Depression in Parkinson’s Disease: A Double-Blind, Randomized, Placebo-Controlled Pilot Study of Omega-3 Fatty-Acid Supplementation
Abstract
Background Effect of fish oil supplementation in parkinsonian patients with depression measured by Montgomery-Asberg Rating Scale (MADRS), the Clinical Global Impressions Scale (CGI) and Beck Depression Inventory (BECK).Method Double-blind, placebo-controlled study analyzed depression in 31 patients with Parkinson's Disease and Major Depression (DSM-IV). The patients were double-blind separated in 2 groups that received fish oil (containing omega-3 fatty acids) or mineral oil capsules for 3 months; each group was separated in 2 new groups: one taking antidepressant medication and another one not taking it.Results 29 patients completed the 12-week trial, 58% were female and the mean age was 64.4 years old. Patients supplemented with fish oil showed a significant decrease in MADRS and CGI-Depression scores, and there was no difference among groups in BDI. 14 patients (42%) met criteria for > or = 50% reduction in MADRS score, 7 patients (22%) met criteria for remission (final MADRS total score < or = 12), and 2 patients (6%) discontinued supplementation of fish oil. HPLC analysis of fatty-acid profile showed increase of omega-3 fatty acid in the erythrocyte membrane of patients taking fish oil.Conclusion These results reveal that PD patients taking fish oil, with or without antidepressants, presented improvement in depressive symptoms and indicate that the intake of omega-3 can be used with an antidepressant effect or as adjuvant therapy with some other medication. This is a first pilot study with parkinsonian patients and omega-3 supplementation and requires replication in a larger sample.
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In a clinical study, PD patients taking fish oil with or without antidepressants showed improvements in depressive symptoms.
“Interestingly, in a clinical study where PD patients were taking fish oil (a great source of ω3) with or without antidepressants presented improvements in depressive symptoms [450].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [450]
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“Omega-3 polyunsaturated fatty acids (u-3 PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been claimed to produce beneficial effects on mental health (Da Silva et al., 2008; Borsonelo and Galduroz, 2008).”
BackgroundOmega-3 long-chain polyunsaturated fatty acids: Metabolism and health implications
Khan, I. R., Hussain, M., Jiang, B., Zheng, L., Pan, Y., Hu, J., Khan, A., Ashraf, A., & Zou, X. (2023) · Progress in Lipid Research · doi:10.1016/j.plipres.2023.101255 · Cited by 119 · see citing works
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Dietary Factors in the Etiology of Parkinson’s Disease
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Evidence for Inflammation-Associated Depression
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The Essentials of Essential Fatty Acids
Pasquale, M. G. D. (2009) · Journal of Dietary Supplements · doi:10.1080/19390210902861841 · Cited by 102 · see citing works
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“…3Mathews et al, 2012 (review); 4Nations et al, 2012; 5Santos et al, 2008; 6Barbee et al, 2011; 7Riesenberg et al, 2012; 8Freund-Levi et al, 2008; da Silva et al, 2008; Freeman et al, 2011; Lespérance et al, 2011; 9van de Rest et al, 2008; Bot et al, 2010; 10Varty et al, 2003; Wallace-Boone et al,…”
Mozaffari–Khosravi, H., Yassini-Ardakani, M., Karamati, M., & Shariati-Bafghi, S.-E. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.08.003 · Cited by 98 · see citing works
“In addition, the 12-week duration of intervention in this study was in line with previous trials in depression (Bot et al., 2010; da Silva et al., 2008; Frangou et al., 2006; Mischoulon et al., 2008; Peet and Horrobin, 2002; Rogers et al., 2008; Silvers et al., 2005) and enabled us to detect…”
BackgroundResultVaresi, A., Campagnoli, L. I. M., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., & Pascale, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012289 · Cited by 88 · see citing works
Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside
Ma, Y., Li, X., Yu, J., & Wang, Y. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00404-1 · Cited by 87 · see citing works
Chiu, H., Venkatakrishnan, K., & Wang, C. (2020) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2020.03.008 · Cited by 86 · see citing works
Drug Choices and Advancements for Managing Depression in Parkinson's Disease
Assogna, F., Pellicano, C., Savini, C., Macchiusi, L., Pellicano, G. R., Alborghetti, M., Caltagirone, C., Spalletta, G., & Pontieri, F. E. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666191016094857 · Cited by 81 · see citing works
Li, X., Liu, H., Fischhaber, P. L., & Tang, T.-S. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.06.004 · Cited by 76 · see citing works
Borisovskaya, A., Bryson, W. C., Buchholz, J. R., Samii, A., & Soo Borson, B. (2016) · Neurodegenerative Disease Management · doi:10.2217/nmt-2016-0002 · Cited by 75 · see citing works
Potential Treatment of Parkinson’s Disease with Omega-3 Polyunsaturated Fatty Acids
Li, P., & Song, C. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2020.1735143 · Cited by 74 · see citing works
Liu, J. J., Galfalvy, H. C., Cooper, T. B., Oquendo, M. A., Grunebaum, M. F., Mann, J. J., & Sublette, M. E. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12m07970 · Cited by 73 · see citing works
Toledo, A. P., Reyna‐Jeldes, M., Ortega, L., Coddou, C., & Yévenes, G. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105390 · Cited by 71 · see citing works
Emerging targets for antidepressant therapies
Rakofsky, J. J., Holtzheimer, P. E., & Nemeroff, C. B. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.04.617 · Cited by 71 · see citing works
“In patients with comorbid PD and MDD, a double-blind, randomized, placebo-controlled study showed that adding omega-3 fatty acids with and without antidepressants, resulted in statistically significant improvements in depressive symptoms [113].”
BackgroundLorente-Picón, M., & Laguna, A. (2021) · Biomolecules · doi:10.3390/biom11030433 · Cited by 69 · see citing works
Troeung, L., Egan, S. J., & Gasson, N. (2014) · BMC Psychiatry · doi:10.1186/1471-244x-14-19 · Cited by 85 · see citing works
“Several treatments have been suggested as safer and potentially more effective alternatives and include dopamine agonists [7], Omega-3 fatty-acid supplementation [8], repetitive transcranial magnetic stimulation [9], and cognitive behavioural therapy (CBT) [10].”
BackgroundBello, K. J., Fang, H., Fazeli, P., Bolad, W., Corretti, M. C., Magder, L. S., & Petri, M. (2013) · Rheumatology International · doi:10.1007/s00296-013-2811-3 · Cited by 62 · see citing works
“Potential health benefits have been reported in cancer [2, 3], cognitive function [4], depression [5], immune and inflammatory processes [6, 7], and the cardiovascular system (dyslipidemia and cardiac function [8– 10].”
Delattre, A. M., Kiss, Á., Szawka, R. E., Anselmo-Franci, J. A., Bagatini, P. B., Xavier, L. L., Rigon, P., Achaval, M., Iagher, F., de David, C., et al. (2009) · Neuroscience Research · doi:10.1016/j.neures.2009.11.006 · Cited by 63 · see citing works
ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review
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Systematic Review of Traditional Chinese Medicine for Depression in Parkinson's Disease
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“, omega-3 fatty acids) (Da et al., 2008) have been demonstrated to have beneficial effects in improving dPD.”
Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease
Huang, C., Zhang, Z., & Cui, W. (2019) · Marine Drugs · doi:10.3390/md17040221 · Cited by 62 · see citing works
Omega-3 fatty acids for depression in adults
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Choudhury, S. P., Bano, S., Sen, S., Suchal, K., Kumar, S., Nikolajeff, F., Dey, S. K., & Sharma, V. (2022) · npj Parkinson's Disease · doi:10.1038/s41531-022-00324-9 · Cited by 52 · see citing works
Neuropsychiatry of Parkinson's disease
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Omega-3 polyunsaturated fatty acids for major depressive disorder
Su, K., Wang, S., & Pae, C. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.836487 · Cited by 47 · see citing works
“Despite well-controlled clinical trials and systematic meta-analyses which have demonstrated the potential utility of omega-3 PUFA in the treatment of MDD [20,26-28,31,91-97,116], it is not clearly shown whether the efficacy of omega-3 PUFAs’ antidepressant effects should be potentially different for specific subtypes…”
MethodResultAngelopoulou, E., Stanitsa, E., Karpodini, C. C., Bougea, A. M., Kontaxopoulou, D., Fragkiadaki, S., Koros, C., GEORGAKOPOULOU, V. E., Fotakopoulos, G., Koutedakis, Y., et al. (2023) · Medicina · doi:10.3390/medicina59081454 · Cited by 46 · see citing works
“The administration of fish oil, which contains omega-3 fatty acids, has been shown to be effective in improving depressive symptoms in PD patients in a small placebo-controlled pilot study [167].”
BackgroundKocatepe, D., & Turan, H. (2012) · Lipids · doi:10.1007/s11745-012-3658-1 · Cited by 46 · see citing works
“functions [9] improvement in depressive symptoms in parkinsonian patients [10], a reduction in the risk of breast cancer [11, 12] and a reduction in the risk of prostate cancer [13].”
BackgroundMood Disorders and Anxiety in Parkinson’s Disease: Current Concepts
Lintel, H. A., Corpuz, T. V., Paracha, S.-U.-R., & Grossberg, G. T. (2021) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/08919887211018267 · Cited by 46 · see citing works
“describe a double-blind RCT of 29 patients finding statistically significant improvement in depression scores in patients augmenting with omega-3-fatty acid supplements.(55) Though more studies are needed, omega-3-fatty acid supplementation can thus be considered as a benign adjuvant for managing depression in PD pati…”
BackgroundWang, C., Wang, D., Zhang, T., Yanagita, T., Xue, C., Chang, Y., & Wang, Y. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2018.09.027 · Cited by 42 · see citing works
Neurobiological findings underlying depressive behavior in Parkinson’s disease: A review
Mendonça, I. P., Duarte-Silva, E. P., Chaves-Filho, A. J. M., Andrade‐da‐Costa, B. L. D. S., & Peixoto, C. A. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106434 · Cited by 42 · see citing works
Hang, X., Zhang, Y., Li, J., Li, Z., Zhang, Y., Ye, X., Tang, Q., & Sun, W. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.691200 · Cited by 42 · see citing works
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Triglyceride Form of Docosahexaenoic Acid Mediates Neuroprotection in Experimental Parkinsonism
Gómez‐Soler, M., Cordobilla, B., Morató, X., Fernández‐Dueñas, V., Domingo, J. C., & Ciruela, F. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00604 · Cited by 39 · see citing works
“Accordingly, a number of agents including caffeine, nicotine, coenzyme Q10, and omega-3 polyunsaturated fatty acids (n-3 PUFA) have been proposed to counteract these processes (Müller et al., 2003; da Silva et al., 2008; Quik et al., 2009; Prediger, 2010; Seidl and Potashkin, 2011).”
BackgroundDepression in Parkinson's Disease: A Narrative Review
Chikatimalla, R., Dasaradhan, T., Koneti, J., Cherukuri, S. P., Kalluru, R., & Gadde, S. (2022) · Cureus · doi:10.7759/cureus.27750 · Cited by 39 · see citing works
Omega-3 fatty acids and stress-induced changes to mood and cognition in healthy individuals
Giles, G. E., Mahoney, C. R., Urry, H. L., Brunyé, T. T., Taylor, H. A., & Kanarek, R. B. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.02.018 · Cited by 38 · see citing works
Impact of DHA intake in a mouse model of synucleinopathy
Coulombe, K., Kerdiles, O., Tremblay, C., Émond, V., Lebel, M., Boulianne, A.-S., Plourde, M., Cicchetti, F., & Calon, F. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.12.002 · Cited by 38 · see citing works
“Beside possible effects on mood-related symptoms (da Silva et al., 2008), no clinical intervention trial has confirmed a neuroprotective effect of n-3 PUFA in PD.”
BackgroundOmega-3 fatty acids influence mood in healthy and depressed individuals
Giles, G. E., Mahoney, C. R., & Kanarek, R. B. (2013) · Nutrition Reviews · doi:10.1111/nure.12066 · Cited by 36 · see citing works
Anta, R. M. O., Rodríguez‐Rodríguez, E., & López-Sobaler, A. M. (2012) · British Journal Of Nutrition · doi:10.1017/s000711451200164x · Cited by 35 · see citing works
Barros, A. S., Crispim, R. Y. G., Cavalcanti, J. U., Souza, R. B., Lemos, J. C., Filho, G. C., Bezerra, M. M., Pinheiro, T. F. M., Vasconcelos, S. M. M., Macêdo, D. S., et al. (2016) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12713 · Cited by 34 · see citing works
Omega‐3 polyunsaturated fatty acids and Parkinson's disease: A systematic review of animal studies
Alves, B. D. S., Schimith, L. E., da Cunha, A. B., Dora, C. L., & Hort, M. A. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16154 · Cited by 33 · see citing works
Transcriptomic Analysis of the Effects of a Fish Oil Enriched Diet on Murine Brains
Hammamieh, R., Chakraborty, N., Gautam, A., Miller, S., Muhie, S. Y., Meyerhoff, J. L., & Jett, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090425 · Cited by 33 · see citing works
(N-3) Fatty Acids: Molecular Role and Clinical Uses in Psychiatric Disorders
Prior, P. L., & Galduróz, J. C. F. (2012) · Advances in Nutrition · doi:10.3945/an.111.001693 · Cited by 33 · see citing works
“Other clinical trials have found positive correlations between an increase in (n-3) fatty acid concentrations and improvement in symptoms, whether in major isolated depression (54–57), pediatric unipolar depression (58), and depression associated with Parkinson’s disease (59), with menopausal transition (60), and with…”
BackgroundWang, X., Feng, S., Wang, Y., Chen, B., Wang, Z., Chen, N., & Zhang, Y. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175070 · Cited by 32 · see citing works
Carabelli, B., Delattre, A. M., Waltrick, A. P. F., Araújo, G., Suchecki, D., Machado, R. B., de Souza, L. E. R., Zanata, S. M., Zanoveli, J. M., & Ferraz, A. C. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112675 · Cited by 33 · see citing works
N-3 (Omega-3) Fatty Acids in Postpartum Depression: Implications for Prevention and Treatment
Levant, B. (2010) · Depression Research and Treatment · doi:10.1155/2011/467349 · Cited by 30 · see citing works
Chakraborty, N., Muhie, S. Y., Kumar, R., Gautam, A., Srinivasan, S., Sowe, B., Dimitrov, G. I., Miller, S., Jett, M., & Hammamieh, R. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.12.006 · Cited by 26 · see citing works
“However, time and again, clinical studies have failed to confirm the beneficial consequences of n-3 PUFA [27,28].”
ResultBeal, M. F., Chiluwal, J., Calingasan, N. Y., Milne, G. L., Shchepinov, M. S., & Tapias, V. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01090-6 · Cited by 28 · see citing works
Forbes, M., O'Neil, A. E., Lane, M. M., Agustini, B., Myles, N., & Berk, M. (2021) · Drugs & Aging · doi:10.1007/s40266-021-00858-2 · Cited by 25 · see citing works
“A double-blind RCT of 3 months’ supplementation of omega-3 fatty acid in 29 older participants with depression and Parkinson’s disease found that 42% had a clinical response (50% reduction in depressive symptoms) and 22% experienced remission (score ≤ 12) on one depression rating scale (Montgomery-Asberg Rating Scale,…”
MethodUpdate to the Treatment of Parkinson’s Disease Based on the Gut-Brain Axis Mechanism
Sun, X., Li, X., Wang, Z., & Xie, A. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.878239 · Cited by 26 · see citing works
“PD patients take ω-3 PUFA to improve depressive symptoms, plus vitamin E can also have a good effect on UPDRS and insulin metabolic markers (da Silva et al., 2008).”
BackgroundKalbe, E., Folkerts, A., Witt, K., Buhmann, C., Liepelt‐Scarfone, I., & for the German Parkinson’s Guidelines Group (2024) · Journal of Neurology · doi:10.1007/s00415-024-12503-0 · Cited by 25 · see citing works
“A 12-week RCT with omega-3 fatty acids showed a significant reduction in depression scores compared with a placebo [190].”
Treatment of Nonmotor Symptoms in Parkinson's Disease
Sauerbier, A., Cova, I., Rosa‐Grilo, M., Taddei, R. N., Mischley, L. K., & Chaudhuri, К. R. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.03.002 · Cited by 24 · see citing works
- Authors
- da Silva, T. M., Munhoz, R. P., Alvarez, C., Naliwaiko, K., Kiss, Á., Andreatini, R., & Ferraz, A. C.
- Affiliations
- Hospital de Clínicas Universidade Federal do Paraná (BR)
- Universidade Federal do Paraná (BR)
- Corresponding author
- Ferraz, Anete Curte
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 111
- Issue
- 2-3
- Pages
- 351-359
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2034824946
- Cited by
- 205
- References
- 54
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 14 · 2023: 13 · 2022: 11 · 2021: 13 · 2020: 13 · 2019: 11 · 2018: 4 · 2017: 14 · 2016: 12 · 2015: 15 · 2014: 13 · 2013: 15 · 2012: 9
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universidade Federal do Paraná
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- Parkinson's disease, depression, omega-3 fatty acids, fish oil supplementation, major depressive disorder, depression remission
- MeSH terms
- Aged, Antidepressive Agents, Antiparkinson Agents, Brazil, Combined Modality Therapy, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Female, Humans, Levodopa, Male, Middle Aged, Mineral Oil, Parkinson Disease, Personality Inventory, Pilot Projects, Placebos, Psychiatric Status Rating Scales, Fatty Acids, Omega-3, Comorbidity, Treatment Outcome, Dietary Supplements
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