Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a naturally occur...
Rapid-acting antidepressants disprove the dogma that antidepressants need several weeks to become clinically effective. Ketamine, the prototype of a rapid-acting antidepressant, is an N-methyl-D-aspartate (NMDA) receptor blocking agent. A single i.v. application of ketamine induces rapid changes in glutamatergic neurotransmitter systems, leading to preferent...
Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of...
The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has inspired tremendous interest in the underlying neurobiological mechanisms. We review preclinical and clinical evidence supporting neuroplasticity as a convergent downstream mechanism of action for these novel fast-acting antidepressants. Through their primary glutamat...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The ...
Approximately 30% of people treated for a major depressive episode will not achieve remission after two or more treatment trials of first-line antidepressants and are considered to have treatment-resistant depression (TRD). Because the odds of remission decrease with every subsequent medication trial, it is important for clinicians to understand the characte...
Introduction Major depressive disorder is a highly prevalent clinical condition, affecting more than 300 million individuals worldwide. About 1/3 of patients with MDD fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD). Novel antidepressants with rapid and sustained effects...
Serotonergic hallucinogens psilocybin, and its active metabolite psilocin, have shown promise as rapid-acting antidepressants. The FDA granted breakthrough therapy designation for psilocybin's use as an antidepressant in 2019, and phase II clinical trials are currently ongoing. Psilocybin is converted to psilocin following oral administration, and this metab...
Introduction Major depressive disorder is a highly prevalent clinical condition, affecting more than 300 million individuals worldwide. About 1/3 of patients with MDD fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD). Novel antidepressants with rapid and sustained effects...
BackgroundPsilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.MethodsIn a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective sero...
Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not ...
Major depressive disorder (MDD) is among the most prevalent mental health disorders worldwide, and it is associated with a reduced quality of life and enormous costs to health care systems. Available drug treatments show low-to-moderate response in most patients, with almost a third of patients being non-responders (treatment-resistant). Furthermore, most cu...
Major depressive disorder (MDD) has become a health crisis of epidemic proportions in the modern world. One in six individuals in the world is experiencing an episode of major depression in his or her lifetime, and it is estimated that major depression will rank second after cardiac disease as a cause of international medical morbidity by the year 2020. Depr...
Mounting evidence suggests safety and efficacy of psychedelic compounds as potential novel therapeutics in psychiatry. Ketamine has been approved by the Food and Drug Administration in a new class of antidepressants, and 3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials for post-traumatic stress disorder. Psilocybin and lysergi...
Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin's antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the po...
Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin’s antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the po...
ObjectiveTo conduct a systematic review of modern-era (post-millennium) clinical studies assessing the therapeutic effects of serotonergic psychedelics drugs for mental health conditions. Although the main focus was on efficacy and safety, study characteristics, duration of antidepressants effects across studies, and the role of the subjective drug experienc...
The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has...
Combinations of psychotherapy with antidepressants are gold-standard psychiatric treatments. They operate through complex and interactional mechanisms, not unlike the reemergent paradigm of psychedelic-assisted psychotherapy, which promising research suggests may also be highly effective in even challenging populations. We review the therapeutic mechanisms b...
Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept ...
