For Discussion: The Dopamine Cocktail

In response to a blog post from two days ago on meds compliance, Cretin, who is on Zyprexa, commented:

"After a neurological test implicated working memory as the problem, my doctor had me try adding dextroamphetamine (Dexadrine). In essence we are adding in more dopamine to the system while blocking enough D2 receptors with olanzapine (Zyprexa) to avoid any psychotic symptoms. So far that has worked. It would be interesting to see if this combination would lead to greater compliance with medications."

Funny you should raise that, Cretin. I've been on a kick about "smart" dopamine meds for some time now. The ones we're working with are pretty dumb. Here's the situation:

Working one side of the street are antipsychotics, which block dopamine. Too much dopamine tends to result in over-excitement and psychosis. Antipsychotics such as Zyprexa work well against psychosis, but often at the expense of cognitive function, awareness, and motivation, not to mention pleasure and reward, which tends to involve instant eunuch-hood.

In addition, shortage of dopamine can result in temporary and permanent Parkinson's-like tremors known respectively as EPS and tardive dyskinesia.

Working the other side of the street, for lack of a better term, are "dopamine enhancers." These include anti-Parkinson's agents, ADD meds such as Ritalin, and the wakefulness agent Provigil. In addition, MAOI antidepressants and the antidepressant Wellbutrin have a modest dopamine effect.

Last but not least, we have methamphetamines, which tend to get abused as street drugs, plus street drugs with no medicinal value. For the sake of extreme over-simplicity, think of ADD meds and Provigil as methamphetamines with brakes.

A "smart" dopamine med would restore dopamine balance without over-shooting the mark in one direction or the other. It would also dispatch dopamine to certain parts of the brain where more is needed and slow it down in other areas where less is needed.

The problem is, a smart dopamine med doesn't exist. But we can still come up with smart strategies based on the meds we have. Cretin and her doctor did just that. Think "dopamine cocktail."

I stumbled upon this by accident about four years ago when someone I know raised with her psychiatrist the idea of Wellbutrin to deal with a particular side effect of the antipsychotic she was on. The Wellbutrin turned out to be a dud in this regard, but unexpectedly her head cleared up. She could "think" again.

Thinking - something people with no mental illness or who have never been on a psychiatric med take for granted.

Two-and-half years ago, I began researching dopamine in earnest. Soon after, a friend landed a part-time research position, which represented a major step in his recovery - if he could hold onto the job.

My friend has a masters degree and teaching experience, but his previous employment was parking cars, and even that was a struggle for him. Between his illness and the antipsychotic he was on, his brain had a hell of a time booting up.

I suggested he ask his psychiatrist about Provigil. In essence, something to counteract the antipsychotic. A dopamine cocktail, if you like. I won't say the med brought his brain completely back online, but what he reported was a miracle. He could function. No longer was he overwhelmed by work and the people around him. He credits the Provigil with saving his job.

There is a twist to this. Thanks to our system of mangled care, my friend was deprived his Provigil. His psychiatrist was smart enough to substitute an ADD med, which didn't work as well, but nevertheless got the job done until my friend managed to get back on the Provigil.

Clearly, psychiatrists are willing to give dopamine cocktails a try, but the fact we don't hear more from people such as Cretin indicates this is clearly not widespread practice. What gives?

For one, there is no evidence base to go on, much less any CME courses to educate physicians, much less FDA indications for using meds in this capacity. In short, the only thing guiding psychiatrists is their own clinical wisdom.

For another, there is legitimate fear of abuse and addiction (a small study that just came out in JAMA found potential for addiction in Provigil).

Add to that my own strong belief that doctors tend to err on the side of overmedicating and over-sedating us. The thought of us cracking jokes and solving differential equations while we dance with the stars seems to set off a primal reaction in just about every card-carrying psychiatrist I have known.

Finally, there may be other and possibly safer alternatives to dopamine-enhancers, such as meds that work on the cholinergic system (for instance, Alzheimer's meds). A good psychiatrist will take these and other matters into consideration.

Obviously, this is an extremely complex issue. Any decision needs to be an informed one between you and your psychiatrist. By all means, let's get a conversation going, but until we learn more, let's not jump to any premature conclusions.

More to come in future blogs ...

From mcmanweb:

Dopamine - Serotonin's Secret Weapon

The April 2007 American Journal of Psychiatry features an editorial by Bruce Cohen MD, PhD and William Carlezon PhD, both of Harvard, entitled "Can’t Get Enough of That Dopamine." As the authors point out, "through their many connections, dopamine neurons participate in the modulation of expectation, reward, memory, activity, attention, drives, and mood - the very substrates of psychiatric illness." ...