Quetiapine for Psychosis in Parkinson’s Disease

Abstract & Commentary

Source: Juncos JL, et al. Quetiapine improves psychotic symptoms and cognition in Parkinson’s disease. Mov Disord. 2004;19:29-35.

Visual hallucinations and delusions are common in patients with moderate to advanced Parkinson’s disease (PD). Typically fleeting images of people, children, or animals are easily ignored; however, hallucinations often become more intense and frequent, with loss of insight. Fixed delusions, in which patients may become fearful, paranoid or even frankly psychotic, are especially problematic. Levodopa and dopamine agonists fuel hallucinations and delusions, and the treating neurologist is often faced with the difficult choice of lowering dopaminergic medications in an attempt to control hallucinations at the expense of impaired motor performance.

Fortunately, atypical neuroleptics offer an attractive option to control hallucinations in PD patients without worsening rigidity or stiffness. Recent studies have evaluated risperidone and olanzapine in hallucinating PD patients, with disappointing results—both agents reliably worsen parkinsonian symptoms and should be avoided in PD patients. Clozapine, the gold-standard atypical neuroleptic, controls hallucinations without worsening motor performance; however, the inconvenience of weekly blood tests to monitor for agranulocytosis and side effects of sedation or hypersalivation often limit the drug’s use.

The present study evaluated 29 patients with PD and hallucinations who had previously failed treatment with clozapine, risperidone, and olanzapine. Using an open-label treatment arm, patients were treated with the newer atypical neuroleptic quetiapine (Seraquel). Dopaminergic therapy was kept constant for the duration of the study, and patients were slowly begun on quetiapine, increasing by 12.5-25 mg per night increments every 1-3 days, to a maximum dose of 400 mg per day. The dose was individually adjusted to achieve adequate control of hallucinations without unacceptable side effects, mirroring what is done in clinical practice. Daytime doses were added if patients experienced psychosis during waking hours. Patients were evaluated using the Unified Parkinson Disease Rating Scale, the Brief Psychiatric Rating Scale, the Neuropsychiatric Inventory, and the Clinical Global Impression Scale. Cognition was assessed, as well, using the mini-mental status exam and subtests from the Wechsler Memory Scale.

The median daily dose of quetiapine was 62.5 mg, and there was a statistically significant improvement in psychiatric rating scores, without change in baseline of the motor scores. Tests of sustained attention and memory surprisingly improved for the duration of the study (24 weeks). Except for 2 cases of symptomatic orthostatic hypotension, patients tolerated the medicine without incident.

Commentary

Although limited by study design (open label, single center, flexible dosing), this elegant study confirms the Columbia experience with hallucinations in PD. Quetiapine is generally well tolerated by PD patients, and adequate control of hallucinations is generally achieved with bedtime dosing of less than 100 mg of the drug. Risperidone and olanzapine are essentially contraindicated in PD patients because they reliably worsen parkinsonism. Patients who require treatment of hallucinations are usually started on quetiapine, and the dose is titrated up until hallucinations are controlled. If adequate control is not achieved or if formed delusions become problematic and unresponsive, then our center’s usual policy is to switch to clozapine. The efficacy and side effect profile of the 2 new "atypical" neuroleptics, ziprasidone and aripiprazole, are unproven in the PD population, and in this author’s opinion, these agents should be used only if quetiapine and clozapine have been tried first. — Steven Frucht

Dr. Frucht, Assistant Professor of Neurology, Movement Disorders Division, Columbia-Presbyterian Medical Center, is Assistant Editor of Neurology Alert.