Levo Dopa

ADVANCE-PD

slow release co-careldopa reduces off time and increases on time without dyskinesia in advanced PD (N = 393)

RCTs (PD MED) showed that - staring L dopa early is not harmful. - In fact, starting with L-dopa allowed persistent benefit on mobility over MAOBi and DA (MAOBi = DA)

Total dose and duration of Rx determines motor fluctuations and dyskinesia rather than the time of initiation

Apo Morphine

CTH300 (2018/Feb) – SL apomorphine film reduces off time in PD (RDBCT, N=109, F/U = 3 months)

MAO B inhibitors

DATATOP study

a. early selegiline delayed onset of disability b. (? Was it just masking the Sy while disease continued to progress)

ADAGIO

Rasageline low dose (1mg/d) provided benefit that could not be achieved by giving the same drug later, suggesting that there might be a neuroprotective effect

COMT Inhibitors

STRIDE PD

no benefit in adding COMTI to dopa in initial therapy

EASE-LID

Amantidine SR, reduces off time, improves on time without dyskinesia when added to LD/CD therapy (RDBCT, N=?, F/U = 6 months

When to start drug Rx

Starting early may lead to early development of motor phenomena (neurodegenerative effect of DOPA?, dyskinesia caused by drug effect?)

Starting early may delay progression of PD (?neuroprotective effect of DOPA / selegilline)