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  • Review Article
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Depression in Parkinson disease—epidemiology, mechanisms and management

Abstract

Depression occurs in around 35% of patients with Parkinson disease (PD) and is often persistent. Symptoms of depression can be evident in individuals at the time of diagnosis and might develop in the premotor stage of the disease. The underlying mechanisms of depression in PD are not known in detail, but changes in brain structure, signaling by neurotransmitters, and levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Psychosocial factors and pain could also have roles in depression. Changes in dopaminergic, noradrenergic and serotonergic systems in patients with PD might help to explain the incidence of depression in these individuals. Antidepressants that have dual serotonergic and noradrenergic effects are the drugs of choice for treating depression in PD. However, antiparkinsonian drugs might have beneficial effects not only on the motor symptoms of disease, but also on a patient's mood. Deep brain stimulation can worsen depression in some patients, but a preliminary study has suggested that transcranial magnetic stimulation could improve symptoms of depression. This Review describes the frequency and course of depression in patients with PD. The mechanisms that underlie depression in this disease are also discussed, and the management strategies for these patients are highlighted.

Key Points

  • Depression occurs in around 35% of patients with Parkinson disease (PD)

  • Mild depression is often persistent in patients with PD, and is a risk factor for moderate to severe depression

  • The etiology of depression in PD is not clear, but changes in neurotransmitter (monoaminergic) signaling and limbic Lewy body pathology might contribute

  • The roles of other pathologies (such as cerebrovascular disease) and neurotrophic changes in depression are not known

  • Pramipexole and nortriptyline are the only agents that have shown antidepressant effects in placebo-controlled clinical trials in patients with PD

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Figure 1: Neuronal factors and signaling pathways implicated in depression in PD.
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Acknowledgements

P. Svenningsson was supported by grants from Vetenskapsrådet and the Swedish Strategic Research Foundation.

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D. Aarsland and P. Svenningsson researched data for the article, contributed to writing the manuscript, and provided substantial contributions to the discussion of the article content and to review and/or editing of the manuscript before submission. S. Påhlhagen and C. G. Ballard contributed to writing the manuscript, and provided substantial contributions to the discussion of content and to the review and/or editing of the manuscript before submission. U. Ehrt researched data for the article, and contributed to writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to Dag Aarsland.

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Competing interests

D. Aarsland has been a consultant for DiaGenic, GE Healthcare, Lundbeck and Novartis. He has received speaker honoraria from DiaGenic, GE Healthcare, GlaxoSmithKline, Lundbeck and Novartis. He has received grants for research from Merck Serono. C. Ballard has been a consultant for and received speaker honoraria from Acadia, Esai, Lundbeck and Novartis. He has received grants for research from Acadia and Novartis. P. Svenningsson has received grants for research from Servier and Dainippon. The other authors declare no competing interests.

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Aarsland, D., Påhlhagen, S., Ballard, C. et al. Depression in Parkinson disease—epidemiology, mechanisms and management. Nat Rev Neurol 8, 35–47 (2012). https://doi.org/10.1038/nrneurol.2011.189

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