Patient-reported efficacy of adjunctive brexpiprazole in major depressive disorder in a phase 4, open-label, interventional study.

Objectives: In ENGAGE, patients with major depressive disorder (MDD) demonstrated improvements in patient-reported depression and life engagement while taking adjunctive brexpiprazole. This analysis aimed to further characterize patient perspectives on the effects of adjunctive brexpiprazole, using patient diary data from ENGAGE, and describe development of a 'word of the day' activity.

Methods: Prior to ENGAGE, word lists describing a 'good,' 'average,' and 'bad' day with depression were generated from semi-structured interviews with patients with MDD.

Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder: Results From a Randomized, Double-Blind, Phase 3 Trial.

Lumateperone, a mechanistically novel antipsychotic, simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This phase 3, randomized, double-blind, placebo-controlled trial investigated efficacy and safety of adjunctive lumateperone 42 mg in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response. From July 2021 to February 2024, eligible adult outpatients (18-65 years) had -defined MDD with inadequate response to 1 or 2 ADTs in the current depressive episode and Montgomery-Åsberg Depression Rating Scale (MADRS) Total score ≥24, Clinical Global Impression Scale-Severity (CGI-S) score ≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14.

Real world effectiveness of maintenance ketamine infusions for treatment-resistant depression in major depressive disorder and bipolar disorder.

Antidepressant effects with sub-anesthetic doses of intravenous ketamine have been previously demonstrated. However, previous studies have primarily evaluated the efficacy of acute treatment protocols, with limited research on maintenance treatment. Moreover, controlled maintenance studies have only included patients with treatment-resistant Major Depressive Disorder (TRD), with no maintenance studies evaluating effects in bipolar disorder.

Safety and Efficacy of the NMDA-2b-Selective Negative Allosteric Modulator BI 1569912: A Phase Ib Randomized Trial in Major Depressive Disorder.

Selective N-methyl-D-aspartate receptor subunit 2b negative allosteric modulators (NR2B NAMs) are being explored as potential new treatment options for major depressive disorder (MDD). This Phase Ib, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in adults (N = 59) with moderate-to-severe MDD and insufficient response to ongoing antidepressant monotherapy. Participants were randomized (1:1:1) to a novel NR2B NAM, BI 1569912 (5 mg or 20 mg tablet) or placebo.

Defining Treatment-Resistant Bipolar Depression: Recommendations From the ISBD Task Force.

Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

The Efficacy of Pharmacological Interventions in the Treatment of Major Depressive Disorder and Bipolar Depression With Mixed Features: A Systematic Review.

Background: There is a need to provide up-to-date, clinically translatable data as it relates to the treatment of a major depressive episode (MDE) with mixed features.

Methods: PubMed and OVID were searched from inception to July 22, 2024. Randomized controlled trials (RCTs) investigating the efficacy of pharmacological agents for adults with bipolar disorder (BD) or major depressive disorder (MDD) in an MDE with mixed features were included.

Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.

G protein-coupled receptors (GPCRs) are involved in many physiological and pathophysiological processes. Conventional pharmacological models categorize the typology of pharmacologic ligands as agonists or antagonists. Biased agonism is a relatively newer pharmacodynamic characteristic that has potential to optimize therapeutic efficacy while minimizing adverse effects in psychiatric and neurological treatments.

Advancing measurement-based care through triangle of care: Development and feasibility of the Transdiagnostic Global Impression - Psychopathology scale for patients and informants.

Background: Measurement-based care (MBC) is widely recommended in psychiatry but remains underutilized in routine clinical settings. The Transdiagnostic Global Impression - Psychopathology (TGI-P) scale was developed to provide a brief yet comprehensive assessment of 10 core transdiagnostic symptom domains. To support more inclusive care and promote patient and caregiver engagement in treatment planning, two new versions of the TGI-P, that is, a patient-rated and a separate informant-rated, were developed, complementing the previously published clinician-rated version.

Evaluating biased agonism of glucagon-like peptide-1 (GLP-1) receptors to improve cellular bioenergetics: A systematic review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective antidiabetic and anti-obesity agents. Recent development and optimisation of these agents includes biased agonism (selective activation of a downstream signalling pathway) of the GLP-1 receptor, which has demonstrated greater weight-lowering effects and improved insulin response in treated persons relative to other GLP-1 RAs. We aim to synthesise current literature reporting on the effects of biased GLP-1 RAs and compare their effects on cellular-level bioenergetics compared to non-biased GLP-1 RAs.

Differential effects of mindfulness and grit on positive mental health outcomes in major depressive and bipolar disorders: A moderation analysis using an ecological momentary assessment approach.

Background: Holistic management of persons living with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) invites the need for evaluation of positive mental health (PMH; pleasure attainment and meaning-in-life), alongside conventional measures of psychopathology. The aforementioned dimensions of PMH involve aspects of mindfulness and grit. Herein, we evaluate these aspects using ecological momentary assessment (EMA) approach.

Is Lumateperone Effective in Bipolar Depression? A Systematic Literature Review and Meta-Analysis on Placebo-Controlled Trials.

Bipolar depression is often difficult to treat and needs a specific therapeutic approach. This systematic review and meta-analysis aimed to evaluate the efficacy of lumateperone to be inclusive of more recently published studies with this agent in depressive episodes of bipolar disorder. Three meta-analyses were conducted to determine whether the mean Montgomery-Asberg Depression Rating Scale (MADRS) values in the placebo groups differ significantly from the mean MADRS scale values in the group receiving lumateperone 42 mg and whether the mean of Clinical Global Impression Bipolar Version - Severity Scale (CGI-BP-S) - (depression subscore and overall bipolar illness) values in the placebo groups differ significantly from the mean CGI-BP-S scale values in the group receiving lumateperone 42 mg.

An examination of symptoms, function and quality of life as conjoint clinical outcome domains for treatment-resistant depression.

Objective: The treatment of depression aims to improve depressive symptoms, daily function and quality of life (QoL). These exploratory analyses of a database of convenience from the RECOVER trial evaluated how a "tripartite" metric based on these 3 outcome domains might perform in treatment-resistant depression (TRD).

Methods: Outcome domains included depressive symptoms (MADRS, QIDS-C, QIDS-SR), function (WPAI item-6) and QoL (Mini-Q-LES-Q) obtained at months 3, 6, 9 and 12 in outpatients with markedly TRD in the double-blind RECOVER trial that compared sham to active adjunctive vagus nerve stimulation (VNS).

Bidirectional associations among positive affect, anhedonia and meaning in life during major depressive episode: ecological momentary assessment study in unipolar and bipolar individuals and healthy controls.

Background: Diagnostic accuracy is an unmet need for major depressive disorder (MDD) and major depressive episode (MDE) in bipolar disorder. Very limited research has evaluated bipolar disorder/MDE and MDD using ecological momentary assessment (EMA) time-series data.

Aims: We aimed to examine differentiating phenomenological characteristics in positive affect dynamics, and temporal relationships with pleasure towards current activity and meaning in life (MIL), among MDD, MDE/bipolar disorder and healthy controls using EMA.

Relationships of Cognitive Function With Subsequent Device-Measured Physical Activity and Sedentary Time in Healthy Individuals and Those With Bipolar Disorder: Findings From the UK Biobank.

Background: In bipolar disorder (BD), physical inactivity and sedentary behaviour are prevalent and have been linked to BD's cognitive symptoms, although the directionality of these links is not clear. This proof-of-concept study examined whether cognitive function during mid- and later-life was prospectively related to physical activity and sedentary time, and whether the association differed in presence or extent between those with BD and healthy controls.

Methods: Relevant UK Biobank data were available for 646 BD participants and 18,041 psychiatrically healthy controls, aged 40-69 years at baseline.

Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression.

Background: Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes.

Interaction between dietary omega-3 polyunsaturated fatty acids, obesity and gut microbiota in preclinical models: A systematic review of randomized controlled trials.

Emerging research underscores the potential of omega-3 polyunsaturated fatty acids (PUFAs) in weight reduction and modulation of the gut microbiota. The current review systematically examines the effects of omega-3 PUFA supplementation on body weight regulation and gut microbiota modulation in high-fat diet (HFD)-induced obesity models. The study protocol was registered with PROSPERO (CRD42024559835).

Acetylcholine and muscarinic receptor targeting in bipolar disorder: does xanomeline-trospium chloride and other investigational muscarinic agonists hold promise as mechanistically informed treatments for manic episodes, mixed features and cognitive deficits in bipolar disorder?

Introduction: Xanomeline-trospium chloride (Cobenfy, KarXT) received FDA approval on September 26, 2024, for the treatment of adults with schizophrenia. Xanomeline-trospium chloride is the first muscarinic M1, M4 acetylcholine receptor partial agonist approved to treat schizophrenia. Preliminary evidence also indicates that xanomeline-trospium chloride improves measures of cognition in Alzheimer's disease and schizophrenia.

A real-world population-based study on the association between cataracts and antipsychotics.

Objective: It is uncertain whether first- (FGAs) and second-generation antipsychotic (SGAs) drugs are associated with development of cataract. We conducted a real-world adverse event (AE) disproportionality analysis of cataracts in individuals exposed to antipsychotics.

Design: An observational, population-based pharmacovigilance study.