Reply to: Correlation of Antidepressant Use and Symptom Time Period in Dream Enactment Behaviors.

Abstract

Firstly, I would like to thank Sumi et al.1 for showing interest in my recently published study2 and providing the opportunity to expand the discussion on this fascinating topic, that has both clinical and theoretical relevance. Sumi et al. had concerns about possible confounding due to medication use. Although all participants in the Parkinson's Progression Markers Initiative (PPMI) database were untreated for Parkinson's disease (PD) at baseline, which is important to highlight, since dopaminergic medications have previously been associated with dream alterations3; I do nevertheless agree that given the frequent comorbidity of depression and REM sleep behavior disorder in people with PD, that the effects of antidepressants and clonazepam used to treat these, ought to be considered. In fact, a previous study identified that 41.2% of PD participants in PPMI reported using antidepressants during the course of the study and 14.2% reported having used clonazepam.4 However, Sumi et al.'s statement that neither PPMI nor the study evaluated the presence of depression, is not entirely correct. In the study, total number of depressive symptoms, assessed using the extensively validated Geriatric Depression Scale,5 was included as a covariate in one of the sensitivity analyses.2 Crucially, the inclusion of depressive symptoms as a covariate did not alter the association between aggressive dream content and either motor or cognitive decline.2 Nonetheless, to ensure that the results were not confounded by antidepressant use specifically, I have now conducted two further analyses. First, I repeated the primary analyses after adjusting for antidepressant use at any time from baseline to the most recent study visit. Second, I repeated the analyses after including self-reported past or present depression (obtained from item 10 of the REM sleep behavior disorder screening questionnaire), as an additional covariate. Neither antidepressant use nor a history of depression attenuated the association between dream content and motor or cognitive decline (P's < 0.05). Similarly, after adjusting for clonazepam use, the associations between aggressive dream content and both outcomes remained significant (P's < 0.05). Finally, with respect to Sumi et al.'s third concern regarding fluctuation of aggressive dreams over time, it is pertinent to emphasize that these participants were all newly diagnosed at baseline, with a mean duration of 6.3 months since diagnosis. As such, it is unlikely that sufficient time had passed for there to be a significant group for whom “aggressive dreams [had] disappeared” during the course of PD. In any case, if such a group were to exist, it could actually have led to an underestimation of the association, since individuals who once had aggressive dreams would have been included in the non-aggressive dream group. Therefore, whilst the insightful concerns raised by Sumi et al are important to consider, I do not believe they challenge the core conclusions of this study, namely, that people with newly diagnosed, untreated PD who report having frequent aggressive dreams, may be at higher risk of early motor and cognitive decline than those who do not report having them. Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org. Data were downloaded from the PPMI database on December 22, 2020. 1. Research Project: Conception, Organization, Execution; 2. Statistical Analysis: Design, Execution; 3. Manuscript Preparation AIO: 1,2,3. Each Parkinson's Progression Markers Initiative site received approval from a local ethical committee on human experimentation before commencement of the study. Written informed consent was obtained from all individuals who participated in the study. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No specific funding was received for this work. I declare that there are no conflicts of interest relevant to this work. The author is funded by a National Institute for Health Research academic clinical fellowship.