Causes of a poor response to levodopa:
(1) diagnosis of Parkinson's disease is wrong (presence of "Parkinson-plus syndrome", etc)
(2) drug interaction affecting levodopa
(2a) increased clearance
(2b) poor absorption
(2c) blocking at receptor sites
(3) insufficient dose of levodopa
(4) poor drug absorption from the GI tract due to concurrent disease
(5) increased metabolism due to concurrent disease, resulting in a shortened therapeutic period
(6) progression of Parkinson's disease with loss of dopaminergic neurons
(7) adverse effects of levodopa, including overdosage
(8) development of problems unrelated to dopaminergic status
(8a) cognitive impairment or dementia
(8b) depression
(8c) dysautonomia
