Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. In August 2024, we published the latest update of the Cochrane Review of the effect of selective serotonin reuptake inhibitors on women with premenstrual syndrome and premenstrual dysphoric disorder. In this podcast, two of the authors, Jeppe Bennekou Schroll and Cecilie Jespersen, both from Cochrane Denmark, talk about the need for the review and its latest findings.

Jeppe: Hi Cecilie. Could you give us an introduction to premenstrual syndrome and premenstrual dysphoric disorder.

Cecilie: Hi Jeppe, of course. Throughout the menstrual cycle, the ovarian sex hormones rise and fall. In the week leading up to the menstruation, both the oestrogen and progesterone levels are low.  That is when most women experience mood swings or negative emotions, that disappear when the menstruation starts.

Jeppe: How does this differ from what women normally experience?

Cecilie: It differs by degree and severity. Some women experience this distress to such a severe degree that it impacts on their daily lives, and they might be diagnosed with premenstrual syndrome - or PMS for short. An even more severe type of the syndrome is called premenstrual dysphoric disorder, PMDD.

Jeppe: Okay, so why is it necessary to know about effective treatments for PMS and PMDD?

Cecilie: It’s a common pitfall to think about these severe premenstrual symptoms as something natural that women should just learn to live with. But that attitude fails to recognize that women diagnosed with PMS or PMDD will have been affected by a variety of intense symptoms in the weeks leading up to menstru ation in every menstrual cycle for at least one year.

Jeppe: What type of symptoms for instance?

Cecilie: The symptoms vary from person to person and can include mood swings, anxiety, irritability, headache, and acne. Some of these women really struggle, and find that the symptoms greatly impact their jobs, careers, and personal lives. There is no unique physical test or laboratory test to diagnose PMS or PMDD, but the symptoms that these women experience differ from normal premenstrual symptoms with regards to both duration and intensity.

Jeppe: What are the treatment options?

Cecilie: There are several, including lifestyle changes, vitamin supplements and certain hormonal contraceptives. However, not all women respond to these treatments. It’s also an option to use Selective Serotonin Reuptake Inhibitors (or SSRIs for short), which is the focus of our review. These drugs work by altering the signaling substances in the brain and are believed to reduce the impact of the hormonal fluctuations that occur in the menstrual cycle, so that these cyclical premenstrual symptoms also decrease.

Jeppe: Which leads us to the review. Why was this update needed?

Cecilie: An important reason for the review is to help women suffering from the two syndromes and help them and clinicians to make the best decisions. In regard to this update, the main reason is that research into the treatment options is still active and we expected that new studies would have been published since the previous version in 2013. We wanted to find out how the results of those studies would add to the existing knowledge on both benefits and potential harms of SSRIs.

Jeppe: What did you find?

Cecilie: We added three new trials for this update, making a total of 34 studies with more than 4500 women. All compared an SSRI in women suffering from PMS or PMDD with placebo treatment, but the trials varied in many ways. For example, in the dose and type of SSRI and whether the drug was taken every day or only in the weeks leading up to the menstruation.

Jeppe: And what did the studies show?

Cecilie: We found that SSRIs are probably effective in treating overall premenstrual symptoms and probably most effective when taken every day, but they also appear to be effective when only taken in the two weeks leading up to the menstruation. However, it is important to note that SSRI treatment did not completely remove the symptoms. It only reduced the severity of them.

Jeppe: Is this anything new?

Cecilie: Previous versions of the review had already found that SSRIs were probably effective in treating the most severe syndrome, PMDD. But, by including more studies in this update, we’ve found that SSRIs probably also reduce the symptoms in women with PMS.

Jeppe: Did you also look at the harms?

Cecilie: Yes we did. SSRIs probably increase the risk of nausea, lack of energy, sexual dysfunction, and sleepiness. For example, if 7 in 100 women in the placebo group experienced nausea, this rose to 20 per hundred in the group taking the SSRIs. Overall, we found evidence of several adverse events, with many 2-3 times more common among women receiving SSRIs. It should also be noted that some adverse events are transient and might subside over time. This means that the benefits should be weighed against the harms by both clinicians and women with PMDD or PMS before starting the treatment.

Jeppe: Was there anything else notable about the studies?

Cecilie: Yes. Firstly, two-thirds of the studies were sponsored by pharmaceutical companies. We know from other research that studies sponsored by pharmaceutical companies tend to report more favourable outcomes and this might influence our results. Also, around half of the studies were conducted before the year 2000 and, among these studies, it was often unclear exactly how the studies were carried out.

Jeppe: Thanks for telling us about the review, Cecilie. If people would like to read it, how can they access it?

Cecilie: The review is online at the Cochrane Library dot com. Just type ‘PMS and SSRI’ into the search box and you will find a link to it.