New Data Show Early Non-Response to Antipsychotic Treatment May Be Strong Predictor of Subsequent Non-Response for People with S
April 03 2007 - 9:00AM
PR Newswire (US)
Findings indicate early non-responders unlikely to subsequently
respond, have substantially more treatment costs, and may benefit
from earlier change in treatment strategy COLORADO SPRINGS, Colo.,
April 3 /PRNewswire-FirstCall/ -- New data presented at the 2007
International Congress on Schizophrenia Research (ICOSR) suggest
that antipsychotic drug response be assessed earlier than is
presently thought, and challenge the current schizophrenia
treatment paradigm for when to evaluate if an antipsychotic
medication is working effectively. The findings show that early
non-response to antipsychotic medication, as early as two weeks
into treatment, appears to strongly predict subsequent lack of
response in patients with schizophrenia. Compared to "early
responders" - patients who responded to their antipsychotic
medication after two weeks of treatment - the "early
non-responders" were less likely to achieve subsequent symptom
remission, viewed medication adherence as less beneficial, had a
lower level of functioning, and incurred twice as many total
healthcare costs. The studies were conducted and funded by Eli
Lilly and Company. Early non-response may be a powerful marker to
not only predict prognosis in schizophrenia, but also tailor
appropriate treatment to the patient's immediate needs. These data
support the need for clinicians' early evaluation of patients'
treatment response, and the possible need for a change in the
medication to potentially help minimize prolonging exposure to
sub-optimal or ineffective treatment. Current schizophrenia
treatment guidelines recommend an initial trial of four to six
weeks to determine if a patient will respond to an antipsychotic
medication(i). However, these new data suggest this may be too
long. Without early and effective treatment, patients with
schizophrenia may experience devastating and costly events, such as
hospitalization(ii), incarceration(iii), homelessness(iv), repeated
relapses(v) and attempted suicide(vi). Current findings, which are
based on post-hoc analyses, are consistent with independent
research, suggesting drug effect seems to occur during the first
two weeks of treatment(vii). However, additional research is still
needed. "These data are potentially very important in helping to
establish the most cost-effective strategies for treating patients
with schizophrenia," said Dr. John Kane, chairman of the department
of psychiatry, neurology and neuroscience, The Zucker Hillside
Hospital, Glen Oaks, New York and professor of psychiatry, Albert
Einstein College of Medicine, Bronx, New York. "Furthermore,
clinicians need better guidelines and predictors of treatment
response in order to make informed treatment decisions. This is a
further step in that direction." Schizophrenia is a brain disorder
characterized by acute episodes of delusions (false beliefs that
cannot be corrected by reason) and hallucinations (usually in the
form of "hearing" voices)(viii), known as positive symptoms(ix).
Patients can also experience negative symptoms - such as diminished
emotion, general lack of interest and depressive signs and symptoms
- that are often more difficult to treat than positive symptoms(x).
More than two million American adults have schizophrenia(xi), and
more than 100,000 new cases are reported each year. The World
Health Organization estimates the annual cost of schizophrenia at
$65 billion, including direct costs and lost productivity(xii).
"These data strongly advocate evaluating the potential benefit of
antipsychotic medications earlier in treatment, so patients with
schizophrenia can be spared from unnecessary increased exposure to
a drug that is very unlikely to help them," said Dr. Cherri Miner,
Lilly U.S. medical director, neuroscience. "Quick and effective
symptom control is especially important for those patients with
urgent needs and may increase the likelihood that patients will
stay on their medication." Key Findings The first study, Predicting
Response to Atypical Antipsychotics Based on Early Response in the
Treatment of Schizophrenia, was a post-hoc analysis of data from
five randomized, double-blind clinical trials comparing atypical
antipsychotic medications in 1,077 patients with schizophrenia,
schizoaffective disorder, or schizophreniform disorder, who were at
least moderately ill at baseline and were treated for a minimum of
two weeks. Patients were assigned into early responder or early
non-responder groups at two weeks based on at least a 20 percent
improvement on the Positive and Negative Syndrome Scale [PANSS]
total score. (PANSS is the primary psychiatric scale used to
measure change in schizophrenia symptoms.) Subsequent response at
endpoint was defined as at least a 20 percent improvement in PANSS
total score (mild improvement), or at least a 40 percent
improvement in PANSS total score (moderate improvement). The
following was determined at the three-month endpoint: -
Seventy-four percent of patients identified as early responders or
early non-responders maintained their status. - Early responders
showed significantly greater improvements in symptoms at all time
points compared to early non-responders. - Early non-response
appears to be an accurate predictor of subsequent non-response to
antipsychotic medications. Researchers for the second study,
Clinical, Functional, and Economic Ramifications of Early
Non-Response to Antipsychotics in the Naturalistic Treatment of
Schizophrenia, performed a post-hoc analysis on data from a one-
year, multi-site, randomized open-label study of antipsychotic
medications. Patients who completed eight weeks of treatment on
their initial medication (n=443) were included in the analysis.
Patients with early response were identified as having at least 20
percent improvement from study start - baseline - on PANSS total
score after two weeks of treatment. Early responders were compared
to early non-responders (patients that did not show at least a
minimal level of early improvement) on symptom remission, physical
and mental health functioning, perceptions of medication influence,
and total healthcare costs at eight weeks. Statistically
significant findings included: - Early response or non-response at
two weeks predicted subsequent response or non-response at eight
weeks with a high overall level of accuracy (73 percent). - Almost
all (88.7 percent) of non-responders at eight weeks were correctly
identified at two weeks (high specificity). - Early non-responders
were less likely to achieve symptom remission after eight weeks of
treatment with the same antipsychotic (only 27.5 percent of early
non-responders achieved remission vs. 46.9 percent of responders, p