Depression in Parkinson's disease

Diagnosis

• Be aware of significant overlap between depressive symptoms with PD
  • psychomotor slowing, lack of facial expression, fatigue, and diminished attention are shared between depression and PD (Timmer et al, 2017)
  • alternatively, symptoms of dysphoria, irritability, pessimism regarding the future, feeling of inadequacy, and sense of guilt are more specific to depression in PD (Assogna et al, 2020)
• Distinguish depression (high degree of subjective suffering) from apathy (low degree of subjective suffering) (Timmer et al, 2017)
• Distinguish psychotic features from depression (mood congruent) from psychotic features 2/2 dopaminergic treatment or cognitive decline (mood incongruent) (Timmer et al, 2017)
• PD patients with depression seem more vulnerable to developing impulse control disorders 103 (see below)

Treatment

• Is depression related to motor fluctuations or undertreatment?
  • In a study examining nonmotor symptoms related to on and off periods, patients presented higher depression and anxiety scores in the wearing-off periods, as well as worse semantic verbal fluency and executive function performance (Caillava-Santos, Margis, and Rieder, 2015)
  • Optimize dopaminergic regimen; levodopa may have an antidepressant effect; other dopamine receptor agonists have shown antidepressant effect, such as pramipexole, which was statistically greater than placebo (Barone et al, 2010) and similar to sertraline antidepressant effect (Barone et al, 2006)
• Psychpharmacologic approach
  • Treatment of depression in PD with antidepressants follows a pattern of initial affective symptom improvement followd by somatic and cognitive symptoms (Broen MPG et al, 2016).
  • SSRIs: citalopram, sertraline, and fluoxetine (+/- paroxetine) have shown modest improvements in depression rating scales (Assogna et al, 2020).
  • SNRIs: venlafaxine demonstrated improvement in depression
  • TCAs: amitriptyline, nortriptyline, and desipramine produced improvements in depression rating scales as well, though can produce cardiac dysautonomic and anticholinergic side-effects (Assogna et al, 2020).
  • Trazodone: 50mg BID demonstrated improvement in depression as well as some motor symptoms within a small single-blind study (Werneck 2009)
  • Atomoxetine: no benefit in depressive symptoms, though some improvement in cognition and daytime sleepiness

References

Assogna F, et al. Drug choices and advancements of managing deprssion in Parkinson's disease. Curr Neuropharmacol. v.18(4); 2020 Apr. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327944/

Barone, P. et al. Pramipexole versus sertraline in the treatment of depression in Parkinson’s disease: A national multicenter parallel–group randomized study. J. Neurol. 253, 601–607 (2006). https://pubmed.ncbi.nlm.nih.gov/16607468/

Barone P, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 9, 573–580 (2010). https://pubmed.ncbi.nlm.nih.gov/20452823/ https://pubmed.ncbi.nlm.nih.gov/26739248/

Broen MP, Leentjens AF, Köhler S, Kuijf ML, McDonald WM, Richard IH. Trajectories of recovery in depressed Parkinson's disease patients treated with paroxetine or venlafaxine. Parkinsonism Relat Disord. 2016 Feb;23:80-5

Caillava-Santos, F., Margis, R. & Rieder, C. Wearing-off in Parkinson’s disease: neuropsychological differences between on and off periods. Neuropsychiatr. Dis. Treat. 1175 (2015) doi:10.2147/NDT.S77060. https://pubmed.ncbi.nlm.nih.gov/25999721/

Timmer, M. H. M., van Beek, M. H. C. T., Bloem, B. R. & Esselink, R. A. J. What a neurologist should know about depression in Parkinson’s disease. Pract. Neurol. 17, 359–368 (2017). https://pubmed.ncbi.nlm.nih.gov/28739866/

Weintraub D, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology. 2010 Aug 3;75(5):448-55 https://pubmed.ncbi.nlm.nih.gov/20679638/

Werneck AL, Rosso AL, Vincent MB. The use of an antagonist 5-HT2a/c for depression and motor function in Parkinson' disease. Arq Neuropsiquiatr. 2009 Jun;67(2B):407-12 https://pubmed.ncbi.nlm.nih.gov/19623435/