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Pharmacopsychiatry Jul 2022There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis.
INTRODUCTION
There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis.
METHODS
We systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of phase II and III trials were identified. The collateral information was gathered via a PubMed search and press releases.
RESULTS
Nine compounds were identified. AXS-05 (a combination of dextromethorphan and bupropion) and ansofaxine hydrochloride showed a positive result over placebo in a phase III study for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, facial injection of botulinum toxin A, prasterone, and casopitant demonstrated at least one positive result in phase II trials. Ayahuasca showed a greater response rate than placebo at week one, indicating the rapid antidepressant effect.
DISCUSSION
These new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed.
Topics: Antidepressive Agents; Clinical Trials, Phase II as Topic; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Humans; Registries
PubMed: 35045580
DOI: 10.1055/a-1714-9097 -
Journal of Substance Abuse Treatment Jul 2022Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating...
BACKGROUND
Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin.
AIMS
The study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine.
METHODS
The team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines.
RESULTS
In total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review.
CONCLUSION
Treatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention.
Topics: Alkaloids; Hallucinogens; Humans; Ibogaine; Observational Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 35012793
DOI: 10.1016/j.jsat.2021.108717 -
Psychiatry Investigation Oct 2021To systematically examine the effectiveness and tolerability of psilocybin for treating end-of-life anxiety symptoms.
OBJECTIVE
To systematically examine the effectiveness and tolerability of psilocybin for treating end-of-life anxiety symptoms.
METHODS
The Medline, Embase, CENTRAL, and PsycINFO databases were searched up to November 25, 2020. We enrolled clinical trials investigating psilocybin for treating end-of-life anxiety symptoms. Meta-analysis was conducted using random-effects model.
RESULTS
Overall, five studies were included, revealing that psilocybin was superior to the placebo in treating state anxiety at 1 day (Hedges' g, -0.70; 95% confidence interval, -1.01 to -0.39) and 2 weeks (-1.03; -1.47 to -0.60) after treatment. Psilocybin was more effective than placebo in treating trait anxiety at 1 day (-0.71; -1.15 to -0.26), 2 weeks (-1.08; -1.80 to -0.36), and 6 months (-0.84; -1.37 to -0.30) after treatment. Psilocybin was associated with transient elevation in systolic (19.00; 13.58-24.41 mm Hg) and diastolic (8.66; 5.18-12.15 mm Hg) blood pressure compared with placebo. The differences between psilocybin and placebo groups with regard to allcause discontinuation, serious adverse events, and heart rates were nonsignificant.
CONCLUSION
Psilocybin-assisted therapy could ameliorate end-of-life anxiety symptoms without serious adverse events. Because of the small sample sizes of the included studies and high heterogeneity on long-term outcomes, future randomized controlled trials with large sample sizes are needed.
PubMed: 34619818
DOI: 10.30773/pi.2021.0209 -
Frontiers in Pharmacology 2021Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT receptors. Besides the...
Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function. We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis. 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, = 343), LSD (5 studies, = 135), and peyote (1 study, = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study ( = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task ( = 0.03) and no differences in the others (all > 0.05). The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.
PubMed: 34603053
DOI: 10.3389/fphar.2021.739966 -
Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
Journal of Affective Disorders Dec 2021The COVID-19 (coronavirus disease 2019)-related pandemic represents a global source of societal and health burden. Yet, the impact of the pandemic on people with severe... (Review)
Review
INTRODUCTION
The COVID-19 (coronavirus disease 2019)-related pandemic represents a global source of societal and health burden. Yet, the impact of the pandemic on people with severe mental illness, including bipolar disorder (BD), remains unclear, warranting scoping review on the matter.
METHODS
The MEDLINE and EMBASE databases were systematically searched from inception up to April 24, 2021, adopting broad inclusion criteria to assess a variety of clinical and public health themes related to people with a primary diagnosis of BD during the COVID-19 pandemics. The present work complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) registered in the Open Science Framework (OSF) repository (https://osf.io/7evpx/).
RESULTS
Fourteen papers informed the present scoping review. Four major themes were identified: (i) impact of COVID-19-related stressors on BD; (ii) impact of COVID-19 on mental health service utilization among people with BD; (iii) impact of BD on the risk of acquiring SARS-CoV-2 infection; (iv) engagement in preventative behaviors among people with BD. Additional themes warranting further research were nonetheless detected.
LIMITATIONS
Further original studies are needed.
CONCLUSION
The present study confirmed the high-vulnerability hypothesis concerning people with BD versus the general population, reinforcing the need for further research related to the COVID-19 pandemic. Additional information is warranted to compare the impact of the pandemic period among BD people against pre-pandemic records, the general population, and other severe mental illnesses, namely people with schizophrenia or major depressive disorder, to inform the public health and the delivery of patient-tailored interventions.
Topics: Bipolar Disorder; COVID-19; Depressive Disorder, Major; Humans; Pandemics; SARS-CoV-2
PubMed: 34517248
DOI: 10.1016/j.jad.2021.08.091 -
Pharmaceuticals (Basel, Switzerland) Aug 2021Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit... (Review)
Review
Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists' attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT). Some studies suggest that these substances might be effective in depression treatment. The aim of this study was to evaluate the efficiency of LSD, psilocybin and DMT in depression treatment in the light of current medical literature. The authors followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for this systematic review. The authors searched the PubMed and Cochrane Library databases to identify relevant publications. Finally, 10 papers were included. Most of the selected studies showed significant correlation between psilocybin and DMT use and reduction in depression symptom intensity. By analyzing qualified studies, it can be concluded that psilocybin and DMT could be useful in depression treatment, but further observations are still required.
PubMed: 34451890
DOI: 10.3390/ph14080793 -
Porto Biomedical Journal 2021Psilocybin is a predominant agonist of 5HT and 5HT receptors and was first isolated in 1958, shortly before it became a controlled substance. Research on the potential... (Review)
Review
BACKGROUND
Psilocybin is a predominant agonist of 5HT and 5HT receptors and was first isolated in 1958, shortly before it became a controlled substance. Research on the potential therapeutic effects of this compound has recently re-emerged alongside what is being addressed as a psychedelic renaissance.
METHODS
In this paper we performed a systematic review of the clinical trials conducted so far regarding the therapeutic effects of psilocybin on psychiatric disorders. The eligibility criteria included clinical trials that assessed psilocybin's potential therapeutic effects on patients with psychiatric disorders. Nine hundred seven articles were found and screened in regard to the title, from which 94 were screened through abstract and 9 met the eligibility criteria and were included.
RESULTS
The papers published focused on 3 disorders: depression, obsessive-compulsive disorder (OCD) and substance use disorder (namely tobacco and alcohol). Psilocybin has shown a relatively safe profile and very promising results, with reductions found on most of the psychiatric rating scales' scores. Research on depression showed the most solid evidence, supported by 3 randomized controlled trials. Studies on OCD and substance use disorder showed more limitations due to their open-label design.
CONCLUSIONS
Altogether, the results from the studies reviewed in this paper suggest a substantial therapeutic potential. This calls for further research to confirm the results observed so far and further explain the underlying mechanisms.
PubMed: 33884324
DOI: 10.1097/j.pbj.0000000000000128 -
ACS Pharmacology & Translational Science Apr 2021Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a... (Review)
Review
Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly, further understanding of the relationship between classic psychedelics and suicidality is needed. Therefore, we conducted a systematic review of the relationship between classic psychedelics (both non-clinical psychedelic use and psychedelic therapy) and suicidality. We identified a total of 64 articles, including 41 articles on the association between non-clinical classic psychedelic use and suicidality and 23 articles on the effects of psychedelic therapy on suicidality. Findings on the association between lifetime classic psychedelic use and suicidality were mixed, with studies finding positive, negative, and no significant association. A small number of reports of suicide and decreased suicidality following non-clinical classic psychedelic use were identified. Several cases of suicide in early psychedelic therapy were identified; however, it was unclear whether this was due to psychedelic therapy itself. In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment. We identify some remaining questions and provide suggestions for future research on the association between classic psychedelics and suicidality.
PubMed: 33860173
DOI: 10.1021/acsptsci.1c00024 -
Journal of Psychopharmacology (Oxford,... Aug 2021OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression.... (Meta-Analysis)
Meta-Analysis
Efficacy of onabotulinumtoxinA in the treatment of unipolar major depression: Systematic review, meta-analysis and meta-regression analyses of double-blind randomised controlled trials.
BACKGROUND
OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression. This putative new antidepressant agent offers minimal systemic side effects and negligible risk of pharmacological interactions. We set out to examine the evidence for the use of onabotulinumtoxinA in major depression.
METHODS
A systematic search of the literature identified double-blind randomised controlled trials (RCTs) investigating the use of onabotulinumtoxinA in the treatment of major depression versus placebo. Data, reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), was combined in meta-analyses (PROSPERO registration ID: CRD42020183538).
RESULTS
The search identified five RCTs (four double-blind) comparing onabotulinumtoxinA to placebo. OnabotulinumtoxinA was more effective than placebo when administered within the 20-40 IU dose range in double-blind RCTs. The analysis was free of publication bias and significantly heterogeneous. Meta-regression analyses indicated that onabotulinumtoxinA was more efficacious in women and in higher doses in female patients and less effective with polypharmacy, especially when an increasing number of antidepressants were prescribed. The effectiveness of onabotulinumtoxinA was higher in more recently published double-blind RCTs.
CONCLUSION
The meta-analysis supports the efficacy of the intervention with the results being highly heterogeneous across studies. In view of the heterogeneity of the findings and the significant moderators of benefit (sex, year of study completion and the interaction between sex and dose), more research is required to better understand the role of onabotulinumtoxinA in the treatment of depression.
Topics: Antidepressive Agents; Botulinum Toxins, Type A; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Neuromuscular Agents; Randomized Controlled Trials as Topic; Sex Factors
PubMed: 33719696
DOI: 10.1177/0269881121991827