Drug-induced extrapyramidal syndromes

Extrapyramidal syndromes (EPS) are a group of movement disorders that result from damage in the basal ganglia and certain related thalamic and brainstem nuclei. EPS are either primary, i.e. due to a neurodegenerative disease, or secondary. Secondary forms can have different causes, the most important of which is the use of drugs. EPS that are seen as a side effect of drug treatment include parkinsonism, dysthonia, akathisa and dyskinesia. Numerous drugs have been reported to induce EPS. Epidemiologic studies showed that as much as one third to over one half of the cases of parkinsonism may be explained by the use of medication. EPS is especially common during treatment with antipsychotic drugs (APDs). Considering their disabling effect, clearly, drug-induced EPS have a strong negative impact on patients well-being, compliance to treatment and as a result on treatment outcome. Thus, minimizing their frequency and severity is of clear clinical importance. This can be achieved either by prevention or by prompt diagnosis and treatment of symptoms. Both are greatly enhanced by knowing which drugs are implicated with EPS, to what extent, and which patients are most susceptible. To be able to reduce the occurrence of drug-induced EPS in the general population, the aim of this thesis is to quantify the risk of drug-induced EPS for drugs commonly associated with this side effect and to quantify the influence of specific risk factors. The first chapter reviews the current literature with regard to the epidemiology of drug-induced parkinsonism and assesses the validity of using prescription records of antiparkinsonian medication as a way to identify drug-induced EPS in medical databases. Chapter two focuses specifically on EPS resulting from antipsychotic medication, since these drugs still are by far the most important cause of EPS. In chapter three, risks and risk factors of EPS with drugs other than APDs are studied. Laslty, chapter four discusses the strengths and limitations of this thesis, the implications for medical and pharmaceutical practice, and suggestions for future research