The clinical syndrome of drug-induced parkinsonism exactly mimics idiopathic Parkinson disease in individual patients, so one cannot reliably distinguish drug-induced parkinsonism from idiopathic Parkinson disease in a patient taking a dopamine-blocking drug. Even though this is a drug-induced syndrome, signs may be asymmetric in half the patients (Hardie and Lees 1988; Sethi and Zamrini 1990). Not all of the cardinal features of idiopathic Parkinson disease are necessarily present, and they are variably severe in an idiosyncratic manner, so some patients have tremor but little else, whereas others may be more akinetic or rigid. Patients tend to be unaware of their parkinsonism when mild except for tremor (Lohr et al 1987). Nonmotor features of idiopathic Parkinson disease have not been well studied in drug-induced parkinsonism, and 2 studies of olfaction have obtained conflicting results of smell impairment (Lee et al 2007; Kruger et al 2008).
Drug-induced parkinsonism tends to develop slowly, over days to weeks (Freyhan 1959; Ayd 1961). The onset is dose-related and most patients develop signs within about 3 weeks (Freyhan 1959; Levinson et al 1990). Some patients develop parkinsonism after years on a stable dose of a drug, raising the question as to whether they have developed idiopathic Parkinson disease or have simply become more sensitive. Rigidity and impaired arm-swing are the most common early signs, with tremor marking the onset in only about one third of cases (Ayd 1961).
The cardinal features of Parkinson disease are rigidity, akinesia, bradykinesia, tremor at rest, and impaired posture and balance. Minor features, helpful but not reliable for diagnosis, include micrographia, difficulty performing 2 different tasks simultaneously, fatigue, and hypophonic speech with hesitancy or even stuttering.
Other problems present in Parkinson disease such as depression, loss of interest and initiative, and a sense of weakness may overlap with the underlying psychiatric illness. There also may be drug side effects that are unrelated to the parkinsonism, such as orthostatic hypotension, weight gain, hormonal dysregulation, diabetes, and others.
Akinesia refers to the absence of, but more accurately the paucity of, spontaneous unconscious movements. Parkinsonian patients blink less and swallow less (hence the drooling) than normal patients. This is usually but not always related to bradykinesia, the slowness of motor activities. Parkinsonian patients initiate movements and complete them more slowly than normal. This is manifest in slower dressing, toileting, walking, writing, cooking, etc. On testing coordinated movements, one sees not only slowness but also a loss of amplitude on repeating tasks such as rapid alternating hand movements, finger tapping, or heel tapping. There is also an irregularity of movement due to occasional brief movement arrests. Patients lose dexterity for tasks such as buttoning, using zippers, and sewing, which then exaggerate the slowness of the grosser movements. It should be noted that occasional patients have a dissociation between akinesia and bradykinesia.
The tremor is a rest tremor that resolves with movement but is often present with sustained postures. Typically, as in Parkinson disease, it affects fingers, hands, jaw, and, less frequently, tongue and feet. The head is almost invariably spared. Rigidity is the resistance felt when moving a limb that is relaxed. Cogwheeling is not a sine qua non of the disorder. Rigidity may affect any joint, including the neck. Postural abnormalities are common. Parkinsonian patients have a flexed posture both sitting and standing, so they appear stooped. This is not always due to rigidity, but rather, can represent an aberrant orientation that may even result in tilting to 1 side in addition to being flexed. Balance may be impaired as well. The parkinsonian gait is stereotypical with a reduced stride, reduced arm-swing, and a tendency to turn en bloc. In younger drug-induced parkinsonism patients, mild stooping and reduced arm-swing are the only gait abnormalities, and these may be so minor as to escape detection on routine exam.
Individual susceptibility to all the extrapyramidal side effects of dopamine-blocking drugs is highly variable. Some patients develop no sign of drug-induced parkinsonism on huge doses whereas others are sensitive. Most people, however, show signs of drug-induced parkinsonism if treated with high doses of neuroleptics. Although drug-induced parkinsonism may exactly mimic idiopathic Parkinson disease, there tends to be significantly less tremor in drug-induced parkinsonism patients (Akbostanci et al 1999). This could be due to the younger age of most patients with drug-induced parkinsonism or to differences between the 2 conditions.
The course of drug-induced parkinsonism is also variable (Hardie and Lees 1988). Many patients maintained only on neuroleptics without antiparkinson drugs improve over time, but what percentage and to what degree are unclear. Most patients reach a plateau in terms of their drug-induced parkinsonism on a stable dose of neuroleptic and maintain this level or improve. Only in the elderly is this not true and progressive parkinsonism may occur, presumably due either to the onset of idiopathic Parkinson disease or to increased sensitivity of the aging brain.