Treatment in Geriatric Mental Health: Research in Action| Volume 29, ISSUE 6, P530-540, June 2021

Download started.


Optimal Treatment of Depression and Anxiety in Parkinson's Disease

Published:February 09, 2021DOI:


      • What is the primary question addressed by this study? This article discusses the optimal treatment of anxiety and depression in Parkinson's disease.
      • What is the main finding of this study? The treatment of anxiety and depression in Parkinson's disease are complicated by overlap with the neurodegenerative process.
      • What is the meaning of the finding? Collaboration and careful coordination of multidisciplinary care are required to achieve optimal outcomes for anxiety and depression in Parkinson's disease.


      Depression and anxiety are highly prevalent and have major adverse effects on function and quality of life in Parkinson's disease (PD). Optimal management requires that motor symptoms and psychiatric symptoms be simultaneously addressed. While there is fairly robust evidence for the treatment of motor symptoms, there are no completed randomized controlled trials to guide pharmacological treatment of anxiety in PD and no nonpharmacologic interventions have proven efficacious. Several high-quality trials for depression in PD suggest a number of antidepressants and cognitive behavioral therapy may help, but there is no data on rates of recurrence, comparative efficacy, or augmentation strategies. In order to address the gaps in knowledge, the authors provide a summary of the current evidence for treating depression and anxiety in PD and offer an algorithm that extends beyond the current literature based on clinical experience working in a multidisciplinary specialty center.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Geriatric Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Balestrino R.
        • Martinez-Martin P.
        Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson's disease.
        J Neurol Sci. 2017; 373: 173-178
        • Kuhlman G.D.
        • Flanigan J.L.
        • Sperling S.A.
        • et al.
        Predictors of health-related quality of life in Parkinson's disease.
        Parkinsonism Relat Disord. 2019; 65: 86-90
        • Lin C.H.
        • Lin J.W.
        • Liu Y.C.
        • et al.
        Risk of Parkinson's disease following anxiety disorders: a nationwide population-based cohort study.
        Eur J Neurol. 2015; 22: 1280-1287
        • Shiba M.
        • Bower J.H.
        • Maraganore D.M.
        • et al.
        Anxiety disorders and depressive disorders preceding Parkinson's disease: a case-control study.
        Mov Disord. 2000; 15 (<669::aid-mds1011>;2-5): 669-677
        • Wang S.
        • Mao S.
        • Xiang D.
        • et al.
        Association between depression and the subsequent risk of Parkinson's disease: a meta-analysis.
        Prog Neuropsychopharmacol Biol Psychiatry. 2018; 86: 186-192
        • Heinzel S.
        • Berg D.
        • Gasser T.
        • et al.
        Update of the MDS research criteria for prodromal Parkinson's disease.
        Mov Disord. 2019; 34: 1464-1470
        • Broen M.
        • Leentjens A.
        • Hinkle J.T.
        • et al.
        Clinical markers of anxiety subtypes in Parkinson disease.
        J Geriatr Psychiatry Neurol. 2018; 31: 55-62
        • Sagna A.
        • Gallo J.J.
        • Pontone G.M.
        Systematic review of factors associated with depression and anxiety disorders among older adults with Parkinson's disease.
        Parkinsonism Relat Disord. 2014; 20: 708-715
        • Wee N.
        • Kandiah N.
        • Acharyya S.
        • et al.
        Depression and anxiety are co-morbid but dissociable in mild Parkinson's disease: a prospective longitudinal study of patterns and predictors.
        Parkinsonism Relat Disord. 2016; 23: 50-56
        • Reijnders J.S.
        • Ehrt U.
        • Weber W.E.
        • et al.
        A systematic review of prevalence studies of depression in Parkinson's disease.
        Mov Disord. 2008; 2: 183-313
        • Carod-Artal F.J.
        • Ziomkowski S.
        • Mourão Mesquita H.
        • et al.
        Anxiety and depression: main determinants of health-related quality of life in Brazilian patients with Parkinson's disease.
        Parkinsonism Relat Disord. 2008; 14: 102-108
        • Müller B.
        • Assmus J.
        • Herlofson K.
        • et al.
        Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson's disease.
        Parkinsonism Relat Disord. 2013; 19: 1027-1032
        • Paumier K.L.
        • Siderowf A.D.
        • Auinger P.
        • et al.
        Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson's disease.
        Mov Disord. 2012; 27: 880-887
        • Pontone G.M.
        • Bakker C.C.
        • Chen S.
        • et al.
        The longitudinal impact of depression on disability in Parkinson disease.
        Int J Geriatr Psychiatry. 2016; 31: 458-465
        • Ravina B.
        • Elm J.
        • Camicioli R.
        • et al.
        The course of depressive symptoms in early Parkinson's disease.
        Mov Disord. 2009; 24: 1306-1311
        • Pagonabarraga J.
        • Kulisevsky J.
        • Strafella A.P.
        • et al.
        Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment.
        Lancet Neurol. 2015; 14: 518-531
        • Pontone G.M.
        • Dissanayaka N.
        • Dobkin R.D.
        • et al.
        Integration and extension of specialty mental healthcare services to community practice in Parkinson disease.
        Am J Geriatr Psychiatry. 2019; 27: 712-719
        • Taylor J.
        • Anderson W.S.
        • Brandt J.
        • et al.
        Neuropsychiatric complications of Parkinson disease treatments: importance of multidisciplinary care.
        Am J Geriatr Psychiatry. 2016; 24: 1171-1180
        • Wade D.T.
        • Gage H.
        • Owen C.
        • et al.
        Multidisciplinary rehabilitation for people with Parkinson's disease: a randomised controlled study.
        J Neurol Neurosurg Psychiatry. 2003; 74: 158-162
        • Zhang Q.
        • Yang X.
        • Song H.
        • et al.
        Cognitive behavioral therapy for depression and anxiety of Parkinson's disease: A systematic review and meta-analysis.
        Complement Ther Clin Pract. 2020; 39101111
        • Seppi K.
        • Ray Chaudhuri K.
        • Coelho M.
        • et al.
        Update on treatments for nonmotor symptoms of Parkinson's disease-an evidence-based medicine review.
        Mov Disord. 2019; 34: 180-198
        • Pontone G.M.
        • Dissanayka N.
        • Apostolova L.
        • et al.
        Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson's disease.
        NPJ Parkinsons Dis. 2019; 5: 30
        • Dobkin R.D.
        • Mann S.L.
        • Gara M.A.
        • et al.
        Telephone-based cognitive behavioral therapy for depression in Parkinson disease: a randomized controlled trial.
        Neurology. 2020; 94: e1764-e1773
        • Pontone G.M.
        • Mills K.A.
        A call for better depression treatment in people with Parkinson disease.
        Neurology. 2020; 94: 691-692
        • Brunoni A.R.
        • Chaimani A.
        • Moffa A.H.
        • et al.
        Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes: a systematic review with network meta-analysis.
        JAMA Psychiatry. 2017; 74: 143-152
        • Chen J
        • He P
        • Zhang Y
        • et al.
        Non-pharmacological treatment for Parkinson disease patients with depression: a meta-analysis of repetitive transcranial magnetic stimulation and cognitive-behavioral treatment [published online ahead of print, 2020 Apr 7].
        Int J Neurosci. 2020; : 1-14
        • Borisovskaya A.
        • Bryson W.C.
        • Buchholz J.
        • et al.
        Electroconvulsive therapy for depression in Parkinson's disease: systematic review of evidence and recommendations.
        Neurodegener Dis Manag. 2016; 6: 161-176
        • Mills K.A.
        • Greene M.C.
        • Dezube R.
        • et al.
        Efficacy and tolerability of antidepressants in Parkinson's disease: a systematic review and network meta-analysis.
        Int J Geriatr Psychiatry. 2018; 33: 642-651
        • Broen M.P.
        • Narayen N.E.
        • Kuijf M.L.
        • et al.
        Prevalence of anxiety in Parkinson's disease: a systematic review and meta-analysis.
        Mov Disord. 2016; 31: 1125-1133
        • Pontone G.M.
        • Williams J.R.
        • Anderson K.E.
        • et al.
        Anxiety and self-perceived health status in Parkinson's disease.
        Parkinsonism Relat Disord. 2011; 17: 249-254
        • Du C.X.
        • Guo Y.
        • Zhang Q.J.
        • et al.
        Involvement of prelimbic 5-HT7 receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats.
        Neurol Res. 2018; 40: 847-855
        • Picillo M.
        • Santangelo G.
        • Erro R.
        • et al.
        Association between dopaminergic dysfunction and anxiety in de novo Parkinson's disease.
        Parkinsonism Relat Disord. 2017; 37: 106-110
        • Sun Y.N.
        • Wang T.
        • Wang Y.
        • et al.
        Activation of 5-HT₁A receptors in the medial subdivision of the central nucleus of the amygdala produces anxiolytic effects in a rat model of Parkinson's disease.
        Neuropharmacology. 2015; 95: 181-191
        • Sun Y.N.
        • Yao L.
        • Li L.B.
        • et al.
        Activation and blockade of basolateral amygdala 5-HT6receptor produce anxiolytic-like behaviors in an experimental model of Parkinson's disease.
        Neuropharmacology. 2018; 137: 275-285
        • By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel
        American Geriatrics Society 2019 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults.
        J Am Geriatr Soc. 2019; 67: 674-694
        • Moonen A.J.
        • Wijers A.
        • Leentjens A.F.
        • et al.
        Severity of depression and anxiety are predictors of response to antidepressant treatment in Parkinson's disease.
        Parkinsonism Relat Disord. 2014; 20: 644-646
        • Pontone G.M.
        • Williams J.R.
        • Anderson K.E.
        • et al.
        Pharmacologic treatment of anxiety disorders in Parkinson disease.
        Am J Geriatr Psychiatry. 2013; 21: 520-528
        • Richard I.H.
        • McDermott M.P.
        • Kurlan R.
        • et al.
        A randomized,double-blind, placebo-controlled trial of antidepressants in Parkinson disease.
        Neurology. 2012; 78: 1229-1236
        • Menza M.
        • Dobkin R.D.
        • Marin H.
        • et al.
        A controlled trial of antidepressants in patients with Parkinson disease and depression.
        Neurology. 2009; 72: 886-892
        • Pal E.
        • Nagy F.
        • Aschermann Z.
        • Balazs E.
        • et al.
        The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: a randomized, double-blind, placebo-controlled study.
        Mov Disord. 2010; 25: 2311-2317
        • Doruk D.
        • Gray Z.
        • Bravo G.L.
        • et al.
        Effects of tDCS on executive function in Parkinson's disease.
        Neurosci Lett. 2014; 582: 27-31
        • Weaver F.M.
        • Follett K.
        • Stern M.
        • et al.
        Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial.
        JAMA. 2009; 301: 63-73
        • Jost S.T.
        • Ray Chaudhuri K.
        • Ashkan K.
        • et al.
        Subthalamic stimulation improves quality of sleep in Parkinson disease: a 36-month controlled study.
        J Parkinsons Dis. 2020; (Advance online publication.
        • Voon V.
        • Krack P.
        • Lang A.E.
        • et al.
        A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson's disease.
        Brain. 2008; 131: 2720-2728
        • Weintraub D.
        • Duda J.E.
        • Carlson K.
        • et al.
        Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial.
        J Neurol Neurosurg Psychiatry. 2013; 84: 1113-1118
        • Hinkle J.T.
        • Perepezko K.
        • Mari Z.
        • et al.
        Perceived treatment status of fluctuations in Parkinson disease impacts suicidality.
        Am J Geriatr Psychiatry. 2018; 26: 700-710
        • Shepard M.D.
        • Perepezko K.
        • Broen M.
        • et al.
        Suicide in Parkinson's disease.
        J Neurol Neurosurg Psychiatry. 2019; 90: 822-829
        • Morgan J.C.
        • Kurek J.A.
        • Davis J.L.
        • et al.
        Insights into pathophysiology from medication-induced tremor.
        Tremor Other Hyperkinet Mov (New York, N.Y.). 2017; 7: 442
        • Lee K.
        • Baron K.
        • Soca R.
        • et al.
        The prevalence and characteristics of REM Sleep without Atonia (RSWA) in patients taking antidepressants.
        J. Clin Sleep Med. 2016; 12: 351-355
        • Kotagal V.
        • Albin R.L.
        • Müller M.L.
        • et al.
        Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease.
        Ann Neurol. 2012; 71: 560-568
        • Weintraub D.
        Impulse control disorders in Parkinson's disease: a 20-year odyssey.
        Mov Disord. 2019; 34: 447-452
        • Reynolds G.O.
        • Otto M.W.
        • Ellis T.D.
        • et al.
        The therapeutic potential of exercise to improve mood, cognition, and sleep in Parkinson's disease.
        Mov Disord. 2016; 31: 23-38
        • Borges S.
        • Chen Y.F.
        • Laughren T.P.
        • et al.
        Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration.
        J Clin Psychiatry. 2014; 75: 205-214
        • Berrios G.E.
        • Campbell C.
        • Politynska B.E.
        Autonomic failure, depression and anxiety in Parkinson's disease.
        Br J Psychiatry. 1995; 166: 789-792
        • Bower E.S.
        • Wetherell J.L.
        • Mon T.
        • et al.
        Treating anxiety disorders in older adults: current treatments and future directions.
        Harv Rev Psychiatry. 2015; 23: 329-342