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Trials
Published in: Trials 1/2019

Open Access 01-12-2019 | Antidepressant Drugs | Study protocol

Contributions of vitamin D in the management of depressive symptoms and cardiovascular risk factors: study protocol for a randomized, double-blind, placebo-controlled clinical trial

Authors: Catarina Magalhães Porto, Tatiana de Paula Santana da Silva, Everton Botelho Sougey

Published in: Trials | Issue 1/2019

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Abstract

Background

Depression is a major cause of chronic disability throughout the world and an important cardiovascular risk factor, increasing the relative risk of coronary artery disease as well as rates of cardiovascular morbidity and mortality. Concomitant to the high prevalence of depression, there has been a reduction in exposure to sunlight with the increase in urbanization and the use of sun protectors, which has led to a reduction in serum levels of 25-hydroxyvitamin D. Therefore, this paper describes a protocol for a clinical trial with the aim of evaluating the effects of vitamin D supplementation on depression and cardiovascular risk factors to contribute evidence regarding the potential influence of supplementation on mood regulation.

Methods

This protocol study was guided by the Standard Protocol Items: Recommendations for Interventional Trials. A randomized, placebo-controlled, double-blind clinical trial will be conducted involving 224 adults (age range 18–60 years) with depression who are taking antidepressants and have no history of vitamin D supplementation, psychiatric comorbidities, chronic kidney disease, hypercalcemia, or neoplasm. The participants will be recruited from the psychiatric outpatient clinics of two universities in northeast Brazil. Eligible participants who provide written consent will be randomly designated to either the intervention group (n = 112; vitamin D supplementation 50,000 IU per week for 6 months) or the control group (n = 112; placebo taken weekly for 6 months). Measures for monitoring depressive symptoms, clinical examinations, and laboratory tests for evaluating cardiovascular risk factors and serum vitamin D levels will be performed before and after the intervention period.

Discussion

To the best of our knowledge, this will be the first clinical trial with the aim of testing the effectiveness of vitamin D supplementation on the reduction of cardiovascular risk and as an adjuvant to depression therapy for a prolonged period (6 months). The findings will contribute to the understanding of the therapeutic effects of vitamin D supplementation in the management of depression and can help guide public policies directed toward vitamin supplementation for the reduction of cardiovascular risk.

Trial registration

Brazilian Clinical Trials Registry, RBR-6yj8sj/Universal Trial Number (UTN) U1111-1217-9237. Registered on 23 July 2018.
Appendix
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Literature
1.
World Health Organization. Depression. Geneva: WHO; 2015.
2.
Parker GB, Brotchie H, Graham RK. Vitamin D and depression. J Affect Disord. 2017;208:56–61.PubMed
3.
4.
Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: a clinical review. Eur Heart J. 2014;351:365–72.
5.
Bertone-Johnson ER. Vitamin D and the occurrence of depression: causal association or circumstantial evidence? Nutr Rev. 2009;67:481–92.PubMedPubMedCentral
6.
Cass WA, Smith MP, Peters LE. Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine. Ann N Y Acad Sci. 2006;1074:261–71.PubMed
7.
Ju S-Y, Lee Y-J, Jeong SN. Serum 25-hydroxyvitamin D levels and the risk of depression: a systematic review and meta-analysis. J Nutr Health Aging. 2013;17:447–55.PubMed
8.
Adamson J, Lally J, Gaughran F, Krivoy A, Allen L, Stubbs B. Correlates of vitamin D in psychotic disorders: a comprehensive systematic review. Psychiatry Res. 2017;249:78–85.PubMed
9.
Fond G, Faugere M, Faget-Agius C, Cermolacce M, Richieri R, Bover L, et al. Hypovitaminosis D is associated with negative symptoms, suicide risk, agoraphobia, impaired functional remission, and antidepressant consumption in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2018. https://​doi.​org/​10.​1007/​s00406-018-0932-0.PubMed
10.
Kocovska E, Gaughran F, Krivoy A, Meier UC. Vitamin-D deficiency as a potential environmental risk factor in multiple sclerosis, schizophrenia, and autism. Front Psychiatry. 2017;8:1–11.
11.
Casseb GAS, Kaster MP, Rodrigues ALS. Potential role of vitamin D for the management of depression and anxiety. CNS Drugs. 2019;33:619–37.PubMed
12.
Schneider B, Weber B, Frensch A, Stein J, Fritz J. Vitamin D in schizophrenia, major depression and alcoholism. J Neural Transm. 2000;107(7):839–42.PubMed
13.
Fond G, Godin O, Schürhoff F, Berna F, Bulzacka E, Andrianarisoa M, et al. Hypovitaminosis D is associated with depression and anxiety in schizophrenia: results from the national FACE-SZ cohort. Psychiatry Res. 2018;270:104–10.PubMed
14.
Kjærgaard M, Joakimsen R, Jorde R. Lowserum 25-hydroxyvitamin D levels are associated with depression in an adult Norwegian population. Psychiatry Res. 2011;190:221–5.PubMed
15.
Stokes CS, Grünhage F, Baus C, Volmer DA, Wagenpfeil S, Riemenschneider M, et al. Vitamin D supplementation reduces depressive symptoms in patients with chronic liver disease. Clin Nutr. 2016;35:950–7.PubMed
16.
Bahrami A, Mazloum SR, Maghsoudi S, Soleimani D, Khayyatzadeh SS, Arekhi S, et al. High dose vitamin D supplementation is associated with a reduction in depression score among adolescent girls: a nine-week follow-up study. J Diet Suppl. 2018;15:173–82.PubMed
17.
Jhee JH, Kim H, Park S, Yun HR, Jung SY, Kee YK, et al. Vitamin D deficiency is significantly associated with depression in patients with chronic kidney disease. PLOS One. 2017;12:e0171009.PubMedPubMedCentral
18.
Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW. Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry. 2008;65:508–12.PubMed
19.
Zhu D, Zhao M, Zhang W, Zhang B, Yang Y, Zhang Y, et al. The relationship between serum concentration of vitamin D, total intracranial volume, and severity of depressive symptoms in patients with major depressive disorder. Front Psychiatry. 2019;10(322):1–7.
20.
Sepehrmanesh Z, Kolahdooz F, Abedi F, Mazroii N, Assarian A, Asemi Z, et al. Vitamin D supplementation affects the beck depression inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: a randomized, controlled clinical trial. J Nutr. 2016;146:243–8.PubMed
21.
Spedding S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients. 2014;6:1501–18.PubMedPubMedCentral
22.
Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, et al. Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosom Med. 2014;76:190–6.PubMedPubMedCentral
23.
Montgomery SA, Asberg M. Anew depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9.PubMed
24.
Organização Mundial da Saúde. CID-10: Classificação Estatística Internacional de Doenças com disquete, vol. 1. São Paulo: EDUSP; 1994.
25.
Dumont CS, Gillette-Guyonnet S, Andrieu C, Cantet PJ, Ousset B, Vellas B. Rapide du Mini Mental State Examination: étude REAL. FR, La Revue de Médecine Interne. 2003;24:345s–50s.PubMed
26.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266–77.PubMedPubMedCentral
27.
Bandeira F, Griz L, Freese E, Lima DC, Thé AC, Diniz ET, et al. Vitamin D deficiency and its relationship with bone mineral density among postmenopausal women living in the tropics. Arq Bras Endocrinol Metab. 2010;54:227–32.
28.
29.
Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10.PubMed
30.
Sepehrmanesh Z, Kolahdooz F, Abedi F, Mazroii N, Assarian A, Asemi Z. Vitamin D supplementation affects the Beck Depression Inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: a randomized, controlled clinical trial. J Nutr. 2016;146:243–8.PubMed
31.
Brazilian Association of Companies in Research. Criterion of economic classification in Brazil. São Paulo: Brazilian Association of Companies in Research; 2015.
32.
33.
Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose – 2017. Arq Bras Cardiol. 2017;109(2Supl.1):1–76.PubMed
34.
Cesar LA, Ferreira JF, Armaganijan D, Gowdak LH, Mansur AP, Bodanese LC, et al. Diretriz de Doença Coronária Estável. Arq Bras Cardiol. 2014;103(2Supl.2):1–59.PubMed
35.
Presti C, Miranda F Jr, Casella IB, De Luccia N, Covre MR. Projeto diretrizes SBACV: Doença arterial periferia obstrutiva de membros inferiores: diagnóstico e tratamento. Recife: Sociedade Brasileira de Angiologia e Cirurgia Vascular; 2015.
36.
37.
William T, Cefalu MD. Standards of medical care in diabetes-2017: American Diabetes Association (ADA). Diabetes Care 2017;40 (Supp 1):S1-S134.
38.
Milech A, Perez Angelucci A, Golbert A, Matheus A, Carrilho Faria AJ, Ramalho AC, et al. Diretrizes da Sociedade Brasileira de Diabetes (2015–2016). São Paulo: A.C. Farmacêutica; 2016.
39.
Maia AL, Scheffel RS, Meyer EL, Mazeto GM, Carvalho GA, Graf H, et al. The Brazilian consensus for the diagnosis and treatment of hyperthyroidism: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism. Arq Bras Endocrinol Metabol. 2013;57:205–24.PubMed
40.
Brenta G, Vaisman M, Sgarbi JA, Bergoglio LM, Andrada NC, Bravo PP, et al. Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metab. 2013;57:265–91.
41.
KDIGO. Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.
42.
Bandeira F, Griz L, Chaves N, Carvalho NC, Borges LM, Lazaretti-Castro M, et al. Diagnosis and management of primary hyperparathyroidism: a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and Metabolism. Arq Bras Endocrinol Metab. 2013;57:406–24.
43.
Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2019:26029. https://​doi.​org/​10.​1016/​j.​jacc.​2019.​03.​010.PubMed
44.
Azevedo TA, Moreira MLV, Nucera ACSN. Cardiovascular risk estimation by the ASCVD Risk Estimator application in a university hospital. Int J Cardiovasc Sci. 2018;31:492–8.
45.
Malachias Bolívar MV, Souza Weimar KSB, Plavnik FL, Rodrigues CIS, Brandão AA, Neves MFT. 7a Diretriz Brasileira de Hipertensão Arterial. Braz J Hipertens. 2017;24:2–91.
46.
Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, Ng CH. Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am J Psychiatry. 2016;173:575–87.PubMed
47.
Holick MF. Vitamin D is not as toxic as was once thought: a historical and an up-to-date perspective. Mayo Clin Proc. 2015;90:561–4.PubMed
48.
Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Metab Syndr Relat Disord. 2017;18:153–65.
49.
Marcinowska-Suchowierska E, Kupisz-Urbańska M, Łukaszkiewicz J, Płudowski P, Jones G. Vitamin D toxicity—a clinical perspective. Front Endocrinol (Lausanne). 2018;9:550.
50.
Tebben PJ, Singh RJ, Kumar R. Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment. Endocr Rev. 2016;37:521–47.PubMedPubMedCentral
51.
OIM (Instituto de Medicina). Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press; 2011. p. 1–1115.
52.
McCullough PJ, Lehrera DS, Amend J. Daily oral dosing of vitamin D3 using 5000 to 50,000 international units a day in long-term hospitalized patients: insights from a seven year experience. J Steroid Biochem Mol Biol. 2019;189:228–39.PubMed
Metadata
Title
Contributions of vitamin D in the management of depressive symptoms and cardiovascular risk factors: study protocol for a randomized, double-blind, placebo-controlled clinical trial
Authors
Catarina Magalhães Porto
Tatiana de Paula Santana da Silva
Everton Botelho Sougey
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-019-3699-3

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