
July 2, 2004
News this month
Early treatment of schizophrenia may improve outcomes
Prevention of schizophrenia has been one of the holy grails of research in
the disease for decades. Researchers are interested in determining whether
early interventionbefore the first full-blown psychotic episodecan
lead to improved outcomes for these patients.
Researchers are interested in determining whether early intervention can lead to improved outcomes.
Some evidence from ongoing research is yielding promising results, suggesting
that clinicians who are able to successfully identify which people are likely
to develop schizophrenia and then treat those patients appropriately can prevent
or delay full-blown psychotic episodes.
Studying early detection and intervention
Thomas
McGlashan, MD, professor of psychiatry at the Yale University School of Medicine,
is currently conducting the Prevention Through Risk Identification Management
and Education (PRIME) study. PRIME is the first early detection and intervention
program in the United States.
Investigators are now using new criteria to diagnose and treat patients who are experiencing early symptoms.
Although early symptoms of psychotic illness are usually recognized after
the first psychotic break, study investigators are now using new criteria to
diagnose and treat patients who are experiencing these early symptoms. In the
PRIME study, 60 subjects were identified through responders to advertisements
about mental illness development or through referrals from practitioners and
health services.
Subjects were assessed using the Structured Interview for Prodromal Symptoms
(SIPS), an instrument developed at Yale. About 80 percent of the participants
are experiencing symptoms such as unusual thought content, social withdrawal,
grandiosity and perceptual abnormalities, but they do not meet the criteria
for schizophrenia. The remaining 20 percent of subjects are considered at risk
for developing schizophrenia because of brief intermittent psychotic episodes
or because they have a family history of schizophrenia and have had a recent,
significant loss of functioning.
Subjects take part in the study for two years. During the first year, patients
receive psychotherapy, an antipsychotic drug, olanzapine, or a placebo, and
family intervention, as needed. Medication is discontinued after 12 months,
and patients are followed. If a subject's diagnosis changes to schizophrenia
at any point during the trial, the medication blind is broken and the subject
receives six months of open-label treatment.
Preliminary data suggest that the instrument under study is not only reliable, but has value for predicting the likelihood that a person will develop schizophrenia.
Predicting schizophrenia
Preliminary data from the trial
suggest that the SIPS is not only reliable, but has value for predicting the
likelihood that a person will develop schizophrenia. For example, six of the
first 13 subjects (46%) whose SIPS scores indicated prodromal status developed
full schizophrenia within six months of enrolling in the trial, whereas none
of the nine subjects who didn't meet prodromal criteria became psychotic during
that time frame.
Similarly, after a year, seven of 12 SIPS-positive subjects (58%) had schizophrenia,
but none of seven SIPS-negative persons did.
Although the study is ongoing and the researchers are still blind to treatment
assignments, some interesting trends are already apparent. Of the 32 patients
randomized thus far, three were still prodromal at the end of the medication
phase, 11 had remitted and eight had dropped out.
Eight remaining subjects developed full blown schizophrenia, and one subject
developed nonpsychotic affective disorder. None of the eight psychotic patients
have been hospitalized, and most have lost only minimal time from work or school.
Moreover, all responded very well to treatment, a finding consistent with
recent evidence that short durations of untreated psychosis may be associated
with better outcomes. This is a group with a duration of untreated psychosis
of zero, and there does appear to be an advantage, Dr. McGlashan said.
Scandinavian study
In a study published in the Archives
of General Psychiatry, Dr. McGlashan
looked at 281 patients in four Scandinavian health sectors with similar treatment
programs. Two of the four sectors had early detection programs and two did
not. Those with such programs provided education for their residents, school
counselors and health care workers about psychotic symptoms such as increasing
isolation, responding to voices no one else hears, delusional thinking, irritability,
difficulty sleeping and overall marked reduction in the ability to cope with
life's daily stresses.
Dr. McGlashan wanted to study early detection programs because the time span
between the onset of disease and treatment is a major concern for clinicians.
There is some indication that the untreated psychotic state itself may increase
the risk of a poor outcome. It looks like the longer the period of time
before treatment, the worse off the patients are not only when they come into
treatment, but how they respond to treatment, Dr. McGlashan said.
“Patients who began treatment earlier tended to be younger, less symptomatic and more responsive to treatment.”
Dr. McGlashan
Study participants were followed at three months, one year and two years
after the study began. The researchers found that the duration of untreated
patient psychosis in the two health sectors with early detection programs was
significantly shorterone compared to four monthsthan in the programs
without early detection.
All factors being equal, early detection efforts will bring people
into treatment at lower symptom levels, Dr. McGlashan said. Patients
who began treatment earlier tended to be younger, less symptomatic and more
responsive to treatment. He said there will be a follow up after one,
two, five and 10 years to see if the early detection and intervention have
lasting effects.


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