Use
of atypical antipsychotic plus divalproex significantly improves recovery
from an acute psychotic episode of schizophrenia
The combination
of either olanzapine or risperidone with divalproex significantly
improves and speeds recovery from an acute psychotic episode of schizophrenia,
according to study results published in the January issue of Neuropsychopharmacology.
"Our findings suggest that combination
therapy with divalproex can decrease the mental pain and suffering
for many patients with schizophrenia and shorten the time they need
to be in the hospital," said study leader Daniel E. Casey,
M.D.
The American team studied 249 patients between
the ages of 18 and 65 years who were hospitalized with an acute
psychotic episode of schizophrenia. Patients who also had mood symptoms
were excluded from the trial. Of the total, 65 were randomized to
olanzapine, 66 to olanzapine plus divalproex, 60 to risperidone
alone, and 58 tp risperidone plus divalproex.
Divalproex is an effective treatment for mood
disorders, seizures, and migraine headache. Researchers found long
ago that the drug was ineffective as a single agent treatment for
schizophrenia. However, about 10 percent of patients with schizophrenia
also have mood-disorder symptoms, and divalproex is often used empirically
for this population in combination with antipsychotics. The current
study was the first large-scale trial to evaluate whether divalproex
in combination with an antipsychotic agent is effective against
acute psychosis.
When compared with patients treated with either
antipsychotic drug alone, patients treated with combination therapy
showed an enhanced reduction of symptoms as early as the third day
of therapy. Furthermore, the combination therapy was as well tolerated
as either antipsychotic drug used alone, with no additional side
effects.
Patients were treated for 28 days and evaluated at 3, 5, 7, 10,
14, 21, and 28 days with the Positive and Negative Syndrome Scale
total score, a common psychiatric diagnostic tool used to measure
changes in patient behavior. Improvements from baseline scores were
observed throughout the treatment period in all four groups.
"At day 3 we were already seeing significant
enhancement of benefits in the combination groups," Casey said.
Clinical improvement, defined as a 20 percent or greater improvement
from baseline scores, was seen in 53 percent of patients in the
combination groups on day 7, but the same degree of improvement
was not achieved until day 14 in the groups treated with either
antipsychotic drug alone. A 20 percent improvement in symptoms is
commonly used as a threshold to determine that a patient is ready
to leave the hospital, Casey pointed out, "so for many patients
the combination therapy has the potential to cut in half the time
they have to spend in the hospital."
Both combination and single-drug therapy were
well tolerated. Adverse effects and rates of discontinued therapy
were similar among all treatment groups.
About 25 to 30 percent of schizophrenia
patients respond poorly to antipsychotic drug therapy. Casey suggested
that potential benefits of longer combination therapy in these patients
should to be explored, as well as whether the enhanced improvements
of combination therapy observed in the study would be sustained,
increased, or diminished over longer periods of follow-up.
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