OBJECTIVE: To assess whether there is an association between initial use of serotonergic antidepressants and changes in antiparkinsonian drug treatment. METHODS: A retrospective cohort study was performed with the PHARMO record linkage system. Allatients from 1994 until 2004 of 40 years or older who were first time users of an antidepressant and who had used a levodopa-containing drug at least 180 days before initiation of the antidepressant were included. The maximum follow-up time was 180 days.The first change in antiparkinsonian drug treatment, defined as an increase in the daily dosage of any antiparkinsonian drug, the start of a new antiparkinsonian drug or a change in the dosage form during the follow-up period, was taken as an endpoint.Antidepressants were classified in two ways: according to their class [selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or other antidepressants] or by the extent of their inhibition of serotonin reuptake (high, intermediate or low). RESULTS: A total of 221 patients was included in our study. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.7 (95% CI 0.3-1.5) comparing SSRI with TCA users, and it was 0.9 (95% CI 0.4-2.1) comparing users of other antidepressants with TCA users. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.6 (95% CI 0.3-1.4) comparing users of antidepressants with high versus low extent of inhibition of serotonin reuptake, and it was 0.7 (95%CI 0.3-1.4) comparing users of antidepressants with intermediate versus low extent of inhibition of serotonin reuptake. CONCLUSION: Based on these observations, we found no evidence to be more cautious using SSRIs or serotonergic antidepressants compared to other antidepressants in patients with Parkinson’s disease.