Trajectories of recovery in depressed Parkinson's disease patients treated with paroxetine or venlafaxine

Introduction: Depression is considered a syndrome with a constellation of symptoms that are frequently categorized into 3 domains including affective, somatic and cognitive. There has been limited research into the domain specific magnitude or relative timing of treatment response in patients with Parkinson's disease (PD). In addition, antidepressant trials involving patients with PD have demonstrated a similar robust placebo response to that seen in other populations. However, the timing of the placebo response has not been carefully studied. Methods: We studied differential responses to antidepressant treatment in affective, somatic and cognitive domains of depression. Patients were treated for twelve weeks with placebo, venlafaxine or paroxetine as part of the Study of Antidepressants in Parkinson's Disease (SAD-PD) randomized controlled trial. Depressive symptoms were evaluated with three commonly used rating scales. Results: All symptom domains improved during the study period, There was a significant placebo effect, especially in the first two weeks that had diminished by week 12. Compared to placebo, the affective symptoms significantly improved during treatment as early as week 4, followed by the somatic symptoms of depression in week 6 and cognitive symptoms in week 8. The largest response was seen in the affective domain. Conclusion: In depressed PD patients treated with venlafaxine or paroxetine, affective symptoms improved first, followed by somatic symptoms and cognitive symptoms. These findings could guide patient counselling and increase patient compliance by informing about the expected treatment responses. The substantial placebo effect underlines the importance of a sufficiently long study period in future studies.