Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151965 - 151965
Published: May 1, 2025
Language: Английский
World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 48 - 74
Published: Jan. 14, 2023
Despite considerable progress in pharmacotherapy over the past seven decades, many mental disorders remain insufficiently treated. This situation is part due to limited knowledge of pathophysiology these and lack biological markers stratify individualize patient selection, but also a still restricted number mechanisms action being targeted monotherapy or combination/augmentation treatment, as well variety challenges threatening successful development testing new drugs. In this paper, we first provide an overview most promising drugs with innovative that are undergoing phase 2 3 for schizophrenia, bipolar disorder, major depressive anxiety trauma‐related disorders, substance use dementia. Promising repurposing established medications psychiatric indications, variations modulation dopamine, noradrenaline serotonin receptor functioning, considered. We then critically discuss clinical trial parameters need be considered depth when developing pharmacological agents treatment disorders. Hurdles perils success drug include inadequacy imprecision inclusion/exclusion criteria ratings, sub‐optimally suited participants, multiple factors contributing large/increasing placebo effect, problems statistical analyses. information should order de‐risk programmes novel known increasing their chances success.
Language: Английский
Citations
83
Therapeutic Advances in Psychopharmacology, Journal Year: 2023, Volume and Issue: 13
Published: Jan. 1, 2023
Research in the last decade has expressed considerable optimism about clinical potential of psychedelics for treatment mental disorders. This is reflected an increase research papers, investments by pharmaceutical companies, patents, media coverage, as well political and legislative changes. However, psychedelic science facing serious challenges that threaten validity core findings raise doubt regarding efficacy safety. In this paper, we introduce 10 most pressing challenges, grouped into easy, moderate, hard problems. We show how these problems internal (treatment effects are due to factors unrelated treatment), external (lack generalizability), construct (unclear working mechanism), or statistical conclusion (conclusions do not follow from data methods). These tend co-occur studies, limiting conclusions can be drawn safety therapy. provide a roadmap tackling share checklist researchers, journalists, funders, policymakers, other stakeholders use assess quality science. Addressing today’s necessary find out whether therapeutic been warranted avoid history repeating itself.
Language: Английский
Citations
59
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Feb. 5, 2024
Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential efficacy safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, current paper explored experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with single session oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges trust-building expectation management; (2) navigating experience; (3) need more comprehensive Subthemes first theme include general distrust mental healthcare, trust study therapists, limited time preparation, managing expectations. The second included following subthemes: trusting to surrender, profound overwhelming experiences, music as guide. third addressed desire multiple sessions, sensemaking. Patients' provided important insights into potential optimization treatment TRD, including individualized investment trust-building, offering additional providing access sustained (psycho)therapy trusted personalizing approaches, which may also enhance real-world adaption treatments.
Language: Английский
Citations
20
American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 29, 2025
Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review meta-analysis of the available data on its efficacy against depression suicidality well side effects. MEDLINE was searched keyword "esketamine" March 24, 2024, using PRISMA method. Data processing statistical analysis were performed R, version 4.3.3, METAFOR package. Of 1,115 articles initially identified, 87 included discussion. At weeks 2-4, randomized controlled trials mostly negative or failed; however, returned weak but significant positive effect (effect size range, 0.15-0.23 at 2-4), similar to augmentation strategies atypical antipsychotics depression. concerning not any time point. sensitivity produced same results. study findings suggest that esketamine's add-on antidepressants is modest in (similar antipsychotics) absent itself. These need be considered light abuse potential fact long-term effects are still fully known. Some alarming signs deaths emerging during testing phase discussed, along other regulatory issues.
Language: Английский
Citations
11
MedComm, Journal Year: 2022, Volume and Issue: 3(3)
Published: July 21, 2022
Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand molecular pathophysiology of depression, it still unclear. Current treatments for depression are inadequate individuals, because limited effectiveness, delayed efficacy (usually two weeks), side effects. Consequently, novel drugs with increased speed action effectiveness required. Ketamine has shown have rapid, reliable, long-lasting antidepressant effects in treatment-resistant MDD patients represent breakthrough therapy MDD; however, concerns regarding its efficacy, potential misuse, remain. In this review, we aimed summarize mechanisms pharmacological depression. We focused on fast treatment clarified safety, tolerability, ketamine metabolites treatment, along review mechanisms, research challenges, future clinical prospects.
Language: Английский
Citations
70
European Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 70, P. 49 - 55
Published: March 1, 2023
Language: Английский
Citations
39
Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(49)
Published: Nov. 27, 2023
Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy treatment-resistant symptoms, protection against relapse distinguish it from prior antidepressants. discovery reconceptualization the neurobiology depression and, in turn, insights elaboration its mechanisms action inform studies pathophysiology related disorders. It been 25 y since we first presented our ketamine findings Thus, is timely this review to consider what have learned suggest future directions optimization rapid-acting antidepressant treatment.
Language: Английский
Citations
35
Published: March 10, 2023
Research in the last decade has expressed considerable optimism about clinical potential of psychedelics for treatment mental disorders. This is reflected a increase research papers, investments by pharmaceutical companies, patents, media coverage, as well political and legislative changes. However, psychedelic science facing serious challenges that threaten validity core findings raise doubt regarding efficacy safety. In this paper, we introduce 10 most pressing challenges, grouped into easy, moderate, hard problems. We show how these problems internal (treatment effects are due to factors unrelated treatment), external (lack generalizability), construct (unclear working mechanism) or statistical conclusion (conclusions do not follow from data methods). These tend co-occur studies, strongly limiting conclusions can be drawn safety therapy. provide roadmap tackling next science, share checklist researchers, journalists, funders, policy makers, other stakeholders use assess quality science. Addressing today’s necessary find out whether been warranted avoid history repeating itself.
Language: Английский
Citations
23
Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15
Published: Feb. 1, 2024
Background Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed synthesized systematic reviews (SRs) meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for unipolar depression. We evaluated the efficacy safety esketamine treating major depressive episodes across forms, including unipolar, bipolar, treatment-resistant, non-resistant depression, patient populations without ideation, aiming comprehensively assess their therapeutic potential profile. Methods Following PRIOR guidelines, this OoR’s protocol was registered Implasy (ID:202150049). Searches PubMed, Scopus, Cochrane Library, Epistemonikos focused English-language meta-analyses RCTs as monotherapy add-on, evaluating outcomes like suicide risk, symptoms, relapse, rates, side effects. included studies both non-suicidal patients; all routes administration intranasal) were considered, well available comparisons control interventions. excluded which intervention used anesthesia electroconvulsive therapy a ascending dose design. The selection, data extraction, quality assessment carried out by pairs reviewers blinded manner. Data efficacy, acceptability, tolerability extracted. Results Our analysis 26 SRs 44 RCTs, 3,316 subjects. is effective well-tolerated, although original poor, resulting low certainty evidence. Limitations study poor-quality studies, Additionally, insufficient prevents differentiation between effects Conclusion While show potential, current evidence suffers from quality. Enhanced methodological rigor future research will allow more informed application these interventions within guidelines Systematic review registration [ https://inplasy.com/inplasy-2021-5-0049/ ], identifier (INPLASY202150049).
Language: Английский
Citations
10
Psychopharmacology, Journal Year: 2023, Volume and Issue: 240(7), P. 1547 - 1560
Published: May 24, 2023
Ketamine and its enantiomers are widely researched increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced experiences their relation psychotherapeutic potential have not yet been systematically investigated.To describe the patient during oral esketamine treatment for depression (TRD) explore therapeutic relevance these experiences.In-depth interviews were conducted with 17 patients after a 6-week, twice-weekly 'off label' generic (0.5-3.0mg/kg) program. Interviews explored participants' perspectives, expectations, treatment. Audio transcribed analyzed using an Interpretative Phenomenological Analysis (IPA) framework.The effects ketamine highly variable, psychological distress was common in most patients. Key themes included (a) perceptual (auditory, visual, proprioceptive), (b) detachment (from body, self, emotions, world), (c) stillness openness, (d) mystical-type (transcendence, relativeness, spirituality), (e) fear anxiety. related post-session reports feeling hungover fatigued, lifting blanket: neutralizing mood effects.Patients reported several potential, such as increased detachment, interruption negativity, experiences. These deserve be further enhance outcomes TRD. Given frequency severity perceived distress, we identify need additional support all stages
Language: Английский
Citations
19