Parkinsonian Syndrome and Drug-induced Extrapyramidal Effects
Amantadine hydrochloride is used in the symptomatic treatment of all forms of parkinsonian syndrome including the postencephalitic, idiopathic, and arteriosclerotic types and for the relief of parkinsonian signs and symptoms of carbon monoxide poisoning and antipsychotic agent-induced (e.g., phenothiazines) extrapyramidal effects. There is no evidence that the drug alters the course of parkinsonian syndrome. Amantadine is less effective than levodopa in the treatment of parkinsonian syndrome. Although amantadine's efficacy in comparison to anticholinergic antiparkinsonian agents has not been definitely established, results of several studies suggest that amantadine is at least as effective as the anticholinergic agents. Similarly, in studies in patients with phenothiazine-induced parkinsonian signs and symptoms, amantadine was at least as effective in decreasing extrapyramidal symptoms as benztropine mesylate or trihexyphenidyl hydrochloride. Amantadine may be especially useful in the treatment of drug-induced extrapyramidal symptoms when drugs with anticholinergic properties should be avoided (e.g., in patients with glaucoma or urinary retention).
Amantadine has been reported to produce objective or subjective improvement in extrapyramidal symptoms, including akinesia, rigidity, tremor, salivation, gait disturbances, and total functional disability, in approximately one-half of the patients treated. Subjective responses such as a sense of well-being or elevation of mood have also been reported. Improvement in extrapyramidal symptoms is apparent within 4-48 hours following initiation of amantadine therapy, and optimum results are achieved within 2 weeks to 3 months. A definite correlation between the degree of improvement and the age or sex of the patient and duration or severity of disease has not been determined. Sustained improvement may last up to 30 months; however, some patients experience a reduction in benefit after 1-3 months of amantadine therapy. In some patients, benefits may be regained by increasing dosage or by discontinuing the drug for several weeks and then resuming therapy.
Addition of amantadine to a therapeutic regimen of anticholinergic antiparkinsonian agents (e.g., benztropine mesylate, trihexyphenidyl hydrochloride, or procyclidine hydrochloride) has produced further improvement. Concomitant administration of amantadine and levodopa has resulted in a greater reduction in parkinsonian symptoms than occurred with amantadine alone. Combined therapy with amantadine and levodopa has been reported to be more effective than levodopa alone in patients who cannot tolerate large doses of levodopa; however, the addition of amantadine to levodopa therapy does not usually provide significant additional benefit when patients are already receiving full therapeutic doses of levodopa.
Amantadine has been used in the treatment of spastic pseudosclerosis (Jakob-Creutzfeldt disease) with some success, although exacerbations of the disease have occurred in some patients. There is no evidence that the drug is effective in the treatment of mental depression, Huntington's chorea, essential tremor, tardive dyskinesia, or other neurologic diseases.
For information on the use of amantadine in the prophylaxis and symptomatic treatment of influenza A virus infections, see Amantadine Hydrochloride 8:18.04.