Psychedelic interventions for major depressive disorder in the elderly: Exploring novel therapies, promise and...

The global population is ageing rapidly, with the number of individuals aged 60 and older reaching 1 billion in 2019 and expected to double by 2050. As people age, neuropsychological health often deteriorates, leading to a higher prevalence of age-related depression. Symptoms may include anxiety, apathy, mood instability, sadness, and, in severe cases, suicidal thoughts. Depression in the elderly is a widespread concern, and conventional treatments such as antidepressants are often limited by side effects, reduced efficacy, and complications arising from polypharmacy. In response, novel therapeutic approaches are being explored, including psychedelic interventions. Recent clinical and preclinical studies suggest that psychedelics could offer a promising treatment for major depressive disorder (MDD) in older adults. These compounds, known for their profound neurobiological effects, have gained attention for their potential to address depression where traditional therapies fall short. This review aims to examine the therapeutic promise of psychedelic substances, focusing on those that show potential for treating MDD in the elderly. We also explore the underlying mechanisms through which psychedelics may exert their effects and highlight the preclinical models that support their use. Finally, we address safety considerations and propose strategies to enhance the effectiveness and safety of psychedelics in future clinical trials, offering new hope for treating age-related depressive disorders.