Esketamine nasal spray has emerged as a promising rapid-relief therapy for treatment-resistant depression (TRD) and suicide prevention. This review examines the chemical structure and pharmacodynamics of esketamine, highlighting its primary action on NMDA receptors and additional effects on AMPA receptors, opioid receptors, monoaminergic receptors, and inflammatory pathways. Despite the...
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Brain mechanisms involved in comorbidity between chronic pain conditions and clinical depression are still largely unknown. Our previous studies demonstrated that expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) is both necessary and sufficient for the development of enhanced behavioral emotionality (i.e., depressive- like behaviors) in rodents. Here, we investigated the...
Modern electroconvulsive therapy (ECT) and ketamine currently represent the most effective treatment options in depressed patients showing non-response to two or more trials of antidepressants. Recently, large sample head-to-head comparisons of intravenous ketamine versus ECT for treatment-resistant depression (TRD) have fuelled the debate on which therapy might be more effective. However, the...
Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action. In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial...
The efficacy and safety of esketamine nasal spray (ESK) were established in registration trials in patients with treatment-resistant depression (TRD). This French real-world study aimed to describe the treatment patterns, effectiveness, and safety of ESK in TRD patients over a 12-month follow-up. This study used secondary data from patient files of hospital-based psychiatrists and started...
Renewed interest in the clinical potential of hallucinogens may lead people with depression to a generally more positive view of the use of lysergic acid diethylamide (LSD). Therefore, past-year LSD use among people with depression may be increasing in prevalence. To assess time trends in the prevalence of past-year nonmedical LSD use by past-year major depression status and the variation in...
Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences,...
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain...
This scientific commentary refers to ‘Brain dynamics predictive of response to psilocybin for treatment-resistant depression’, by Vohryzek et al. (https://doi.org/10.1093/braincomms/fcae049)
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, associated with substantial burden and large economical costs. Notwithstanding various conventional antidepressant treatment options, a large portion of depressed people (ca. 30%) fails to respond to first-line treatment, resulting in treatment-resistant depression (TRD). Although non-response to multiple antidepressant...