Letters to the Editor
Ziprasidone in Parkinson’s Disease Psychosis
Dear Editor:
Hallucinations and delusions are frequent side effects of dopaminergic treatment in Parkinson’s disease (PD) patients. These patients do not generally tolerate typical antipsychotic therapy with D2 antagonist drugs. Ziprasidone is a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. Clinical trials suggest that the drug is effective in treating schizophrenia (1). We report remission of psychosis and improvement of motor symptoms in a PD patient taking ziprasidone.
Case Report
Mr A, a 70-year-old man with a 16-year history of PD, was admitted to our department for levodopa-induced psychosis. Antipsychotic treatment with clozapine had been effective but had to be discontinued owing to agranulocytosis. At admission, the patient was treated with L-DOPA/carbidopa 1200 mg, L-DOPA/benserazide 375 mg, entacapone 1200 mg, and quetiapine 800 mg daily. He had pronounced visual, auditory, and tactile hallucinations, as well as delusions of persecution. Physical examination showed hypomimia, stooped posture, and a slight resting tremor of the right hand. There were infrequent (< 1 daily) off-episodes, with akinesia and rigidity lasting up to 1.5 hours. Otherwise, activities of daily life were only moderately affected. The Uniform Parkinson Disease Rating Scale (UPDRS) score was 43/199. The results of laboratory tests and the findings on cranial magnetic resonance imaging, ECG, and EEG were unremarkable.
L-DOPA/benserazide and quetiapine were discontinued without apparent effect. Aripiprazole 10 mg thrice daily was tried but revealed no benefit and had to be discontinued after 4 weeks, owing to motor side effects. At discontinuation, the UPDRS score was 101. Ziprasidone was initiated at 40 mg once daily and increased to 80 mg once daily over 3 days. Within 2 weeks, delusions and hallucinations subsided, and motor function improved fundamentally. Sitting, walking, dressing, showering, and eating without assistance became possible. On discharge, the UPDRS score was 42.
Ziprasidone is one of the newer atypical antipsychotic drugs; these drugs tend to cause fewer extrapyramidal side effects (EPSEs) than classic neuroleptics. Within the group, atypical neuroleptics have varying propensities to cause EPSEs. Clozapine appears to be superior in this regard and is widely recognized as a standard treatment for dopaminergic psychosis in PD. Experience with ziprasidone is lacking, and EPSE frequency has been estimated to equate that of olanzapine, which is not well tolerated in PD (2). In our opinion, however, the choice of a neuroleptic drug in PD should depend on the probability of drug-induced Parkinson’s symptoms and not of drug-induced dystonia, hyper- kinesia, akathisia, and myoclonus—all of which are EPSEs. Two substances with the same overall EPSE frequency may not be equally safe in patients with PD. Akathisia has been reported with ziprasidone (3), and we have also encountered acute dystonia. However, Parkinson’s symptoms occur rarely if at all, and therefore, ziprasidone may become a real alternative treatment for PD psychosis.
References
1. Arato M, O’Connor R, Meltzer HY; ZEUS Study Group. A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study. Int Clin Psychopharmacol 2002;17:207–15.
2. Tarsy D, Baldessarini RJ, Tarazi FI. Effects of newer antipsychotics on extrapyramidal function. CNS Drugs 2002;16:23–45.
3. Keck PE Jr, Versiani M, Potkin S, West SA, Giller E, Ice K. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry 2003;160:741–8.
Bernhard J Connemann, MD
Carlos Schönfeldt-Lecuona, MD
Ulm/Donau, Germany
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