Abstract
Depression in Parkinson’s Disorder (DPD) has been estimated to appear in up to 40% of people with PD and negatively impacts quality of life, motor and cognitive deficits and functional disability. Knowledge of the pathophysiology of DPD is unclear, DPD may be related to dysfunction in subcortical nuclei and the prefrontal cortex, striatal–thalamic–prefrontal and basotemporal limbic circuits, brainstem monoamine, and indolamine (i.e. dopamine, serotonin, and norepinephrine) systems. DPD is characterized by sadness, loss of interest, increased exhaustibility, feelings of helplessness, reduced drive, dysphoria, irritability, and pessimism about future. The diagnosis is complicated by overlap with PD symptoms, Detection of depression in PD should be made by psychometric depression scales. DPD is underrecognized and undertreated in clinical practice. Treatment mainly includes antidepressive medications and behavioral interventions as psychotherapy. Dopamine agonists showed some antidepressant effects, there are no sufficient numbers of RCTs. Important randomized clinical trials (RCTs) are summarized. SSRIs and SNRIs have a satisfying efficacy in DPD. TCAs are also good for improving depression. Side effects of different antidepressants (e.g. TCAs, SSRIs, SNRIs, bupropion, MAOIs) and potential interactions should be considered. In existing guidelines so far no statements, algorithms and recommendations are given for diagnosis and treatment of DPD. Methodologically adequate designed RCTs and comparative studies (NIS) which offer evidence-based results are urgently needed having the impact of DPD in mind.
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References
Aarsland D, Marsh L, Schrag A (2009) Neuropsychiatric symptoms in Parkinson’s disease. Mov Disord 24:2175–2186
Aarsland D, Pahlhagen S, Ballard CG et al (2011) Depression in Parkinson disease - epidemiology, mechanisms, and management. Nat Rev Neurol 8:35–47
Agüera-Ortiz L, García-Ramos R, Grandas Pérez FJ et al (2021) Focus on depression in Parkinson’s Disease: A Delphi consensus of experts in psychiatry, neurology, and geriatrics. Parkinsons Dis 2021:6621991. https://doi.org/10.1155/2021/6621991
Andersen J, Aabro E, Gulmann N et al (1980) Anti-depressive treatment in Parkinson’s disease A controlled trial of the effect of nortriptyline in patients with Parkinson’s disease treated with L-DOPA. Acta Neurol Scand 62:210–219
Antonini A, Tesei S, Zecchinelli A et al (2006) Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson’s disease and depression: effect on quality of life. Mov Disord 21:1119–1122
Armento M, Stanley M, Marsh L et al (2012) Cognitive behavioral therapy (CBT) for depression and anxiety in Parkinson’s disease: a clinical review. J Park Dis 2:135–151
Armstrong MJ, Okun MS (2020) Diagnosis and treatment of Parkinson disease: a review. JAMA 323:548–560. https://doi.org/10.1001/jama.2019.22360
Assogna F, Pellicano C, Savini C et al (2020) Drug choices and advancements for managing depression in Parkinson’s disease. Curr Neuropharmacol 18:277–287. https://doi.org/10.2174/1570159X17666191016094857
Barone P, Scarzella L, Marconi R et al (2006) Pramipexole versus sertraline in the treatment of depression in Parkinson’s disease: a national multicenter parallel-group randomized study. J Neurol 253:601–607
Barone P, Antonini A, Colosimo C et al (2009) The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 24:1641–1649. https://doi.org/10.1002/mds.22643
Barone P, Poewe W, Albrecht S et al (2010) 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
Barone P, Santangelo G, Morgante L, Onofrj M et al (2015) A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients. Eur J Neurol 22:1184–1191
Borgonovo J, Allende-Castro C, Laliena A et al (2017) Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson’s disease. Parkinsonism Relat Disord 35:17–24. https://doi.org/10.1016/j.parkreldis.2016.11.009
Cummings JL (1992) Depression and Parkinson’s disease: a review. Am J Psychiatry 149:443–454
Dobkin RD, Menza M, Allen LA et al (2011a) Cognitive-behavioral therapy for depression in Parkinson’s disease: a randomized, controlled trial. Am J Psychiatry 168:1066–1074
Dobkin RD, Menza M, Bienfait KL et al (2011b) Depression in Parkinson’s disease: symptom improvement and residual symptoms after acute pharmacologic management. Am J Geriatr Psychiatr 19:222–229
Feigin VL, Nichols E, Alam T et al (2019) Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 18:459–480. https://doi.org/10.1016/S1474-4422(18)30499-X
Fregni F, Santos CM, Myczkowski ML et al (2004) Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:1171–1174
Goetz CG, Tanner CM, Klawans HL (1984) Bupropion in Parkinson’s disease. Neurology 34:1092–1094
Grachev ID (2013) Dopamine transporter imaging with [123I]FP-CIT (DaTSCAN) in Parkinson’s disease with depressive symptoms: a biological marker for causal relationships? J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2013-305380
Han JW, Ahn YD, Kim WS, Shin CM et al (2018) Psychiatric Manifestation in Patients with Parkinson’s Disease. J Korean Med Science 33:e300. https://doi.org/10.3346/jkms.2018.33.e300
Huot P, Fox SH (2013) The serotonergic system in motor and non-motor manifestations of Parkinson’s disease. Exp Brain Res 230:463–476
Ishihara L, Brayne C (2006) A systematic review of depression and mental illness preceding Parkinson’s disease. Acta Neurol Scand 113:211–220
Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912. https://doi.org/10.1016/S0140-6736(14)61393-3
Leentjens AF (2011) The role of dopamine agonists in the treatment of depression in patients with Parkinson’s disease: a systematic review. Drugs 71:273–286
Lemke MR (2002) Effect of reboxetine on depression in Parkinson’s disease patients. J Clin Psychiatry 63:300–304
Liu J, Dong J, Wang L, Su Y, Yan P, Sun S (2013) Comparative efficacy and acceptability of antidepressants in Parkinson’s disease: a network meta-analysis. PLoS ONE 8:e76651. https://doi.org/10.1371/journal.pone.0076651
Marsh L (2013) Depression and Parkinson’s disease: Current knowledge. Curr Neurol Neurosci Rep 13:409. https://doi.org/10.1007/s11910-013-0409-5
McDonald WM, Richard ICH, DeLong MR (2003) Prevalence, etiology, and treatment of depression in Parkinson’s disease. Biol Psychiatry 54:363–375
Menza M, Dobkin RD, Marin H, Mark MH et al (2009) A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 72:886–892
Mills KA, Greene MC, Dezube R, Goodson, et al (2018) Efficacy and tolerability of antidepressants in Parkinson’s disease: A systematic review and network meta-analysis. Int J Geriatr Psychiatry 33:642–651. https://doi.org/10.1002/gps.4834
Nazem S, Siderowf AD, Duda JE et al (2008) Suicidal and death ideation in Parkinson’s disease. Mov Disord 23:1573–1579
Paumier KL, Siderowf AD, Auinger P et al (2012) Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson’s disease. Mov Disord 27:880–887
Peña E, Mata M, López-Manzanares L, Kurtis M et al (2016) Antidepressants in Parkinson’s disease Recommendations by the movement disorder study group of the Neurological Association of Madrid. Neurologia. https://doi.org/10.1016/j.nrl.2016.02.002
Raskin S, Durst R (2010) Bupropion as the treatment of choice in depression associated with Parkinson’s disease and it’s various treatments. Med Hypotheses 75:544–546. https://doi.org/10.1016/j.mehy.2010.07.024
Reijnders JS, Ehrt U, Weber WE et al (2008) A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord 23:183–189
Rektorová I, Rektor I, Bares M et al (2003) Pramipexole and pergolide in the treatment of depression in Parkinson’s disease: a national multicentre prospective randomized study. Eur J Neurol 10:399–406
Richard IH, McDermott MP, Kurlan R et al (2012) A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology 78:1229–1236
Richelson E (2002) The clinical relevance of antidepressant interaction with neurotransmitter transporters and receptors. Psychopharmacol Bull 36:133–150
Riedel O, Klotsche J, Spottke A et al (2010) Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson’s disease. J Neurol 257:1073–1082
Riedel O, Dodel R, Deuschl G et al (2012) Depression and car-dependency in Parkinson’s disease: results from a nationwide study of 1449 outpatients. Parkinsonian Rel Disord 18:598–601
Riederer P, Bartl J, Laux G, Grünblatt E (2011) Diabetes type II: a risk factor for depression-Parkinson-Alzheimer? Neurotox Res 19:253–265. https://doi.org/10.1007/s12640-010-9203-1
Rocha FL, Murad MG, Stumpf BP, Hara C, Fuzikawa C (2013) Antidepressants for depression in Parkinson’s disease: systematic review and meta-analysis. J Psychopharmacol 27:417–423. https://doi.org/10.1177/0269881113478282
Ryan M, Eatmon CV, Slevin JT (2019) Drug treatment strategies for depression in Parkinson disease. Expert Opin Pharmacother 20:1351–1363. https://doi.org/10.1080/14656566.2019.1612877
Seppi K, Chaudhuri KR, Coelho M, Fox SH et al (2019) Update on treatments for the non-motor symptoms of Parkinson’s disease –an evidence-based medicine review. Mov Disord 34:180–198
Shabnam GN, Th C, Kho D et al (2003) Therapies for depression in Parkinson’s disease. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003465
Simon DK, Tanner CM, Brundin P (2020) Parkinson Disease epidemiology, pathology, genetics, and pathophysiology. Clin Geriatr Med 36:1–12. https://doi.org/10.1016/j.cger.2019.08.002
Skapinakis P, Bakola E, Salanti G et al (2010) Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson’s disease: a systematic review and meta-analysis of randomized controlled trials. BMC Neurol 10:49
Skorvanek M, Gdovinova Z, Rosenberger J, Saeedian RG et al (2015) The associations between fatigue, apathy, and depression in Parkinson’s disease. Acta Neurol Scand 131:80–87. https://doi.org/10.1111/ane.12282
Steur EN, Ballering LA (1997) Moclobemide and selegeline in the treatment of depression in Parkinson’s disease. J Neurol Neurosurg Psychiatry 63:547
Takahashi M, Tabu H, Ozaki A, Hamano T, Takeshima T, REBORN study group (2019) Antidepressants for depression, apathy, and gait instability in Parkinson’s disease: a multicenter randomized study. Intern Med 58:361–368. https://doi.org/10.2169/internalmedicine.1359-18
Tesei S, Antonini A, Canesi M et al (2000) Tolerability of paroxetine in Parkinson’s disease: a prospective study. Mov Disord 15:986–989
Troeung L, Egan SJ, Gasson N (2013) A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson’s disease. PLoS ONE 8:e79510. https://doi.org/10.1371/journal.pone.0079510
Tursi MF, Baes CV, Camacho FR, Tofoli SM, Juruena MF (2013) Effectiveness of psychoeducation for depression: a systematic review. Aust N Z J Psychiatry 47:1019–1031
Weintraub D, Mamikonyan E (2019) The neuropsychiatry of Parkinson Disease: A perfect Storm. Amer J Geriatr Psychiatry 27:998–1018. https://doi.org/10.1016/j.jagp.2019.03.002
Weintraub D, Moberg PJ, Duda JE et al (2003) Recognition and treatment of depression in Parkinson’s disease. J Geriatr Psychiatry Neurol 16:178–183
Williams JR, Hirsch ES, Anderson K, Bush AL et al (2012) A comparison of nine scales to detect depression in Parkinson disease: which scale to use? Neurology 78:998–1006
Wolters ECH, Braak H (2006) Parkinson’s disease: premotor clinico-pathological correlations. J Neural Transm Suppl. https://doi.org/10.1007/978-3-211-45295-0-47
Xie CL, Chen J, Wang XD, Pan JL et al (2015) Repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in Parkinson disease: a meta-analysis of randomized controlled clinical trials. Neurol Sci 36:1751–1761. https://doi.org/10.1007/s10072-015-2345-4
Yang S, Sajatovic M, Walter BL (2012) Psychosocial interventions for depression and anxiety in Parkinson’s disease. J Geriatr Psychiatry Neurol 25:113–121
Zhuo C, Xue R, Luo L et al (2017) Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis. Medicine (baltimore) 96:e6698. https://doi.org/10.1097/MD.0000000000006698
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Laux, G. Parkinson and depression: review and outlook. J Neural Transm 129, 601–608 (2022). https://doi.org/10.1007/s00702-021-02456-3
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DOI: https://doi.org/10.1007/s00702-021-02456-3