OBJECTIVE: Electroconvulsive therapy (ECT) is a highly effective intervention for treatment-resistant depression; however, its use has been limited partly because of concerns about cognitive side effects. Evidence for the sustained (>1 month) efficacy of ketamine versus ECT for treatment-resistant depression has only recently been demonstrated. This study aimed to examine the...
Treatment-resistant depression (TRD) affects 30-60% of individuals with major depressive disorder and carries substantial morbidity and healthcare costs. Intravenous (IV) ketamine (KET) is a rapid-acting antidepressant, but benefits are often transient, prompting augmentation to sustain efficacy or improve tolerability. We conducted a systematic review and meta-analysis of randomized controlled...
PsychopharmacologyJuly 1, 2026Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
Interest in psychedelic drugs has increased rapidly because of their potential therapeutic role in psychiatric disorders. Impairments in the sociocognitive skills needed to build and maintain social relationships are prominent features of many psychiatric and neurodevelopmental disorders. Emerging evidence suggests that compounds such as 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid...
Postpartum Depression (PPD) is a common condition with serious consequences for both mother and baby if left untreated. Currently, few effective strategies exist for prevention of PPD. Ketamine and Esketamine are rapid acting and potent antidepressants, and emerging evidence is showing promising results for PPD. This review searched the MEDLINE, CINAHL, PsycINFO, EMBASE, and Cochrane databases,...
Psilocybin, a serotonergic psychedelic, has gained attention as a potential treatment for various psychiatric conditions. In this review, the authors summarize current clinical evidence related to psilocybin’s efficacy, safety, and mechanisms of action across psychiatric disorders. Findings from early-phase and small-scale clinical trials suggest rapid but variable reductions in depressive...
Intravenous (IV) ketamine is an emerging intervention for treatment-resistant depression (TRD), yet the temporal dynamics of response and the optimal number of infusions remain unclear, particularly in real-world clinical populations with psychiatric comorbidities. We conducted a retrospective chart review of 209 adults with TRD treated with IV ketamine at an interventional psychiatry program....
Abstract Background Psychedelic-assisted psychotherapy has shown potential for psychiatric disorders. However, the magnitude of symptom change in control groups remains poorly understood. We aim to evaluate within-group effects in control groups and compare them to treatment groups in psychedelic trials. Methods A systematic search was conducted up to 1 July 2025. The study protocol was...
Nitrous oxide may possess antidepressant effects; however, limited data exist on repeated administrations and active placebo-controlled studies in treatment-resistant depression (TRD). We aimed to test the feasibility of a randomised controlled trial examining a 4-week course of nitrous oxide or midazolam, an active placebo. In this randomised, active, placebo-controlled pilot trial, 40...
Posttraumatic stress disorder (PTSD) is a severe, often difficult-to-treat condition, highlighting the need for innovative therapies. Interventional treatments, including neuromodulation, rapid-acting pharmacotherapies such as intravenous ketamine (IV-KET) and esketamine (ESK), and emerging psychedelic-assisted psychotherapies, offer promising solutions. This systematic review evaluates the...
Traditional trauma-focused psychotherapies (TFPs) were developed based on an anxiety disorder model of posttraumatic stress disorder (PTSD). However, PTSD is a more complex disorder with heterogeneous onset, presentation, trajectory, and treatment responsivity. As half of treated patients do not respond to first-line treatments, innovative therapies are emerging to improve outcomes. This...
Substance Use Disorders (SUDs) involve diminished control, risky use, impaired social interactions, and physical dependence. Despite their global prevalence and burden, treatment options remain limited. Ketamine (KET), an NMDA receptor antagonist, may aid SUD treatment by modulating glutamatergic neurotransmission. This systematic review evaluates KET's role in SUD treatment. This review...
Psilocybin, a serotonergic psychedelic, may have therapeutic benefits for Substance Use Disorders (SUDs), but its overall efficacy and safety remain uncertain. This systematic review assessed the safety and efficacy of psilocybin for SUDs through a systematic database search conducted via OVID on May 22, 2024, and summarized 26 ongoing clinical trials registered on clinicaltrials.gov. Among 16...
Introduction: High-dose psilocybin has shown potential in treating various psychiatric disorders, but its perceptual and cognitive effects, along with the risk of adverse events, highlight the need for alternative treatment approaches. One such approach is the use of low-dose psilocybin, which does not significantly alter cognition or perception. While low-dose psilocybin has garnered growing...
Background: Psilocybin has shown promise in therapeutic applications for mental disorders. Understanding the pharmacokinetics of psilocybin and its active metabolite psilocin is crucial for optimizing its clinical use and minimizing adverse effects. Methods: This systematic review involved a comprehensive search across MEDLINE, APA PsycINFO, and Embase databases, from inception to December...
Background/Objectives: Suicide accounts for 1.4% of global deaths, and the slow-acting nature of traditional treatments for suicide risk underscores the need for alternatives. Psychedelic therapies may rapidly reduce suicide risk. This systematic review evaluates impact of psychedelic therapies on suicide-related outcomes. Methods: A systematic search of MEDLINE, Embase, PsycINFO, and...
Background Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence supports the potential therapeutic action...
Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to...
PLoS One2024Josh Martin, Fatemeh Gholamali Nezhad, Alice Rueda et al.2 citations
Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to...
Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week...
To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N2 O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape. A comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLINE, Embase, APA PsycInfo) and the clinical trial registries...
Sandra J Drozdz,1 Akash Goel,1â 3 Matthew W McGarr,4 Joel Katz,3,5â 7 Paul Ritvo,5,7 Gabriella F Mattina,1 Venkat Bhat,8â 10 Calvin Diep,3 Karim S Ladha1,3,10 1Department of Anesthesia, St. Michaelâs Hospital, Toronto, ON, Canada; 2Department of Anesthesiology, Pain and Perioperative Medicine, Stanford University, Stanford, CA, USA; 3Department of Anesthesiology and Pain Medicine,...
Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking example is glutamate, the brain's foremost...
Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42...
Pain and depression frequently co-occur. Due to its antidepressant and analgesic properties, ketamine has been used for the management of treatment-resistant depression and pain. This systematic review examined the literature on the efficacy of sub-anesthetic doses of ketamine in individuals experiencing comorbid depression and chronic pain (CDCP), as well as comorbid depression and acute pain...
Background Recent evidence underscores the utility of rapid-acting antidepressant interventions, such as ketamine, in alleviating symptoms of major depressive episodes (MDE). However, to date, there have been limited head-to-head comparisons of intravenous (IV) ketamine infusions with other antidepressant treatment strategies in large randomized trials. This study protocol describes an ongoing...