• Parkinson’s disease
• l-dopa
• amantadine
• anticholinergic
• apomorphine

It is chastening to reflect that although the portfolio of available drug treatments for Parkinson’s disease has multiplied, l-dopa, in its fourth decade of clinical use is still the most potent and effective medication. The newer drugs have refined, rather than revolutionised treatment and no available therapy can do more than temporarily control motor disability. Depression, abulia, severe constipation, pain, and sleep disturbance can all have devastating effects, and the benefits of any new treatment need to be judged on the basis of its impact on quality of life as well as relief of the cardinal motor symptoms. About a quarter of patients will severely dement and at least as many will have visual hallucinations, episodic confusional states, and daytime somnolence.

Systematic reviews have been published recently by the Movement Disorder Society¹; the Standards Committee of the American Academy of Neurology² and the Cochrane Movement Disorders group have also provided reports on a number of therapeutic interventions.³ However, the available data on which most of these analyses are founded, is often sketchy and incomplete because of the dearth of high quality data.⁴ New drug treatments have a headstart because trial design has changed radically over the past 20 years and many of the studies conducted with older drugs are now considered inadequate or insubstantial. This, however, should not be equated with inferiority or inefficacy, and indeed from a safety point of view proven treatments with a long track record have advantages. Serious adverse events, as for example occurred with the COMT inhibitor, tolcapone, may only come to light in the first few years of postmarketing surveillance.

Scrutiny of even the best available evidence, therefore, leaves the physician with doubt and uncertainty in relation to what constitutes best clinical practice. A paradox …