Antipsychotic induced parkinsonism in the elderly: assessment, causes and consequences

Abstract

Elderly people are prone to develop antipsychotic induced parkinsonism (AIP), and there are notable variations in occurrence of this adverse effect in individual elderly people. Factors that influence the variation in occurrence of AIP have not been well elucidated. The main objectives of this thesis were to qualify the available rating scales for drug induced parkinsonism (DIP) and to give a recommendation for use in daily practice, to quantify the influence of several potential determinants that may explain variability of AIP, including the role of genetic factors, and to investigate consequences of AIP in elderly patients. None of the seventeen scales, identified in a systematic review, fulfil all criteria of an appropriate rating scale for DIP. The Simpson Angus Scale (SAS), the St Hans Rating Scale for Extrapyramidal Syndromes and the Drug-Induced Extrapyramidal Symptom Scale seem the most valid, reliable and easy to use instruments to evaluate DIP in clinical practice. Subsequently, we evaluated the clinimetric properties of the SAS by assessing fifteen elderly diagnosed with DIP by three independent investigators. The SAS appears to be a valid and by different instructed health care professionals easy to perform research tool to evaluate DIP in daily clinical practice. In a cross-sectional study with 150 inpatients, with mean age of 83 years old we found a prevalence of parkinsonism of 46% during use of haloperidol. Dose nor plasma concentration of haloperidol was associated with occurance of AIP. A not statistically significant trend toward a higher risk with a longer duration of use of haloperidol was observed. Furthermore we investigated whether previous identified genetic polymorphisms at DRD2, ANKK1, DRD3, HTR2A, HTR2C, RGS2, COMT and BDNF genes are associated with AIP in elderly patients. The results suggest that carriership of the -759 T allele in females may be protective against development of parkinsonism in elderly patients during treatment with haloperidol. No significant associations were found between AIP and the remaining selected polymorphisms. Our study adds to the existing evidence that support is lacking for a major role of the peripheral pharmacokinetic hypothesis in the explanation for the variation in AIP sensitivity in elderly. The results do also not allow a firm conclusion on whether pharmacogenetics is a important factor. Finally we focused on consequences of AIP in elderly patients.We evaluated quality of life (QoL) with the QUALIDEM. The presence of AIP adversely affects the QoL of elderly patients treated with haloperidol. The presence of AIP resulted in lower scores on domains assessing positive and negative affect and social functioning. Patients with AIP had less to do, and performed fewer activities without the support of caregivers. Previous studies suggest that treatment with antipsychotics may increase mortality in elderly. The causes of death appeared to be cardiovascular or infectious (pneumonia). The relation between pneumonia and antipsychotics is not entirely clear. We investigated this association in a nested case-control study. Use of antipsychotics in elderly is associated with an increased risk of pneumonia. This risk is highest shortly after the initiation of treatment with the greatest increase in risk found for atypical antipsychotics.