ORIGINAL ARTICLE Quetiapine and Clozapine in Parkinsonian Patients With Dopaminergic Psychosis Letterio Morgante, MD,* Antonio Epifanio, MD,* Edoardo Spina, MD,† Mario Zappia, MD,‡§ Antonio E. Di Rosa, MD,* Roberto Marconi, MD,  Giorgio Basile, MD,¶ Giorgio Di Raimondo, MD,* Paolo La Spina, MD,* and Aldo Quattrone, MD‡§ Objective: This study aimed to compare the efficacy and safety of quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis in a randomized, open-label, blinded-rater, parallel group trial. Methods: Forty-five patients with Parkinson disease (PD) and psy- chosis induced by antiparkinsonian drugs were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. Forty patients, 20 in each treatment group, completed the study. The final dose of quetiapine (mean ± SD) was 91 ± 47 mg/d and that of clozapine 26 ± 12 mg/d. The severity of psychosis was as- sessed using the Brief Psychiatric Rating Scale (BPRS) and the Clini- cal Global Impression Scale–Severity Subscale (CGI-S). The Unified Parkinson’s Disease Rating Scale (UPDRS) III was used to assess motor conditions during the study period. The Abnormal Involuntary Movement Scale (AIMS) was performed to evaluate dyskinesias. Results: Forty patients, 20 on clozapine and 20 on quetiapine, com- pleted the study. The psychopathologic state improved significantly (P < 0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at any assessment time. Motor conditions remained unchanged after clozapine and quetia- pine. Dyskinesias decreased significantly (P < 0.05) in both groups. Side effects were mild, generally transient, and well tolerated. Conclusions: Quetiapine and clozapine appear equally efficacious for treatment of dopaminergic psychosis in patients with PD. Key Words: Parkinson disease, quetiapine, clozapine, dopaminergic psychosis (Clin Neuropharmacol 2004;27:153–156) D rug-induced psychosis is a common complication in pa- tients with Parkinson disease (PD) and is the major factor leading to their placement in nursing homes. 1 Psychotic symp- toms including hallucinations, delusions, confusion, and dis- orientation have been reported to occur in about 16–40% of parkinsonian patients chronically treated with dopaminergic drugs. 2,3 They are more frequent in patients with cognitive im- pairment, 4 depression, 2 a longer disease duration, 5 higher age at onset, 4 sleep disorder, 6 akinetic form of PD, 7 dose and du- ration of treatment with L-dopa 2,4,5 and dopamine agonists, 4,8 and the apolipoprotein E4 allele. 9 Traditional treatment op- tions included either reducing the dosage of antiparkinsonian medication or using typical antipsychotics. Both strategies were unsatisfactory and could lead to worsening of motor dis- ability. The introduction of atypical antipsychotics with low po- tential of causing extrapyramidal adverse effects has repre- sented a promising option for treating psychosis in PD. 10 Cur- rently, clozapine is considered the drug of choice in this con- dition. In this respect, double-blind studies have indicated that clozapine may improve psychosis without causing a signifi- cant exacerbation of parkinsonism. 11,12 However, its use is limited by the potential risk of developing agranulocytosis, which is estimated between 0.4–2%, 13 requiring weekly leu- kocyte monitoring. While other newer antipsychotics, such as risperidone and olanzapine, have been reported to worsen par- kinsonian motor function, 14,15 a number of uncontrolled stud- ies have documented that quetiapine may improve psychotic symptoms in patients with PD, without compromising motor function. 16–20 Quetiapine is a dibenzothiazepine agent, struc- turally similar to clozapine, 21 with moderate affinity for the D2 and 5HT2 receptors with a higher 5HT2A relative to D2 recep- tors. 22 While no randomized controlled studies have evaluated the efficacy of quetiapine in PD psychosis, open trials have From the *Department of Neuroscience, Psychiatry and Anesthesiology, Uni- versity of Messina, Policlinico Universitario, Italy; †Institute of Pharma- cology, University of Messina, Italy; ‡Institute of Neurology, University of Catanzaro, Italy; §Institute of Neurological Sciences, National Re- search Council, Cosenza, Italy;  Department of Neurology, Misericordia Hospital, Grosseto, Italy; ¶Chair of Geriatrics and Gerontology, Univer- sity of Messina, Italy. Preliminary results of this study were presented at the 38th Annual Meeting of the Italian League Against Parkinson’s Disease and published in the con- ference proceedings as a selected short paper without peer review (Neurol Sci. 2002;23:S89–S90). Reprints: Letterio Morgante, MD, Department of Neuroscience, Psychiatry and Anesthesiology University of Messina, Policlinico Universitario, Via Consolare Vauria n. 1, 98125 Messina Italy (e-mail: morgante@unime.it). Copyright © 2004 by Lippincott Williams & Wilkins Clin Neuropharmacol • Volume 27, Number 4, July - August 2004 153