Kazemi F, Vosough I, Sepahi S, Mohajeri SA. Effect of crocin versus fluoxetine in treatment of mild to moderate obsessive-compulsive disorder: A double blind randomized clinical trial. Hum Psychopharmacol. February 2021;36(4):e2780. doi:10.1002/hup.2780.
Obsessive compulsive disorder (OCD) is a condition defined by recurrent, intrusive, and unwanted thoughts and repetitive behaviors. It is a chronic and heterogeneous disorder that affects 1-2% of the general population and 1-3% of adolescents. The first-line medication treatment is serotonin reuptake inhibitors; however, this treatment is not effective in all patients or only lasts a short time. Saffron (Crocus sativus, Iridaceae) stigmas have traditionally been used as an antispasmodic, anti-catarrhal, nerve sedative, eupeptic, expectorant, and emmenagogue. Pharmacological research on saffron has shown it to have positive effects as an antidepressant, antitumor, anticonvulsant, anti-inflammatory, and radical scavenger. It has been shown to improve memory and learning effects. This is thought to be because of crocin, a water-soluble carotenoid pigment, which has demonstrated anti-cancer, anti-inflammatory, antioxidant, cardioprotective, neuroprotective, and antidepressant effects. The authors proposed an eight-week double-blind randomized clinical trial to evaluate the efficacy of crocin on patients with mild-to-moderate OCD compared to fluoxetine.
This study took place between July 2018 and September 2019 at Dr. Vosough’s Clinic of Psychiatric Disorders in Mashhad, Iran. The inclusion criteria included patients aged 18- 60 years with diagnosed OCD according to the Diagnostic and Statistical Manual of Mental Disorders criteria. Patients had a score of 12 to 25 in the Yale-Brown obsessive-compulsive scale (Y-BOCS) and did not receive any psychiatric medication during the six weeks prior to the trial. Exclusion criteria included individuals with any other psychiatric disorder, substance, or alcohol addiction, and those sensitive to medications. Individuals who were breast feeding, pregnant, or had any important medical illness that could prevent the patient from finishing the trial were also excluded.
Saffron stigmas were obtained from the Saharkhiz Saffron Company (Mashhad, Iran) and extracted using method of Hadizadeh F & Seifi, 2010. Crystalization and extraction was done at Bu-ali (Avicenna) Research Institute (Mashhad University of Medical Sciences; Mashhad, Iran). The resulting extract contained over 90% crocin. The Industrial Pharmacy Lab (Faculty of Pharmacy, Mashhad University of Medical Sciences; Mashhad, Iran) prepared 15 mg capsules of crocin powder with Avicel (microcrystalline cellulose) powder as a filler. The 20 mg fluoxetine capsule was similar in shape and size. Both groups received one capsule daily for the first four weeks of the study, then were instructed to increase to twice daily during the remaining four weeks. It was not stated if the capsule was ingested in the morning or evening during the first four weeks. Patients were not to take any other psychiatric medication or behavioral therapy during the trial.
OCD symptoms were assessed using the Y-BOCS and Hamilton scale of anxiety (HAM-A) at baseline, week 4, and week 8. Patients were telephoned weekly to assess illnesses, adverse effects, and compliance.
Of the 58 patients included, eight discontinued the study. The flow diagram states that five individuals discontinued treatment in the crocin group due to adverse effects (n =2), sensitivity to the medication (n=1), and one withdrew consent. In the fluoxetine group, three discontinued treatment due to adverse effects, and two withdrew consent. Note: there was a discrepancy between the information written in the text and the information contained in the flow chart; yet, 25 in each group completed the study. The mean age of the crocin group was 32.84 ± 8.56 with 76% women and 27.84 ± 7.1 in the fluoxetine group with 80% women.
Both the crocin group and fluoxetine group saw a significant improvement for Y-BOCS score between baseline and week 4 (P = 0.001 for both) and between baseline and week 8 (P = 0.0001 for both). For HAM-A, the fluoxetine group saw a significant improvement between baseline and week 4 (P = 0.01) and between baseline and week 8 (P = 0.008). For the crocin group, there was improvement in HAM-A between baseline and week 4 (P = 0.163) and between baseline and week 8 (P = 0.01). There was no significant difference between the crocin and fluoxetine groups at week 8 for Y-BOCS and HAM-A scores. The number of patients with moderate OCD in the crocin group decreased from 52% to 12% at week 8.
There were 16 reported adverse events in the fluoxetine group and seven in the crocin group. The fluoxetine group reported gastrointestinal problems (n = 5), drowsiness (n = 7), change in weight (n = 2), chest pain (n = 1), and dry mouth (n = 1). The crocin group reported sweating (n = 2), menorrhagia (n = 3), allergy (n = 1), and hair loss (n = 1).
The authors conclude crocin is effective in treating OCD with fewer observed side effects. Study limitations include small experimental size, OCD heterogeneity, reliance on self-report assessments, treatment compliance issues, short study timeframe, and lack of a placebo group. Further research on the mechanism of action and a larger trial with a placebo group should be conducted. SAM is involved with producing crocin for the pharmaceutical industry; all other authors state no conflict of interest.