Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls: a national register-based study

Aim: Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD) and a matched group without PD.

Method: We identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007.

Results: All-cause mortality was significantly higher with the use of most groups of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04-1.36; Control HR = 1.77, 95% CI = 1.64-1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0.99-1.38; Control HR = 1.39, 95% CI = 1.29-1.51; benzodiazepine-like drugs, PD HR = 1.33, 95% CI = 1.11-1.59; Control HR = 1.27, 95% CI = 1.18-1.37; first-generation antipsychotics, PD HR = 1.89, 95% CI = 1.42-2.53; Control HR = 2.12, 95% CI = 1.82-2.47; second-generation antipsychotics, PD HR = 1.46, 95% CI = 1.20-1.76; Control HR = 2.00, 95% CI 1.66-2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups.

Conclusions: The use of psychotropic medication in the elderly is associated with increased mortality, independent of concurrent neurodegeneration due to PD. Confounding by indication may partly explain the higher hazard ratios in medicated controls compared with medicated PD patients. Our findings indicate that neurodegeneration should not be a separate contraindication per se for the use of psychotropic drug in patients with PD, but its use should be based on careful clinical evaluation and follow-up.