The new generation of antipsychotic drugs, the
so-called atypical antipsychotic drugs, has placed the treatment of
schizophrenia on the edge of a new frontier, according to a panel at the
American Psychiatric Association's 48th Annual Institute on Psychiatric
Services, whose meeting is under way here.
"Raising the standard of care is no longer just a hypothesis, [or] a legal
or managed care term," noted Dr. Jeffrey Lieberman during yesterday's
symposium. "It's now within our reach."
The atypical antipsychotic drugs are characterized by clinical criteria
ranging from superior efficacy--including effectiveness against negative
symptoms--to fewer side effects related to elevated prolactin levels, said
Dr. Lieberman, a professor of psychiatry and pharmacology and vice
chairman of the Department of Psychiatry at the University of North
Carolina at Chapel Hill School of Medicine. While the exact mechanisms of
the drugs are not fully understood, the net effect is a markedly separated
dose-response curve, providing a wider separation between efficacy and
side effects, he said.
The most successful atypical compounds appear to be those that block not
only dopamine 2 receptors but other neurotransmitter receptors
simultaneously, Dr. Lieberman reported. Antipsychotic drugs using this
mixed neuroreceptor approach include Olanzapine (Lilly), Ziprasidone
(Pfizer), Sertindole (Abbott) and Seroquel (Zeneca), all in late stages of
development or, in Olanzapine's case, recently approved.
These drugs "...place us in a very exciting position. The atypicals are
better not only in terms of [reduced] side effects, but in terms of
efficacy also," Dr. Lieberman said.
Effective treatment of schizophrenia also hinges on aggressive, systematic
psychopharmacologic treatment at the first episode, noted panelist Dr.
Diana Perkins, director of the Schizophrenia Treatment and Evaluation
Program at UNC Hospitals and UNC School of Medicine.
This includes administration of the lowest possible doses of atypical
antipsychotic drugs, she advised, especially with the first episode at
which time patients will be more sensitive to neuroleptic side effects.
"The '70s and '80s were a time when things were big - big hair, big shoes,
big drugs," she joked. "Lots and lots of haloperidol was considered good.
Now we know better--you don't want to overshoot your therapeutic window."
Fewer side effects may increase long-term patient compliance, she added.
If the drug's side effects are considerable, she observed: "Patients will
vote with their feet."
Other conference highlights included a weekend workshop detailing one
community mental health center's approach to reducing rehospitalizations
among its clientele.
The Connecticut Mental Health Center at Yale University was experiencing
an increase of readmissions from 17% to more than 25% within 90 days of
discharge, noted Dr. H. Rowland Pearsall, associate professor and director
of inpatient services at Yale School of Medicine. To reduce that rate, the
center introduced a relapse-prevention program for psychiatric patients in
The program incorporates a symptom checklist culled from the literature
and refined through interviews with patients, explained Dr. Pearsall.
Interestingly, some of the warning indicators commonly used by
physicians--patients who stop taking or reduce their medications or who
miss appointments, for example--were not endorsed by the patients as being
important, he said. Instead, signs such as feeling distant from family
friends, being bothered by persistent, troubling thoughts and feeling that
religion has become increasingly important are common among patients prior
to experiencing a relapse, he said.
Improving the link between inpatient and outpatient services has been a
critical component of the program, noted Elizabeth Grottole, MPH, the
center's associate director for clinical services, outpatient division.
Under the program, outpatient clinicians are required to participate in
the inpatient admission conferences, which are held weekday mornings from
10 to 10:30. "The outpatient doctors know not to schedule any appointments
then, and are expected to be there if one of their patients has been
admitted during the night," Ms. Grottole explained. Outpatient clinicians
are also expected to meet with their hospitalized patients and must meet
with them within 3 working days of their discharge.
As a result of these changes, observed Ms. Grottole, "our outpatient
clinicians are much more aggressive in following up their patients, rather
than saying, 'They'll show up in the emergency room when they need help.'
Re-engineering physician attitudes is another key component to such a
program, Dr. Pearsall said. "Clinicians aren't used to thinking about
relapsed patients in this population. They think of them as the
'unlapsed,' people who never get well enough to relapse."