From The Last Psychiatrist - August 2, 2007

Aren't Two Antipsychotics Better Than One?

MY PSYCHIATRIST WANTS TO GIVE ME TWO ANTIPSYCHOTICS AT THE SAME TIME. WHAT SHOULD I DO?

Undoubtedly, your first impulse will be to punch him in the testicles, but as you know, the Kellogg-Briand pact (1928) expressly forbids this. However, it is notably silent on the issue of voodoo/ shark attacks, which can be used with discretion.

Antipsychotics exhibit their antipsychotic effect through D2 blockade. (1) Got it?

Take a look at the following figure again, showing % blockade of receptors (serotonin or dopamine) as a function of dose.



So you'll observe a few things.

First, these antipsychotics will have equivalences in dosage. If you use 10mg olanzapine as a baseline, how much dopamine does it block? 70%. How much risperidone does it take to block the same amount? 3mg. Therefore, 10mg olanzapine = 3mg risperidone. If you look at the graphs for the other antipsychotics (not shown-- sheer laziness), you get the following conversion for antipsychotic effects:

10mg olanzapine = 3mg risperidone= 500mg quetiapine= 120mg ziprasidone

Interestingly, most comparator trials done-- which look at symptom responses-- show these same equivalences. For example, ZEUS ziprasidone vs. olanzapine trial: 126mg ziprasidone=11mg olanzapine. This shouldn't be surprising since THAT'S HOW THE DRUGS ARE WORKING.

Second, no drug company can claim their drug has superior efficacy, because, again, they're all working through the same mechanism. Certainly, people tolerate each drug differently, but that's not efficacy, is it? Certainly an individual might respond to one better, but you have no way of predicting that. You simply cannot tell, by looking at someone, which drug will work and which won't. I'll show you: which drug will work best for this guy?

It's a trick question: the correct answer is penicillin.

The only way a drug company or study could claim to find superiority is if they don't use comparable dosages. "We found that risperidone 6mg was significantly more effective than 100mg of quetiapine." Really? Bite me.

Third, and this is really a math question: Since there are a finite number of D2 receptors in your skull, if you are on 6mg or risperidone-- which blocks 90% of them, and the doctor decides to augment with some olanzapine, where's the olanzapine going to go? Answer: your thighs.

Tom recognized her instantly despite the red anonymity bar

It's not going to D2 receptors, because they're all already blocked with risperidone. So it's just going to go around to other receptors-- H1, a1, M1, etc-- all of which have nothing to do with bipolar or psychosis. Issues of tolerability aside, mixing two antipychotics is no different than giving more of just one antipsychotic.

"Abiliquel"-- taking Abilify and adding quetiapine-- is sheer idiocy of such magnitude that even Eli Roth is repulsed. The first time someone told me what Abiliquel was, the room became filled with the sounds of six guys screaming in horrific pain, and that was because I was punching them in the testicles. Why not just give him Motrin + Advil? Oh: "But I use it cleverly: I give 15mg of Abilify and 25mg of quetiapine. See?" I see. I see that you're bleeding from the testicles. Guess why. You give 15mg Abilify-- that's acting as a D2 blocker. 25mg quetiapine isn't even a D2 blocker, it's an H1 blocker, you're paying for an antipsychotic and getting Benadryl. You say, "well, I know," (liar), "but I'm using the Abilify as an antipsychotic and quetiapine as a sedative." But, Gwyneth, you could have gotten the exact same effect by giving Abilify and Benadryl+trazodone-- which would be cheaper, and safer; or giving simply 500mg quetiapine alone, which would have gotten you both antipsychotic effect and sedative effect, thus reducing the cost by half, etc, etc. Remember that scene in the movie Hostel where Matthew McConaughey gets bitten by a radioactive lab rat and transforms into an immortal superhero?

Matthew McConaughey (Owen Wilson) proves there can be only one.

No? Do you know why? Because you knew better than to see that celluloid atrocity. How come you didn't know better than to prescribe two antipsychotics at once? You don't mix Zoloft and Paxil together, do you? Haldol and Prolixin? Seriously, do you just make crap up as you go along, or do you have pharmacological non-sequitors prepared in your Moleskine?

The same, by the way, goes for all you nutboxes who work in hospitals. If you have a patient on, say, 10,000mg of quetiapine, and he goes into an ER and gets indignant and flips a table over, and you inject him with 5mg of Haldol (90% blockade), you think that 10,000mg of quetiapine is doing him any good as an antipsychotic? I gots news for youse all: every time you prn (emergency dose) someone with Haldol, their brain is only on Haldol. Any other antipsychotic you give them that day is strictly a monetary gift to Big Pharma; you may as well PayPal them $180 and spare the patient the exposure.

On second thought, you may as well PayPal me.

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1. There may come a day where a drug is invented that works through some other mechanism, maybe glutamate, but as of right now, all the available antipsychotics work through D2 blockade. Everything else is irrelevant. Now, these other receptors might be relevant for other effects (reducing anxiety, antidepression, etc) but let's try to focus on the specific problem and not get all Andrew Weil here.