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Abstract: Background: Antidepressants have appeared to be more effective than placebo treatment in treating depressive syndromes in patients with Parkinson's disease (PD). Objective: To identify factors that predict improvement in depressive symptoms during antidepressant treatment in depressed PD patients. Methods: A secondary analysis was performed on the dataset of the Randomized Placebo-controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received active treatment with either paroxetine or venlafaxine extended release (XR), and 39 patients received placebo treatment. Backward stepwise regression analyses were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24) score between assessments at baseline and week 12 as the main outcome measure, and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the Clinical Anxiety Scale (CAS) as independent variables. Results: In both the active treatment and placebo groups, higher baseline HAMD-24 score and lower UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher anxiety scores predicted less response in the active treatment group. Higher MMSE scores predicted greater response only in the placebo-treated group. Sex and age were no predictors of response. Conclusions: Higher pre-treatment depression scores and lower pre-treatment anxiety scores are the two most important predictors for improvement during antidepressant treatment in depressed PD patients, which is in line with those found in treatment studies of depressed non-PD patients. Furthermore, our results indicate the requirement for different or more intensive treatment for depressed PD patients with more severe anxiety symptoms. [Copyright &y& Elsevier]