Cited by 205Fatty Acid Research and HealthParkinson's Disease Mechanisms and TreatmentsTreatment of Major Depression

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Depression in Parkinson’s Disease: A Double-Blind, Randomized, Placebo-Controlled Pilot Study of Omega-3 Fatty-Acid Supplementation

da Silva, Ticyana Moralez, Munhoz, Renato Puppi, Alvarez, Cristiano, Naliwaiko, Katya, Kiss, Ágata, Andreatini, Roberto, Ferraz, Anete Curte·2008·Journal of Affective Disorders

DOI 10.1016/j.jad.2008.03.008

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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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“, 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
Omega-3 fatty acids for depression in adults
Appleton, K. M., Voyias, P. D., Sallis, H. M., Dawson, S., Ness, A. R., Churchill, R., & Perry, R. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004692.pub5 · Cited by 84
Anti-Inflammatory Treatment Efficacy in Major Depressive Disorder: A Systematic Review of Meta-Analyses
Simon, M. S., Arteaga-Henríquez, G., Algendy, A. F., Siepmann, T., & Illigens, B. M. W. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s385117 · Cited by 60
State of the art paper Application of polyunsaturated fatty acids in internal medicine: beyond the established cardiovascular effects
Cicero, A. F. G., Reggi, A., Parini, A., & Borghi, C. (2012) · Archives of Medical Science · doi:10.5114/aoms.2012.31613 · Cited by 55
Disentangling the Molecular Mechanisms of the Antidepressant Activity of Omega-3 Polyunsaturated Fatty Acid: A Comprehensive Review of the Literature
Kalkman, H. O., Hersberger, M., Walitza, S., & Berger, G. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094393 · Cited by 54
Altered neural cell junctions and ion-channels leading to disrupted neuron communication in Parkinson’s disease
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
Neuropsychiatry of Parkinson's disease
Kümmer, A., & Teixeira, A. L. (2009) · Arquivos de Neuro-Psiquiatria · doi:10.1590/s0004-282x2009000500033 · Cited by 49
The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications
Menozzi, E., & Schapira, A. H. V. (2024) · CNS Drugs · doi:10.1007/s40263-024-01073-4 · Cited by 50
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 49
“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…”
MethodResult
Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson’s Disease: An Updated Review
Angelopoulou, 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
“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].”
Background
Proximate and Fatty Acid Composition of Some Commercially Important Fish Species from the Sinop Region of the Black Sea
Kocatepe, D., & Turan, H. (2012) · Lipids · doi:10.1007/s11745-012-3658-1 · Cited by 46
“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].”
Background
Mood 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 51
“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…”
Background
A comparative study about EPA-PL and EPA-EE on ameliorating behavioral deficits in MPTP-induced mice with Parkinson’s disease by suppressing oxidative stress and apoptosis
Wang, 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
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
Comparative Efficacy and Acceptability of Anti-inflammatory Agents on Major Depressive Disorder: A Network Meta-Analysis
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 44
Effect of omega-3 polyunsaturated fatty acid treatment over mechanical allodynia and depressive-like behavior associated with experimental diabetes
Redivo, D. D. B., Schreiber, A. K., Adami, E. R., Ribeiro, D. E., Joca, S. R. L., Zanoveli, J. M., & da Cunha, J. M. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.10.058 · Cited by 44
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
“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).”
Background
Depression 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 45
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 40
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
“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.”
Background
Omega-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
Effects of omega 3 fatty acids supplementation in behavior and non-neurodegenerative neuropsychiatric disorders
Anta, R. M. O., Rodríguez‐Rodríguez, E., & López-Sobaler, A. M. (2012) · British Journal Of Nutrition · doi:10.1017/s000711451200164x · Cited by 36
Impact of the Chronic Omega‐3 Fatty Acids Supplementation in Hemiparkinsonism Model Induced by 6‐Hydroxydopamine in Rats
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
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 38
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
(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 35
“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…”
Background
Comparative efficacy and acceptability of drug treatments for Parkinson’s disease with depression: A systematic review with network meta-analysis
Wang, 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
Fish-oil supplementation decreases Indoleamine-2,3-Dioxygenase expression and increases hippocampal serotonin levels in the LPS depression model
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 34
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 33
Contributions of polyunsaturated fatty acids (PUFA) on cerebral neurobiology: an integrated omics approach with epigenomic focus
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 27
“However, time and again, clinical studies have failed to confirm the beneficial consequences of n-3 PUFA [27,28].”
Result
Isotope-reinforced polyunsaturated fatty acids improve Parkinson’s disease-like phenotype in rats overexpressing α-synuclein
Beal, 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 29
Major Depressive Disorder in Older Patients as an Inflammatory Disorder: Implications for the Pharmacological Management of Geriatric Depression
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
“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,…”
Method
Update 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 29
“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).”
Background
German Society of Neurology guidelines for the diagnosis and treatment of cognitive impairment and affective disorders in people with Parkinson’s disease: new spotlights on diagnostic procedures and non-pharmacological interventions
Kalbe, 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
“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

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
ORCID: Munhoz, Renato Puppi
Naliwaiko, Katya
Andreatini, Roberto
Venue: Journal of Affective Disorders
Publisher: Elsevier BV
Published: 2008-12
Volume: 111
Issue: 2-3
Pages: 351-359
ISSN: 0165-0327 (ISSN-L)
DOI: 10.1016/j.jad.2008.03.008
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology (medical) › 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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Depression in Parkinson’s Disease: A Double-Blind, Randomized, Placebo-Controlled Pilot Study of Omega-3 Fatty-Acid Supplementation

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