Excitability—Bad and Good2024-01-29

I've been on Prozac for 12 years and I'm off it now. I know what it feels like to be excited and sad again. I haven't felt like this in 12 years; I'm like a giddy little kid.

Jonathan Davis (Korn)

Neuronal excitability is reduced by SSRIs (such as fluoxetine-Prozac), and even more so by mood stabilizer medications (such as valproate), most of which work as anti-seizure medications, as well as by the ketogenic diet, which works for seizures as well.

In people with mental health challenges, there is a pronounced negativity bias, which is the result of a survival mechanism run amok, in response to past trauma of the individual (coded in gene expression and epigenetic changes), or of the ancestors (coded in genes). Excitability in these individuals mostly occurs as part of the negativity bias response, and reducing it is beneficial.

In people without a history of trauma or who are recovered from it, and even more so in optimists with a positivity bias, excitability occurs equally in reaction to good things, not just bad things. Blunting it with SSRIs, mood stabilizers or perhaps even a strict ketogenic diet can reduce joie de vivre, drive, and creativity, and has to be minimized if possible. The exception is in bipolar individuals, where the over-excitability of mania in reaction to good things needs to be curtailed. Lithium (at low doses) may strike the right balance between stabilizing mood without excessive reduction of excitability.

Like with everything in medicine nowadays, context, personalization of treatment, and precision based on biological measures are important. We have done our bit to enable that for mental health with our digital and molecular approaches, in particular MindX One Blood Testing, which provides objective information about disease severity and medication matching (see Others are working hard as well on other approaches, notably imaging and EEG. Mental health will be transformed in the next few years, to the benefit of patients, families, and society at large!