Oct 14, 2003 03:00 AM

Scientists at the University of Pennsylvania are developing a controversial implant designed to deliver small doses of antipsychotic medicines for up to a year to people with schizophrenia.

Knowing that this approach raises a host of medical and ethical issues, the researchers held a medical “town hall” meeting last month.

“This needs to be debated in a public forum,” said Paul Root Wolpe, a senior fellow for the university’s Center for Bioethics who is not involved in the research. “This is still an experiment. And it’s important to have a dialogue between patients, doctors and families to understand what their concerns may be.”

The idea for the implant belongs to Dr. Steven Siegel, who, as a medical resident in 1999, noticed that most of the schizophrenia patients readmitted to the hospital – sick with symptoms of hallucinations and delusions – had stopped taking their medicines.

Failure to comply with medical prescriptions is probably the most important reason that symptoms re-emerge. Siegel had an idea about creating an implant that delivers the doses, much like Norplant pumps out uniform doses of contraceptive. There was nothing like it on the market.

“There is no reason scientifically that someone couldn’t have done this,” said Siegel, who has spent the past four years designing and developing an implant to deliver antipsychotic medicine. A test polymer holding the medicine has been implanted in the backs of mice, rats and monkeys. His next test subject will be dogs. Human use could be years off.

He employs the antipsychotic drug haloperidol, which is the oldest and most prescribed medicine for schizophrenia. Its stability (it has a shelf life of two years) and high potency made it a good tool for testing his idea, Siegel said. It also doesn’t require refrigeration. The animal studies suggest that the concept works – the animals even after 14 months had medicine in their brains and in their blood. But before it moves into human testing, Siegel and his colleagues want to make sure that it’s something that patients would want.

That’s where the ethics roundtable comes in. The psychiatrist’s vision was to bring the experts – an ethicist, a mental health lawyer, a psychiatrist and a patient advocate – together to talk about the science and the need for such a technology.

“Even if it works, if no one wants to use it, then it’s not worth going forward,” Siegel said. “It’s a real paradigm shift. We take medicines by mouth. And embracing such a shift takes time.”

He and his colleagues, through support from the Stanley Foundation, have sent questionnaires to hundreds of patients, doctors and family members to see what they think about a yearlong therapy. Wolpe, the ethicist who was part of last week’s town hall medical meeting, said many questions are on the table. Obviously, the first is safety. “This is a difficult technology to pretest,” he said.

Can doctors give it to people without schizophrenia to test its safety? “Probably not,” Wolpe said. Can they add on the implant and see if it makes a bigger difference than the standard oral treatment they are taking? “Probably not,” he said again.

What about the possibility of misuse? Psychiatric patients have many issues that surround their treatment, including whether they need drugs to combat a spiraling thought disorder. Many stop taking these medicines because of side effects, such as shaking, and once they are off for a few days and the side effects disappear, they feel better and don’t understand that they may be at risk for relapse.

“They have free choice with a pill,” Siegel said. “Will they have adequate informed consent to understand the nature of the delivery system and know that it will be inside their body for a year?”

Mark Salzer, a psychologist at the University of Pennsylvania’s Center for Mental Health Policy and Services Research, worries that Siegel and his colleagues are offering “a more invasive approach than is necessary.” He said there are less intrusive interventions, including psychosocial ones, memory aids, pillboxes and better dialogue between patient and doctor.

He believes such a device could be seen as coercion. “This potentially takes the choice away from patients,” Salzer said.

He also worries that patients who have troublesome side effects will have no way to avoid them with such an invasive and long-term delivery system. Many patients say they stop their medication because the side effects are hard to bear.

Another problem that Wolpe envisions: Will physicians stop monitoring patients when they technically will be on medicines for a year? “We really need to start this conversation now,” Siegel said.

Ultimately, Siegel hopes that his questionnaires will help decide the direction of his research. So far, with 250 questionnaires now in, he said that 45 percent of patients said they would like to have such a treatment. The psychiatrist has just sent out fliers to scientists all over the world asking them to give out the questionnaires to patients. He’s hoping to glean information from 1,000 patients.

Copyright © 2003, Newsday, Inc.