Risk of Developing Parkinson Disease in Bipolar Disorder: A Systematic Review and Meta-analysis

IMPORTANCE: Parkinson disease (PD) manifests by motor and nonmotor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD. OBJECTIVE: To assess the association of BD with a later diagnosis of idiopathic PD. DATA SOURCES: An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied. STUDY SELECTION: Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. DATA EXTRACTION AND SYNTHESIS: Two review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I2. MAIN OUTCOME AND MEASURES: Odds ratios of PD. RESULTS: Seven studies were eligible for inclusion and included 4 374 211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in people with BD (odds ratio, 3.21; 95% CI, 1.89-5.45; I2 = 94%). Preplanned subgroup analyses according to study design and diagnostic certainty failed to show a significant effect. CONCLUSIONS AND RELEVANCE: This review suggests that patients with BD have a significantly increased risk of developing PD compared with the general population. Subgroup analyses suggested a possible overestimation in the magnitude of the associations. These findings highlight the probability that BD may be associated with a later development of PD and the importance of the differential diagnosis of parkinsonism features in people with BD.