Tuesday, May 4, 2010

A Smart Dopamine Med May Do Wonders For You (the problem is one doesn't exist)

Another extract from a much lengthier mcmanweb article published three years ago:

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."

Not surprisingly, dopamine dysregulation is implicated in schizophrenia, bipolar, depression, ADD, and substance use. Stimulants and various recreational drugs enhance dopamine signaling while antipsychotics set up a dopamine blockade.

Now here’s the catch. The editorial cites a University of Toronto study appearing in the same issue that shows what dopamine blockade does throughout the brain. Yes, antipsychotics work well in clearing up mania and psychosis, but often at the expense of making patients feel worse.

The study involved 12 patients diagnosed with schizophrenia who had been placed on either Zyprexa or Risperdal. They were given PET scans and queried about their subjective feelings. Those who reported lower states of well-being and higher dysphoria tended to turn up scans that showed greater dopamine blockade.

The striatum region of the brain, above the brainstem, is "dopamine central." From there, dopamine-active neurons project into other brain regions. The study found that blockade of dopamine receptors in the striatum strongly corresponded to a sense of impaired mental function. The study also found that blockade in "extrastriatal" regions such as the temporal lobe correlated to altered emotional regulation.

The effect is about as subtle as the IRS freezing all your bank accounts. True, your mania or psychosis may be gone, but now you may not be able to adequately think or feel. Who wants to live like that? Naturally, the patient gets blamed for noncompliance. According to the editorial:

Without adequate dopamine signaling, our patients do not feel "well." When dopamine systems are dysfunctional, patients seek a change. This may involve stopping a medication, such as antipsychotic drugs that block dopamine. Alternatively, it may be manifest as taking a drug, such as cocaine, that enhances dopamine activity. Either way patients are probably seeking to restore dopamine function.

Obviously, for a lot of us, antipsychotics and stimulants are a godsend. But we also know that our dopamine meds are too dumb to figure out in which regions of the brain they are not wanted. Our current inventory works directly on the dopamine system, but the editorial suggests that a smarter strategy may lie in developing meds with an indirect effect. One possibility is targeting the endorphin, dynorphin, whose neurons are engaged in a feedback loop with dopamine. Another is by learning more about the intracellular signaling connected with dopamine transmission and reception.

In the meantime, we are stuck with the low-tech solutions of considering easing off on antipsychotics doses and just saying no to (street) drugs. Maybe your psychiatrist can come up with some creative work-arounds, but first he or she needs to listen your concerns, really listen.

Full article

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