Saffron May Help SSRI-Related Sexual Dysfunction

Medscape

23-05-2025

LOS ANGELES — Saffron may help treat sexual dysfunction related to selective serotonin reuptake inhibitors (SSRIs), new research suggests.
Results of a preliminary new review found saffron, a spice derived from the flower of Crocus sativus , commonly known as the 'saffron crocus,' reduced erectile dysfunction in men and boosted arousal in women.
Jeremy Wolfe, MD
'Considering our limited toolbox for addressing sexual side effects in patients, it's important to continue assessing and researching potential treatments,' study author Jeremy Wolfe, MD, third-year psychiatry resident, Chicago Medical School, Chicago, told Medscape Medical News .
'A large proportion of patients who experience these side effects will ultimately fail the few adjunctive treatments we have available, and saffron may be an alternative for these patients.'
The findings were presented on May 17 at the American Psychiatry Association (APA) 2025 Annual Meeting.
A Common Problem
Sexual dysfunction is a common side effect of SSRIs, with some 14% of patients self-reporting the condition. However, Wolfe noted this 'sensitive topic' is frequently underreported.
He noted that when patients are directly asked, the proportion of those who report experiencing some form of sexual dysfunction is closer to 58%.
He noted that sexual dysfunction is a significant concern not only with antidepressants but also with many other classes of medications. It is also a common symptom of certain mental health conditions, including depression.
Switching medications might help alleviate the issue, but therapists are often reluctant to make a change if the SSRI is effectively treating the depression, as 'we may not find another one that works,' said Wolfe.
Currently, physicians may attempt to address the sexual dysfunction by lowering the SSRI dose or by prescribing medications such as bupropion, buspirone, or a phosphodiesterase-5 inhibitor like sildenafil (Viagra).
Ancient Treatment
Saffron has been used since ancient times to treat melancholy and insomnia, as well as to enhance sexual well-being. After hearing anecdotal reports that saffron might help with sexual dysfunction in patients with psychiatric disorders, Wolfe decided to explore the research to see what evidence he could find.
After conducting a literature search, Wolfe and his colleagues included five studies in their review, all conducted in Iran between 2009 and 2017. Wolfe noted that Iran is the world's leading exporter of saffron, producing about 90% of the global supply. It has long been used there both in cuisine and for medicinal purposes, he added.
Four of the studies were randomized controlled trials (RCTs), while the fifth was a single-group clinical trial.
The studies investigated saffron capsules, gels, or tablets compared with placebo. Wolfe noted capsules are 'by far' the most common form of saffron, although it's also available in teas, liquid extracts, and powders in addition to tablets and gels.
Three studies focused on men with erectile dysfunction; one enrolled women with sexual dysfunction, and another included both men and women with sexual desire disorder. Participants were matched for depression severity and any concurrent treatments for sexual dysfunction.
A 4-week, double-blind RCT included 30 men with a mean age of 32.5 years, whose depressive symptoms were stabilized on fluoxetine (an SSRI) but who reported sexual dysfunction.
The results showed significantly greater improvement in erectile function among participants taking 5 mg of saffron twice daily compared with those receiving a placebo (mean difference on the International Index of Erectile Function scale, 7.0; 95% CI, 4.2-9.7; P < .001). They also reported higher intercourse satisfaction (mean difference, 2.3; 95% CI, 1.1-3.5; P = .001).
A randomized, double-blind trial involving 34 women stabilized on fluoxetine showed significant improvements by week 4 on the Female Sexual Function Index. Participants taking 30 mg of saffron daily showed greater improvements in arousal (mean difference vs placebo: −0.72; 95% CI, −1.36 to −0.08; P = .028) and lubrication (mean difference, −1.08; 95% CI, −2.02 to −0.08; P = .035) and experienced less pain during intercourse (mean difference, −1.34; 95% CI, −2.42 to −0.26; P = .016).
Since depressive symptoms did not differ significantly between groups, the improvement in sexual function was likely attributable to saffron rather than a reduction in depression, said Wolfe.
Potential Mechanisms
The exact mechanism by which saffron affects sexual dysfunction remains unclear, said Wolfe. It may influence multiple neurotransmitter systems, particularly serotonin, and also appears to have anti-inflammatory, antioxidant, neuroprotective, and hypothalamic–pituitary–adrenal axis-regulating effects. Additionally, it may act on nitric oxide pathways to enhance blood flow.
The frequency of side effects did not differ significantly between the saffron and placebo groups in the studies. However, Wolfe noted that other reports have documented side effects that should be considered before recommending saffron to a patient.
These may include gastrointestinal issues such as nausea, diarrhea, constipation, dizziness, changes in blood pressure, and anxiety. In rare cases, saffron may trigger manic episodes in susceptible individuals or cause allergic reactions. There is also some evidence that saffron may stimulate uterine contractions, posing a potential risk during pregnancy, he added.
'Many of these side effects make sense from the perspective of [saffron's] serotonergic effects,' he said.
Wolfe also cautioned that it is possible to take too much saffron. 'From what I've read, dosages above 5 g are considered unsafe,' he said.
Symptoms of overdose may include vomiting, severe dizziness, jaundice, and serotonin syndrome — a group of symptoms that can include hypertension, accelerated heart rate, and agitation.
'As with other antidepressant medications, use should be monitored, with annual labs at a bare minimum including blood count, electrolytes, liver function, renal function, and thyroid function,' Wolfe noted.
A Possible Solution to a Major Issue
Uma Naidoo, MD, an instructor in the Department of Psychiatry at Harvard Medical School and Director of Nutritional and Lifestyle Psychiatry at Massachusetts General Hospital in Boston, commented on the research for Medscape Medical News . She described the findings as both interesting and promising and said she was pleased to see the APA highlight this work — particularly given that this year's meeting focused on lifestyle approaches to improving mental and physical health.
Research on the topic is needed as SSRI-related sexual dysfunction is 'a massive issue,' said Naidoo. 'The potential impact on libido is a reason many young people don't want to start an SSRI,' she added.
However, Naidoo noted the studies were confined to Iran, and the sample sizes were small, so the generalizability of the results is limited.
She said she would like to see the researchers collaborate with other groups, including academic centers, to conduct larger studies in order to confirm the findings.