Development of tolerance to the therapeutic effect of amantadine on akathisia

Four patients with akathisia as a result of neuroleptic administration were treated with amantadine. Although substantial improvement occurred initially, all four patients developed tolerance to this therapeutic effect within 1 week. An increase in dosage also had only a transient effect. The rapid development of tolerance significantly limits the usefulness of amantadine in the treatment of akathisia. One patient who suffered from akathisia and drug-induced parkinsonism experienced significant attenuation of both movement disorders in response to treatment with amantadine. Although she became tolerant to the effect of amantadine on her akathisia within the first week of treatment, her parkinsonism did not recur. The possibility that these two neuroleptic-induced extrapyramidal syndromes are pharmacologically separable is discussed.