Associations between Anticholinergic Burden and Skeletal Muscle Indices and Physical Function in Older Adults: A Scoping Review.

“Brain health” is a comprehensive concept encompassing optimal brain functioning across cognitive, sensory, social–emotional, behavioural, and motor domains, enabling individuals to reach their full potential throughout life, regardless of the presence or absence of disorders. Promoting and understanding brain health is becoming increasingly important due to the growing burden of neurological disorders and their associated comorbidities. A key aspect of this broader focus is the recognition of the interplay between neurological and psychiatric conditions. Within this framework, depression and epilepsy are closely interconnected, significantly impacting physical, cognitive, emotional, and social functioning. This highlights the need for integrated approaches to better understand and manage the complex relationship between the two conditions. Several population-based studies, supported by experimental research, have suggested a bidirectional relationship between major depressive disorders (MDD) and epilepsy. People with epilepsy (PWE) have a 2–3 times greater risk of developing a psychiatric comorbidity than those without, with MDD being the most prevalent comorbidity. Conversely, the cumulative incidence of epilepsy after an MDD diagnosis is higher compared to the population without MDD. At 5 years, the incidence is 1.10% (vs 0.32% in the group without depression) increasing to 4.19% at 35 years of follow-up (vs 2.06%). Moreover, depression is the most frequently observed psychiatric comorbidity in individuals with drug-resistant epilepsy (DRE). The pooled prevalence of depression in PWE has been reported as 27% and 34% in population-based and clinical settings, respectively. In some studies, the prevalence of depression in patients with uncontrolled epilepsy, has been reported to be as high as 54%. Similarly, the hazard ratios for patients with depressive symptoms developing DRE were 3.3 times greater than those for patients without these symptoms. Additionally, a strong link has been found between the severity of a newly diagnosed depression and the subsequent development of epilepsy, along with poorer seizure outcomes, and evidence has shown that the risk of developing epilepsy is more than two times higher in individuals with incident depression compared with people without depression. Moreover, individuals with epilepsy have a higher risk of suicide, even if coexisting psychiatric disease, demographic differences, and socioeconomic factors are taken into account. The well-established bidirectional relationship between depression and epilepsy presents significant challenges for both patients and healthcare providers (HCPs). A major gap remains in the awareness, diagnosis, and management of depression in PWE among both HCPs (neurologists, psychiatrists) and patients. Key barriers include under recognition, undertreatment, and overlapping symptoms, which can complicate diagnosis and intervention. Treatment-related challenges further exacerbate these issues. Interactions between antiseizure medications (ASMs) and antidepressants (ADs) can influence the efficacy of both treatments and increasing the risk of side-effects. Some ADs may lower the seizure threshold, potentially exacerbating epilepsy symptoms in certain patients; similarly, some ASMs have mood-modulating properties, having a significant therapeutic effect on depression symptoms, depressive cognitive symptoms, and related conditions and certain ASMs may also trigger or worsen depressive symptoms.