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Am J Psychiatry 1997; 154:466-474
Copyright © 1997 by American Psychiatric Association
Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine
GD Tollefson and TM Sanger
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
OBJECTIVE: The authors investigated whether primary negative symptoms of
schizophrenia are enduring or treatment-responsive. METHODS: Previously, a
double-blind, random-assignment trial of the novel antipsychotic olanzapine
(in low, medium, and high dose ranges), placebo, or haloperidol (10-20
mg/day) for 335 schizophrenic inpatients was conducted for up to 52 weeks.
Changes in the treatment groups from baseline to endpoint in summary scores
on the Scale for the Assessment of Negative Symptoms (SANS) and several
secondary measures were compared. This article describes a path analysis to
determine to what extent the total treatment effect on negative symptoms
was direct or indirect (i.e., mediated by differential effects on positive
symptoms, extrapyramidal symptoms, or mood). RESULTS: Significantly greater
improvement was achieved with high-dose olanzapine than with placebo or
haloperidol. Olanzapine had a significantly greater direct effect than
placebo on all SANS dimensions except anhedonia-asociality. Olanzapine also
demonstrated a significantly greater direct effect than haloperidol on
negative symptoms, especially on the dimensions of affective flattening and
avolition-apathy. Olanzapine's superior effects were replicated in a
subgroup with SANS-defined prominent negative symptoms (N = 116) and a
subgroup with a BPRS-defined cross- sectional proxy for the deficit state
(N = 117). CONCLUSIONS: These results suggest that the negative symptoms of
schizophrenia are directly responsive to treatment. The significantly
greater direct and indirect effects of olanzapine than of haloperidol on
negative symptoms are likely related to olanzapine's pleotrophic
pharmacology, which includes dopaminergic, serotonergic, muscarinic, and
adrenergic activities. The results contribute to the hypothesis that
negative symptoms may be under the influence of several neurotransmitters
within one or more neuroanatomic circuits.
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|
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|
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|
|
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|
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|
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