Bipolar Disorder Linked to Increased Risk of Parkinson's Disease

October 17, 2019

Patients with bipolar disorder (BD) may be at significant risk for developing Parkinson's disease (PD), new research suggests.

A literature review of seven studies that included more than 4 million participants showed that patients with BD were three times more likely than the general population to develop PD.

"Our findings have important implications for clinical practice senior author Joaquim J. Ferreira, MD, University of Lisbon, Portugal, told Medscape Medical News.

"Clinicians need to be more alert for signs of Parkinson's disease in patients with a history of bipolar disorder," he added.

The findings were published online October 14 in JAMA Neurology.

"Robust Findings"

After Ferreira had come across several patients with a history of BD who had also developed Parkinson's, he wanted to investigate whether there were data on any link between the two conditions.

"We conducted a literature search and found several studies suggesting that there may indeed be such a link. We have pooled all the available data which together shows a strong association between previous bipolar disorder and later Parkinson's disease," he said.

He noted that although neurologists or psychiatrists will probably not be surprised by the results, as they likely have seen patients with both conditions, combining all the data has now led to "robust findings."

"As parkinsonian symptoms can be an adverse effect of some of the drugs used to treat bipolar disorder, clinicians may not investigate further; but now we have data to suggest that . . . these patients may really be developing Parkinson's disease," Ferreira said.

Therefore, "they need to be formerly investigated with neuroimaging studies and treated if appropriate. Early treatment can make a difference," he added.

For their investigation, the researchers conducted a literature search for studies on the likelihood of developing Parkinson's disease in populations with BD vs without BD. Seven such studies were found that were eligible for inclusion into their meta-analysis.

This included four cohort studies and three cross-sectional studies with a total of 4,374,211 participants overall.

Threefold Increased Risk

Results showed that a previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD by more than threefold (odds ratio [OR], 3.35; 95% confidence interval [CI], 2.00 - 5.60).

A sensitivity analysis performed by removing studies that had a high risk of bias also showed an increased risk for PD in patients with BD (OR, 3.21; 95% CI, 1.89 - 5.45).

"When placed in the context of other systematic reviews looking at risk factors for Parkinson's disease, our statistical evidence is highly suggestive. Only 7 of 38 reviews included in an overview of systematic reviews presented results at least as robust as the evidence we present," the investigators write.

"This is a result of the large number of events in our review, the very small P values for the association, and the fact that the 95% confidence intervals of the largest study does not cross the null value," they add.

The pathophysiological rationale between BD and PD might be explained by the dopamine dysregulation hypothesis, the researchers note.

It states that the cyclical process of BD in manic states leads to a downregulation of dopamine receptor sensitivity, which is later compensated by upregulation. Over time, this may lead to an overall reduction of dopaminergic activity, which is the prototypical PD state.

"Real" Effect?

Ferreira noted that he cannot be sure the findings were not just a result of adverse effects of bipolar medication.

However, "when we excluded the studies with higher risks of bias we still showed a strong positive association, so I think the increased risk of Parkinson's we saw is real," he said.

On the mechanism linking BD and Parkinson's, Ferreira said this probably involves dopamine "as this is the most important neurotransmitter involved in Parkinson's disease and it is also thought to be involved in bipolar disorder."

He pointed out that patients with PD also experience mood fluctuations — with depression often occurring during "off" periods and manic/psychotic symptoms presenting during "on" periods."

He also believes the findings will have implications for future research.

"This association ideally needs to be replicated and the mechanisms involved explored further. I think many new lines of research could be activated after this publication," Ferreira said.

Ferreira reported grants and personal fees from Allergan, GlaxoSmithKline, Novartis, and Teva Pharmaceutical Industries; grants from Merck Sharp & Dohme, Grünenthal, and Medtronic; consulting fees from AbbVie, Acadia Pharmaceuticals, BIAL, Biogen, Ipsen, Lundbeck, Merck Serono, Merz Pharma, Solvay, and Sunovion Pharmaceuticals; and personal fees for serving on the advisory board from BIAL. Disclosures for the other study authors are listed in the original article.

JAMA Neurol. Published online October 14, 2019. Abstract

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