Can Antihistamines Treat PMDD?

Can over-the-counter antihistamines like Benadryl and Pepcid help with menstrual symptoms or premenstrual dysphoric disorder (PMDD)? For many women with this debilitating condition, the answer appears to be yes — and many are posting their treatment success stories on social media.

In the TikTok video “Zyrtec for PMDD changed my life,” the nutrition influencer Lauren Cadillac (@feelgooddietitian) says, “I don’t feel like I can put into words how much Zyrtec changed my life.”

According to Cadillac, the OTC antihistamine helped her feel more like herself again. It gave her relief from severe PMDD symptoms that were causing major friction with her partner and making her feel like a bad mom.

Doctors and pharmacists are also posting videos on the trend and offering their own theories on why antihistamines may work for PMDD.

But trying to find research or guidance about using antihistamines for PMDD is nearly impossible — because such research and guidelines simply don’t exist today — leaving many women to try to piece together a DIY treatment program that may not be effective or safe.

Wondering what to make of these claims about PMDD and antihistamines? Here’s what a women's health naturopathic doctor and two academic health center medical experts had to say about using the over-the-counter drugs to treat PMDD, as well as a rundown of the most effective evidence-based treatments.

Antihistamines block the action of histamine, the chemical best known for its role in allergies.

As a stimulating neurotransmitter that affects the brain, histamine goes up and down with the menstrual cycle because it’s influenced by estrogen and progesterone, says Lara Briden, a naturopathic medicine practitioner and author of many books from Queensland, New Zealand.

”Signs of high histamine share many of the same classic symptoms with PMS,” she says.

Premenstrual syndrome (PMS) symptoms start during the week before your period and end within a few days after it starts, and can include mood swings, fatigue, irritability, and depression.

“Antihistamines may help with PMDD symptoms such as anxiety, irritability, and insomnia,” says Briden.

Importantly, antihistamines are not likely to work for all women with PMDD because there’s no single biological mechanism behind premenstrual mood symptoms, Briden says.

“Researchers understand some of the basics: for example, that estrogen can stimulate mast cells, the histamine-releasing cells of the immune system. There's also growing recognition that histamine may play a role in mood disorders more broadly. So, it makes sense that it could be involved in at least some cases of PMDD,” says Briden.

Clinical studies are still needed to confirm these theoretical links, but there are many anecdotal reports of symptom improvement with antihistamines, she says.

“In our current understanding of PMDD, we don’t think histamine plays a terribly critical role,” says Ripal Shah, MD, MPH, a clinical professor at Stanford Medicine in California who specializes in reproductive psychiatry, including PMDD.

The last decade of research on PMDD has pointed to the key roles of neurosteroids and the GABA receptors (gamma-aminobutyric acid) in PMDD, Dr. Shah explains.

But that doesn’t mean that antihistamines can’t help with some PMDD symptoms, she says. “I compare it to cold and flu medicine. If you take Tylenol, you're not killing the virus, but you're managing your symptoms with it. You're decreasing your fever. You might feel better, but you're not actually getting rid of the cause,” Shah explains.

In the case of antihistamines and PMDD, some people may find antihistamines to be a little bit sedating and help with symptoms like anxiety or insomnia, but it's not necessarily treating the reason why they're having those symptoms, she says.

“Most medications for PMDD work on the GABA receptor, also something that helps with calming, sedation, and sleep, but in a very different way,” says Shah.

“Selective serotonin reuptake barriers (SSRIs) are extremely effective for PMDD,” says Andrew Novick, MD, PhD, an assistant professor of psychiatry at CU Anschutz and psychiatrist at the Women’s Behavior Health and Wellness Center in Aurora, Colorado.

SSRIs are actually more effective at treating PMDD than they are for major depressive disorder or generalized anxiety disorder, says Dr. Novick.

“SSRIs are first-line treatment, and we often see really quick, amazing results with the drugs,” he says.

Interestingly, SSRIs aren’t used for their serotonin properties for PMDD, as is the case when people take them every day for anxiety and depression, says Shah. “We use them to stimulate the brain into making sure the steroid hormones are as stable as they can be during the end of the menstrual cycle,” says Shah.

While there may be a link between inflammation and PMDD symptoms, there isn't evidence that histamine is causing or controlling symptoms in PMDD, says Novick.

“If strong research does end up coming out that we should be using antihistamines in PMDD, I would be excited to embrace it — the more tools we have in our arsenal to treat this disorder, the better,” he says.

But for right now, Novick doesn’t believe there’s enough evidence to start recommending antihistamines for PMDD.

Shah agrees with Novak: Right now, the gold standard care and the only treatments approved by the U.S. Food and Drug Administration (FDA) for PMDD are SSRIs.

Could an antihistamine be taken alongside an SSRI for PMDD symptoms?

“I don’t see why not,” Shah says, “but I will include the disclaimer that you should always check with your doctor to make sure there's no contraindications based on the other medications that you’re taking — not only for PMDD but for any condition, because it could be something that doesn’t respond well to antihistamines,” she says.

• Some women with PMDD report relief from symptoms like anxiety and insomnia by using over-the-counter antihistamines — but for now, there’s no quality research to support this trend.
• Antihistamines may help manage PMDD symptoms temporarily, but they don't address the root causes, which involve complex brain chemistry and hormonal imbalances that may not relate to histamine at all.
• More research is needed to understand the role of antihistamines in treating PMDD. For now, SSRIs and hormonal treatments are recommended for long-term symptom management.