Chapter 163
Promoting Mental Health — 11
However, the use of selective serotonin reuptake inhibitors is remarkably common, with approximately one in eight Americans taking one of these drugs (the common ones are Prozac, Zoloft, Celexa, Paxil, and Lexapro). The “serotonin hypothesis,” which dates to the 1960s, is controversial and has been challenged, but evidence remains that depression is a disorder of serotonin-based signaling in certain regions of the brain. More recently, we’ve seen the broadening of medications for depression from the classic SSRIs to potentially include ketamine and psychedelics. The problem with all these drugs—SSRIs, ketamine, and psychedelics—is that we don’t know they work clinically even though, for example, ketamine is known to increase extracellular serotonin levels. Oral ketamine tablets, assessed in a randomized trial for treatment-resistant depression, demonstrated some efficacy. A systematic review of nine randomized trials of psilocybin, a psychedelic, indicated self-reported improvement of symptoms of depression. A single dose of psilocybin in a small study of healthy adults undergoing serial functional MRI showed a massive dissolution of brain circuitry networks, particularly those involved with perception of space, time, and self, some of which persisted for weeks.
We have much to learn why medications don’t work at all for many people. Then there’s the long list of side effects. With improved understanding of brain circuits and inflammation, there’s a renaissance in new drugs for mental illness and an optimistic outlook for the emergence of “precision psychiatry.” Blood biomarkers of inflammation have been linked to lack of response to SSRIs and ketamine. The use of AI to predict the optimal treatment for depression for an individual is being actively pursued. Structure-based drug design and discovery have given rise to multiple new drug candidates that are entering clinical trials. It’s early, but there’s clearly good reason for hope that we’ll see better understood, more effective, and fewer side effect pharmacologic approaches in the future.
We can’t meaningfully promote healthy aging without attention to its interdependence on our mental health. We all experience stress, but it’s good and adaptive if we use it to exercise and double down on key lifestyle+ factors that are known to help. That includes nature, music, and social interactions. With the ongoing digital transformation of mental health support, a conversational chatbot or digital CBT app is just a click or download away. Ironically, at a time when there is the greatest mismatch of need for mental health support and lack of available professionals, there are more ways to get immediate 24/7 access for nonhuman help than ever before. As large language models continue to improve, the latter will undoubtedly get further validation, help reduce inequities (as we’ve already begun to see), and become more alluring with more use of human avatars than just text or voice. It is hard to imagine how human touch could be fabricated, but who knows? In any case, we will always need real human touch, metaphorically and literally. But anything, including an engaging AI chatbot or avatar that truly promotes our mental health, is something not to miss in our quest to age healthily.