Simple Meds, Complex Brain: Do You See a Problem?

John McManamy Health Guide
  • On the “Ask” feature, Downandout writes: “I have no desire to be around people. It seems all I want to do is sleep ...”

    Welcome to my world, and yours too, no doubt. Trust me, I’m getting off this sharepost under duress. My brain is telling me to take a nap. The catch is I just had one. Fortunately, I know I’m merely having one of those days. Tomorrow, I will be attending a meeting with people I enjoy, and I will perk up. But what about poor Downandout?

    “There seems to be no excitement or joy in my life,” she goes on to say. “I am so tired of not living the life I see other people living and enjoying.  ... I feel so guilty when [my kids] see me sleeping on the couch or not being able to jump up in the mornings and begin being the wife and mother I know I should be.  Is this the way my life will be forever?”

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    I’ve been stuck in those forever modes, and so, I presume, have most of you. It’s like being dead, only we’re breathing. Intriguingly, Downandout has this to say: “I would think the Adderall would give me motivation and help get me going, but it does not.”

    It seems Downandout possesses excellent insight into her condition. Adderall, an ADD med is a dopamine-enhancer. Here’s how the reasoning goes:

    Dopamine plays a major role in pleasure and reward (and anticipation of the two), motivation, mental clarity, the ability to feel emotions, and no end of vital brain functions. When dopamine is down, the frontal lobes literally go off-line, as do parts of the limbic system. The two parts of the brain literally don’t talk to each other.

    Serotonin gets all the attention, but a major reason we may get depressed may have a lot to do with dopamine. No energy, no pleasure, no motivation, is as good a description for depression as any.

    Wait, there’s more:

    Dopamine deficits are also thought play a major role in addiction and antisocial behavior. Street drugs such as meth and cocaine feed the dopamine craving for a brief time, only to set off another round of insatiable cravings. In a similar manner, those with antisocial behavior are inclined to be novelty seekers. Not enough dopamine is getting through to certain areas of the brain. They feel emotionally dead. They come alive by doing something outrageous.

    On the other side of the coin, too much dopamine has been linked to psychosis, schizophrenia, and possibly mania. There is too much going on in the brain. Antipsychotic medications block dopamine from entering neurons. Sometimes they work like a charm. Sometimes, they are very problematic.

    I remember attending a conference about five years ago involving players from the drug industry. In my conversations with the people there, I came away with the impression that Pharma views all mental illness as some kind of dopamine dysregulation disease. Oversimplistic? Yes, and that is why dopamine meds aren’t magic bullets.

    In theory, in Downandout’s case, a med like Adderall should work for her. If not Adderall, perhaps some other ADD med, if not an ADD med, some other dopamine-enhancer, perhaps Provigil (indicated for narcolepsy) or perhaps Wellbutrin or perhaps various Parkinson’s meds.


  • The dopamine in the brain is down, the thinking goes, let’s raise the levels.

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    But the brain isn’t chemical soup needing only the right mix of neurotransmitters to restore balance. If only life were that simple. Think of the brain, instead, as an ecosystem, highly complex, non-linear, and self-organizing.

    Just to give you the idea of the complexity of what we’re talking about, sample this piece of prose:

    This is a point that Dr Weinberger drove home with great force at the 2006 American Psychiatric Association’s annual meeting in Toronto. He was referring to a different gene and its variation (COMT val/met), coincidentally involving yet another molecule that acts on dopamine in a way that affects cognition. The "met" variation may enhance thought processing, which sounds good until we consider that this same variation may also interfere with emotional processing. So, depending on the total picture of a given individual, this particular gene variation could be either an asset or liability.

    Understand any of that? Neither do I, and I wrote it.

    What you can take home from this is our meds are highly simple tools not made for a complex brain. Yes, a dopamine-enhancer may be just what the doctor ordered for people in Downandout’s situation. As are other psychiatric meds for other individuals in other situations. But, frustratingly, too often nothing happens. Or something happens, but at an unacceptably high cost of doing business.

    One day, a new generation of smart meds, ones built for the brain’s true complexity, will hold out hope for Downandout and the rest of us. But we’re not there yet. We are stuck with our dumb meds, or - to put a more hopeful spin on it - smarter ways of working with dumb meds.

    In the meantime, the effort in putting this piece together has partially lifted me out of my funk. I’m sure I’ll wind up taking a nap just the same, but at least my head won’t hit the pillow feeling guilty.

    As for Downandout, in the long run, the brain’s complexity has a very good chance of working in her favor. Self-regulating ecosystems have a way of resetting to normal. But the key ingredient is time. We may be a long way from comprehending the infinite universe that resides inside our skulls, but we know enough to appreciate its limitless capacity to heal.


    Have faith, Downandout, have faith.

Published On: April 02, 2010