Pharmaceuticals
April 1, 2023
Aleksander Kwaśny, A. Włodarczyk, Damian Ogonowski et al.
27 citations
Ketamine reduces the severity of sleep insomnia in depression. Two studies reported significant improvement in sleep measured by MADRS and QIDS-SR16 scales after intravenous ketamine and intranasal esketamine. One case report showed mitigation of symptoms in PSQI and ISI during 3-month treatment with esketamine. Two studies with objective nocturnal EEG measurements showed a decrease in nocturnal wakefulness accompanied by an increase in slow wave and REM sleep. Robust data are lacking, and more research is needed.
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.
Psychiatry research
February 1, 2025
Damian Swieczkowski, Aleksander Kwaśny, Michal Pruc et al.
17 citations
In patients with Major Depressive Disorder, psilocybin reduces depression symptoms more than placebo by Day 8 and Day 15 after treatment, but not by Day 2. A 25 mg dose is the most effective among those tested (0.215 mg/kg, 10 mg, and 25 mg). Psilocybin carries a higher risk of adverse events, especially nausea. These findings come from a meta-analysis of three randomized placebo-controlled trials involving 389 adults.
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.
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.
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.
The International Journal of Psychiatry in Medicine
April 25, 2025
Damian Swieczkowski, Aleksander Kwaśny, Michal Pruc et al.
4 citations
Psilocybin rapidly reduced depressive and anxiety symptoms in cancer patients, though the effect on depression was not sustained at two weeks. Based on two randomized controlled trials, a network meta-analysis found that Beck Depression Inventory scores improved one day after administration but not at follow-up. State anxiety scores showed substantial reductions both at one day and two weeks; trait anxiety scores also improved at both time points. The highest dose tested (0.3 mg/kg) was the most effective. The small number of trials limits confidence in the findings, and larger, high-quality studies are needed.
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.
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.
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 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.
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.
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, 2025
Aleksander Kwaśny, Wiesław Jerzy Cubała, Alina Wilkowska
Intravenous ketamine is effective for treatment-resistant bipolar depression, with dosing typically based on actual body weight. In a retrospective analysis of 22 inpatients, doses recalculated using formulas for lean body mass, ideal body weight, and body surface area were compared between responders and nonresponders. Body surface area-normalized doses ranged from 17.63 to 23.09 mg/m² in nonresponders and 15.73 to 23.89 mg/m² in responders. Lean body mass and ideal body weight recalculations at 0.5 mg/kg yielded lower relative doses, especially among nonresponders, suggesting potential underdosing. These preliminary findings do not support alternative dosing formulas over actual body weight, but replication in larger controlled studies is warranted.
Magnesium research
Jakub Słupski, Adam Włodarczyk, Natalia Górska et al.
Impulsive behaviors are common in major depressive disorder and bipolar disorder, raising suicide risk and mood instability. Ketamine, an NMDA receptor antagonist, can produce rapid antidepressant and antisuicidal effects, and magnesium given with low-dose NMDA antagonists reduces anxiety- and depression-like behaviors in animals. This observational study of 49 inpatients with treatment-resistant mood disorders measured impulsivity with the Barratt Impulsiveness Scale (BIS-11) and magnesium levels before and during a four-week course of eight ketamine infusions. Magnesium ion concentration during treatment was not associated with changes in BIS-11 scores. The findings provide no evidence for a relationship between magnesium levels and impulsivity during ketamine therapy.