Latest / The Sirona Health Podcast: PMDD, Hormones & Mental Health / How SSRIs, SNRIs and Quetiapine Fit Into PMDD Treatment

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How SSRIs, SNRIs and Quetiapine Fit Into PMDD Treatment · The Sirona Health Podcast: PMDD, Hormones & Mental Health

• 0:04
  Hormones don't just run your cycle.
• 0:07
  They run your mood, your mind, your whole sense of self.
• 0:11
  I'm Dr.
• 0:12
  Georgina Standen, GP and founder of Sirona Health, and this is the Sirona Health Podcast, where we talk about the relationship between female hormones and mental health properly, without the mystique and without the dismissal.
• 0:26
  So far, I've talked a lot about hormonal treatments.
• 0:29
  Today, I want to move into a completely different category: medication that works on serotonin and other brain chemistry directly rather than on your hormones.
• 0:39
  SSRIs are one of the most effective tools we have for PMDD, and I want to explain why they can work so differently here compared to standard depression treatment, when to reach for an SNRI instead, and what happens when none of this is quite enough.
• 0:57
  Remember the mechanism I described a few episodes back in PMDD, the brain serotonin system, alongside GABA, seems to respond abnormally to completely normal hormonal changes.
• 1:10
  SSRIs work by increasing the availability of serotonin, and in PMDD specifically, that appears to help buffer the brain against exactly that kind of sharp hormonal transition.
• 1:23
  Here's what I think is striking about this, and it's something I've mentioned before, but want to explain fully now.
• 1:30
  In standard depression, SSRIs typically take several weeks to have a real effect.
• 1:37
  In PMDD, women often respond within days, sometimes even with the first cycle of treatment.
• 1:44
  That speed of response is actually a clue about the mechanism, not just a nice side benefit.
• 1:49
  It suggests SSRIs are doing something quite specific and quite fast in this condition, rather than working through the slower changes in brain chemistry we usually associate with treating depression.
• 2:03
  That speed is also why PMDD opens up a dosing option that doesn't really exist for standard depression, taking the SSRI only during part of your cycle rather than every day.
• 2:18
  Randomised studies have shown that this half-cycle approach, essentially dosing only through the luteal phase, works about as well as taking it continuously.
• 2:29
  Typical regimen might be citalopram or escitalopram taken from around day 15 of your cycle through to day 28, and this approach has been shown to be effective even in some women whose previous continuous SSRI treatment hadn't worked well.
• 2:48
  I think this matters for reasons beyond just convenience.
• 2:52
  Women on this kind of intermittent regimen are less likely to feel they're dependent on medication long-term.
• 2:58
  The benefit is immediate rather than something you're waiting weeks to notice, and a lot of women find it easier to accept precisely because it feels meaningfully different from how antidepressants are usually used for depression itself.
• 3:14
  I do want to flag a real downside to dosing this way, though, because I think it's underappreciated.
• 3:21
  With continuous everyday use, the early side effects of SSRIs, things like nausea, jitteriness, or disrupted sleep, tend to settle down over roughly the first month as your body adjusts.
• 3:35
  With cyclical dosing, you're essentially restarting the medication every single cycle, which means you can end up repeatedly hitting that early, more uncomfortable adjustment window cycle after cycle without ever getting the benefit of that settling-in period that continuous users experience.
• 3:56
  For some women, that trade-off is completely worth it.
• 3:59
  A few days of mild nausea each month in exchange for not being on medication daily.
• 4:05
  For others, particularly if those early side effects are more than mild, continuous dosing can actually end up being the more comfortable option overall, even though it means taking the medication every day rather than just half the month.
• 4:20
  It's worth discussing both patterns with whoever's prescribing rather than assuming cyclical dosing is automatically the gentler choice.
• 4:29
  There's one more thing worth knowing about SSRIs specifically, and I think it's easy to overlook.
• 4:36
  Unlike every hormonal treatment we've covered so far in this series, an SSRI isn't contraceptive.
• 4:43
  That makes it a particularly good fit for women who are actively trying to conceive or who don't want their PMDD treatment doubling up as a contraceptive they don't need.
• 4:54
  And if you do conceive while taking one, it's not an automatic stop.
• 4:59
  Whether you continue through pregnancy or come off it is really an individual decision, weighed against your own risk of perinatal depression or anxiety, or of an existing mental health condition worsening if you do stop.
• 5:14
  For some women, particularly those with a history of significant depression or anxiety, the risk of stopping can outweigh the risk of continuing, and that's a conversation worth having with whoever's prescribing, rather than assuming pregnancy automatically means coming off medication If an SSRI is the right starting point, which one actually matters?
• 5:38
  And this is where some really useful new evidence has come out recently.
• 5:42
  A large analysis published in The Lancet in twenty twenty-five, pulling together data from over fifty-eight thousand people, compared how different antidepressants affect the body, not just mood, but weight, heart rate, and blood pressure too.
• 5:59
  Sertraline, escitalopram, and fluoxetine came out as the most physiologically neutral of the group.
• 6:07
  Minimal effects on weight, heart rate, or blood pressure.
• 6:11
  Paroxetine, by contrast, was associated with a bit more weight gain and a modest rise in resting heart rate.
• 6:18
  Practically, this is useful information when you're choosing between them sertraline is often favored partly because of its low side effect burden and because it's considered particularly safe during breastfeeding, which matters if you're thinking about this in the context of postnatal depression too.
• 6:37
  Fluoxetine tends to suit women who want something a bit more activating during the day rather than sedating, and it has particularly good evidence around the use in depression in adolescence SNRIs, medication like venlafaxine and duloxetine, work on noradrenaline as well as serotonin, and I think they're worth knowing about specifically because they suit a particular symptom pattern.
• 7:03
  If anxiety, tension, or a kind of physical restlessness is dominating the picture alongside low mood, an SNRI can be a lot more effective than an SSRI alone.
• 7:14
  However, the same Lancet analysis found that SNRIs have a more noticeable physiological footprint than SSRIs.
• 7:23
  Both venlafaxine and duloxetine were linked to modest but real increases in blood pressure and heart rate, which makes sense given their effect on noradrenaline.
• 7:33
  So in practice, I think of SNRIs as particularly useful for PMDD, where irritability and fatigue dominate.
• 7:42
  But I'd use them with more caution in anyone who already has a high blood pressure or who's already dealing with palpitations, which is relevant for some women moving through perimenopause specifically.
• 7:55
  There's actually a nice crossover benefit here, too.
• 7:58
  SSRIs and S- NRIs can help reduce hot flushes.
• 8:03
  So for a woman whose PMDD-type symptoms are tangled up with perimenopausal symptoms, an antidepressant can sometimes do double duty.
• 8:14
  I want to take a short detour here because I think it connects nicely to something from much earlier in this series.
• 8:21
  A few episodes back, I talked about the genetics of PMDD itself, why some brains are more sensitive to hormonal change in the first place.
• 8:31
  This is a related but distinctly different kind of genetics, not about why you have PMDD, but about how your body actually processes the medication you're given for it.
• 8:43
  There's a field called pharmacogenomics, and it looks at genes that control how quickly your liver breaks down many antidepressants.
• 8:52
  Some people are what's called poor metabolizers.
• 8:56
  They process the drug slowly, so levels build up and side effects become more likely even at a standard dose.
• 9:04
  Others are ultra-rapid metabolizers, clearing the drug so quickly that it may never reach an effective level in the first place.
• 9:12
  If you've ever felt like you react badly to every medication you try, or that nothing ever seems to work despite what should be an adequate dose, this is worth knowing about because it might be pharmacological rather than something being wrong with you.
• 9:29
  I think it's fair to be clear about the limits here too, because this gets marketed as more of a solution than the evidence fully supports.
• 9:37
  Pharmacogenomic testing is genuinely good at predicting tolerability, why you might have felt awful on a particular drug.
• 9:46
  It's much less reliable at predicting efficacy, which specific antidepressant will actually work for you.
• 9:55
  Trials looking at genetically guided prescribing have shown a real, if modest, improvement in outcomes compared to standard prescribing.
• 10:03
  But it doesn't replace clinical judgment, And it definitely doesn't account for the hormonal and psychological side of PMDD specifically.
• 10:13
  I think this next point matters as much as any of the pharmacology, honestly.
• 10:18
  In my experience, women are far more comfortable starting a hormonal treatment, the pill or progesterone, than they are starting an antidepressant, even when the antidepressant might actually be the more effective option for their specific symptoms.
• 10:34
  I understand why hormones feel like a natural continuation of reproductive healthcare, something women are used to being prescribed across their whole reproductive life.
• 10:44
  Antidepressants, on the other hand, still carry real stigma, a sense that taking one means something's fundamentally wrong, a fear of being on medication forever, concern about side effects that often get amplified online, well beyond what the evidence actually shows.
• 11:03
  I think this reluctance has a real cost, and it's one I want to name.
• 11:08
  There's a condition I've mentioned earlier in this series, premenstrual exacerbation, where an existing mood disorder, like depression or anxiety, gets significantly worse premenstrually.
• 11:21
  Women with PME are sometimes misclassified as having straightforward PMDD and started on a hormonal treatment that does very little for the underlying mood disorder actually driving things when what they needed was antidepressant treatment or a mood stabilizer alongside proper diagnosis.
• 11:41
  The stigma around antidepressants can delay women getting to the treatment that would have helped them most.
• 11:48
  So I'd really encourage you, if an SSRI or SNRI is suggested to you, to weigh it on the actual evidence rather than on how it feels compared to a hormonal option.
• 12:00
  Sometimes hormones are the right first step.
• 12:03
  Sometimes they're not, and that's not a failure.
• 12:05
  It's just a different, equally legitimate route to feeling like yourself again I want to end today with something that sits right at the far end of the treatment pathway because I think it's important you know it exists, even though it's not something most women will ever need.
• 12:23
  For a small group, likely fewer than 5% of women with PMDD, symptoms remain severe despite proper trials of SSRIs, hormonal suppression, transdermal estrogen, and psychological support.
• 12:38
  This is what we'd call treatment-resistant PMDD, and for this specific group, there's a small but genuine evidence base for adding low-dose quetiapine, one of the medications from a class called antipsychotics, though I think that word makes it sound far more alarming than it usually is in this context.
• 12:59
  Many modern antipsychotic medications are actually used at low doses across psychiatry for all sorts of things: depression, anxiety, insomnia, emotional dysregulation, not exclusively for psychosis A small randomized placebo-controlled trial looked specifically at low-dose quetiapine added on top of antidepressant treatment, given only during the luteal phase, and found real improvements in mood swings, anxiety, irritability, and overall symptom burden compared with placebo.
• 13:35
  A more recent scoping review concluded quetiapine augmentation may have a role in carefully selected women with treatment-resistant PMDD, while being honest that the evidence base is still small.
• 13:50
  I want to be equally honest about the downsides.
• 13:53
  This isn't a benign medication.
• 13:55
  Side effects can include sedation, weight gain, increased appetite, effects on cholesterol and diabetes risk, dizziness, and rarely at these low doses, movement-related side effects.
• 14:09
  That's exactly why this sits so far down the treatment pathway, after SSRIs, after hormonal suppression, after GnRH agonists if needed, and why it's generally a specialist decision made jointly between a women's health specialist and a psychiatrist rather than something started early or lightly.
• 14:31
  So to bring today together, SSRIs are one of our most effective PMDD treatments, and the fact that they can work within days and can be taken for just part of your cycle tells us something real about the underlying mechanism, not just about convenience.
• 14:48
  SNRIs have their place when anxiety or fatigue dominate.
• 14:53
  How you actually metabolize these medications matters too, and it's worth knowing about if nothing ever seems to work at a standard dose.
• 15:02
  Stigma really does get in the way of women accessing the most effective treatment for them, and I'd encourage you to push past it if it's relevant to you.
• 15:12
  And for the small number of women for whom none of this is enough, there are further options carefully considered at the far end of the pathway.
• 15:22
  If there's one thing I'd want you to take from this whole run of treatment episodes, it's that there's a real stage pathway here from lifestyle changes right through to the most specialist interventions, and where you sit on it isn't a reflection of how unwell you are as a person, it's just where your particular biology happens to respond.
• 15:43
  Next time, I want to shift focus entirely away from medication and talk about psychological therapy for PMDD and why understanding your own cycle can be a turning point in itself That's it for today.
• 15:57
  I'm Georgina.
• 15:58
  Thanks for listening.
• 16:00
  A quick note before you go.
• 16:01
  This podcast is for general information, not individual medical advice.
• 16:06
  It doesn't replace seeing your own GP or a specialist.
• 16:09
  So if anything you've heard today feels relevant to you, please do talk to someone, and if you're struggling, please reach out to your GP, to someone you trust, or to a crisis line if you need one right now.
• 16:22
  You can find Sirona Health and book your appointment at sironahealth.co.uk.
• 16:27
  See you next time