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.
Frontiers in Psychiatry
December 2, 2021
Maria Gałuszko‐węgielnik, Adam Włodarczyk, Wiesław Jerzy Cubała et al.
5 citations
Repeated series of intravenous ketamine infusions, given as an add-on treatment, can be effective and safe for patients with treatment-resistant depression. In a case series of five inpatients aged 43–63 with major depressive disorder or bipolar I disorder, four achieved remission after the first series of eight infusions, and three after the second series. Adverse reactions were mild and transient. The results are limited to short-term, add-on intravenous ketamine and cannot be generalized to long-term maintenance or other formulations.
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 Swieczkowski 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.
BJPsych Open
July 1, 2023
Allan H. Young, Wiesław Jerzy Cubała, René Ernst Nielsen et al.
2 citations
Among people with treatment-resistant depression, those who had failed three or more prior treatments were more likely to achieve remission after eight weeks of esketamine nasal spray (28.0%) than after quetiapine extended release (10.9%). For those with only two prior treatment failures, remission rates were similar between the two treatments (26.5% vs. 21.8%). Esketamine also led to faster remission in both subgroups. The results suggest esketamine may be especially effective for patients with more extensive treatment histories.
Pharmaceuticals
May 3, 2021
Natalia Górska, Wiesław Jerzy Cubała, Jakub Słupski et al.
2 citations
Magnesium levels in the blood change over the course of ketamine treatment for depression. In patients with major depressive disorder or bipolar disorder, serum magnesium concentration was significantly higher before treatment began than after five or seven ketamine infusions. However, changes in magnesium levels were not correlated with depression scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) or with mania scores on the Young Mania Rating Scale (YMRS). The study also found no link between magnesium concentration and somatic comorbidities. While the findings support the idea that magnesium plays a role in treatment-resistant depression, especially with ketamine, there is no clear evidence of a straightforward relationship between magnesium levels and treatment response or other health conditions.
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.
Ther Adv Psychopharmacol
June 29, 2026
Damian Swieczkowski, Aleksander Kwaśny, Wiesław Jerzy Cubała
Informed consent forms for ketamine clinical trials listed on ClinicalTrials.gov are often written at a reading level that exceeds the average adult's ability, potentially limiting participants' understanding of risks and benefits. The analysis found that most forms required a college-level reading proficiency, which is higher than recommended for patient materials. This gap in readability may compromise informed consent in mental health research.
International journal of psychiatry in clinical practice
June 1, 2026
Damian Swieczkowski, Aleksander Kwaśny, Michal Pruc et al.
Women made up 62.9% of participants across 13 esketamine clinical trials for mental health disorders, while men comprised 37.1%. The racial distribution showed White participants at 69.08%, Asian at 13.31%, Black or African American at 3.60%, American Indian or Alaska Native at 0.08%, and Native Hawaiian or Other Pacific Islander at 0.04%. Hispanic or Latino representation ranged from 10.57% to 11.02% due to reporting discrepancies in one trial. These trials demonstrate significant racial and ethnic disparities, with underrepresentation of minority groups, highlighting the need for regulatory efforts to improve diversity and fair representation in future research.
Pharmacol Rep
May 20, 2026
Aleksander Kwaśny, Alina Wilkowska, Michał Pastuszak et al.
A retrospective analysis of patient-reported outcomes found that psychiatric adverse events emerged during ketamine treatment for major depressive disorder. The text does not specify the frequency, severity, or nature of these events, nor does it provide comparative data or a control group. The analysis suggests that such events can occur, but the magnitude and clinical significance remain unclear based solely on the abstract.
Research Square
February 17, 2026
Zofia Winczewska, Magdalena Górska‐ponikowska, Wiesław Jerzy Cubała
Ketamine at 25 ng/mL increased the viability of mouse hippocampal HT22 neuronal cells exposed to hydrogen peroxide, but only at the highest concentration tested (1000 µM H₂O₂). At that level, cell viability rose from 12% (±1.63%) without ketamine to 38% (±9.12%) with ketamine. This suggests a protective, nonlinear effect that depends on the intensity of oxidative stress, activating only at critical H₂O₂ overload typical of severe depression. The findings indicate a threshold antioxidant mechanism that may contribute to ketamine's antidepressant action and inform future predictive models for individualized treatment.
Therapeutic advances in psychopharmacology
January 1, 2026
Zofia Kachlik, Wiesław Jerzy Cubała, Michał Walaszek et al.
Anhedonia, a core symptom of bipolar depression, often fails to improve with ketamine treatment in patients with treatment-resistant bipolar depression. In a retrospective analysis of 31 patients who received eight doses of ketamine, 45.2% did not achieve a 50% or greater reduction in anhedonia scores. Nonresponders tended to have higher body mass index, later illness onset, fewer hypomanic episodes, and lower employment rates. These metabolic, illness-course, and psychosocial factors may help predict which patients are less likely to benefit from ketamine's anti-anhedonic effects.
Therapeutic advances in psychopharmacology
January 1, 2026
Zofia Kachlik, Wiesław Jerzy Cubała, Michał Walaszek
Ketamine and esketamine offer rapid antidepressant and anti-suicidal effects for treatment-resistant depression and bipolar depression, but differ from conventional antidepressants in their acute subjective effects, physiological profile, delivery models, and misuse potential. This narrative review synthesizes evidence from regulatory guidance, clinical trials, observational studies, and qualitative research to identify key patient information needs and proposes practical psychoeducational strategies. Core elements include explanations of indications, mechanisms, and treatment algorithms; guidance on visit preparation, scheduling, and monitoring; management of acute adverse effects; counselling on suicidality and substance misuse; and tailored considerations for special populations such as older adults, women of reproductive potential, and medically complex patients. The review proposes a patient-centred framework for psychoeducation and identifies priorities for future research.
Frontiers in Psychiatry
December 4, 2025
Adam Włodarczyk, Jakub Słupski, Joanna Szarmach et al.
Ketamine may be a viable treatment option for patients with treatment-resistant post-stroke depression. Further research is needed to better understand its efficacy and safety in this specific patient population.