Antidepressant Effects of a Persian Medicine Remedy on Multiple Sclerosis Patients: A Double-Blinded Randomized Clinical Trial
DOI:
https://doi.org/10.31661/gmj.v8i.1212Keywords:
Persian Medicine, Multiple Sclerosis, Depression, Herbal Extract, Alternative MedicineAbstract
Background: Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system, is accompanied by some psychiatric disorders, one prominent example of which is depression. The aim of this study was to investigate the effects of a Persian herbal medicine treatment that contains Crocus sativus, Hypericum perforatum, Cinnamon verum, and Vitis vinifera on fatigue and sleep disorders in MS patients. Materials and Methods: A Persian medicine remedy containing C.sativus, H.perforatum, C.verum, and V.vinifera was tested for its ability to improve the symptoms of depression in MS patients. This randomized double-blind clinical study was performed among 52 patients with MS who were allocated to their respective research groups through blocked randomization. The patients were treated for 4 weeks with either the drug or the placebo. To quantify the symptoms of depression, Beck depression inventory (BDI) was used. Results: Forty-six patients completed the study. In the course of the study, as the primary outcome, BDI decreased in the drug group (p=0.000) and the placebo group (p=0.001) significantly, but the rate of change in the drug group was significantly higher than in the placebo group (-13.9 ± 8.6 vs. -3.9 ± 4.3, p=0.000). While analyzing time and treatment effect for BDI, significant decreases in BDI were observed for the drug group, but not in the placebo group (p= 0.001). Conclusion: The present study suggests that Persian medicine remedy treatment in combination with chemical drugs may improve depression symptoms in MS patients. More investigations are needed to discover the exact mechanisms and processes involved. [GMJ.2019;8:e1212]
References
McGuigan C, Hutchinson M. Unrecognised symptoms of depression in a community-based population with multiple sclerosis. J Neurol. 2006;253(2):219-23. https://doi.org/10.1007/s00415-005-0963-0PMid:16177840 Khalili M, Eghtesadi S, Mirshafiey A, Eskandari G, Sanoobar M, Sahraian MA et al. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial. Nutr Neurosci. 2014;17(1):16-20. https://doi.org/10.1179/1476830513Y.0000000060PMid:23485514 Raskind MA. Diagnosis and Treatment of Depression Comorbid with Neurologic Disorders. Am J Med. 2008;121(11):S28-S37. https://doi.org/10.1016/j.amjmed.2008.09.011PMid:18954590 Sanoobar M, Dehghan P, Khalili M, Azimi A, Seifar F. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: a double blind randomized clinical trial. Nutr Neurosci. 2016;19(3):138-43. https://doi.org/10.1179/1476830515Y.0000000002PMid:25603363 Giordano A, Granella F, Lugaresi A, Martinelli V, Trojano M, Confalonieri P et al. Anxiety and depression in multiple sclerosis patients around diagnosis. J Neurol Sci. 2011;307(1):86-91. https://doi.org/10.1016/j.jns.2011.05.008PMid:21621796 Ziemssen T. Multiple sclerosis beyond EDSS: depression and fatigue. J Neurol Sci. 2009;277:S37-S41. https://doi.org/10.1016/S0022-510X(09)70011-5 Thachil AF, Mohan R, Bhugra D. The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007;97(1):23-35. https://doi.org/10.1016/j.jad.2006.06.021PMid:16926053 Dayapoglu N, Tan M. Use of complementary and alternative medicine among people with multiple sclerosis in Eastern Turkey. Neurol Asia. 2016;21(1): 63-71. Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A. Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol. 2011;21(12):841-60. https://doi.org/10.1016/j.euroneuro.2011.04.002PMid:21601431 Akhondzadeh S. Herbal medicines in the treatment of psychiatric and neurological disorders. Low-Cost Approaches to Promote Physical and Mental Health. 2007:119-138. https://doi.org/10.1007/0-387-36899-X_6 Bahmani M, Zargaran A. Ethno-botanical medicines used for urinary stones in the Urmia, Northwest Iran. Eur J Integr Med. 2015;7(6):657-62. https://doi.org/10.1016/j.eujim.2015.09.006 Makhzan-ol-Advieh AM. Storehouse of Medicaments. Intisharat va Amoozesh Enghelab Islami Press, Tehran, Iran. 1992. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):118-127. https://doi.org/10.1016/j.pnpbp.2008.10.018PMid:19028540 Nosratabadi R, Rastin M, Sankian M, Haghmorad D, Tabasi N, Zamani S et al. St. John's wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells. J Immunotoxicol. 2016;13(3):364-374. https://doi.org/10.3109/1547691X.2015.1101512PMid:26634391 Sohrabi R, Pazgoohan N, Seresht HR, Amin B. Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and antidepressant activities in mice. Iran J Basic Med Sci. 2017;20(6):708-714. Frydman-Marom A, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S et al. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models. PLoS One. 2011;6(1):e16564. https://doi.org/10.1371/journal.pone.0016564PMid:21305046 PMCid:PMC3030596 Waggas AM. Grape seed extract (Vitisvinifera) alleviate neurotoxicity and hepatotoxicity induced by lead acetate in male albino rats. J Behav Brain Sci. 2012;2(02):176-184. https://doi.org/10.4236/jbbs.2012.22021 Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M et al. Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol. 2012;3. https://doi.org/10.3389/fneur.2012.00084PMid:22654783 PMCid:PMC3359579 Basti AA, Moshiri E, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2):439-442. https://doi.org/10.1016/j.pnpbp.2006.11.010PMid:17174460 Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi A-H, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med. 2004;4(1):12. https://doi.org/10.1186/1472-6882-4-12PMid:15341662 PMCid:PMC517724 McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127. https://doi.org/10.1002/ana.1032PMid:11456302 Moran PJ, Mohr DC. The validity of Beck Depression Inventory and Hamilton Rating Scale for Depression items in the assessment of depression among patients with multiple sclerosis. J Behav Med. 2005;28(1):35-41. https://doi.org/10.1007/s10865-005-2561-0PMid:15887874 Amin KA, Nagy MA. Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats. Diabetol Metab Syndr. 2009;1(1):17. https://doi.org/10.1186/1758-5996-1-17PMid:19835614 PMCid:PMC2772188 Moshiri E, Basti AA, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Crocus sativus L.(petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomedicine. 2006;13(9):607-611. https://doi.org/10.1016/j.phymed.2006.08.006PMid:16979327 Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. Bmj. 2000;321(7260):536-539. https://doi.org/10.1136/bmj.321.7260.536PMid:10968813 PMCid:PMC27467 Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. Bmj. 2005;330(7490):503. https://doi.org/10.1136/bmj.38356.655266.82PMid:15708844 PMCid:PMC552808 Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002;159(8):1361-6. https://doi.org/10.1176/appi.ajp.159.8.1361PMid:12153829 Yoshitake T, Iizuka R, Yoshitake S, Weikop P, Müller WE, Ögren SO et al. Hypericum perforatum L (St John's wort) preferentially increases extracellular dopamine levels in the rat prefrontal cortex. Br J Pharmacol. 2004;142(3):414-418. https://doi.org/10.1038/sj.bjp.0705822PMid:15148244 PMCid:PMC1574978 Butterweck V. Mechanism of action of St John's wort in depression. CNS Drugs. 2003;17(8):539-62. https://doi.org/10.2165/00023210-200317080-00001PMid:12775192 Chang Y, Wang S-J. Hypericin, the active component of St. John's wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitogen-activated protein kinase-dependent pathway. Eur J Pharmacol. 2010;634(1):53-61. https://doi.org/10.1016/j.ejphar.2010.02.035PMid:20193678 Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):676-692. https://doi.org/10.1016/j.pnpbp.2010.05.004PMid:20471444 Roussel A-M, Hininger I, Benaraba R, Ziegenfuss TN, Anderson RA. Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese. J Am Coll Nutr. 2009;28(1):16-21. https://doi.org/10.1080/07315724.2009.10719756PMid:19571155 Moselhy SS, Ali HK. Hepatoprotective effect of cinnamon extracts against carbon tetrachloride induced oxidative stress and liver injury in rats. Biol Res. 2009;42(1):93-98. https://doi.org/10.4067/S0716-97602009000100009PMid:19621136 Jana A, Modi KK, Roy A, Anderson JA, Van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol. 2013;8(3):739-755. https://doi.org/10.1007/s11481-013-9447-7PMid:23475543 PMCid:PMC3663914 Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry J-M. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002;109(2):143-8. https://doi.org/10.1016/S0165-1781(02)00005-7 Hurley LL, Akinfiresoye L, Kalejaiye O, Tizabi Y. Antidepressant effects of resveratrol in an animal model of depression. Behav Brain Res. 2014;268:1-7. https://doi.org/10.1016/j.bbr.2014.03.052PMid:24717328 PMCid:PMC4033784 Pang C, Cao L, Wu F, Wang L, Wang G, Yu Y et al. The effect of trans-resveratrol on post-stroke depression via regulation of hypothalamus-pituitary-adrenal axis. Neuropharmacology. 2015;97:447-56. https://doi.org/10.1016/j.neuropharm.2015.04.017PMid:25937213 Ahmed RF, Abdel-Rahman RF, Farid OA, El-Marasy SA, Hessin AF. Combined hepatoprotective and antidepressant effects of resveratrol in an acute model of depression. Bulletin of Faculty of Pharmacy, Cairo University. 2014;52(2):191-197. https://doi.org/10.1016/j.bfopcu.2014.06.002 Xu Y, Li S, Chen R, Li G, Barish PA, You W et al. Antidepressant-like effect of low molecular proanthocyanidin in mice: Involvement of monoaminergic system. Pharmacol Biochem Behav. 2010;94(3):447-453. https://doi.org/10.1016/j.pbb.2009.10.007PMid:19857512 Lee G, Bae H. Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression. Biomed Res Int. 2017;2017. https://doi.org/10.1155/2017/6596241PMid:28503571 PMCid:PMC5414506 Ge J-F, Peng L, Cheng J-Q, Pan C-X, Tang J, Chen F-H et al. Antidepressant-like effect of resveratrol: involvement of antioxidant effect and peripheral regulation on HPA axis. Pharmacol Biochem Behav. 2013;114:64-69. https://doi.org/10.1016/j.pbb.2013.10.028PMid:24201049 Richard T, Pawlus AD, Iglésias ML, Pedrot E, Waffoâ€Teguo P, Mérillon JM et al. Neuroprotective properties of resveratrol and derivatives. Ann N Y Acad Sci. 2011;1215(1):103-108. https://doi.org/10.1111/j.1749-6632.2010.05865.xPMid:21261647 Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med. 2013;11(6):377-383. https://doi.org/10.3736/jintegrmed2013056PMid:24299602 PMCid:PMC4643654 Christodoulou E, Kadoglou NP, Kostomitsopoulos N, Valsami G. Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol. 2015;67(12):1634-1649. https://doi.org/10.1111/jphp.12456PMid:26272123 Ghazavi A, Mosayebi G, Salehi H, Abtahi H. Effect of ethanol extract of saffron (Crocus sativus L.) on the inhibition of experimental autoimmune encephalomyelitis in C57bl/6 mice. Pak J Biol Sci. 2009;12(9):690-695. https://doi.org/10.3923/pjbs.2009.690.695PMid:19634472 Nam KN, Park Y-M, Jung H-J, Lee JY, Min BD, Park S-U et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol. 2010;648(1):110-116. https://doi.org/10.1016/j.ejphar.2010.09.003PMid:20854811
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