Parkinsonism and Bipolar Disorder

Abstract

Parkinsonism is a frequently encountered clinical feature in patients with bipolar disorder (BD). It is usually attributed to side effects of medication, but can also be a result of concomitant cerebrovascular disease and even an emerging idiopathic Parkinson's disease (PD). In a recent meta-analysis by Faustino et al published in JAMA Neurology, the association of BD with a later diagnosis of PD was assessed. 1 Four cohort studies and three cross-sectional studies reporting data on the likelihood of developing PD in BD vs non-BD populations were included, with a total of 4.374.211 participants overall. Two of the seven studies were considered to have an elevated risk of bias: one due to inclusion of a specific subgroup of veterans limiting comparability and one due to unreliable data collection (self-reported diagnoses of PD) and a different source of the control group resulting in limited selection and comparability. In the meta-analysis excluding these two, the likelihood of a subsequent diagnosis of idiopathic PD in patients previously diagnosed with BD was increased (odds ratio, 3.21; 95% CI, 1.89-5.45; I 2 = 94%). Previous studies have suggested that PD is probably more common in BD than in the general population, but this review provides for the first time evidence supporting this notion based on a systematically analyzed, large pooled data set. The strength of this study is that a large number of subjects were included. However, several limitations are to be noted. It is not clear how PD-diagnoses were established, most data were derived from medical records, both cross-sectional and longitudinal (retrospective and prospective) data were included in the meta-analysis leading to variation in data quality. Overestimation of the presence of PD is possible, as the diagnostic coding may not have differentiated PD from other causes of parkinsonism, and cases of atypical parkinsonism may have been included. Furthermore, the age of onset of BD in relation to the development of PD over time is not clear, therefore PD cases debuting with mood symptoms may have been included as patients with BD that developed PD subsequently. In a subgroup analysis longer follow-up was associated with smaller increase in the risk of PD diagnosis. Bearing in mind the difference in the expected age at onset of BD (around 25 years) and PD (around 55 years) this is remarkable and requires further exploration to see if mostly young subjects have been followed longer or that specifically older late-onset BD cases have an increased risk for PD. All together the review and meta-analysis suggest that patients with BD have a significantly increased risk of developing PD compared with the general population. 1 This study has both clinical and research implications for BD and PD. The identification of the underlying cause of parkinsonism in patients with BD is of significant clinical relevance. It is a challenge to determine the underlying cause of parkinsonism (defined by resting tremor, bradykinesia, rigidity and/or postural instability) in B...

Preexisting Bipolar Disorder Influences the Subsequent Phenotype of Parkinson's Disease

“…Our study confirms epidemiological studies 35 , 36 , 37 , 38 , 39 , 40 , 41 and case reports 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 indicating that BSDs are associated with PD and suggests that BSDs may be a prodrome to PD, which is associated with a greater prevalence of psychiatric, somatoform, and cognitive complications; inadequate improvements after STN‐DBS; and higher mortality. High genetic susceptibility for BSD‐PD is suggested by the high prevalence of a family history of PD and BSD.…”

“…Moreover, a recent large population study and a meta‐analysis study 35 , 36 confirmed earlier epidemiological findings 37 , 38 , 39 and indicated that BSDs are associated with a 3.4 (2–5.6, confidence interval [CI] 95%) increased risk for PD—a result highlighted by editorials. 40 , 41 These studies suggested that the prevalence of BSDs in PD is higher than in control populations. Following the epidemiological reports, new studies addressed BSDs in PD, generically naming the described disorders as hypomania.…”

Characteristics of Bipolar Patients with Cognitive Impairment of Suspected Neurodegenerative Origin: A Multicenter Cohort

“…This patient showed very poor tolerance of various mood stabilizers-including lithium carbonate-that caused worsening of Parkinsonism. This observation suggested a complex interaction between neurodegenerative and iatrogenic features in the determinism of Parkinsonism observed in patients with BD and CI-SNO that had been previously emphasized by others [28]. Results of subgroup analyses performed in our cohort that found similar frequencies of Parkinsonism and antipsychotic use in patients with and without dopamine deficiency on DAT-Scan (Table S1) support these conclusions.…”

Bipolar Disorder and Parkinson's Disease: A 123I-Ioflupane Dopamine Transporter SPECT Study

“…However, a subgroup analysis showed a greater likelihood of PD diagnosis in studies with shorter followup, suggesting a possible misdiagnosis of PD (4). BD treatment includes lithium, antipsychotics, and antiepileptic drugs (AEDs), all of which can cause drug-induced parkinsonism (DIP) (5); thus, overestimation of the presence of PD in BD could have been possible since the individual studies included in the meta-analysis might not have differentiated PD from DIP (6).…”