Risk of Developing Parkinson Disease in Bipolar Disorder

Abstract

ipolar disorder (BD) is a mood disorder that has an early onset at a median age of 20 years. It is a long-term and recurrent disorder characterized by cyclic episodes of depression and either mania (BD type 1) or hypomania (BD type 2). Although the etiology of BD has not been established, it is a multifactorial disorder with genetic and environmental factors playing an important role. 1 Despite the pathophysiology of BD being uncertain, there is a putative role of the dopaminergic system, as levodopa has been shown to induce hypomania or mania in patients with BD, 2 and antipsychotic medications that block dopamine receptors can improve manic symptoms. 3 There is also evidence that the switch from a depressive to a manic state occurs concurrently with an upregulation of dopamine receptors. 4 The standard treatment for BD that includes lithium, antipsychotic medications, and antiepileptic medications may be associated with drug-induced parkinsonism, which is not clinically distinguishable from Parkinson disease (PD), both being characterized by bradykinesia, resting tremor, rigidity, and postural instability. [5][6][7] Since drug-induced parkinsonism is more common among patients with BD, physicians may be more inclined to misdiagnose PD as drug-induced parkinsonism. On the other hand, PD is typically seen in older patients. Small studies have previously shown that BD may be more common in patients with PD compared with the general population. 6 Therefore, we conducted a systematic review to assess the possible association of BD with a later diagnosis of idiopathic PD. 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 SYNTHESISTwo 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 I 2 . 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; I 2 = 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 pe...

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

“…Interestingly, we note that there was a male preponderance in our BD population. Since PD is more common in men (41), we cannot exclude that gender might also play a role in the development of degenerative parkinsonism in BD, an issue that has not been carefully examined in the previous studies (4,30) and deserves future ad hoc investigations, further considering possible different clinical profiles of BD between men and women (42).…”

“…A recent meta-analysis has suggested that BD would be associated with later development of PD, with a 3-fold higher risk than the general population (4). 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).…”

Parkinsonism and Bipolar Disorder

“…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 …”

“…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 . 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.…”

Prevalence of Extrapyramidal Symptoms in In-Patients With Severe Mental Illnesses: Focus on Parkinsonism

“…EPS are linked to lower treatment adherence, poorer psychiatric prognosis and increased mortality ( 1 , 2 ) and are more severe and frequent in patients with SMI than in other psychiatric disorders, with higher prevalence (68–74%) among hospitalized patients ( 3 , 4 ). Patients with bipolar disorder are particularly likely to develop Parkinson's Disease (PD) ( 5 ).…”