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Letters to the Editor
June 2002

Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation in the Elderly: Correlation Between Effect Size and Coil-Cortex Distance

Arch Gen Psychiatry. 2002;59(6):573-575. doi:

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.

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