Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson's disease

This study examined whether antidepressants delay the need for dopaminergic therapy or change the degree of motor impairment and disability in a population of early Parkinson's disease (PD) patients. Preclinical studies have indicated that antidepressants modulate signaling pathways involved in cell survival and plasticity, suggesting they may serve to both treat PD-associated depression and slow disease progression. A patient-level meta-analysis included 2064 patients from the treatment and placebo arms of the following trials: FS1, FS-TOO, ELLDOPA, QE2, TEMPO, and PRECEPT. Depression severity was determined at baseline, and antidepressant use was reported in a medication log each visit. Kaplan-Meier curves and time-dependent Cox proportional hazards models determined associations between depression severity and antidepressant use with the primary outcome, time to initiation of dopaminergic therapy. ANCOVAs determined associations with the secondary outcome, degree of motor impairment and disability, reported as annualized change in UPDRS scores from baseline to final visit. When controlling for baseline depression, the initiation of dopaminergic therapy was delayed for subjects taking tricyclic antidepressants compared with those not taking antidepressants. No significant differences were found in UPDRS scores for subjects taking antidepressants compared with those not taking antidepressants. Tricyclic antidepressants are associated with a delay in reaching the end point of need to start dopaminergic therapy. The lack of change in overall UPDRS scores suggests the delay was not attributable to symptomatic effects.