Cognitive Effects of Olanzapine Treatment in Schizophrenia

Susan R. McGurk, PhD; M.A. Lee, MD; K. Jayathilake, PhD; Herbert Y. Meltzer, MD

In This Article


The means and SDs of all clinical and cognitive measures are given in Table 2 . Following 6 weeks of treatment, significant improvements were demonstrated for: (1) Stroop Interference Trial, (2) two measures of verbal fluency, Animal Naming and CWAT, (3) Trail Making A, (4) CVLT, Immediate and Delayed Recall, and (5) Visual Reproduction, Immediate and Delayed Recall. Following 6 months of olanzapine treatment, significant improvements were noted in: (1) Digit Span, (2) CPT-D Prime, (3) Auditory Consonant Trigrams, (4) Digit Symbol Substitution test, (5) Trail Making A, and (6) CVLT, Immediate and Delayed Recall. The Digit Symbol Substitution and Digit Span tests, in contrast with ACT and CPT-D Prime, were the only 2 cognitive tests in which inspection of the data revealed no evidence for improvement at 6 weeks, followed by significant improvement at 6 months. For the ACT and CPT-D Prime, there was nonsignificant improvement at the 6-week assessment, which reached significance at 6 months. Performance on Digit Symbol significantly improved between 6 weeks and 6 months of treatment (F(1,23 = 8.50, P < .01). There was no evidence of an across-the-board improvement in performance between baseline and 6 weeks, or between 6 weeks and 6 months, which would suggest an overall practice effect. No cognitive test performance was impaired by olanzapine treatment at either time interval.

The BPRS Total score, and Positive Symptom subscale of the BPRS were significantly improved at the 6-week and 6-month follow-up. The change in the BPRS Withdrawal-Retardation subscale score was not statistically significant. In order to determine whether cognitive improvements were related to improvement in positive symptoms, ANCOVA were performed to determine the influence of covarying the change in positive symptoms on the change in each cognitive measure. Improvements in the Stroop Interference Trial, the CVLT Immediate and Delayed Recall, CPT-D Prime, Digit Symbol Substitution, Animal Naming, and CWAT remained significant but the Visual Reproduction, Trail Making A, Auditory Consonant Trigrams, and Digit Span did not. Performance on Animal Naming, CWAT, and Digit Symbol remained significant after controlling for positive symptom change.

Regression analyses were conducted to determine significant predictors of cognitive improvement with olanzapine. Age of subjects, sex, duration of illness, and neuroleptic resistance were entered into the model, and change scores from baseline to 6 weeks for each cognitive test were entered as the dependent variable. Age, sex, duration of illness, and neuroleptic resistance did not significantly predict cognitive response to olanzapine for any of these measures.

The early termination sample (N = 24) was compared with the 6-month, prospective group (N = 10) and was not found to differ on any demographic (age, sex, years of education, age of illness onset, duration of illness), clinical, or cognitive measure. Reasons for study discontinuation included move out of region (N = 8), consent withdrawal (N = 4), unable to locate (N = 6), treatment nonresponse (N = 3), and medication side effects including weight gain and/or EPS (N = 3).


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