Antipsychotics

Making that Rx just right

Nothing has done as much to revolutionize treatment of serious mental illness as the development of drugs like Thorazine. Since their introduction about a generation ago, these powerful antipsychotics have freed tens of thousands of patients from the despair of mental institutions. Some patients have even resumed normal, useful lives. Yet as important as the miracle drugs have been, they are not without serious drawbacks.

Because the antipsychotics affect different patients in different ways, doctors can never be sure just how effective a particular agent or dosage will be; they simply prescribe by trial and error. The medication may not work at all or, if the dose is too high, it may produce annoying, even dangerous, side effects.

So far, doctors have had little help out of this bind, since few precise tests have been generally available to tell them if and how well the body will respond to a prescribed drug. But aid may now finally be on the way.

-- At Johns Hopkins University, Dr. Solomon Snyder and his colleagues, Ian Creese and Dr. Larry Tune, have developed a simple blood test that should be especially useful in treating the nation's estimated 2 million to 5 million schizophrenics. Already tested on 30 patients, it is based on pioneering studies of the brain's receptors, or molecular sites to which its own drug-like chemicals bind--almost as if they were keys in a lock. A blood sample from a patient is added to a tube containing animal brain tissue and a radioactively tagged chemical known to bind to particular receptors. Whatever drug is in the patient's blood displaces the test chemical at these sites, and the radioactive tracer left behind can easily be measured, giving doctors a precise indication of the levels of the prescribed drug in the blood--and thus a firm indication of how the body is utilizing it.

> At Harvard, Dr. Joseph Schildkraut and his colleagues have devised a urine test that can distinguish types of depressive disorders and hence indicate the best available drug for treatment.

The trick: they measured urine levels of MHPG, a breakdown product of a brain chemical.

By comparing results from more than 30 patients suffering varying degrees of depression, they were able to establish two groups: those below a certain urine level responded to relatively low dosages of a test drug; those above either did not respond or had to be given stiff dosages.

Both tests are clearly still in the preliminary stage of development and may not be generally available for several years. For doctors and patients, that will be none too soon.

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