Disclaimer: I do not recommend this drug cocktail. I also do not discourage it. I just want to talk about it, because it is increasingly fashionable.

Background:

A few years ago, some psychiatrists decided to try combining Remeron (mirtazapine) with Effexor (venlafaxine) for use in treatment-resistant depression. They actually published a few peer-reviewed double-blind randomized controlled trials. Now the mix has been dubbed California Rocket Fuel and its popularity is booming.

The Drugs:

Remeron (mirtazapine) is a very strange antidepressant. It is an alpha-2 adrenergic antagonist, just like the stimulant yohimbine. This is the opposite of the sedative clonidine. This effect causes serotonin (5-HT) and norepinephrine (NE) release. This effect takes over at high doses and can make Remeron very stimulating.

Remeron is also an antagonist at a bunch of monoamine receptors, and also at the histamine receptor. This can help with side effects like nausea and anxiety, and it also causes sedation, especially at low doses. Most patients develop tolerance to the sedation, especially if they increase the dose high enough to really push the NE levels up.

Effexor (venlafaxine) is an SNRI, a serotonin and norepinephrine reuptake inhibitor. It thus boosts levels of 5-HT and NE, but via a different mechanism than Remeron. One might expect their effects to multiply, instead of just adding. Effexor is an especially stimulating antidepressant. Remeron probably helps to minimize the Effexor side effects.

What People Are Saying:

People are saying it is very effective for treatment-resistant depression. People also say it is very energizing, hence the "rocket fuel" name.

I suspect it wouldn't be so good for anxiety, but I am wondering if anyone here has tried it, or knows anyone who has tried it.