Amantadine treatment of hemispatial neglect: a double-blind, placebo-controlled study

The resemblance of some aspects of the hemispatial neglect syndrome (hypokinesia, decreased arousal) to aspects of Parkinsonian syndromes, and the success of amantadine in treating disorders of attention, prompted a placebo-controlled, double-blind trial of amantadine, an inhibitor of the N-methyl D-aspartate (NMDA) glutamate receptor that modulates dopamine transmission, in four patients with chronic hemispatial neglect.

Patients received placebo or 100 mg of amantadine twice a day in an ABA design. Dependent measures of drug effect included an extensive battery of tests assessing arousal, hemiinattention, hemihypokinesia, personal neglect, disability, anosognosia, family burden, and naturalistic action.

There was no evidence of increased adverse effects with the treatment drug compared with placebo. Of the 17 measures used to assess treatment response in the four patients (68 measures total), linear regressions revealed significant positive treatment effects on very few (four) measures (uncorrected for multiple comparisons), and scattered negative responses to treatment were evident on three measures. The vast majority of measures showed no change in response to treatment.

Possible reasons for failure of treatment effects in the present study are discussed. Additional study will be required to determine whether there are neglect patients who may benefit from amantadine.