Abilify: A Breakthrough For Schizophrenia Patients

November 18, 2002

Abilify, the new schizophrenia drug, could represent a breakthrough for the 2.4 million Americans suffering from the disease.

Abilify was approved by the U.S. Food and Drug Administration on Friday and could be in pharmacies two weeks from now. The drug, which was invented by Japan's Otsuka Pharmaceuticals and co-marketed by New York City-based Bristol-Myers Squibb has much less severe side effects than current anti-psychotic treatments. Better yet, it works differently than existing drugs--leading some researchers to call it a breakthrough.

"The side-effect profile looks amazingly clean," says Jeffrey A. Lieberman, vice chair of psychiatry at the University of North Carolina in Chapel Hill Medical School. "It's almost too-good-to-be-true clean."

Abilify, or aripiprazole, doesn't appear to cause weight gain like Eli Lilly's Zyprexa, nor does it stiffen muscles like Johnson & Johnson's Risperdal. It also doesn't cause the cardiac rhythm disturbances that have plagued another entrant, Pfizer's Geodon.

That's good news, especially given some studies showing that one-fifth of all patients go off their medicines because of side effects. But clinicians like Lieberman and George Washington University's David Daniel are excited for another reason. They say Abilify is a new kind of schizophrenia medicine--only the third such advance in more than 50 years.

One of the main ways schizophrenia drugs differ is in how they inhibit a brain receptor for dopamine, a key neurotransmitter that is overactive in some parts of a schizophrenic's brain. The oldest drugs, like Haldol and thorazine, clomp onto the receptor like glue, completely shutting it down so tenaciously that they work for some time after patients stop taking them. Second-generation drugs introduced in the 1990s stick to the receptor some of the time, but not always.

Abilify sticks to the receptor but does not shut it off entirely. Instead of turning the patient's overactive dopamine receptor off, it dims it a bit. This should, at least in theory, make patients' brains function much more like those of healthy people.

There may be a big therapeutic upside. Serious symptoms like psychosis, hallucinations, voices and an inability to distinguish fantasy from reality are treated by existing drugs--perhaps more powerfully than by Abilify. But schizophrenics also suffer from depression and an inability to feel emotion--symptoms that existing anti-psychotic drugs don't treat. By making the dopamine thermostat more normal, Abilify seems to treat the second set of symptoms as well.

One qualitative aspect of the drug is that many of the patients will experience a sense of becoming alert, in touch and connected to other people," says Daniel. "These are the patients whose families will tell you that you've given their son or daughter back."

Donald Hayden, who heads Bristol's American division, sees this difference as one of Abilify's major selling points. Doctors emphasize that no one drug will treat all schizophrenics and that psychiatrists will take time to get used to prescribing Abilify. At first, it will probably be used for patients who went off their pills because of side effects or for whom other medicines didn't work. At some point, however, it may be the drug doctors reach for when confronted with a new case of schizophrenia.

"Ultimately," says Lieberman, "if it works like it's advertised and like the studies indicate, then it's a strong candidate for first-line treatment because you're putting people on it and never exposing them to side effects." If you participated in the Abilify clinical trials or have comments on this new schizophrenia drug, how about sharing them on our bulletin board."