Lamotrigine

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated promising neuropsychiatric properties in animal research.

We aimed to examine whether SGLT2i exposure is associated with reduced incidence of suicidality, all-cause mortality, and hospitalization in bipolar disorder (BD).

This cohort study utilized the TriNetX network (2008-2025) to identify 1,230,821 adults with BD, including 36,092 SGLT2i users and 1,194,729 non-users. The outcomes were incident suicidality, all-cause mortality, and hospitalization over 5-years of follow-up. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models, with additional 1:1 propensity score matching (PSM) for survival analysis conducted to control for confounding. Subgroup analyses stratified results by sex, race/ethnicity, concurrent mood stabilizer use, and somatic comorbidities.

SGLT2i exposure was associated with significantly reduced risk of suicidality (aHR 0.75, 95% CI 0.71-0.79), all-cause mortality (aHR 0.55, 95% CI 0.52-0.57), and hospitalization (aHR 0.71, 95% CI 0.69-0.72). Protective associations remained consistent across subgroups, including patients receiving lithium, lamotrigine, or valproate. After PSM (31,001 matched pairs), five-year outcomes favored SGLT2i users: suicidality-free survival 94.51% versus 93.56%, overall survival 88.99% versus 79.57%, and hospitalization-free survival 72.39% versus 66.72% (all p < 0.001).

In this large cohort of over 1.23 million adults with BD, SGLT2i therapy was associated with substantially lower risks of suicidality, hospitalization, and all-cause mortality, with consistent benefits across demographic and clinical subgroups. These novel findings suggest SGLT2is may represent a promising therapeutic strategy to improve psychiatric and survival outcomes in BD. Prospective RCTs are warranted to evaluate long-term safety and efficacy.

Epilepsy is a common neurological disorder that is often associated with drug resistance and adverse effects of anti-seizure medications (ASMs). Recent studies have highlighted the role of the gut-brain axis and gut microbiota in seizure activity and neurological health. This review summarizes current preclinical and clinical evidence examining probiotics as a potential adjunctive approach in epilepsy management. This review summarizes findings from 79 studies, including 19 preclinical investigations and 3 clinical studies examining probiotics as a potential adjunctive strategy in epilepsy management. Of the 19 preclinical studies, 14 focused on the effects of probiotics in experimental models of epilepsy, while 5 evaluated interactions between probiotics and ASMs. Preclinical studies suggest that probiotic supplementation may be associated with reduced seizure severity, delayed seizure onset, and improvements in cognitive and emotional outcomes. These effects appear to be related to neuroinflammatory modulation, oxidative stress, neurotransmitter levels, and gut barrier integrity. However, clinical evidence remains limited and largely exploratory. Available studies indicate that probiotic use may be associated with a reduction in seizure frequency and improved quality of life in some patients and may also interact with the pharmacokinetics of ASM, but these results are based on small, heterogeneous groups and predominantly uncontrolled studies. In summary, probiotics may be a potentially useful adjunct to epilepsy therapy, with current evidence based primarily on mechanistic data and preclinical studies. However, the available clinical evidence remains limited and does not allow for firm conclusions regarding their therapeutic efficacy. Further, well-designed and controlled clinical trials are needed to determine the true clinical significance of probiotics, identify optimal strains, formulations, and dosing regimens, and assess long-term safety and potential interactions with ASM.