Introduction

Drug-induced parkinsonism (DIP) is probably the most common form of parkinsonism after Parkinson's disease (PD) in terms of overall prevalence (Hubble 1993). Elderly subjects have the greatest risk of developing DIP. The reason for this susceptibility is unknown. In some older individuals DIP may represent pharmacological exposure of latent PD (preexisting nigrostriatal degeneration). Alternatively, less specific pathological changes in the aging brain may simply increase the risk of DIP and other types of drug-induced side effects. While drugs of various classes can produce DIP, the antipsychotic or neuroleptic drugs are most often the agents responsible (Montastruc et al. 1994). DIP is attributed to the primary pharmacological action of this class of drugs, i.e. dopamine receptor blockade. Other medications without overt antidopaminergic action only rarely produce parkinsonism (Hubble 1997). These occurrences are so infrequent that single case reports are often the only documentation of these phenomena. Not surprisingly, DIP due to drugs falling outside the antidopaminergic class of medications is not well understood. This chapter will deal first and most extensively with DIP secondary to antidopaminergic drugs and, subsequently, will review reports of other causative drugs. It is important to emphasize that this chapter cannot serve as a complete or final treatise on DIP because of the ongoing development of new medications and the constantly evolving recognition of drug-induced side effects (Marti-Masso et al. 1996).

Neuroleptic-induced parkinsonism

In the early 1950s, following its introduction for the treatment of psychiatric illness, reports were issued linking the neuroleptic chlorpromazine with various neurological side effects including parkinsonism (Anton-Stephens 1954, Lehmann and Hanrahan 1954).