In reply
Dr Sharma's criticism of the neuropsychological comparison of olanzapine,
risperidone, and haloperidol1 accurately
suggests that the dose of the treatments may be relevant to the results. A
recent demonstration of the value of relatively low-dose risperidone in the
alleviation of psychotic symptoms in patients with early phase schizophrenia
who were treated for more than 1 year2
provides the first direct empirical support for the comments of Dr Sharma
regarding the potential value of similarly low doses of risperidone in treating
the cognitive deficits associated with schizophrenia. As Dr Sharma acknowledged,
my colleagues and I advised caution in generalization beyond the particular
sample and dose ranges examined in our study, and we speculated on the importance
of further studies with risperidone, given a perceived trend toward the use
of lower doses in clinical practice. Although a stratification analysis failed
to detect cognitive improvement from risperidone in the low-dose conditions,
and we did not detect additional cognitive improvement in the risperidone
subsample not receiving anticholinergic supplements, it is possible that larger-sample
investigations with greater power to detect smaller effect sizes and a broader
dose range for risperidone may produce results different from the reported
findings. However, Dr Sharma's characterization of our dose range as "aberrant"
or "unrealistic" seems to be overzealous. Prior to the recently published
low-dose study,2 the assumption of value
from low-dose risperidone was based on anecdotal reports from clinicians,
whereas an optimal dose range of 4 mg to 10 mg per day was advised in the
product monograph and supported by a large-sample study that had used a flexible
dose strategy3 and by a naturalistic survey
of 2657 patients in Spain.4 Moreover, the
actual dose of risperidone used in our study1
was flexible within the range of 4 mg to 10 mg per day, and the clinician
responsible for the care of each patient determined the dose deemed necessary
for symptom management. The discrepancy between the daily dose required in
the low-dose study2 and that of our study
could relate to a variety of patient-specific or clinician-specific features.
For example, the low-dose report indicated that 25% of the patients assigned
to risperidone had their regimens discontinued and were assigned to treatment
with clozapine or a depot first-generation neuroleptic, perhaps relating to
difficulties in sustaining the low-dose strategy in a subsample of patients.
Additional data are required to confirm the general value of the low-dose
strategy to patients with schizophrenia and to evaluate the possibility of
a greater cognitive change with a lower dose of risperidone.