Psilocybin for the Treatment of Depression: A Promising New Pharmacotherapy Approach.
Ontology highlight
ABSTRACT:
SUBMITTER: Agin-Liebes G
PROVIDER: S-EPMC10072288 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Psilocybin for the Treatment of Depression: A Promising New Pharmacotherapy Approach.
Agin-Liebes Gabrielle G Davis Alan K AK
Current topics in behavioral neurosciences 20220101
Depression is highly prevalent and represents the leading cause of global disability and primary contributor to overall global burden of disease. Several lines of evidence from early-phase experimental trials suggest that serotonergic psychedelics, particularly psilocybin, with therapeutic support show great promise in the treatment of depression with large effect sizes. Neuroimaging data have also revealed the dynamic effects of psilocybin on functional activity within and between neural region ...[more]
Similar Datasets
Project description:Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.
| S-EPMC5640601 | biostudies-literature
Project description:The most appropriate next step in depression treatment after the initial treatment fails is unclear. This study explores the suitability of the Markov decision process for optimizing sequential treatment decisions for depression. We conducted a formal comparison of a Markov decision process approach and mainstream state-transition models as used in health economic decision analysis to clarify differences in the model structure. We performed two reviews: the first to identify existing applications of the Markov decision process in the field of healthcare and the second to identify existing health economic models for depression. We then illustrated the application of a Markov decision process by reformulating an existing health economic model. This provided input for discussing the suitability of a Markov decision process for solving sequential treatment decisions in depression. The Markov decision process and state-transition models differed in terms of flexibility in modeling actions and rewards. In all, 23 applications of a Markov decision process within the context of somatic disease were included, 16 of which concerned sequential treatment decisions. Most existing health economic models relating to depression have a state-transition structure. The example application replicated the health economic model and enabled additional capacity to make dynamic comparisons of more interventions over time than was possible with traditional state-transition models. Markov decision processes have been successfully applied to address sequential treatment-decision problems, although the results have been published mostly in economics journals that are not related to healthcare. One advantage of a Markov decision process compared with state-transition models is that it allows extended action space: the possibility of making dynamic comparisons of different treatments over time. Within the context of depression, although existing state-transition models are too basic to evaluate sequential treatment decisions, the assumptions of a Markov decision process could be satisfied. The Markov decision process could therefore serve as a powerful model for optimizing sequential treatment in depression. This would require a sufficiently elaborate state-transition model at the cohort or patient level.
| S-EPMC9550715 | biostudies-literature
Project description:Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a healthy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-hydroxytryptamine 2a and 5-hydroxytryptamine 1a, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression, and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.
| S-EPMC10957168 | biostudies-literature
Project description:Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with a single session of oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients' perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments.
| S-EPMC10844281 | biostudies-literature
Project description:RationaleDepressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.ObjectivesThe objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases.MethodsSeventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.ResultsWe found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).ConclusionsPsilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.
| S-EPMC5813058 | biostudies-literature
Project description:RationaleRecent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.ObjectivesHere, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.MethodsTwenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.ResultsTreatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.ConclusionsAlthough limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
| S-EPMC5813086 | biostudies-literature
Project description:Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes. Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD). Methods: Patients with TRD (n = 15) and matched, untreated non-depressed controls (n = 15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10 and 25 mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session. Results: Patients showed a significant pessimism bias at baseline [t(14) = -3.260, p = 0.006; 95% CI (-0.16, -0.03), g = 1.1] which was related to the severity of their depressive symptoms (rs = -0.55, p = 0.017). One week after psilocybin treatment, this bias was significantly decreased [t(14) = -2.714, p = 0.017; 95% CI (-0.21, -0.02), g = 0.7] and depressive symptoms were greatly improved [t(14) = 7.900, p < 0.001; 95% CI (16.17, 28.23), g = 1.9]; moreover, the magnitude of change in both variables was significantly correlated (r = -0.57, p = 0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events [t(14) = 1.857, p = 0.042; 95% CI (-0.01, 0.12), g = 0.6] whereas no such change was observed in the control subjects. Conclusion: These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
| S-EPMC6194345 | biostudies-literature
Project description:BackgroundPsilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.MethodsIn a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.ResultsPT was associated with decreases in neuroticism (B = -0.63), introversion (B = -0.38), disagreeableness (B = -0.47), impulsivity (B = -0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = -0.47) and disagreeableness (B = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = -0.38), disagreeableness (B = -0.26), impulsivity (B = -0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = -0.46) remaining decreased at month 6. No significant between-condition differences were observed.ConclusionsPersonality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.
| S-EPMC10692311 | biostudies-literature
Project description:BackgroundGrowing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient procedure of administering a fixed dose.AimsThe present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose.MethodsWe analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N = 288) in which psilocybin was administered in the range 20 to 30 mg/70 kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg (n = 120), participants receiving 30 mg/70 kg (n = 182), and participants whose weight-adjusted dose was about 25 mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) (n = 103).ResultsIn the 20 mg/70 kg and 30 mg/70 kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113 kg) the present results showed no evidence that body weight affected subjective effects of psilocybin.ConclusionsThese results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.
| S-EPMC8056712 | biostudies-literature
Project description:This study investigated the association between the duration of pharmacotherapy treatment for depression, or discontinuation from treatment, and work functioning impairment. This was a retrospective cohort study examining 30,409 workers. Work functioning impairment was assessed using a questionnaire, and treatment status was assessed using medical claims data. Odds ratios (ORs) of workers with severe work functioning impairment compared with healthy workers (control group) were calculated using logistic regression analysis. Continuous medical treatment was associated with severely impaired work functioning regardless of treatment period [continuous medical treatment; 4 months <: OR = 3.2, 4 months ≥, 10 months <: OR = 2.6, 10 months ≥, 14 months <: OR = 2.3, 14 months ≥, 16 months <: OR = 2.3, which are all statistically significant (p < 0.05)]. Workers who initially received pharmacotherapy treatment but discontinued in < 11 months had a significantly higher OR (treatment discontinuation period; 3 months <: OR = 2.3, 3 months ≥, 8 months <; OR = 2.0, 8 months ≥, 11 months <; OR = 3.0), while those who discontinued at ≥ 11 months did not (OR = 1.4, 95% CI 0.6-3.5). The sensitivity analysis excluding participants with at least one psychiatric comorbidity other than depression did not change the final result. It is important for the occupational health practitioners and attending psychiatrists to follow up in cooperation with each other, paying attention to the decrease in work functioning in addition to the symptoms.
| S-EPMC7519139 | biostudies-literature