Mood disorders and anxiety significantly impact the prognosis and disease course of Parkinson’s disease. Non-motor symptoms of Parkinson’s disease such as apathy, anhedonia, and fatigue overlap with diagnostic criteria for anxiety and depression, thus making accurate diagnosis of mood disorders in Parkinson’s disease patients difficult. Furthermore, treatment options for mood disorders can produce motor complications leading to poor adherence and impaired quality of life in Parkinson’s disease patients. This review aims to clarify the current state of diagnostic and treatment options pertaining to anxiety and mood disorders in Parkinson’s disease. It explores both the pharmacologic and non-pharmacologic treatment modalities for various mood disorders in comorbid Parkinson’s disease with a brief discussion of the future outlook of the field given the current state of the literature.
MarrasCBeckJCBowerJH, et al.Prevalence of Parkinson’s disease across north America. NPJ Parkinsons Dis. 2018;4:21. doi:10.1038/s41531-018-0058-0
2.
HirschLJetteNFrolkisASteevesTPringsheimT. The incidence of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology. 2016;46(4):292–300. doi:10.1159/000445751
HanJWAhnYDKimWS, et al.Psychiatric manifestation in patients with Parkinson’s disease. J Korean Med Sci. 2018;33(47):e300. Published 2018 Nov 1. doi:10.3346/jkms.2018.33.e300
5.
Diagnostic and Statistical Manual of Mental Disorders. [Electronic Resource]: DSM-5. 5th ed. American Psychiatric Association; 2013.
6.
RyanMEatmonCVSlevinJT. Drug treatment strategies for depression in Parkinson disease. Expert Opin Pharmacother. 2019;20(11):1351–1363. doi:10.1080/14656566.2019.1612877. PMID: 31120798.
7.
ReijndersJSAMEhrtUWeberWEJAarslandDLeentjensAFG. A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord. 2008;23(2):183–189; quiz 313. doi:10.1002/mds.21803
8.
SchapiraAHVChaudhuriKRJennerP.Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017;18(7):435–450. doi:10.1038/nrn.2017.62. Erratum in: Nat Rev Neurosci. 2017 Aug;18(8):509. PMID: 28592904.
9.
SeritanALRienasCDuongTDelucchiKOstremJL. Ages at onset of anxiety and depressive disorders in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 2019;31(4):346–352. doi: 10.1176/appi.neuropsych.18090201. PMID: 31117906.
10.
SchragABaronePBrownRG, et al.Depression rating scales in Parkinson’s disease: critique and recommendations. Mov Disord. 2007;22(8):1077–1092. doi:10.1002/mds.21333
11.
BaqueroMMartínN. Depressive symptoms in neurodegenerative diseases. World J Clin Cases. 2015;3(8):682–693. doi:10.12998/wjcc.v3.i8.682
12.
TorbeyEPachanaNADissanayakaNNW. Depression rating scales in Parkinson’s disease: a critical review updating recent literature. J Affect Disord. 2015;184:216–224. https://doi.org/10.1016/j.jad.2015.05.059
13.
GoodarziZMrklasKJRobertsDJJetteNPringsheimTHolroyd-LeducJ.Detecting depression in Parkinson disease: a systematic review and meta-analysis. Neurology. 2016;87(4):426–437. doi:10.1212/WNL.0000000000002898
14.
MeleBHolroyd-LeducJSmithEEPringsheimTIsmailZGoodarziZ.Detecting anxiety in individuals with Parkinson disease: a systematic review. Neurology. 2018;90(1):e39–e47. doi:10.1212/WNL.0000000000004771
15.
Martinez-MartinPLeentjensAFGde Pedro-CuestaJChaudhuriKRSchragAEWeintraubD. Accuracy of screening instruments for detection of neuropsychiatric syndromes in Parkinson’s disease. Mov Disord. 2016;31(3):270–279. doi:10.1002/mds.26522
16.
ParkMReynoldsCFIII. Depression among older adults with diabetes mellitus. Clin Geriatr Med. 2015;31(1):117–137, ix. doi:10.1016/j.cger.2014.08.022
17.
ZhangYChenYMaL.Depression and cardiovascular disease in elderly: current understanding. J Clin Neurosci. 2018;47:1–5. doi:10.1016/j.jocn.2017.09.022
18.
ParmeleePATigheCADautovichND. Sleep disturbance in osteoarthritis: linkages with pain, disability, and depressive symptoms. Arthritis Care Res (Hoboken). 2015;67(3):358–365. doi:10.1002/acr.22459
19.
BaoY-PHanYMaJ, et al.Cooccurrence and bidirectional prediction of sleep disturbances and depression in older adults: meta-analysis and systematic review. Neurosci Biobehav Rev. 2017;75:257–273. doi:10.1016/j.neubiorev.2017.01.032
20.
WeisenbachSLBooreLAKalesHC. Depression and cognitive impairment in older adults. Curr Psychiatry Rep. 2012;14(4):280–288. doi:10.1007/s11920-012-0278-7
21.
ZhangXNortonJCarrièreIRitchieKChaudieuIAncelinML. Risk factors for late-onset generalized anxiety disorder: results from a 12-year prospective cohort (the ESPRIT study). Transl Psychiatry. 2015;5(3):e536. doi:10.1038/tp.2015.31
22.
FiskeAWetherellJLGatzM. Depression in older adults. Annu Rev Clin Psychol. 2009;5:363–389. doi:10.1146/annurev.clinpsy.032408.153621
23.
ParkMUnützerJ. Hundred forty eight more days with depression: the association between marital conflict and depression-free days. Int J Geriatr Psychiatry. 2014;29(12):1271–1277. doi:10.1002/gps.41070
24.
MarinusJZhuKMarrasCAarslandDvan HiltenJJ. Risk factors for non-motor symptoms in Parkinson’s disease. Lancet Neurol. 2018;17(6):559–568. doi:10.1016/S1474-4422(18)30127-3
25.
BarnesRVeithRCRaskindMA. Depression in older persons: diagnosis and management. West J Med. 1981;135(6):463–468.
26.
RogersDPiesR. General medical with depression drugs associated. Psychiatry (Edgmont). 2008;5(12):28–41.
27.
HakimiMMaurerCW. Pseudobulbar affect in parkinsonian disorders: a review. J Mov Disord. 2019;12(1):14–21. doi:10.14802/jmd.18051
28.
SiddiquiMSFernandezHHGarvanCW, et al.Inappropriate crying and laughing in Parkinson disease and movement disorders. World J Biol Psychiatry. 2009;10(3):234–240. doi:10.1080/15622970701639445
29.
PetraccaGMJorgeREAciónLWeintraubDRobinsonRG. Frequency and correlates of involuntary emotional expression disorder in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 2009;21(4):406–412. doi:10.1176/jnp.2009.21.4.406
30.
PatteeGLWymerJPLomen-HoerthCAppelSHFormellaAEPopeLE. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions. Curr Med Res Opin. 2014;30(11):2255–2265. doi:10.1185/03007995.2014.940040
31.
ParyRSaraiSKMicchelliALippmannS. Anxiety disorders in older patients. Prim Care Companion CNS Disord. 2019;21(1):18nr02335. doi:10.4088/PCC.18nr02335
32.
VinkDAartsenMJSchoeversRA. Risk factors for anxiety and depression in the elderly: a review. J Affect Disord. 2008;106(1-2):29–44. doi:10.1016/j.jad.2007.06.005
33.
RamosKStanleyMA. Anxiety disorders in late life. Clin Geriatr Med. 2020;36(2):237–246. doi:10.1016/j.cger.2019.11.005
34.
CanutoAWeberKBaertschiM, et al.Anxiety disorders in old age: psychiatric comorbidities, quality of life, and prevalence according to age, gender, and country. Am J Geriatr Psychiatry. 2018;26(2):174–185. doi:10.1016/j.jagp.2017.08.015
35.
DissanayakaNNSellbachAMathesonS, et al.Anxiety disorders in Parkinson’s disease: prevalence and risk factors. Mov Disord. 2010;25(7):838–845. doi:10.1002/mds.22833
36.
DeMartiniJPatelGFancherTL. Generalized anxiety disorder. Ann Intern Med. 2019;170(7):ITC49–ITC64. doi:10.7326/AITC201904020
LockeABKirstNShultzCG. Diagnosis and management of generalized anxiety disorder and panic disorder in adults. Am Fam Physician. 2015;91(9):617–624.
39.
BalsamoMCataldiFCarlucciLFairfieldB. Assessment of anxiety in older adults: a review of self-report measures. Clin Interv Aging. 2018;13:573–593. doi:10.2147/CIA.S114100
40.
Bomasang-LaynoEFadlonIMurrayANHimelhochS.Antidepressive treatments for Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2015;21(8):833. doi:10.1016/j.parkreldis.2015.04.018
41.
TroeungLEganSJGassonN. A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson’s disease. PLoS One. 2013;8(11):e79510. doi:10.1371/journal.pone.0079510
42.
RochaFLMuradMGStumpfBPHaraCFuzikawaC. Antidepressants for depression in Parkinson’s disease: systematic review and meta-analysis. J Psychopharmacol. 2013;27(5):417–423. doi:10.1177/0269881113478282
43.
DevosDDujardinKPoirotI, et al.Comparison of desipramine and citalopram treatments for depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled study. Mov Disord. 2008;23(6):850–857. doi:10.1002/mds.21966
44.
RichardIHMcDermottMPKurlanR, et al.A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology. 2012;78(16):1229–1236. doi:10.1212/WNL.0b013e3182516244
45.
HauserRAZesiewiczTA. Sertraline for the treatment of depression in Parkinson’s disease. Mov Disord. 1997;12(5):756–759. doi:10.1002/mds.870120522
46.
MarinoSSessaEDi LorenzoG, et al.Sertraline in the treatment of depressive disorders in patients with Parkinson’s disease. Neurol Sci. 2008;29(6):391–395. doi:10.1007/s10072-008-1021-3
47.
GaltsCPCBettioLEBJewettDC, et al.Depression in neurodegenerative diseases: common mechanisms and current treatment options. Neurosci Biobehav Rev. 2019;102:56–84. doi:10.1016/j.neubiorev.2019.04.002
48.
MenzaMDobkinRDMarinH, et al.A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. 2009;72(10):886–892. doi:10.1212/01.wnl.0000336340.89821.b3
49.
BaronePPoeweWAlbrechtS, et al.Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(6):573–580. doi:10.1016/S1474-4422(10)70106-X
50.
MuellerCRajkumarAPWanYM, et al.Assessment and management of neuropsychiatric symptoms in Parkinson’s disease. CNS Drugs. 2018;32(7):621–635. doi:10.1007/s40263-018-0540-6
51.
BaronePScarzellaLMarconiR, et al.Pramipexole versus sertraline in the treatment of depression in Parkinson’s disease: a national multicenter parallel-group randomized study. J Neurol. 2006;253(5):601–607. doi:10.1007/s00415-006-0067-5
52.
RektorováIRektorIBaresM, et al.Cognitive performance in people with Parkinson’s disease and mild or moderate depression: effects of dopamine agonists in an add-on to L-dopa therapy. Eur J Neurol. 2005;12(1):9–15. doi:10.1111/j.1468-1331.2004.00966.x
53.
ChungSJAsgharnejadMBauerLRamirezFJeonB. Evaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson’s disease. Expert Opin Pharmacother. 2016;17(11):1453–1461. doi:10.1080/14656566.2016.1202917
54.
PahwaRStacyMAFactorSA, et al.Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology. 2007;68(14):1108–1115. doi:10.1212/01.wnl.0000258660.74391.c1
55.
da SilvaTMMunhozRPAlvarezC, et al.Depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J Affect Disord. 2008;111(2-3):351–359. doi:10.1016/j.jad.2008.03.008
56.
NagayamaHKanoOMurakamiH, et al.Effect of istradefylline on mood disorders in Parkinson’s disease. J Neurol Sci. 2019;396:78–83. doi:10.1016/j.jns.2018.11.005
57.
YamadaKKobayashiMShiozakiS, et al.Antidepressant activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002) on learned helplessness in rats. Psychopharmacology (Berl). 2014;231(14):2839–2849. doi:10.1007/s00213-014-3454-0
58.
VecchiaDDKanazawaLKSWendlerE, et al.Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson’s disease. Brain Res Bull. 2020;168:63–73. doi:10.1016/j.brainresbull.2020.12.011
59.
BonatoJMBassaniTBMilaniHVitalMABFde OliveiraRMW. Pioglitazone reduces mortality, prevents depressive-like behavior, and impacts hippocampal neurogenesis in the 6-OHDA model of Parkinson’s disease in rats. Exp Neurol. 2018;300:188–200. doi:10.1016/j.expneurol.2017.11.009
60.
MackJMSchamneMGSampaioTB, et al.Melatoninergic system in Parkinson’s disease: from neuroprotection to the management of motor and nonmotor symptoms. Oxid Med Cell Longev. 2016;2016:3472032. doi:10.1155/2016/3472032
61.
DobkinRDMenzaMAllenLA, et al.Cognitive-behavioral therapy for depression in Parkinson’s disease: a randomized, controlled trial. Am J Psychiatry. 2011;168(10):1066–1074. doi:10.1176/appi.ajp.2011.10111669
62.
ShinmeiIKobayashiKOeY, et al.Cognitive behavioral therapy for depression in Japanese Parkinson’s disease patients: a pilot study. Neuropsychiatr Dis Treat. 2016;12:1319–1331. Published 2016 Jun 8. doi:10.2147/NDT.S104777
63.
VeazeyCCookKFStanleyMLaiECKunikME. Telephone-administered cognitive behavioral therapy: a case study of anxiety and depression in Parkinson’s disease. J Clin Psychol Med Settings. 2009;16(3):243–253. doi:10.1007/s10880-009-9167-6
64.
WuthrichVMRapeeRM. Telephone-delivered cognitive behavioural therapy for treating symptoms of anxiety and depression in Parkinson’s disease: a pilot trial. Clin Gerontol. 2019;42(4):444–453. doi:10.1080/07317115.2019.1580811
65.
DobkinRDInterianADurlandJLGaraMAMenzaMA. Personalized telemedicine for depression in Parkinson’s disease: a pilot trial. J Geriatr Psychiatry Neurol. 2018;31(4):171–176. doi:10.1177/0891988718783274
66.
PopeoDKellnerCH. ECT for Parkinson’s disease. Med Hypotheses. 2009;73(4):468–469. doi: 10.1016/j.mehy.2009.06.053. PMID: 19660875.
67.
BorisovskayaABrysonWCBuchholzJSamiiABorsonS. Electroconvulsive therapy for depression in Parkinson’s disease: systematic review of evidence and recommendations. Neurodegener Dis Manag. 2016;6(2):161–176. doi:10.2217/nmt-2016-0002
68.
TakamiyaASekiMKudoS, et al.Electroconvulsive therapy for Parkinson’s Disease: a systematic review and meta-analysis. Mov Disord. 2020;36(1):50–58. 10.1002/mds.28335. doi:10.1002/mds.28335
69.
AarslandDLarsenJPWaageOLangeveldJH. Maintenance electroconvulsive therapy for Parkinson’s disease. Convuls Ther. 1997;13(4):274–277.
70.
GeorgeMSTaylorJJShortEB. The expanding evidence base for rTMS treatment of depression. Curr Opin Psychiatry. 2013;26(1):13–18. doi:10.1097/YCO.0b013e32835ab46d
71.
ChouYHHickeyPTSundmanMSongAWChenNK. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432–440. doi:10.1001/jamaneurol.2014.4380
72.
MakkosAPálEAschermannZ, et al.High-frequency repetitive transcranial magnetic stimulation can improve depression in Parkinson’s disease: a randomized, double-blind, placebo-controlled study. Neuropsychobiology. 2016;73(3):169–177. doi:10.1159/000445296
73.
PalENagyFAschermannZBalazsEKovacsN. 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(14):2311–2317. doi:10.1002/mds.23270
74.
BrysMFoxMDAgarwalS, et al.Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: a randomized trial. Neurology. 2016;87(18):1907–1915. doi:10.1212/WNL.0000000000003279
75.
MansouriATaslimiSBadhiwalaJH, et al.Deep brain stimulation for Parkinson’s disease: meta-analysis of results of randomized trials at varying lengths of follow-up. J Neurosurg. 2018;128(4):1199–1213. doi:10.3171/2016.11.JNS16715
76.
NegidaAElminawyMEl AshalGEssamAEysaAAbd Elalem AzizM. Subthalamic and pallidal deep brain stimulation for Parkinson’s disease. Cureus. 2018;10(2):e2232. Published 2018 Feb 26. doi:10.7759/cureus.2232
77.
CombsHLFolleyBSBerryDT, et al.Cognition and depression following deep brain stimulation of the subthalamic nucleus and globus pallidus pars internus in Parkinson’s disease: a meta-analysis. Neuropsychol Rev. 2015;25(4):439–454. doi:10.1007/s11065-015-9302-0
78.
BirchallELWalkerHCCutterG, et al.The effect of unilateral subthalamic nucleus deep brain stimulation on depression in Parkinson’s disease. Brain Stimul. 2017;10(3):651–656. doi:10.1016/j.brs.2016.12.014
79.
WuPLLeeMHuangTT. Effectiveness of physical activity on patients with depression and Parkinson’s disease: a systematic review. PLoS One. 2017;12(7):e0181515. doi:10.1371/journal.pone.0181515
80.
PicelliAVaraltaVMelottiC, et al.Effects of treadmill training on cognitive and motor features of patients with mild to moderate Parkinson’s disease: a pilot, single-blind, randomized controlled trial. Funct Neurol. 2016;31(1):25–31. doi:10.11138/fneur/2016.31.1.025
81.
CussoMEDonaldKJKhooTK. The impact of physical activity on non-motor symptoms in Parkinson’s disease: a systematic review. Front Med (Lausanne). 2016;3:35. doi:10.3389/fmed.2016.00035
82.
BridleCSpanjersKPatelSAthertonNMLambSE. Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2012;201(3):180–185. doi:10.1192/bjp.bp.111.095174
83.
ReynoldsGOOttoMWEllisTDCronin-GolombA.The therapeutic potential of exercise to improve mood, cognition, and sleep in Parkinson’s disease. Mov Disord. 2016;31(1):23–38. doi:10.1002/mds.26484
84.
TuonTValvassoriSSLopes-BorgesJ, et al.Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson’s disease. Neuroscience. 2012;227:305–312. doi:10.1016/j.neuroscience.2012.09.063
85.
MondalBChoudhurySSimonBBakerMRKumarH. Noninvasive vagus nerve stimulation improves gait and reduces freezing of gait in Parkinson’s disease. Mov Disord. 2019;34(6):917–918. doi:10.1002/mds.27662
86.
BottomleyJMLeReunCDiamantopoulosAMitchellSGaynesBN. Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: a systematic review and meta-analysis. Compr Psychiatry. 2019;98:152156. doi:10.1016/j.comppsych.2019.152156
87.
WillisAWThibaultDPSchmidtPNDorseyERWeintraubD. Hospital care for mental health and substance abuse conditions in Parkinson’s disease. Mov Disord. 2016;31(12):1810–1819. doi:10.1002/mds.26832
88.
FaustinoPRDuarteGSChendoI, et al.Risk of developing Parkinson disease in bipolar disorder: a systematic review and meta-analysis. JAMA Neurol. 2020;77(2):192–198. doi:10.1001/jamaneurol.2019.3446
89.
BruggerFBhatiaKPBesagFM. Valproate-associated parkinsonism: a critical review of the literature. CNS Drugs. 2016;30(6):527–540. doi:10.1007/s40263-016-0341-8
90.
KimEZwilASMcAllisterTWGlosserDSSternMHurtigH. Treatment of organic bipolar mood disorders in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 1994;6(2):181–184. doi:10.1176/jnp.6.2.181
91.
ChiangKJTsaiJCLiuDLinCHChiuHLChouKR. Efficacy of cognitive-behavioral therapy in patients with bipolar disorder: a meta-analysis of randomized controlled trials. PLoS One. 2017;12(5): e0176849. Published 2017 May 4. doi:10.1371/journal.pone.0176849
92.
SeppiKRay ChaudhuriKCoelhoM, et al.Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review [published correction appears in]. Mov Disord. 2019;34(5):765. Mov Disord. 2019;34(2):180–198. doi:10.1002/mds.27602
93.
Martinez-RamirezDGiugniJCAlmeidaL, et al.Association between antidepressants and falls in Parkinson’s disease. J Neurol. 2016;263(1):76–82. doi:10.1007/s00415-015-7947-5
94.
DissanayakaNNWPyeDMitchellLK, et al.Cognitive behavior therapy for anxiety in Parkinson’s disease: outcomes for patients and caregivers. Clin Gerontol. 2017;40(3):159–171. doi:10.1080/07317115.2016.1240131
95.
AsmundsonGJFetznerMGDeboerLBPowersMBOttoMWSmitsJA. Let’s get physical: a contemporary review of the anxiolytic effects of exercise for anxiety and its disorders. Depress Anxiety. 2013;30(4):362–373. doi:10.1002/da.22043
96.
Aviles-OlmosIKefalopoulouZTripolitiE, et al.Long-term outcome of subthalamic nucleus deep brain stimulation for Parkinson’s disease using an MRI-guided and MRI-verified approach. J Neurol Neurosurg Psychiatry. 2014;85(12):1419–1425. doi:10.1136/jnnp-2013-306907
97.
CoutoMIMonteiroAOliveiraALunetNMassanoJ. Depression and anxiety following deep brain stimulation in Parkinson’s disease: systematic review and meta-analysis. Acta Med Port. 2014;27(3):372–382. doi:10.20344/amp.4928
