ABSTRACT
BACKGROUND: Converging evidence suggests electroencephalography (EEG) methods may elucidate alterations in global structural and functional connectivity that underlie the pathophysiology of depressive disorders. Extant literature suggests SSRIs and SNRIs may broadly induce alterations to EEG-measured neural activity. Herein, this systematic review comprehensively evaluates changes to EEG spectral signatures associated with vortioxetine and each FDA-approved agent within the SSRI and SNRI class. METHODS: We conducted a systematic review of studies investigating changes to EEG spectral signatures associated with SSRI, SNRI, and/or vortioxetine treatment in persons with MDD. Database search occurred from database inception to May 3, 2024. RESULTS: Our search yielded 15 studies investigating overall spectral signature changes associated with SSRI- and/or SNRI-treatment. The existing literature presents with mixed findings. Notwithstanding, we did observe a pattern in which the SSRI and SNRI agents reproducibly affect EEG spectral signatures. We observed overlapping yet distinct spectral patterns for each agent within- and between-drug classes of SSRIs and SNRIs. Changes in resting/wake EEG were also observed. LIMITATIONS: The findings from our systematic review are mixed. Heterogeneity exists with sample size, composition, dosing of antidepressants, duration of antidepressant exposure, as well as the type of EEG devices used. DISCUSSIONS: Our findings provide support to the notion that although SSRIs, SNRIs and vortioxetine block reuptake of the serotonin transporter; they are different in their profile of pharmacology as evidenced by differential EEG signatures. EEG changes associated with SSRIs, SNRIs and vortioxetine are also highly replicated findings across mixed studies and populations.
ABSTRACT
INTRODUCTION: Suicidal ideation and behaviors are a leading cause of disability worldwide. Approximately 90 % of suicide completers have a diagnosable mood disorder. Extant literature reports rumination mediates functional impairment across mood disorders. Herein, we report the association between rumination and suicidality amongst persons with psychiatric disorders and healthy controls. METHODS: Our systematic review and meta-analysis included relevant articles retrieved from Web of Science, OVID and PubMed from inception to March 20, 2024. Random effects model was used to calculate the correlation between rumination, suicidal ideation and attempt. RESULTS: A total of 27 eligible studies were included in our systematic review and meta-analysis. Rumination (r = 0.25 [95 % CI: -0.03, 0.49]), reflection (r = 0.15 [-0.71, 0.83]) and brooding (r = 0.13 [-0.58, 0.73]) were nonsignificantly correlated with suicidal ideation in mood disorders. Suicide attempt history was significantly associated with greater odds of rumination in persons with depressive disorders (OR = 1.13 [0.42, 3.02]). In healthy controls, rumination (r = 0.30 [0.21, 0.38]), reflection (r = 0.23 [0.13, 0.32]) and brooding (r = 0.24 [0.12, 0.36]) were significantly correlated with suicidal ideation. Rumination also predicted lifetime history of suicide attempts in healthy controls (OR = 1.70 [1.16, 2.49]). LIMITATIONS: There were inadequate sample sizes of persons with different mood and psychiatric disorders which may have underpowered our ability to detect clinically meaningful associations. DISCUSSION: Our study reports a transdiagnostic association between measures of rumination and suicidality. Future research vistas should parse the neurobiological substrates subserving rumination and identify targeted therapies and their association with general cognition and treatment response.
ABSTRACT
BACKGROUND: Approximately 30 % of persons with Major Depressive Disorder (MDD) inadequately respond to conventional antidepressants. Kappa opioid receptor (KOR) antagonists, aticaprant and navacaprant, are in development as treatments for MDD. Herein, we aim to comprehensively evaluate the safety, efficacy and pharmacology of aticaprant and navacaprant for MDD. METHODS: We performed a systematic review of primary research investigating aticaprant and navacaprant on PubMed, OVID, and Scopus databases from inception to April 2024. Studies that reported on the pharmacological profile and/or safety and efficacy of aticaprant and navacaprant were included. RESULTS: Navacaprant monotherapy and aticaprant adjunctive therapy are in development for MDD. Navacaprant exhibits 300-fold selectivity for the KOR compared to the mu-opioid receptor, while aticaprant exhibits 30-fold selectivity. At clinically-relevant doses, navacaprant and aticaprant occupy 87-95 % and 73-94 % of KORs, respectively. Clinical trials of the foregoing agents (navacaprant as monotherapy and actiprant as adjunctive therapy) reported significant improvement in depressive symptoms and may clinically benefit measures of anhedonia. Both agents appear well-tolerated, with most adverse events mild and no known safety concerns. LIMITATIONS: Aticaprant and navacaprant treatment for MDD are in early stages of clinical trials and results from Phase 3 pivotal trials are not yet available. CONCLUSIONS: Kappa opioid receptor antagonists may serve as mechanistically-novel treatments for MDD and persons who inadequately respond to index conventional antidepressants. Anhedonia is debilitating and insufficiently treated with conventional antidepressants. Future research vistas should establish the efficacy and safety of KORAs in phase 3 studies in both acute and maintenance paradigms.