Interventions to reduce wait times for adolescents seeking mental health services: a scoping review protocol.

INTRODUCTION: The demand for adolescent mental health services has increased significantly in recent years, leading to excessive wait times for adolescents seeking mental health services and poor mental health outcomes. Timely access to mental health services is critical to reducing the risk of symptom chronicity and progression to mental disorder. A better understanding of whether and how interventions to reduce wait times impact mental health outcomes is needed to guide mental health policymakers and service planners in their approach to reducing wait times. METHODS AND ANALYSIS: The scoping review will use Arksey and O'Malley's six-stage framework for scoping reviews and Rayyan to support screening, data extraction and evidence synthesis. The review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. We will search the Cochrane Library, EBSCOhost, MEDLINE (Ovid), PsycArticles (Ovid), PsycINFO (Ovid), EMBASE (Ovid), Web of Science, ProQuest and Scopus databases for peer-reviewed texts published in English between 1 January 2000 and 28 February 2023. We will also search Google Scholar for additional grey literature. To be eligible for inclusion, studies must focus on adolescent populations aged 13-18 years and report on interventions to reduce wait times for any mental health service except crisis and emergency services. Title, abstract and full-text screening will be done by two reviewers. We will extract data describing the interventions and their effects on wait times and adolescent mental health outcomes, and we will identify strengths and limitations in the evidence base to inform recommendations for future research. A youth advisory group with lived experience of mental health difficulties will be consulted throughout the review process. ETHICS AND DISSEMINATION: Ethics approval is not required. Findings will be disseminated via peer-reviewed publications and presented at conferences. STUDY REGISTRATION: The protocol was registered with the Open Science Framework on 20 February 2023 (https://osf.io/qt4zy).

Rapid and sustained antidepressant properties of an NMDA antagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening.

Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests). Moreover, chronic administration (21day, 10mg/kg, bid) reduced drinking latencies comparable to fluoxetine (10mg/kg, bid) in the novelty-induced hypophagia test, which requires chronic treatment to produce antidepressant-like effects. MI-4 (10mg/kg, bid) produced rapid (three-day) antidepressant-like effects in the social avoidance test following 10days of social defeat stress. Unlike ketamine, chronic administration of MI-4 increased social interaction scores while improving resiliency to the mood-altering effects of stress to over 70%. Importantly, MI-4 exhibited minimal abuse liability in behavioral and neurological models (conditioned place preference and dopamine in vivo microdialysis). MI-4 was found to be Ro-25-6981, an ifenprodil analog and reputed NMDA antagonist. The data suggest that Ro-25-6981, previously known for rapid-acting glutamatergic antidepressant actions, may also functionally inhibit monoamine reuptake and produces sustained antidepressant effects in vivo. This demonstrates, as proof of principle, the viability of combining these mechanisms to produce rapid and sustained antidepressant-like effects. Overall, these findings suggest MAT computational model-based virtual screening is a viable method for identifying antidepressant lead compounds of unique scaffold.