Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis DOI Creative Commons
Giovanni Vita, Angelantonio Tavella, Giovanni Ostuzzi

et al.

Therapeutic Advances in Psychopharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 1, 2024

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral (OAPs) in preventing relapse and hospitalization chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence first-episode/recent-onset, that is, early-phase-SSDs is less clear. Objectives: To assess the relative medium- long-term efficacy safety of LAIs versus OAPs maintenance treatment early-phase SSDs. Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing early-phase-SSDs. Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences or between OAPs. Results: Across 11 RCTs ( n = 2374, median age 25.2 years, males 68.4%, illness duration 45.8 weeks) lasting 13–104 (median 78) weeks, no significant emerged relapse/hospitalization prevention (RR 0.79, 95%CI 0.58–1.06, p 0.13) 0.92, 0.80–1.05, 0.20). The included highly heterogeneous regarding methodology patient populations. outperformed studies stable 0.65, 0.45–0.92), pragmatic design 0.67, 0.54–0.82), strict intent-to-treat approach 0.64, 0.52–0.80). Furthermore, associated better schizophrenia only 0.87, 0.79–0.95), longer 0.88, 0.80–0.97), unstable 0.89, 0.81–0.99) allowed OAP supplementation 0.90, 0.81–0.99). Conclusion: did not differ significantly prevention/hospitalization acceptability. However, nine subgroup analyses, superior EP-SSDs indicators higher quality and/or (four analyses) reduced all-cause discontinuation (five analyses), without any instance superiority LAIs. More high-quality are needed. Trial registration: CRD42023407120 (PROSPERO).

Language: Английский

Major depressive disorder DOI
Wolfgang Marx, Brenda W.J.H. Penninx, Marco Solmi

et al.

Nature Reviews Disease Primers, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 24, 2023

Language: Английский

Citations

247
Muscarinic Receptor Activators as Novel Treatments for Schizophrenia DOI Creative Commons
S. Paul, Samantha E. Yohn, Stephen K. Brannan

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: 96(8), P. 627 - 637

Published: March 25, 2024

Achieving optimal treatment outcomes for individuals living with schizophrenia remains challenging, despite 70 years of drug development efforts. Many chemically distinct antipsychotics have been developed over the past seven decades improved safety and tolerability but only slight variation in efficacy. All currently prescribed act as antagonists or partial agonists at dopamine D2 receptor. With a few possible exceptions, antipsychotic drugs similar modest efficacy treating positive symptoms are relatively ineffective addressing negative cognitive disease. The novel treatments focused on targeting muscarinic acetylcholine receptors (mAChRs) has interest more than 25 following reports that dual M1/M4 preferring mAChR agonist resulted antipsychotic-like effects procognitive properties Alzheimer's disease schizophrenia; recent clinical trials confirmed these findings. In addition, advances our understanding receptor binding activation xanomeline specific mAChRs potential to inform future design mAChRs.

Language: Английский

Citations

22
Targeting metaplasticity mechanisms to promote sustained antidepressant actions DOI
Kyle A. Brown, Todd D. Gould

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 1114 - 1127

Published: Jan. 4, 2024

Language: Английский

Citations

18
New Drug Treatments for Schizophrenia: A Review of Approaches to Target Circuit Dysfunction DOI Creative Commons
Oliver Howes,

Eleanor Dawkins,

Maria Lobo

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: 96(8), P. 638 - 650

Published: May 28, 2024

Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side effects and have limited efficacy for many patients, highlighting the need to develop new approaches that target other aspects neurobiology schizophrenia. Preclinical, in vivo imaging, postmortem, genetic, pharmacological studies highlighted key role cortical GABAergic (gamma-aminobutyric acidergic)-glutamatergic microcircuits their projections subcortical dopaminergic circuits pathoetiology negative, cognitive, psychotic symptoms. Antipsychotics primarily act downstream component this circuit. However, multiple drugs currently development could elements circuit treat These include or glutamatergic targets, including glycine transporters, D-amino acid oxidase, sodium channels, potassium channels. Other likely on pathways regulate system, such as muscarinic trace amine receptors 5-HT

Language: Английский

Citations

18
The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia DOI
Daniela L. Uliana,

João Roberto Lisboa,

Felipe V. Gomes

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116298 - 116298

Published: May 21, 2024

Language: Английский

Citations

17
Knowing is Half the Battle: The Factors Leading to Efficient Recruitment of Representative Samples in Schizophrenia Research DOI
Joohyun Yoon, Megan Mayer, Tala Berro

et al.

Pharmaceutical Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Language: Английский

Citations

2
Exercise as a transdiagnostic intervention for improving mental health: an umbrella review DOI Creative Commons

Marco Solmi,

Ilaria Basadonne, Luca Bodini

et al.

Journal of Psychiatric Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

2
New Developments in the Treatment of Schizophrenia: An Expert Roundtable DOI Creative Commons
Joshua T. Kantrowitz, Christoph U. Correll, Rakesh Jain

et al.

The International Journal of Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 26(5), P. 322 - 330

Published: March 18, 2023

Abstract Background Schizophrenia is a disabling disorder that profoundly affects functioning and quality of life. While available antipsychotics have improved outcomes for patients with schizophrenia, they are relatively ineffective negative cognitive symptoms associated range troublesome side effects. A significant unmet medical need more effective better-tolerated therapies remains. Methods roundtable consisting 4 experts in the treatment schizophrenia convened to discuss current landscape, needs from patient societal perspectives, potential emerging novel mechanisms action (MOAs). Results Key areas include optimal implementation treatments, symptoms, improvements medication adherence, MOAs, avoidance postsynaptic dopamine blockade–related adverse effects, individualized approaches treatment. With possible exception clozapine, all currently primarily act by blocking D2 receptors. Agents MOAs urgently needed effectively target full facilitate an approach. Discussion focused on promising demonstrated phase 2 3 trials muscarinic receptor agonism, trace amine-associated 1 serotonin antagonism/inverse glutamatergic modulation. Conclusions early clinical agents encouraging, particularly agonists. These offer renewed hope meaningful improvement management schizophrenia.

Language: Английский

Citations

23
The definition of treatment resistance in anxiety disorders: a Delphi method‐based consensus guideline DOI Open Access
Katharina Domschke,

Patrik D. Seuling,

Miriam A. Schiele

et al.

World Psychiatry, Journal Year: 2024, Volume and Issue: 23(1), P. 113 - 123

Published: Jan. 12, 2024

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials innovative therapeutic interventions. However, an explicit definition treatment-resistant anxiety (TR-AD) informing such is currently lacking. We used Delphi method-based consensus approach to provide internationally agreed, consistent clinically useful operational criteria for TR-AD in adults. Following summary the current state knowledge based on international guidelines available systematic review, survey free-text responses 29-item questionnaire relevant aspects TR-AD, online meeting, panel 36 multidisciplinary experts stakeholders voted anonymously written statements three rounds. Consensus was defined as ≥75% agreeing statement. The agreed set 14 recommendations providing detailed pharmacological and/or psychotherapeutic treatment, well potential staging model. also evaluated further regarding epidemiological subgroups, comorbidities biographical factors, terminology vs. "difficult-to-treat" preferences attitudes persons these future research directions. This expected serve systematic, practical guideline aid designing mechanistic studies facilitate purposes. effort could ultimately lead development more effective evidence-based stepped-care algorithms patients disorders.

Language: Английский

Citations

13
Pharmacological Treatment of Cognitive Impairment Associated With Schizophrenia: State of the Art and Future Perspectives DOI Creative Commons
Antonio Vita, Gabriele Nibbio, Sergio Barlati

et al.

Schizophrenia Bulletin Open, Journal Year: 2024, Volume and Issue: 5(1)

Published: Jan. 1, 2024

Abstract Cognitive Impairment Associated with Schizophrenia (CIAS) represents one of the core dimensions Spectrum Disorders (SSD), an important negative impact on real-world functional outcomes people living SSD. Treatment CIAS a therapeutic goal considerable importance, and while cognition-oriented evidence-based psychosocial interventions are available, effective pharmacological treatment could represent game-changer in lives The present critical review reports discusses evidence regarding effects several agents that available clinical practice or under study, commenting both current future perspectives treatment. In particular, antipsychotic medications, anticholinergic benzodiazepines, which currently commonly used SSD, iclepertin, d-serine, luvadaxistat, xanomeline-trospium, ulotaront, anti-inflammatory molecules, oxytocin, undergoing regulatory trials can be considered as experimental agents, will reported discussed. Currently, do not appear to provide substantial benefits CIAS, but accurate management medications avoiding treatments further exacerbate strategies. Some molecules being investigated Phase 2 3 have provided very promising preliminary results, more information is required assess their effectiveness contexts clear recommendations use practice. results ongoing studies reveal whether any these awaited CIAS.

Language: Английский

Citations

12