Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression:a pilot randomized, placebo-controlled continuation trial

The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-close intravenous (i.v.) ketamine; (2) test the efficacy of the glutamate-modulating agent riluzole in preventing post-ketamine relapse; and (3) examine whether pretreatment with lamotrigine would attenuate ketamine's psychotomimetic effects and enhance its antidepressant activity. Twenty-six medication-free patients received open-label i.v. ketamine (0.5 mg/kg over 40 min). Two hours prior to infusion, patients were randomized to lamotrigine (300 mg) or placebo. Seventeen patients (65%,) met response criterion (>= 50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale) 24 h following ketamine. Lamotrigine failed to attenuate the mild, transient side-effects associated with ketamine and did not enhance its antidepressant effects. Fourteen patients (54%) met response criterion 72 h following ketamine and proceeded to participate in a 32-d, randomized, double-blind, placebo-controlled, flexible-dose continuation trial of riluzole (100-200 mg/d). The main outcome measure was time-to-relapse. An interim analysis found no significant differences in time-to-relapse between riluzole and placebo groups [log-rank chi(2) = 0.17, d.f. = 1, p = 0.68], with 80% of patients relapsing on riluzole vs. 50% on placebo. The trial was thus stopped for futility. This pilot study showed that a sub-anaesthetic close of i.v. ketamine is well-tolerated in TRD, and may have rapid and sustained antidepressant properties. Riluzole did not prevent relapse in the first month following ketamine. Further investigation of relapse prevention strategies post-ketamine is necessary

Dynamic Interactive Social Cognition Training in Virtual Reality (DiSCoVR) for People With a Psychotic Disorder: Single-Group Feasibility and Acceptability Study

Background: People with a psychotic disorder commonly experience problems in social cognition and functioning. Social cognition training (SCT) improves social cognition, but may inadequately simulate real-life social interactions. Virtual reality (VR) provides a realistic, interactive, customizable, and controllable training environment, which could facilitate the application of skills in daily life. Objective: We developed a 16-session immersive VR SCT (Dynamic Interactive Social Cognition Training in Virtual Reality [DiSCoVR]) and conducted a single-group feasibility pilot study. Methods: A total of 22 people with a psychotic disorder and reported problems in social cognition participated. Feasibility and acceptability were assessed using a survey for participants and therapists, and by examining relevant parameters (eg, dropouts). We analyzed preliminary treatment effects on social cognition, neurocognition, and psychiatric symptoms. Results: A total of 17 participants completed the study. Participants enjoyed DiSCoVR (mean 7.25, SD 2.05; range 3-10), thought it was useful for daily social activities (mean 7.00, SD 2.05; range 3-10), and enjoyed the combination of VR and a therapist (mean 7.85, SD 2.11; range 3-10). The most frequently mentioned strength of DiSCoVR was the opportunity to practice with personalized social situations (14/20, 70%). A significant improvement of emotion perception was observed (Ekman 60 Faces; t16=–4.79, P<.001, d=–0.67), but no significant change was found in other measures of social cognition, neurocognition, psychiatric symptoms, or self-esteem. Conclusions: DiSCoVR was feasible and acceptable to participants and therapists, and may improve emotion perception

Ketamine as an anesthetic, analgesic and anti-depressant

ACHTERGROND Therapieresistentie komt voor bij ongeveer 30% van de patiënten met een depressie. Er is dan ook grote behoefte aan nieuwe behandelmogelijkheden. Ketamine, oorspronkelijk ontwikkeld als anestheticum, wordt onderzocht en incidenteel reeds toegepast bij patiënten met een therapieresistente depressieve stoornis. DOEL Kritische beschouwing over het huidige gebruik van ketamine als antidepressivum. METHODE Literatuuronderzoek. RESULTATEN Een kortdurend antidepressief effect van ketamine is aangetoond. Veel minder is bekend over het in stand houden van dit effect, de potentiële risico’s van herhaalde toediening, en de effectiefste toedieningsmethoden en behandelschema’s. CONCLUSIE Aanvullend onderzoek naar ketamine als antidepressivum blijft noodzakelijk. Eventuele (offlabel-) behandeling dient in de tussentijd alleen onder voorbehoud van zorgvuldige patiëntselectie en strikte monitoring te worden toegepast.BACKGROUND Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression. AIM A critical review of the current use of ketamine as an antidepressant. METHOD Literature study. RESULTS Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules. CONCLUSION Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.</p

Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3β antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies

Translating Glutamate: From Pathophysiology to Treatment

The neurotransmitter glutamate is the primary excitatory neurotransmitter in mammalian brain and is responsible for most corticocortical and corticofugal neurotransmission. Disturbances in glutamatergic function have been implicated in the pathophysiology of several neuropsychiatric disorders—including schizophrenia, drug abuse and addiction, autism, and depression—that were until recently poorly understood. Nevertheless, improvements in basic information regarding these disorders have yet to translate into Food and Drug Administration–approved treatments. Barriers to translation include the need not only for improved compounds but also for improved biomarkers sensitive to both structural and functional target engagement and for improved translational models. Overcoming these barriers will require unique collaborative arrangements between pharma, government, and academia. Here, we review a recent Institute of Medicine–sponsored meeting, highlighting advances in glutamatergic theories of neuropsychiatric illness as well as remaining barriers to treatment development.National Institute of Mental Health (U.S.) (grant R37MH49334)National Institute of Mental Health (U.S.) (Intramural Research Program)National Institute of Mental Health (U.S.) (R01DA03383)National Institute of Mental Health (U.S.) (P50MH086385)National Institutes of Health (U.S.)FRAXA Research FoundationHoward Hughes Medical InstituteSimons Foundatio

The role of proteomics in depression research

Depression is a severe neuropsychiatric disorder affecting approximately 10% of the world population. Despite this, the molecular mechanisms underlying the disorder are still not understood. Novel technologies such as proteomic-based platforms are beginning to offer new insights into this devastating illness, beyond those provided by the standard targeted methodologies. Here, we will show the potential of proteome analyses as a tool to elucidate the pathophysiological mechanisms of depression as well as the discovery of potential diagnostic, therapeutic and disease course biomarkers

Manipulating the Hype: contemporary art's response to media cliches

Manipulating the Hype addresses art’s reaction to the barrage of signs produced by the media. The paper researches contemporary art’s response to clichéd media stereotypes and elucidates artists’ multifaceted perspective on overtly obvious yet widely embraced paradigms marketed by the media. Contemporary art’s strategic reconfiguration of media stereotypes is a valuable introspection upon the superficiality and impracticability of advertising and entertainment industry constructs. By reconsidering the mediated image, art has the ability to inspire reevaluation of cultural values. The thesis additionally attempts to ascertain the reinterpretation of media stereotypes as a common thread linking principal art movements and historically significant artworks from around the world since 1960. How does contemporary art respond to the extensive cultural influence of the media? Is a reaction to mass media a thematic commonality linking contemporary artists in the age of globalization? Manipulating the Hype is a dual outcome investigation comprised of written thesis and studio practice. The written thesis combines experience from a lengthy professional practice with historical and theoretical research. The visual thesis consists of twelve photographic works taken at on the Big Island of Hawaii. The images juxtapose artificial icons of power from popular culture with the natural force of the active lava flow. The process of research discloses how the advertising and entertainment industries capitalize upon innate human desires through the manipulative proliferation of archetypal imagery. Furthermore, the thesis establishes the widespread retort to media clichés as a palpable commonality in studio practices worldwide. The findings in the research make evident that although contemporary art does not have sufficient influence to reform the media, it can heighten public awareness of media tactics