Selective Serotonin Rewait what

[st_rev]

The SSRIs--selective serotonin reuptake inhibitors--are a class of drugs commonly used as antidepressants. They 'work' by keeping neurons from absorbing serotonin from the synaptic cleft back into the cell, increasing the amount of available serotonin. This is good because serotonin is made of tiny pixies who want to be free, so keeping it out of the cells makes them happy, and that makes the patient happy by the magickal principle of contagion.

Well, that's about as close to the truth as any other version, and closer than the popular 'chemical imbalance' non-explanation, which is just updated humoralism. You need more serotonin, or black bile, one of the two.

If you don't believe me, consider tianeptine.  Tianeptine is a selective serotonin reuptake enhancer--it encourages the neurons to suck more serotonin out of the synaptic cleft, reducing the amount of available serotonin.

Yep, it's an antidepressant. Apparently a pretty effective one.

What the hell is going on?  Well, either:

• Nobody actually knows how the hell these things work, or...
• Tweaking serotonin in either direction can treat depression.

Actually, the first option is pretty much true regardless. Do SSRIs actually work directly via serotonin, or by indirectly promoting neurogenesis, or what? Last I checked (which I admit was a few years ago) it seemed very much up in the air.  But the second option appeals to my interest in dynamical systems, and my own 'punching the TV set' hypothesis of psychopharmacology.  You youngsters may not remember such things, but when an old CRT TV set was on the blink, hitting/shaking it would often knock its components back into their sockets and get it to work again.  By analogy, some psychiatric disorders may amount to getting stuck in a pathological stable orbit of a dynamical system, and perturbing the parameters of the system may knock it back into a healthy orbit*.

*: Yes, this is super-waffly, things are vastly more complicated than that, and it's unlikely that this is a fruitful metaphor for treating most illnesses. On the other hand, look at bipolar disorder.  What is that but an eigenvalue wandering into the right half-plane**?

**: This is also a super-waffly metaphor but perhaps slightly less so***.

***: Note also that there's a separate medical application for this metaphor where it works quite well: cardiac arrhythmia. Perturbing the system to knock it back into a healthy orbit is precisely what a defibrillator does.