The Last Psychiatrist writes about a lot of things. Toward the end of the collection, there's a lot of analysis on pop culture and media. Critiques about movies and what they say about us (if you're watching it, it's for you). But toward the beginning there's a lot more about the medical system, psychiatry and prescription drugs. And there is where you'll find The Most Important Article On Psychiatry You Will Ever Read. It's an article about the way anti-psychotic drugs really work and the surprising consequences that arise.

Most anti-psychotic drugs work by binding to receptors and occupying them with no effect, blocking the pieces that are supposed to bind to those receptors to cause a change. The strange thing is, these drugs often bind to more than one receptor. As an example, he chooses Seroquel. Seroquel binds to histamine (H1), dopamine (D2) and Alpha1 (A1), among others.

This explains the raft of side effects we've gotten so used to hearing in conjunction with medications. You see in the Wiki article on Seroquel where it also causes dry mouth, constipation, orthostasis and sleepiness? The D2 blocker is what actually gives the anti-psychotic effect, but the H1 will cause sleepiness and the A1 affects blood pressure, leading to orthostasis (dizziness when standing).

Now if that was all there was, it would be interesting. But there's another little twist. These medicines that bind to multiple receptor sites... don't bind equally. They don't float around and the first A1/H1/D2 receptor they bump into, the bind to it. They actually have affinities for certain receptors over others. Seroquel has an affinity for H1, so in the presence of all the different receptors, it will bind to H1 first, before any others. TLP says to think of it like a champagne fountain (although he says he doesn't like champagne, so he imagines a rum fountain), where the top glass is filled up before it trickles down to the glasses below, and when they're full it trickles down further to the next tier of glasses.

Going back to Seroquel, that means that the great majority of the H1 receptors have to be occupied before it will start blocking anything else. And even then, Seroquel's next biggest affinity is for A1... so you're still not really hitting the anti-psychotic effect yet. You have to take enough Seroquel to saturate H1 and A1 receptors and only then does it start blocking D2. This is why you get sleepiness and dizziness side effects along with the anti-psychotic effects.

And here's the most important thing you'll ever learn about these drugs: half the dosage does not give you half the effects. Half the dosage becomes an entirely different drug! Let's say that the required dose of Seroquel (printed on the box) is 300mg. You might be tempted to say "Well, I'm feeling pretty good today, I'll only take half a pill." But here's the issue: 150mg of Seroquel might not block enough H1 and A1 to get to the D2 receptors. 150mg of Seroquel doesn't have half the anti-psychotic effects of a full does, it has none of the anti-psychotic effects of a full dose!

Mind blown?

This means that doctors could be tempted to start a patient on a low-dose of Seroquel to see how they react to it. You know, kinda ease into the treatment. But 75mg or 150mg or maybe even 200mg of Seroquel might yield no beneficial effects toward treating psychosis and lead the doctor to think that the patient doesn't respond to Seroquel. It's entirely possible that if they had given them the full dose from the start, they would have seen the proper response.

This also works in the other direction: 25mg of Seroquel is sedating (H1 blockers). 50mg of Seroquel is even more sedating. So why isn't the recommended dose of 300mg of Seroquel fatal? Because at some point you have enough H1 receptors blocked that the Seroquel moves on to A1 and D2 and other receptors. The sedation maxes out and other effects appear.

It's tempting to say "But the FDA says Seroquel is an anti-psychotic! Are they liars?" They're not, it's just only an anti-psychotic at the dosage that they list. Anything other than that, and all bets are off.

Now that you understand how receptor-blocking drugs work, you hopefully understand why the dosages are set the way they are. You may think you're handling your bipolar pretty well and that you can ease off your prescribed dosage. But then don't be surprised that while taking half-doses of the drug, your bipolar comes back full-force.