PubMed · 9835894
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H Mönig, P Krack. 1998-11-06. [Cabergoline].. https://doi.org/10.1055/s-0029-1237286
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OBJECTIVE: To report the results of the 12-week, prospective, open label extension of the 4-week, multicenter, placebo-controlled, double-blind PSYCLOPS (PSYchosis and CLOzapine in the treatment of Parkinsonism) trial. This extension examined the chronic safety and efficacy of clozapine in the treatment of drug-induced psychosis in Parkinson's disease (PD). BACKGROUND: Psychosis is a serious late complication of PD and may be a harbinger to increased mortality. Clozapine, the first atypical antipsychotic, was shown in several small open label studies to improve psychosis without worsening of motor symptoms. This was recently confirmed in the double-blind PSYCLOPS trial. METHODS: The 53 patients who completed the double-blind portion of PSYCLOPS were evaluated on their original randomized treatment (clozapine or placebo), then had study medication stopped. All were started on clozapine. The patients from both treatment groups were evaluated every 4 weeks over a 12-week period using standardized measures for psychosis and PD. RESULTS: The mean dose of clozapine was 28.78 mg/day. Those originally treated with placebo improved significantly in Brief Psychiatric Rating Scale and clinical global scores for psychosis to the same degree as the group originally randomized to clozapine in the double-blind study. Both groups maintained their response to week 16 (end of the combined double-blind and open label portions). There was no worsening of motor features as measured by the Unified Parkinson's disease rating scale. Eighteen patients were either hospitalized or died during the trial. The most common reasons were pulmonary. CONCLUSIONS: Low-dose clozapine is effective in treating drug-induced psychosis without worsening motor features of PD, and the response is maintained for at least 4 months. Patients with psychosis and PD were previously described as a group with high risk for morbidity and mortality. The high risk continues despite antipsychotic therapy.
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Apomorphine is a potent, nonselective, direct-acting dopamine-receptor agonist. Given subcutaneously, it has a rapid onset of antiparkinsonian action qualitatively comparable to that of levodopa. Despite its long history, it was not until peripheral dopaminergic side effects could be controlled by oral domperidone that the clinical usefulness of apomorphine in Parkinson's disease began to be investigated thoroughly in the mid-1980s. Although several routes have been tried, subcutaneous administration, either as intermittent injections or continuous infusion, is so far the best and most applied in the treatment of advanced, fluctuating Parkinson's disease. Clinical trials have shown stable efficacy with markedly reduced time spent in "off" phases as well as, for infusion therapy, reduced levodopa requirements. In the most successful cases, motor fluctuations disappear and the need for oral medication is eliminated. Adverse events are usually mild and dominated by cutaneous reactions. Neuropsychiatric side effects occur, but the influence of apomorphine on these remains controversial. Controlled long-term clinical trials are highly warranted to reveal the full potentials of this treatment. Careful patient selection and follow-up, where the specialized movement disorder nurse has a crucial role, are paramount for a successful long-term outcome. Apomorphine warrants a wider application in the treatment of advanced Parkinson's disease and should be tried before more invasive interventions are considered.