Background Anhedonia is a debilitating core feature of mood disorders, and is associated with significant functional impairment and poor quality of life. Psilocybin has recently emerged as a novel antidepressant treatment in MDD, however, its effects on anhedonia specifically have yet to be systematically reviewed. This review evaluates available clinical and pre-clinical research, exploring...
Importance Antidepressant efficacy of intravenous (IV) ketamine has been demonstrated in major depressive disorder; however, the efficacy and safety of ketamine for bipolar depression remain largely unknown, with limited data available in this specific population. Objective To evaluate the efficacy, safety, and tolerability of adjunctive IV ketamine compared with midazolam for...
Borderline personality disorder (BPD) is a serious mental illness with high rates of morbidity and stigma; however, successful remission is frequently limited by a paucity of accessible treatment options. In an era of growing interest in psychedelics as novel psychiatric treatment modalities, patients with BPD are often excluded from research due to perceived safety risks, particularly...
Major depressive disorder (MDD) and treatment-resistant depression (TRD) remain leading causes of disability, providing the impetus for receptor-level treatment strategies beyond monoamine reuptake. The serotonin 5-HT2B receptor (5-HT2BR) is uniquely positioned at the interface of central-antidepressant mechanisms and peripheral cardiac risks. Herein, we reviewed preclinical, translational and...
Ketamine and esketamine exhibit rapid antidepressant effects in persons with treatment-resistant depression (TRD) and bipolar depression (TRBD). However, the synaptic mechanisms governing dose, frequency, and durability of response remain unclear. This review aims to evaluate the dosing parameters, including minimum dose and optimal dosing intervals, that reliably induce or maintain long-term...
Importance: Psychedelic drugs possess acute psychoactive effects that can compromise blinding integrity in randomized clinical trials (RCTs). Functional unblinding, when participants or raters correctly identify treatment allocation based on subjective effects, may bias outcomes through expectancy effects, challenging the validity of efficacy estimates and regulatory acceptance. Objective: To...
PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect...
Psychedelics have re-emerged as promising treatments for mood disorders. The current model provides a moderate-to-high dose of a psychedelic agent (e.g., psilocybin) to reliably induce an altered state of consciousness. Unfortunately, the hallucinatory effects limit the treatment's potential scalability given patients' vulnerability and extensive monitoring costs, leading to growing interest in...
Childhood trauma is a well‐established risk factor for major depressive disorder (MDD) and is often associated with attenuated response to conventional antidepressant therapies. Ketamine has emerged as an effective treatment for treatment‐resistant depression (TRD), but the impact of childhood trauma on its effectiveness remains unclear. Herein, we aimed to determine whether childhood trauma...
Objective: To compare changes in depression, anxiety, and suicidality symptoms after a single 25 mg oral dose of psilocybin between treatment-resistant depression participants not on antidepressants at screening to participants that discontinued antidepressant medications leading up to receiving psilocybin-assisted psychotherapy (PAP). Methods: Participants (n = 27) received at least one 25 mg...
Depression with comorbid posttraumatic stress disorder (PTSD) is associated with more severe symptoms and a reduced response to traditional treatments. Although ketamine shows promise as a rapid-acting antidepressant for treatment-resistant depression (TRD), its effectiveness in patients with comorbid PTSD remains underexplored. Therefore, we conducted a retrospective analysis of 134 patients...
Posttraumatic stress disorder (PTSD) is a condition that can develop after a traumatic event, causing distressing symptoms, including intrusive re-experiencing symptoms, alterations in mood and cognition, and changes in arousal and reactivity. Few treatment options exist for patients who find conventional psychotherapy and pharmacotherapy to be inaccessible, ineffective, or intolerable. We...
Psilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in...
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome...
Abstract Objectives: Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ketamine, esketamine and...
Background: The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD) remains uncertain. Objective: This systematic review aimed to summarize findings on the use of ketamine for the treatment of BD by assessing its efficacy, safety, and tolerability. Design: Systematic review. Methods: We...