. Two trials were double-blind. The findings underscore the need for stricter adherence to regulatory standards in psychedelic clinical research and for exploring efficacy in broader populations.
Pharmacological reports : PR
December 1, 2024
Aleksander Kwaśny, Wiesław Jerzy Cubała, Adam Włodarczyk et al.
2 citations
In a small observational study of 28 inpatients with treatment-resistant major depressive disorder, neither those who responded to ketamine treatment nor those who did not reported significant changes in self-reported sleep problems—including insomnia, nighttime restlessness, early morning waking, or hypersomnia—after eight intravenous ketamine infusions over seven days. These results contrast with previous research that had suggested modest sleep improvements with ketamine. The authors caution that the small sample size limits the reliability of the findings.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
January 16, 2026
Damian Swieczkowski, Aleksander Kwaśny, Krzysztof Sadko et al.
1 citation
Psilocybin-assisted therapies are being tested for major depressive disorder and treatment-resistant depression, but rigorous research requires not only measuring the drug's effects but also consistently reporting non-pharmacological factors—such as the physical and social environment (set and setting)—that can influence outcomes. To address this, the ReSPCT guidelines were developed as a 30-item framework for standardized reporting. This review evaluated 13 clinical trial protocols (11 Phase II and 2 Phase III) from ClinicalTrials.gov and the EU Clinical Trials Information System. Using the ReSPCT checklist, only 15.6% of 390 item-level assessments showed full compliance; 64.6% had partial compliance, and 19.
Journal of Clinical Medicine
December 25, 2025
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik
1 citation
Patients with treatment-resistant depression report a range of experiences with ketamine therapy that go beyond symptom scores. Motivations, expectations, the subjective treatment experience, post-treatment changes, side effects, reasons for stopping, and the importance of the treatment setting and relationship with clinicians all shape how patients perceive the value and acceptability of ketamine. These findings highlight the need for patient-centered service design that aligns with what matters most to those receiving the treatment.
Frontiers in Nutrition
August 21, 2025
Jakub Słupski, Agnieszka Mechlińska, Adam Włodarczyk et al.
1 citation
A systematic review of five studies involving 678 participants examined how ketamine treatment affects appetite in people with treatment-resistant mood disorders. Two studies found significant improvement in reduced appetite after ketamine or esketamine treatment; one found no significant change; one reported a paradoxical worsening; and one noted minimal effect on increased appetite and atypical symptoms. The evidence suggests ketamine may improve depressive symptoms including appetite, or have neutral effects. Measuring appetite could help detect antidepressant effects beyond traditional medications and aid treatment planning for patients with metabolic disorders or malnutrition risk.
Journal of psychoactive drugs
April 18, 2025
Damian Swieczkowski, Aleksander Kwaśny, Krzysztof Sadko et al.
1 citation
Ibogaine, a non-classical psychedelic, is being studied as a potential treatment for substance use disorders, but safety concerns and lack of commercial interest hinder its development. A cross-sectional analysis of nine clinical trials from major registries found wide variability in trial designs, including dosing regimens and outcome measures. Most trials are early-phase, focusing on pharmacokinetics, withdrawal symptoms, and safety, with particular attention to cardiovascular risks. Preliminary evidence suggests possible therapeutic benefits, but the absence of large, late-phase trials prevents firm conclusions. Standardized clinical frameworks and lessons from research on classical psychedelics and MDMA could improve trial design and address issues like blinding and expectancy bias.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
December 1, 2024
Mariusz Stanisław Wiglusz, Zuzanna Chmielewska, Wiesław Jerzy Cubała
1 citation
Low-dose intravenous ketamine was safe and well tolerated in six patients with both depression and epilepsy. Side effects were mild and temporary, and no worsening of seizures occurred. Four of the six patients showed a significant reduction in depression scores on the Montgomery-Åsberg Depression Rating Scale, with two achieving full remission. Three patients reported a subjective decrease in seizure activity over twelve months. No serious adverse events happened. The authors caution that this is a small, post-hoc observation and that larger prospective studies are needed to confirm effects on seizures, depression, and side effects.
Journal of affective disorders
August 15, 2026
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik et al.
Anhedonia, a core symptom of major depressive disorder linked to poor outcomes, may be reduced by ketamine. In a retrospective analysis of 34 inpatients with treatment-resistant depression receiving short-term ketamine as an add-on to standard care, 16 patients (47.1%) did not respond to treatment, defined as less than a 50% reduction on the Snaith-Hamilton Pleasure Scale. Non-responders were more likely to be single, had fewer lifetime depressive episodes, and lower rates of prior substance use disorder. These factors suggest that psychosocial and demographic characteristics influence anhedonia treatment outcomes, supporting a personalized approach to mood disorder treatment.