A man with AUD achieves sobriety on treatment with an SSRI and naltrexone, but then stops taking the SSRI to participate in a psilocybin “ceremony.” What factors contributed to his subsequent relapse to alcohol use?
Background: Low-dose ketamine infusion has been demonstrated to exert antisuicidal effects on patients with treatment-resistant depression (TRD) and strong suicidal ideation. Although evidence suggests an association between hopelessness and suicidality, very few studies have investigated the antihopelessness effects of ketamine. Methods: This study included 84 patients with TRD and strong...
Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic (R,S)-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior...
Among the greatest unmet needs in major depressive disorder (MDD) is a lack of effective pharmacotherapies for patients who do not respond to first- and second-line antidepressant medications. After decades of muted progress, optimism regarding the future of MDD therapy rose after scientists serendipitously uncovered the antidepressant effects of ketamine. The discovery of ketamine's...
Despite their legality, alcohol and tobacco both have a well-documented potential for misuse and elevate users' likelihood for disease. Dependence on alcohol also contributes to opioid overdoses, which claim 130 lives every day. Although awareness of the opioid epidemic is rising broadly among health care professionals, a majority of Americans still do not receive adequate, FDA-approved...
To systematically review control conditions of all available randomized psychedelic trials. We searched PubMed, PsycINFO, and EMBASE for randomized trials of psychedelics in humans from 1940 through May 2020 with no language restrictions. PRISMA guidelines were followed. (PROSPERO registration number: PROSPERO-CRD42020205341.). All randomized trials of psychedelics in humans from 1940 through...
Although consensus in the field is lacking, the most common definition for treatment-resistant depression (TRD) requires a minimum of 2 prior treatment failures with confirmed adequate dose and duration. This article presents a clinical example of TRD in a patient with a long history of depression and inadequate response to treatment. The prominent feature is the patient's persistent...
Objective: Ketamine has been redeveloped as a rapid-acting antidepressant for treatment-resistant depression (TRD). There is a paucity of literature comparing subanesthetic intravenous (IV) ketamine and US Food and Drug Administration (FDA)-approved intranasal (IN) esketamine for TRD in real-world clinical settings. We compared the efficacy and time to achieve remission/response with repeated...
Objective: Nightmares seem to predict suicidal behaviors, and the aim of this study is to explore the chronology and trajectories of alterations in dream contents before a suicidal crisis, distinguishing 3 different experiences: bad dreams, nightmares, and suicidal scenarios during dreams. Methods: This naturalistic study included individuals hospitalized between January 2021 and May 2021 in a...
Objective: Ketamine is a novel and rapidly acting treatment for major depressive disorder (MDD). Benzodiazepines are commonly coprescribed with antidepressants in MDD. This study sought to examine data from a randomized clinical trial that compared a single infusion of intravenous (IV) ketamine to midazolam placebo in treatment-resistant depression (DSM-IV-TR MDD) and to assess whether the use...
Objective: Ketamine is increasingly prescribed for treatment-resistant depression (TRD), often as add-on to regular antidepressants. Augmentation of ketamine to monoamine oxidase inhibitors (MAOIs) is advised against, as this practice might increase blood pressure or cause serotonin syndrome. Despite the potential relevance for patients, little is known about actual side effects of combined...
Introduction: Few studies have been published to date exploring the effectiveness of ketamine for treatment-resistant depression (TRD) in large clinical samples. We report on the clinical outcomes of a large cohort treated with ketamine as part of clinical practice. Methods: Deidentified electronic chart data were obtained from a multisite private ketamine infusion clinic for 424 patients with...
Objective: Altered glutamatergic neurotransmission has been implicated in the pathogenesis of depression. This trial evaluated the efficacy and safety of AXS-05 (dextromethorphan-bupropion), an oral N-methyl-D-aspartate (NMDA) receptor antagonist and σ1 receptor agonist, in the treatment of major depressive disorder (MDD). Methods: This double-blind, phase 3 trial, was conducted between June...
To the Editor: Our group recently published in JCP the first meta-analysis of patient-level data on the effects of psychedelics on suicidality. 1 While not described in our article, it is noteworthy that 2 suicidality-related events that had been deemed not attributable to the administration of a psychedelic (by the authors of the primary outcome studies) occurred within the studies included in...
Five randomized controlled trials (RCTs) have compared racemic ketamine, mostly administered intravenously in the dose of 0.5 mg/kg across 40-45 minutes, with right unilateral or bilateral electroconvulsive therapy (ECT). These RCTs were conducted in samples of severely ill patients with mostly unipolar depression (with or without psychotic features) who were referred for ECT. Of these, 2 RCTs...
A research on classic psychedelic–assisted treatments continues to expand, we can expect that findings will sometimes challenge or elucidate long-held conventional beliefs about the purported dangers of these substances. One such notion has been that they precipitate suicidality1 and other self-harm behaviors (eg, jumping off of buildings believing one can fly, walking in front of traffic2) in...
Objective: Suicide is a global health concern, and innovative interventions that target suicidality are needed. While psychedelic therapy shows promise for a range of mental health concerns, including suicidality, not all psychedelic therapy trials have published their suicidality results and no meta-analysis has been published on the topic. Therefore, we completed the first meta-analysis of...
Objective: This study evaluated whether Mindfulness-Based Cognitive Therapy for Preventing Suicide Behavior (MBCT-S) effectively augmented treatment-as-usual enhanced for suicide prevention (eTAU).Methods: From December 2013 through March 2018, veterans (N = 140) at high risk for suicide were recruited mostly (88.6%) during a suicide-related inpatient admission and randomly assigned to either...
) and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment. The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease...
Objective: Ketamine shows rapid and robust antidepressant effects in clinical studies. Psychotic features are an exclusion criterion in most ketamine treatment studies based on the assumption that psychosis will increase with ketamine administration. As patients with treatment-resistant depression (TRD) often have psychotic features, and treatment-resistant depressive symptoms are also common...
Objective: To elucidate the incidence rates and predictive factors for parasomnias (disorders of arousal, nightmare, and sleep paralysis) in adolescents. Methods: This was a prospective cohort study of high school students. In 2010, we conducted a baseline survey of first-year students enrolled in randomly selected Japanese schools (10 junior high schools and 14 senior high schools); 2 years...
PsilocybinPsilocybin, derived from mushrooms belonging to the genus Psilocybe, and psilocin, its active metabolite, are indolamines.Recent studies have shown that psilocybin has effects on brain functional connectivity.14 Its effects include reducing negative affect and amygdala response to emotional faces at 1 week, with enduring changes in resting state functional connectivity (RSFC) at 1...
P sychedelics have recently gained attention as compounds with therapeutic potential in the treatment of psychiatric disorders.The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designations for (±)-3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy in severe posttraumatic stress disorder (PTSD) (in 2017) and for the adjunctive use of psilocybin with...
OBJECTIVE: Esketamine, the S-enantiomer of ketamine, was recently approved as a rapid-acting intranasal therapy for depression and is currently under development for suicidality. The authors sought to determine the efficacy of adjunctive intranasal esketamine in major depressive disorder (MDD). DATA SOURCES: A systematic search of PubMed/MEDLINE was conducted up to January 2019, in addition to...
OBJECTIVE: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. METHODS: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of...