Our experience is in general agreement with that of Marsden, who found that of 263 patients given dopamine agonists as the sole treatment, 181 had abandoned medication after 6 months because of lack of effect or adverse reactions. Nevertheless, the fact that a large enough proportion of patients continue to benefit for up to 3 to 5 years indicates that the initial use of dopamine agonists has merit (see also Rascol et al). A development of some interest is the transdermally absorbed dopamine agonist such as rotigotine. Several trials suggest that the transdermal system can maintain a stable plasma level of the drug. In the study by LeWitt and associates, the main effect was a doubling of “on” time without unwanted dyskinesias. The effects on the quality of life in Parkinson patients appear to be positive but minor in degree. Skin reactions are common and the sulfites used in the patch formulation can cause severe systemic reactions in sensitive individuals.
The relative merits of dopamine agonists and l-dopa are difficult to contrast. One insight was given by the PD Med trial (PD Med Collaborative Group), which compared, in an open-label fashion, l-dopa, dopamine agonists and monoamine oxidase-B inhibitors (see further on). Rather than the metric of the UPDRS scale or similar instruments, this trial used a patient’s quality of life questionnaire and found that after a median of 3 years l-dopa received slightly higher scores. What was more telling was that there were far higher rates of discontinuation of the other 2 medications, mainly due to psychological side effects.
Even small doses of dopaminergic drugs, when first introduced, may induce orthostatic hypotension, but most patients are, or become, tolerant of them. They may also produce abrupt and unpredictable sleepiness, and patients should be warned of this possibility in relation to driving. In some individuals, particularly the elderly, dopamine agonists may produce hallucinosis or confusion; these problems are most profound in patients who are later determined to have Lewy body disease (see further on). Excessive and dysfunctional behaviors particularly gambling (including on line gambling in some of our patients) and hypersexuality have been serious problems in a few individuals (also see further on).
Many clinicians initiate treatment with small amounts of a dopamine agonist, at least as much for the putative delay of dyskinesias that they offer in comparison to starting l-dopa. Alternatively, carbidopa/l-dopa tid can be initiated and supplemented over a month with a dopamine agonist. The side effects and subtleties of dosing are explained in the sections above on each of these classes of drug. The issue of also starting an MAO inhibitor such as rasagiline early in the illness is discussed below.
Adjunctive medications Because of the side effects of levodopa and of dopaminergic agents, some neurologists avoid pharmacotherapies if the patient is in the early phase of the disease and the parkinsonian symptoms are not troublesome. When the predominant manifestation is tremor, very satisfactory results can be obtained in some patients for up to several years with anticholinergic agents alone. The anticholinergic drugs have limited effect on the postural, hypokinetic, and other manifestations of disease. Koller’s study, which quantified the effect of anticholinergic medication on tremor and compared it to l-dopa, concluded that there was considerable variability in response between patients but that l-dopa was on average more effective. Nonetheless, anticholinergic agents have long been in use for the treatment of tremor in younger patients and we still use them occasionally, either in conjunction with l-dopa or in patients who cannot tolerate the latter drug. The optimum dosage level is the point at which the greatest relief from tremor is achieved within the limits of tolerable side effects, mainly dry mouth. In older patients, one must be alert to changes in cognitive function, hallucinations, and urinary outflow obstruction.