Fibromyalgia (FM) is a neurologic disorder characterized by chronic and widespread pain, anxiety, depression, fatigue, sleep disturbances, and cognitive dysfunction. Treatment may include pain relievers and antidepressants. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) approved for the treatment of FM in North America. Adherence to duloxetine is reported to be poor because of side effects and the intractable nature of FM symptoms. There is a need for safe and effective alternatives for long-term management of FM. Human and animal studies indicate saffron (Crocus sativus, Iridaceae) dried stigmata has antidepressant, antioxidant, and neuroprotective activity and maybe a potential candidate for FM treatment. The purpose of this randomized, double-blind, controlled trial was to compare the effects of saffron and duloxetine on symptoms in patients with FM.
Patients with FM (n = 54, aged 18-60 years) were enrolled at Imam Khomeini Hospital in Tehran, Iran from September 2016 to April 2017. Patients were included if they had a diagnosis of FM using the American College of Rheumatology criteria and had pain scores > 40 out of 100 using a Visual Analog Scale (VAS). Patients were excluded if they were pregnant or breastfeeding, had neuropsychiatric diseases other than depression, had rheumatic diseases other than FM, had pain due to traumatic injuries, had suicidal ideation, had a history of substance abuse, had previous treatment with duloxetine or saffron, were currently taking psychoactive medications, or used muscle relaxants, steroids, benzodiazepines, or opioid analgesics within the past seven days.
Patients were randomly assigned to take one capsule containing 30 mg duloxetine (provided by Sobhan Darou; Tehran, Iran) or one capsule containing 15 mg saffron extract (provided by Impiran – Green Plants of Life Co., Ltd.; Tehran, Iran) daily during the first week. Patients then took two capsules of duloxetine or saffron daily during the second through eighth weeks. The saffron capsules were prepared by ethanolic extraction of 120 g dried stigmata. Each saffron capsule contained 1.65-1.75 mg crocin. Primary outcomes were changes in the Hamilton Rating Scale for Depression score, Fibromyalgia Impact Questionnaire score, and Brief Pain Inventory pain score from baseline to eight weeks. Secondary outcomes were changes in VAS pain score, fatigue assessments, and Hospital Anxiety and Depression scores from baseline to eight weeks. Patients were instructed to avoid taking muscle relaxants, steroids, opioid analgesics, or benzodiazepines during the study. Adverse events (AEs) were assessed using a checklist during study visits.
Baseline demographics were similar between patients in the two groups, except for marital status. Four patients in the saffron group withdrew their consent and left the study for unknown reasons. Four patients in the duloxetine group left the study for unknown reasons (n = 3) or because of ineligibility to continue (n = 1). Mean scores for all outcome scales improved after eight weeks in both the saffron and duloxetine groups (P values not reported). Mean score changes from baseline to eight weeks were not significantly different between groups for any of the scales. Patients reported the following AEs: abdominal pain, nausea, diarrhea, decreased appetite, and headache. There was no significant difference in the number of AEs reported in the saffron and duloxetine groups.
The authors state this trial is the first to evaluate the effectiveness of saffron in patients with FM and the first to compare the effectiveness and safety of saffron with an SNRI. They conclude “This study provided preliminary evidence on the comparative efficacy of saffron and duloxetine in the treatment of FM.” Active constituents in saffron have anti-inflammatory and antioxidant effects in the central nervous system and have been shown to increase levels of the neurotransmitters serotonin, norepinephrine, and dopamine. Benefits of saffron seen in this trial may be due to the cumulative effects of different constituents with different mechanisms of action. The authors discuss limitations in interpreting and generalizing these findings. The trial lacked a placebo arm, and the sample size was not large enough to conduct a non-inferiority analysis. The trial used a fixed dose of saffron for a short period of time, and longer studies are needed to evaluate long-term safety and effectiveness of saffron in people with FM. The authors recommend future trials should evaluate the effects of saffron in different subtypes of FM and measure biochemical markers of FM to better understand saffron’s mechanisms of action.
The authors declare no conflict of interest.
Shakiba M, Moazen-Zadeh E, Noorbala AA, et al. Saffron (Crocus sativus) versus duloxetine for treatment of patients with fibromyalgia: A randomized double-blind clinical trial. Avicenna J Phytomed. November-December 2018;8(6):513-523. doi: 10.22038/AJP.2018.28835.2020.