Neuroimaging studies show that the functional connectivity of the brain changes with age. Resting state functional connectivity (rsFC) in the brain appears to decrease with aging in key networks associated with higher order thinking and effective emotional regulation. Interventions that potentially preserversFC in the brain include 1) physical activity and 2) contemplative practice commonly...
Psychedelic treatments are considered to involve unique treatment challenges relative to other psychiatric interventions, though these are typically not explored in detail within clinical trial reports. To determine the types of challenges that providers encounter while administering psychedelic drugs in research settings and to assess provider opinions on safeguards that may be pursued to...
Psilocybin (PSIL) is a psychedelic drug and a promising experimental therapeutic for many psychiatric conditions. Precision functional mapping (PFM) combines densely repeated resting state fMRI sampling and individual-specific network mapping to improve signal-to-noise ratio (SNR) and effect size in brain imaging research. We present a randomized cross-over study in which PFM was used to...
Psychedelic therapies are promising new treatment options in psychiatry. Including the use of physical touch as part of treatment is an area of debate. This study aimed to characterize the viewpoints of practitioners on the use of touch in psychedelic therapy. An anonymous survey was distributed via e-mail to the contacts listed on ClinicalTrials.gov for trials of psilocybin and lysergic acid...
There is a push to shrink the anticipated 17-year research-to-practice gap for psychedelic-assisted therapy (PAT), offering precarious hope to those with disabling mental health conditions. However, numerous questions regarding how PAT works, how well it works, for whom and in what context remain. Substantial changes to current systems of care, including regulatory approvals, clinical training...
Objective: To assess the viewpoints of psychedelic practitioners in research settings on approaches to psychological support for psychedelic treatments. Methods: An anonymous survey was distributed via email to contacts listed on ClinicalTrials.gov for clinical trials of psilocybin and LSD, personal contacts of authors, and through snowball sampling. The survey included Likert type, multiple...
A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here...
To examine whether psychological well‐being, sleep, and suicidality improved with treatment with intravenous (IV) ketamine for late‐life treatment‐resistant depression (TRD).
The 21st century has brought novel therapies and new therapeutic targets for major depressive disorder (MDD). Until recently all antidepressant medications targeted monoamines-serotonin, norepinephrine, and dopamine- and their regulatory systems. But growing evidence has suggested that individuals who fail to respond to a monoaminergic treatment are likely to fail to respond to other...
JAMADecember 13, 2022Eric J Lenze, Michelle Voegtle, J Philip Miller et al.
Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites...
Objective: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. Methods: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this...
Precision medicine, optimized interventions, and access to care are catchphrases for the future of behavioral treatments. Progress has been slow due to the dearth of clinical trials that optimize interventions' benefits, individually tailor interventions to meet individual needs and preferences, and lead to rapid implementation after effectiveness is demonstrated. Two innovations have emerged...
Ketamine is an anesthetic drug which is now used to treat chronic pain conditions and psychiatric disorders, especially depression. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic...
Individuals with subjective memory complaints and symptoms of depression and/or anxiety are at high risk for further cognitive decline, and possible progression to dementia. Low-burden interventions to help slow or prevent cognitive decline in this high-risk group are needed. The objective of this study is to assess the feasibility of combining Mindfulness-Based Stress Reduction (MBSR) with...
Introduction Low-burden and accessible interventions are needed to prevent cognitive decline in individuals at high-risk for decline. Mindfulness-Based Stress Reduction (MBSR) and transcranial direct current stimulation (tDCS) are two interventions which can be delivered remotely, improving their reach and scalability. This aim of this study is to assess the feasibility, safety and tolerability...
Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of...
Age-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such...
Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)]...
Electroconvulsive therapy (ECT) employs the elective induction of generalizes seizures as a potent treatment for severe psychiatric illness. As such, ECT provides an opportunity to rigorously study the recovery of consciousness, reconstitution of cognition, and electroencephalographic (EEG) activity following seizures. Fifteen patients with major depressive disorder refractory to pharmacologic...
To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints. To explore decreased hypothalamic-pituitary-adrenal (HPA) axis activity as a possible mechanism. 103 adults aged 65 years or older with an anxiety or depressive disorder (diagnosed according to DSM-IV criteria) and...
The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of...
As mobile data capture tools for patient-reported outcomes proliferate in clinical research, a key dimension of measure performance is sensitivity to change. This study compared performance of patient-reported measures of mindfulness, depression, and anxiety symptoms using traditional paper-and-pencil forms versus real-time, ambulatory measurement of symptoms via ecological momentary assessment...
ABSTRACT Objectives We examined the feasibility of a high-dose, 96-h infusion of ketamine in treatment-resistant depression. Methods Ten participants were randomised to receive a 96-h ketamine infusion, titrated as tolerated to a target rate of 0.6 mg/kg/h, while 10 received a 40-min ketamine infusion (0.5 mg/kg). Both groups received clonidine, titrated to a maximum of 0.6 mg orally daily,...
Background: Mindfulness-based stress reduction (MBSR) has the potential to reduce worry and improve cognitive functioning. Objectives: In this treatment development project, we examined MBSR in older adults with worry symptoms and co-occurring cognitive dysfunction. We examined (i) acceptability of MBSR, (ii) whether MBSR needs to be lengthened providing more repetition, (iii) MBSR's benefits...