Replacement of chronically administered anticholinergic drugs by amantadine in outpatient management of chronic schizophrenia.

Anticholinergic drugs have been shown to impair new memory acquisition. In a double-blind study, 22 chronically schizophrenic patients had the anticholinergic drugs that they had been taking to control the extrapyramidal side effects (EPSE) of neuroleptic drugs discontinued and were randomly assigned to treatment either with benztropine (an anticholinergic) or with amantadine (which has little or no anticholinergic effect). The EPSE of five of the ten patients assigned to amantadine could not be adequately controlled with that drug alone, and these patients were withdrawn from the study prematurely. The five patients who completed the six-week trial on amantadine showed improved performance on tests of memory acquisition in comparison with patients treated with benztropine. Global inspection of the results showed that only 36% of the patients taking benztropine showed improvement in memory acquisition at the four- and six-week assessments, whereas 80% of the amantadine users showed improvement at the four-week assessment. Analysis of covariance, however, revealed that the performance of the latter group decreased almost to baseline at six weeks, as an additional two of the remaining patients developed distressing EPSE.