After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.

Neuropsychiatric side effects often complicate anti-Parkinsonian therapy and pose a significant problem in the optimal management of idiopathic Parkinson's disease. Several publications report a relative lack of neuropsychiatric side effects in Parkinsonian patients treated with subcutaneous apomorphine. To investigate this further, we have used subcutaneous apomorphine to treat 12 non-demented IPD patients with previous oral drug-related neuropsychiatric problems. Treatment with apomorphine allowed alteration of anti-Parkinsonian medication and led to the abolition or reduction of neuropsychiatric complications in all patients. The mechanism remains unclear but may be due, in part, to a reduction in oral medication or a psychotropic action of apomorphine, possibly due to the piperidine moiety in its structure, or both.

No abstract

The dopamine receptor agonist apomorphine has been used successfully to treat on-off swings in Parkinson's disease. Its value as a predictor of dopa responsiveness in idiopathic Parkinson's disease (IPD) was assessed and its potential role in differentiating IPD from the Parkinsonian plus syndromes (PPS) of multisystem atrophy, progressive supranuclear palsy and olivopontocerebellar atrophy was investigated. The response to an injection of apomorphine was observed in 20 patients with IPD and eight with PPS after being off levodopa for 12 hours. Patients were reassessed after taking levodopa for one month. Nineteen of the 20 patients (95%) with IPD showed a positive response to apomorphine and 18 (90%) to oral levodopa. Statistical methods: non-parametric methods using the Wilcoxon signed rank test and Spearman's rank correlation were used to analyse the results. The significance value of the correlations was calculated using a t test. ResultsThe results of the two groups are shown in the table. The mean age for the IPD and PPS groups was 50 and 66 years and the mean duration of the disease 3-8 and 3 0 years respectively. Nineteen patients (95%) with IPD and two patients (25%) with PPS showed a positive response to apomorphine.In the IPD group, the baseline tap scores,

CSF gamma-aminobutyric acid (GABA) levels were reduced in patients with idiopathic Parkinson's disease when compared with age matched controls, but the difference was not signiificant. However, when the Parkinsonian patients were subdivided, CSF GABA levels were lower in the levodopa treated group than in the untreated group and the controls. There was no difference in plasma GABA levels between Parkinsonian patients and controls.