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Journal of Chinese Integrative Medicine ›› 2013, Vol. 11 ›› Issue (6): 377-383.doi: 10.3736/jintegrmed2013056

• Meta-analysis • Previous Articles     Next Articles

Saffron (Crocus sativus L.) and major depressive disorder: A meta-analysis of randomized clinical trials

Heather Ann Hausenblasa(), Debbie Sahab, Pamela Jean Dubyakb, Stephen Douglas Antonb   

  1. a. Department of Sport and Exercise Sciences, Jacksonville University, Jacksonville, Florida 32211, USA
    b. Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida 32611, USA
  • Received:2013-05-28 Accepted:2013-10-15 Online:2013-11-10 Published:2013-11-15

Background

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted.


Objective

The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD.


Search strategy

We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies.


Inclusion criteria

The criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or antidepressant comparison group.


Data extraction and analysis

Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data.


Results

Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001), revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups (M ES = -0.15) indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials.


Conclusion

Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron’s efficacy and safety for treating depressive symptoms.

Key words: Crocus, Depressive disorder, Dietary supplements, Mood disorders, Quality of life, Medicine, Herbal, Meta-analysis

Figure 1

Flow diagram for study selectionTable 1 Summary of clinical trials examining effects of saffron supplementation on patients with major depression"

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[1] Hirschfeld R . Depression epidemiology and its treatment evolution[J]. J Clin Psychiatry, 2012,73(10):e29
doi: 10.4088/JCP.11096tx3c
[2] Maj M . Development and validation of the current concept of major depression[J]. Psychopathology, 2012,45(3):135-146
doi: 10.1159/000329100
[3] Maj M . Validity and clinical utility of the current operational characterization of major depression[J]. Int Rev Psychiatry, 2012,24(6):530-537
doi: 10.3109/09540261.2012.712952
[4] González HM, Tarraf W . Comorbid cardiovascular disease and major depression among ethnic and racial groups in the United States[J]. Int Psychogeriatr, 2013,25(5):833-841
doi: 10.1017/S1041610212002062
[5] Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication.The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication(NCS-R)[J]. JAMA, 2003,289(23):3095-3105
doi: 10.1001/jama.289.23.3095
[6] Olfson M, Marcus SC, Druss B, Elinson L, Tanielian T, Pincus HA . National trends in the outpatient treatment of depression[J]. JAMA, 2002,287(2):203-209
doi: 10.1001/jama.287.2.203
[7] Williams JW Jr, Rost K, Dietrich AJ, Ciotti MC, Zyzanski SJ, Cornell J . Primary care physicians’ approach to depressive disorders. Effects of physician specialty and practice structure[J]. Arch Fam Med, 1999,8(1):58-67
doi: 10.1001/archfami.8.1.58
[8] Ferguson JM . SSRI antidepressant medications: adverse effects and tolerability[J]. Prim Care Companion J Clin Psychiatry, 2001,3(1):22-27
doi: 10.4088/PCC.v03n0105
[9] Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A . Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence[J]. Eur Neuropsychopharmacol, 2011,21(12):841-860
doi: 10.1016/j.euroneuro.2011.04.002
[10] Dwyer AV, Whitten DL, Hawrelak JA . Herbal medicines, other than St. John’s Wort, in the treatment of depression: a systematic review[J]. Altern Med Rev, 2011,16(1):40-49
[11] Georgiadou G, Tarantilis PA, Pitsikas N . Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder[J]. Neurosci Lett, 2012,528(1):27-30
doi: 10.1016/j.neulet.2012.08.081
[12] Wang Y, Han T, Zhu Y, Zheng CJ, Ming QL, Rahman K, Qin LP . Antidepressant properties of bioactive fractions from the extract of Crocus sativus L[J]. J Nat Med, 2010,64(1):24-30
doi: 10.1007/s11418-009-0360-6
[13] Kamalipour M, Jamshidi AH, Akhondzadeh S . Antidepressant effect of Crocus sativus: An evidence based review[J]. J Med Plants, 2010,9(6):35-38
[14] Modabbernia A, Akhondzadeh S . Saffron, passionflower, valerian and sage for mental health[J]. Psychiatr Clin North Am, 2013,36(1):85-91
doi: 10.1016/j.psc.2012.12.007
[15] Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement[J]. Ann Intern Med, 2009,151(4):264-269, W64
doi: 10.7326/0003-4819-151-4-200908180-00135
[16] Conn VS, Valentine JC, Cooper HM, Rantz MJ . Grey literature in meta-analyses[J]. Nurs Res, 2003,52(4):256-261
doi: 10.1097/00006199-200307000-00008
[17] Ulbricht C, Conquer J, Costa D, Hollands W, Iannuzzi C, Isaac R, Jordan JK, Ledesma N, Ostroff C, Serrano JM, Shaffer MD, Varghese M . An evidence-based systematic review of saffron(Crocus sativus) by the Natural Standard Research Collaboration[J]. J Diet Suppl, 2011,8(1):58-114
doi: 10.3109/19390211.2011.547666
[18] Akhondzadeh Basti A, Ghoreishi 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]. J Med Plants, 2008,7(4):29-36
[19] 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[J]. Phytother Res, 2005,19(2):148-151
doi: 10.1002/(ISSN)1099-1573
[20] Akhondzadeh Basti A, 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[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2007,31(2):439-442
doi: 10.1016/j.pnpbp.2006.11.010
[21] 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[J]. Phytomedicine, 2006,13(9-10):607-611
doi: 10.1016/j.phymed.2006.08.006
[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]. J Ethnopharmacol, 2005,97(2):281-284
doi: 10.1016/j.jep.2004.11.004
[23] 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][J]. BMC Complement Altern Med, 2004,4:12
doi: 10.1186/1472-6882-4-12
[24] Morris S . Estimating effect sizes from pretest-posttest-control group designs[J]. Organ Res Methods, 2008,11(2):364-386
doi: 10.1177/1094428106291059
[25] Hedges L, Olkin I, Statistiker M. Statistical methods for meta-analysis. New York: Academic Press. 1985.
[26] Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D , G?tzsche PC, Lang T; CONSORT GROUP (Consolidated Standards of Reporting Trials).The revised CONSORT statement for reporting randomized trials: explanation and elaboration[J]. Ann Intern Med, 2001,134(8):663-694
doi: 10.7326/0003-4819-134-8-200104170-00012
[27] Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ , McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996; 17(1):1-12.
doi: 10.1016/0197-2456(95)00134-4
[28] Berger F, Hensel A, Nieber K . Saffron extract and trans-crocetin inhibit glutamatergic synaptic transmission in rat cortical brain slices[J]. Neuroscience, 2011,180:238-247
doi: 10.1016/j.neuroscience.2011.02.037
[29] Agha-Hosseini M, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, Akhondzadeh S . Crocus sativus L.(saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial[J]. BJOG, 2008,115(4):515-519
doi: 10.1111/bjo.2008.115.issue-4
[30] Joshi JV, Pandey SN, Galvankar P, Gogate JA . Prevalence of premenstrual symptoms: Preliminary analysis and brief review of management strategies[J]. J Midlife Health, 2010,1(1):30-34
[31] Tschudin S, Bertea PC, Zemp E . Prevalence and predictors of premenstrual syndrome and premenstrual dysphoric disorder in a population-based sample[J]. Arch Womens Ment Health, 2010,13(6):485-494
doi: 10.1007/s00737-010-0165-3
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