Introduction and objective: Major depressive disorder (MDD) is a heterogeneous psychiatric condition characterized by affective, cognitive and somatic symptoms that considerably impair daily functioning. It is defined clinically by prolonged low mood, diminished interest or pleasure, and a range of associated disturbances, including changes in cognitive skills, appetite, and sleep patterns. Although many treatment strategies are well-established and available, not all patients achieve satisfactory improvement. Treatment-resistant depression (TRD), often defined as insufficient response to at least two antidepressant trials of proper dose and duration, represents a major therapeutic challenge. This review aims to present and assess emerging treatment strategies for TRD, focusing on their mechanisms, effectiveness and safety.
Brief description of the state of knowledge: Recent advances in the understanding of depression pathophysiology have initiated the development of new therapeutic approaches targeting various systems thought to be involved in mood regulation. Glutamatergic modulators, such as ketamine and esketamine, have demonstrated prompt antidepressant effects, particularly in patients with severe or refractory symptoms. Neuromodulatory techniques, including repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT), remain important treatment options with growing research interest. Simultaneously, heightened attention has been directed toward psychedelic-assisted therapies, especially psilocybin, which may produce sustained antidepressant effects through modulation of various neural networks. Additionally, invasive interventions such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are being studied for resistant cases, although their use remains limited.
Summary: Emerging therapies for TRD offer promising alternatives to conventional treatment strategies, particularly for patients not responding to routine interventions. Further research is crucial for the optimization of therapeutic outcomes and integration of those novel approaches into clinical practice.
Maciej Kisielewski, Natalia Fidut, Jakub Skrzypek et al.· Quality in Sport· 0 citations
Introduction: Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. In addition to its well-documented gynaecological symptoms, endometriosis is increasingly associated with psychiatric disorders, particularly depression and anxiety disorders. The neurobiological and immunological mechanisms underpinning this comorbidity remain poorly understood.
Objective: This systematic review aims to synthesise current data on the neurobiological, neuroendocrine and immunological mechanisms linking endometriosis to depression and anxiety disorders, taking into account additional psychiatric symptoms such as sleep disorders, post-traumatic stress disorder (PTSD) and sexual dysfunction.
Methods: A systematic search of the PubMed/MEDLINE database was conducted to identify articles published between January 2008 and March 2026, using predefined search terms relating to endometriosis, mental health, neuroinflammation and immune dysregulation. Study selection was carried out in accordance with the PRISMA 2020 guidelines. Studies analysing the association between endometriosis and psychiatric outcomes, or investigating the underlying biological mechanisms, were included.
Results: Thirty studies met the inclusion criteria. The data consistently indicate elevated rates of depression (prevalence 9.8-98.5 per cent) and anxiety (11.5-87.5 per cent) in women with endometriosis compared with the general population. Key mechanisms identified include: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis; systemic and central neuroinflammation mediated by pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha), oestrogen-induced neurotransmitter imbalances, central sensitisation, oxidative stress and gut-brain axis dysfunction.
Conclusions: The relationship between endometriosis and psychiatric disorders is bidirectional and mediated by combined neuroendocrine-immunological pathways. These findings highlight the need for integrated, multidisciplinary management strategies that take into account both the somatic and psychological dimensions of endometriosis.
Julia Wawerska, Martyna Grzywacz, Bartosz Okliński et al.· International Journal of Inn...· 0 citations
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