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Psychiatry Research Jun 2024Treatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies.
BACKGROUND
Treatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies.
METHODS
A network meta-analysis following PRISMA guidelines examined the efficacy and safety of TRD treatments, analyzing 72 randomized controlled trials from eight databases, assessing response and remission rates, tolerability, and safety through the Cochrane Risk of Bias Tool and CINeMA framework.
FINDINGS
Including 12,105 participants, the analysis highlighted ECT, Ketamine, Esketamine, and Psilocybin as superior first-line treatments due to their optimal balance between effectiveness and tolerability. Brexpiprazole and Quetiapine showed no significant efficacy over placebo in response rates, while Esketamine and Psilocybin exhibited lower tolerability.
INTERPRETATION
The results advocate for ECT, Ketamine, Esketamine, and Psilocybin as preferred treatments for TRD, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes. This study underscores the importance of considering both efficacy and safety in selecting augmentation strategies for TRD.
PubMed: 38924903
DOI: 10.1016/j.psychres.2024.116018 -
Journal of Clinical and Experimental... Jun 2024Psilocybin, a naturally occurring serotonergic agonist in some mushroom species, has shown promise as a novel, fast-acting pharmacotherapy seeking to overcome the... (Review)
Review
INTRODUCTION
Psilocybin, a naturally occurring serotonergic agonist in some mushroom species, has shown promise as a novel, fast-acting pharmacotherapy seeking to overcome the limitations of conventional first-line antidepressants. Studying psilocybin effects on cognition and emotional processing may help to clarify the mechanisms underlying the therapeutic potential of psilocybin and may also support studies with people suffering from depression. Thus, this review aims to provide a comprehensive overview of the current literature regarding the effects of psilocybin on these two key areas in both healthy and depressed populations.
METHOD
A systematic search was performed on 29 January 2024, in the PubMed, EBSCOhost, Web of Science and SCOPUS databases. After duplicates removal, study selection was conducted considering pre-specified criteria. Data extraction was then performed. The quality assessment of the studies was carried out using the Cochrane Collaboration tools for randomized (RoB 2.0) and non-randomized (ROBINS-I) controlled trials.
RESULTS
Twenty articles were included, with 18 targeting healthy adults and two adults with depression. Results point to impairments within attentional and inhibitory processes, and improvements in the domains of creativity and social cognition in healthy individuals. In the population with depression, only cognitive flexibility and emotional recognition were affected, both being enhanced. The comparison of outcomes from both populations proved limited.
CONCLUSIONS
Psilocybin acutely alters several cognitive domains, with a localized rather than global focus, in a dose- and time-dependent manner. However, the significant methodological constraints call for further research, in the context of depression and with standardized protocols, with longitudinal studies also imperative.
PubMed: 38842300
DOI: 10.1080/13803395.2024.2363343 -
Psychiatry Research Jul 2024
Meta-Analysis
Topics: Humans; Psilocybin; Depressive Disorder, Treatment-Resistant; Hallucinogens; Treatment Outcome
PubMed: 38781672
DOI: 10.1016/j.psychres.2024.115960 -
L'Encephale May 2024Current scientific literature supports classical psychedelic efficacy in many psychiatric disorders. However, less attention has been given to the neurological effects...
BACKGROUND
Current scientific literature supports classical psychedelic efficacy in many psychiatric disorders. However, less attention has been given to the neurological effects of these substances. The aim of this medical thesis was to conduct a systematic review examining the neuroimaging correlates of the effects of psychedelics.
METHOD
We performed an electronic research through Medline and Science Direct databases. A comprehensive search yielded 460 articles published up to May 2022. After a cautious screening process, we selected 49 scientific papers for further analysis.
RESULTS
Major findings included reduced functional network integration, increased between-network functional connectivity, and expansion of functional connectivity patterns repertoire under psychedelics. Thalamic gating and emotional processing were also impaired. These results positively correlated with symptom improvement in pathological populations.
CONCLUSION
To this day, our knowledge concerning psychedelic effects remains partial. Several neurocognitive theories have been developed in recent years to model psychedelic phenomenology, but no unifying theory has emerged. Studies involving larger populations investigating various psychiatric disorders, including several neuroimaging modalities and considering medium- and long-term effects, would be necessary to deepen current knowledge.
PubMed: 38724430
DOI: 10.1016/j.encep.2024.02.007 -
BMJ (Clinical Research Ed.) May 2024
PubMed: 38704154
DOI: 10.1136/bmj.q1025 -
BMJ (Clinical Research Ed.) May 2024To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.
DATA SYNTHESIS AND STUDY QUALITY
Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies' sample sizes. Study quality was appraised using Cochrane's Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.
ELIGIBILITY CRITERIA
Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.
RESULTS
Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating.
CONCLUSION
Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023388065.
Topics: Humans; Antidepressive Agents; Depression; Hallucinogens; Psilocybin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38692686
DOI: 10.1136/bmj-2023-078084 -
Psychopharmacology Jun 2024Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine... (Review)
Review
Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelics and placebo for the treatment of psychiatric disorders. The aim of this work is to identify factors that may inform future RTC design for conducting psychedelics research. We conducted a systematic review of PubMed, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Psycinfo, Embase, and Web of Science Core Collection to examine: (1) placebo selection, (2) study design, and (3) integrity of blinding measures. Sixteen publications were identified as meeting the criteria for a systematic review. Our findings suggest that traditional placebo administration is insufficient to control for expectancy confounds. Consequently, experimental methodology that limits personnel unblinding and the use of an active placebo are important considerations when designing prospective clinical studies involving psychedelics.
Topics: Hallucinogens; Humans; Randomized Controlled Trials as Topic; Mental Disorders; Research Design; Double-Blind Method
PubMed: 38683460
DOI: 10.1007/s00213-024-06598-6 -
JAMA Network Open Apr 2024Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.
OBJECTIVE
To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety.
DATA SOURCES
MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023.
STUDY SELECTION
Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results.
MAIN OUTCOMES AND MEASURES
The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety.
RESULTS
Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.
Topics: Humans; Female; Adult; Male; Psilocybin; Drug-Related Side Effects and Adverse Reactions; Anxiety Disorders; Anxiety; Dizziness; Randomized Controlled Trials as Topic
PubMed: 38598236
DOI: 10.1001/jamanetworkopen.2024.5960 -
Psychiatry Research May 2024Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and meta-analysis was to evaluate safety data in human subjects. We carried out a search on MEDLINE, Embase and PsycINFO databases between 2000 and 2022. Standardized mean differences between different dose ranges and between acute and subacute phases were calculated for cardiovascular data after psychedelic administration. Risk differences were calculated for serious adverse events and common side effects. Thirty studies were included in this meta-analysis. There were only nine serious adverse events for over 1000 administrations of psychedelic substances (one during the acute phase and 8 during the post-acute phase). There were no suicide attempts during the acute phase and 3 participants engaged in self-harm during the post-acute phase. There was an increased risk for elevated heart rate, systolic and diastolic blood pressure for all dose range categories, as well as an increased risk of nausea during the acute phase. Other common side effects included headaches, anxiety, and decreased concentration or appetite. This meta-analysis demonstrates that psychedelics are well-tolerated, with a low risk of emerging serious adverse events in a controlled setting with appropriate inclusion criteria.
Topics: Humans; Hallucinogens; Psychotherapy; Anxiety; Anxiety Disorders; Risk Assessment
PubMed: 38579460
DOI: 10.1016/j.psychres.2024.115880 -
Psychiatry Research May 2024We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating... (Meta-Analysis)
Meta-Analysis Review
We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.
Topics: Humans; Hallucinogens; Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Lysergic Acid Diethylamide; Mental Disorders; Obsessive-Compulsive Disorder
PubMed: 38574699
DOI: 10.1016/j.psychres.2024.115886