Initiating pharmacotherapy in early Parkinson's disease

摘要

We would like to address the Comment1 that accompanied our Review2 on the initiation of pharmacotherapy in patients with Parkinson's disease. We agree with Anthony Schapira on the importance of taking into consideration the views of the patient in deciding on treatment.1 However, it is the responsibility of the treating physician to use the relevant evidence in guiding early treatment decisions. The Comment1 espouses the pragmatic approach taken by many physicians of initiating treatment with once daily monoamine oxidase-B inhibitors or dopamine agonists, and then switching to the alternative, before considering levodopa. In our Review,2 we pointed out that this approach remains entrenched in clinical practice, despite evidence to the contrary related to both efficacy and tolerability. Patient preference for the convenience of once-daily therapy needs to be balanced with the recognition that these treatments often provide suboptimal benefit and, particularly in the case of dopamine agonists, a very problematic side-effect profile. As discussed in our Review,2 the earlier development of motor fluctuations with levodopa, compared with a levodopa-sparing strategy, is not only associated with its short half-life, but also its greater efficacy; patients are less likely to recognise an off state if they have never experienced a true on state. As we further outlined, the development of troublesome motor fluctuations later in the disease requiring complex dose fractionation schedules, as highlighted in the Comment,1 is probably not substantially affected by initiating levodopa-sparing treatments first. We disagree that dopamine agonists “are well tolerated in most people if titrated slowly”.1 There is little evidence that a slower titration schedule influences the development of the disabling impulse control disorders that we highlighted as a major reason to reconsider their widespread early use. With regards to considering the views of the patient before initiating therapy, it is our experience that, with full disclosure of the side-effect profiles of treatment options, many patients choose to avoid dopamine agonists, even when they are presented as a good therapeutic alternative.