July 1, 2015

Crocin and Major Depressive Disorder

Using an herbal medicine to augment antidepressant medication
In this randomized, double-blind, placebo-controlled pilot study, researchers found that adding crocin (a constituent of saffron) to a patient’s selective serotonin reuptake inhibitor dosage led to greatly improved scores on several depression indices.


Talaei A, Moghadam MH, 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. 


Randomized, double-blind, placebo-controlled pilot study  


Participants were 40 patients diagnosed with major depressive disorder between the ages of 24 and 50 years (mean: 36.2 y) at a psychiatric hospital in Mashhad, Iran. There were 34 female participants and 6 male participants. Exclusion criteria included use of psychotropic medications in previous months; current or past mood, neurological, cognitive, or psychotic disorder; a history of substance abuse or dependence; or having a risk of suicide. 

Study Intervention

Twenty patients were given 1 selective serotonin reuptake inhibitor (SSRI) plus crocin in 15 mg tablets twice daily for 4 weeks. SSRIs were fluoxetine (Prozac, 20 mg per day), sertraline (Zoloft, 50 mg per day), or citalopram (Celexa, 20 mg per day). Patients in the placebo group were also given 1 SSRI plus 1 placebo tablet twice daily for 4 weeks. The crocin and placebo tablets were the same shape and color. Participants did not receive any other antidepressant medications or behavioral therapy throughout the trial.

Primary Outcome Measures

All participants completed the Beck Depression Inventory (BDI), General Health Questionnaire (GHQ), Beck Anxiety Inventory (BAI), and Mood Disorder Questionnaire (MDQ) at baseline and at the end of the 4-week trial. 

Key Findings

The coadministration of crocin tablets and SSRIs improved scores in all inventories compared to inventory scores of patients taking SSRIs alone. BDI scores dropped by 42.2% in the SSRI-plus-crocin group and 15.9% in the SSRI-plus-placebo group. BAI scores dropped by 33% in the intervention group and 7.5% in the placebo group. GHQ scores dropped by 21.5% in the SSRI-plus-crocin group and 12.3% in the SSRI-plus-placebo group. No serious adverse effects were reported during the trial. 

Practice Implications

Depression is one of the top 5 most prevalent chronic, debilitating diseases worldwide1 and is commonly treated in the primary care office. Patients with depression present with depressed mood, anhedonia, fatigue, social withdrawal, change in appetite and sleep, and lowered libido.2 Depression is thought to be the result of biochemical imbalances in the brain and is thus treated with pharmacological therapies that increase and regulate neurotransmitters (eg, SSRIs, tricyclic antidepressants, monoamine oxidase inhibitors).3 Not all patients respond favorably to these medications, and some patients may experience a wide range of side effects, including but not limited to sexual dysfunction, weight gain, arrhythmias, and nausea. In addition to side effects, antidepressant medications do not improve mood at all in some patients, and these patients may seek care from naturopathic physicians, who can prescribe either antidepressants or natural medicines to normalize neurotransmitter levels and improve mood. 
This study demonstrates that crocin tablets given with selective serotonin reuptake inhibitors (SSRI) lead to a greater improvement in symptoms of depression and anxiety when compared to SSRIs alone.
One such natural medicine is saffron (known by its Latin name as Crocus sativus). Saffron is a beautiful and aromatic plant in the Iridaceae family and consists of compounds like safranal, picrocrocin, and crocin. Saffron and particularly its constituent crocin have been shown to affect dopamine, norepinephrine, and serotonin levels in the brain.4,5 This study demonstrates that crocin tablets given with SSRIs lead to a greater improvement in symptoms of depression and anxiety when compared to SSRIs alone and supports the use of the oral administration of crocin tablets in conjunction with SSRIs to treat mild-to-moderate depression, as well as anxiety. Based on previous studies on the antioxidant effects of crocin,6 the authors of the present study infer that crocin’s role in improving depressive and anxiety symptoms arises from its ability to improve oxidative stress in the brain.
While the study demonstrated that crocin may be a beneficial adjunct treatment for depression and anxiety, there were some limitations in the study, including a short trial period, small sample size, and the use of self-reported assessments. Further long-term clinical studies on the effects of crocin on mood disorders and research to elucidate its mechanism of action would be beneficial. Given that there are no adverse reactions associated with its use, naturopathic physicians treating patients for depression and anxiety can consider the use of crocin to augment the therapeutic effects of antidepressants. 

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  1. Bauer M, Dell’osso L, Kasper S, et al. Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder. J Affect Disord. 2013;151(1):209-219.
  2. Kircanski K, Joormann J, Gotlib IH. Cognitive aspects of depression. Wiley Interdiscip Rev Cogn Sci. 2012;3(3):301-313.
  3. Hermann DM, Mies G, Hossmann KA. Biochemical changes and gene expression following traumatic brain injury: role of spreading depression. Restor Neurol Neurosci. 1999;14(2-3):103-108.
  4. Hosseinzadeh H, Motamedshariaty V, Hadizadeh F. Antidepressant effect of kaempferol, a constituent of saffron (Crocus sativus) petal, in mice and rats. Pharmacologyonline. 2007;2:367-370.
  5. Zhang Y, Shoyama Y, Sugiura M, Saito H. Effects of Crocus sativus L. on the ethanolinduced impairment of passive avoidanceperformances in mice. Biol Pharm Bull. 1994;17(2):217-21.
  6. Gautam M, Agrawal M, Gautam M, Sharma P, Gautam AS, Gautam S. Role of antioxidants in generalised anxiety disorder and depression. Indian J Psychiatry. 2012;54(3):244-247.