Planta Med 2019; 85(01): 24-31
DOI: 10.1055/a-0660-9565
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis

Barbara Tóth
1   Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
2   Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, Hungary
,
Péter Hegyi
3   Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
,
Tamás Lantos
4   Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, Szeged, Hungary
,
Zsolt Szakács
3   Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
,
Beáta Kerémi
5   Department of Oral Biology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
,
Gábor Varga
5   Department of Oral Biology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
,
Judit Tenk
3   Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
,
Erika Pétervári
3   Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
,
Márta Balaskó
3   Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
,
Zoltán Rumbus
3   Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
,
Zoltán Rakonczay
6   Department of Pathophysiology, University of Szeged, Szeged, Hungary
,
Emese Réka Bálint
6   Department of Pathophysiology, University of Szeged, Szeged, Hungary
,
Tivadar Kiss
1   Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
2   Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, Hungary
,
Dezső Csupor
1   Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
2   Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, Hungary
› Author Affiliations
Further Information

Publication History

received 18 May 2018
revised 02 July 2018

accepted 13 July 2018

Publication Date:
23 July 2018 (online)

Abstract

Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedgesʼ g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochranʼs Q test and calculating Higginsʼ I2 indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 – 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = − 0.246; 95% CI: − 0.495 – 0.004, p = 0.053).

Supporting Information

 
  • References

  • 1 Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO. Available at: http://www.who.int/mental_health/management/depression/prevalence_global_health_estimates/en/ Accessed July 3, 2018
  • 2 Arroll B, Elley CR, Fishman T, Goodyear-Smith FA, Kenealy T, Blashki G, Kerse N, Macgillivray S. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev 2009; (03) CD007954
  • 3 Magni LR, Purgato M, Gastaldon C, Papola D, Furukawa TA, Cipriani A, Barbui C. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev 2013; (17) CD004185
  • 4 Yeung KS, Hernandez M, Mao JJ, Haviland I, Gubili J. Herbal medicine for depression and anxiety: A systematic review with assessment of potential psycho-oncologic relevance. Phytother Res 2018; 32: 865-891
  • 5 Javadi B, Sahebkar A, Emami SA. A survey on saffron in major islamic traditional medicine books. Iran J Basic Med Sci 2013; 16: 1-11
  • 6 Bukhari SI, Manzoor M, Dhar MK. A comprehensive review of the pharmacological potential of Crocus sativus and its bioactive apocarotenoids. Biomed Pharmacother 2018; 98: 733-745
  • 7 Shafiee M, Arekhi S, Omranzadeh A, Sahebkar A. Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. J Affect Disord 2018; 227: 330-337
  • 8 Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk M. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry 2016; 77: e457-e466
  • 9 Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc 2017; 18: 503-508
  • 10 Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology 2015; 51: 164-175
  • 11 Liu T, Zhong S, Liao X, Chen J, He T, Lai S, Jia Y. A meta-analysis of oxidative stress markers in depression. PLoS One 2015; 10: e0138904
  • 12 Moosavi SM, Ahmadi M, Amini M, Vazirzadeh B. The effects of 40 and 80 mg hydro- alcoholic extract of Crocus sativus in the treatment of mild to moderate depression. J Mazandaran Univ Med Sci 2014; 24: 47-53
  • 13 Akhondzadeh Basti A, Choreishi SA, Noorbala AA, Akhondzadeh SH, Rezazadeh SH. Petal and stigma of Crocus sativus L. in the treatment of depression: a pilot double – blind randomized trial. J Med Plants Res 2008; 7: 29-36
  • 14 Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord 2017; 207: 188-196
  • 15 Cicero AF, Bove M, Colletti A, Rizzo M, Fogacci F, Giovannini M, Borghi C. Short-term impact of a combined nutraceutical on cognitive function, perceived stress and depression in young elderly with cognitive impairment: A pilot, double-blind, randomized clinical trial. J Prev Alzheimers Dis 2017; 4: 12-15
  • 16 Jelodar G, Javid Z, Sahraian A, Jelodar S. Saffron improved depression and reduced homocysteine level in patients with major depression: A randomized, double-blind study. Avicenna J Phytomed 2018; 8: 43-50
  • 17 Sahraian A, Jelodar S, Javid Z, Mowla A, Ahmadzadeh L. Study the effects of saffron on depression and lipid profiles: A double blind comparative study. Asian J Psychiatr 2016; 22: 174-176
  • 18 Jam IN, Sahebkar AH, Eslami S, Mokhber N, Nosrati M, Khademi M, Foroutan-Tanha M, Ghayour-Mobarhan M, Hadizadeh F, Ferns G, Abbasi M. The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Adv Clini Exp Med 2017; 26: 925-930
  • 19 Talaei A, Hassanpour Moghadam M, Sajadi Tabassi SA, Mohajeri SA. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord 2015; 174: 51-56
  • 20 Moazen-Zadeh E, Abbasi SH, Safi-Aghdam H, Shahmansouri N, Arjmandi-Beglar A, Hajhosseinn Talasaz A, Salehiomran A, Forghani S, Akhondzadeh S. Effects of saffron on cognition, anxiety, and depression in patients undergoing coronary artery bypass grafting: a randomized double-blind placebo-controlled trial. J Altern Complement Med 2018; 24: 361-368
  • 21 Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH, Khani M. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res 2005; 19: 148-151
  • 22 Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol 2005; 97: 281-284
  • 23 Kashani L, Esalatmanesh S, Eftekhari F, Salimi S, Foroughifar T, Etesam F, Safiaghdam H, Moazen-Zadeh E, Akhondzadeh S. Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial. Arch Gynecol Obstet 2018; 297: 717-724
  • 24 Abedimanesh N, Ostadrahimi A, Bathaie SZ, Abedimanesh S, Motlagh B, Jafarabadi MA, Sadeghi MT. Effects of saffron aqueous extract and its main constituent, crocin, on health-related quality of life, depression, and sexual desire in coronary artery disease patients: A double-blind, placebo-controlled, randomized clinical trial. Iranian Red Crescent Med J 2017; 19: e13676
  • 25 Tabeshpour J, Sobhani F, Sadjadi SA, Hosseinzadeh H, Mohajeri SA, Rajabi O, Taherzadeh Z, Eslami S. A double-blind, randomized, placebo-controlled trial of saffron stigma (Crocus sativus L.) in mothers suffering from mild-to-moderate postpartum depression. Phytomedicine 2017; 36: 145-152
  • 26 Ghajar A, Neishabouri SM, Velayati N, Jahangard L, Matinnia N, Haghighi M, Ghaleiha A, Afarideh M, Salimi S, Meysamie A, Akhondzadeh S. Crocus sativus L. versus citalopram in the treatment of major depressive disorder with anxious distress: a double-blind, controlled clinical trial. Pharmacopsychiatry 2017; 50: 152-160
  • 27 Kashani L, Eslatmanesh S, Saedi N, Niroomand N, Ebrahimi M, Hosseinian M, Foroughifar T, Salimi S, Akhondzadeh S. Comparison of saffron versus fluoxetine in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial. Pharmacopsychiatry 2017; 50: 64-68
  • 28 Mazidi M, Shemshian M, Mousavi SH, Norouzy A, Kermani T, Moghiman T, Sadeghi A, Mokhber N, Ghayour-Mobarhan M, Ferns GAA. A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. J Complement Integr Med 2016; 13: 195-199
  • 29 Shahmansouri N, Farokhnia M, Abbasi SH, Kassaian SE, Noorbala Tafti AA, Gougol A, Yekehtaz H, Forghani S, Mahmoodian M, Saroukhani S, Arjmandi-Beglar A, Akhondzadeh S. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affect Disord 2014; 155: 216-222
  • 30 Basti AA, Moshiri E, Noorbala AA, Jamshidi AH, 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: 439-442
  • 31 Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, 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: 607-611
  • 32 Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, 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: 12
  • 33 Khanali M, Shahvarooghi Farahani S, Shojaei H, Elhami B. Life cycle environmental impacts of saffron production in Iran. Environ Sci Pollut Res Int 2017; 24: 4812-4821
  • 34 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: 377-383
  • 35 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56-62
  • 36 Beck AT, Steer RA. Beck Depression inventory Manual. New York: Guildford Press; 1993
  • 37 Beck AT, Steer RA, Brown GK. Manual for the Beck Depression Inventory-II. San Antonio: Psychological Corporation; 1996
  • 38 Schmidt M, Betti G, Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 2007; 157: 315-319
  • 39 Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M, Hosseinzadeh H. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother Res 2014; 28: 539-543
  • 40 Wüthrich B, Schmid-Grendelmeyer P, Lundberg M. Anaphylaxis to saffron. Allergy 1997; 52: 476-477
  • 41 Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097
  • 42 Higgins JPT, Green S. eds. Cochrane handbook for systematic reviews of interventions, version 5.1.0. The Cochrane Collaboration. Available at: http://www.handbook.cochrane.org Accessed February 26, 2018
  • 43 Hedges L. Distribution theory for Glassʼs estimator of effect size and related estimators. J Educ Behav Stat 1981; 6: 107-128
  • 44 Cochran WG. The combination of estimates from different experiments. Biometrics 1954; 10: 101-129
  • 45 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
  • 46 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719-748
  • 47 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188