KELLIE NWSOME: When psychiatric symptoms worsen before menses, should you adjust the psych meds or treat the premenstrual syndrome directly? Come along as we grapple with the question. Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003.

CHRIS AIKEN: I’m Chris Aiken, the editor in chief of the Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue. We're counting down the top psychopharmacology pearls for female patients. Today: how to manage premenstrual worsening — not just in depression, but across the disorders from ADHD to psychosis. First, a preview of the CME quiz. You'll find the answer in the research update at the end.

1. The FDA recently approved Modius Spero, the first at-home neuromodulation device for PTSD. How does it work?

A. It delivers magnetic pulses directly to the prefrontal cortex

B. It stimulates the vestibular nerve behind the ears with low-level electrical current

C. It uses transcranial direct current stimulation (tDCS) to the temporal lobe

D. It sends electrical signals through the scalp to the amygdala

CHRIS AIKEN: Pearl number four: When menstrual hormones rise and fall, mental health can get shaken. Sometimes you need to address the hormones, and sometimes you need to adjust the medication.

KELLIE NEWSOME: Last week, we covered the three SSRIs with FDA approval for premenstrual dysphoric disorder: fluoxetine, paroxetine, and sertraline. If you go the SSRI route, fluoxetine is a reasonable starting point. Its long half-life means you can stop and start it — dosing only in the two weeks before menses — without significant withdrawal, since the drug lingers in the system for about six weeks after stopping it.

CHRIS AIKEN: But wait, thoughtful listeners might rightly ask: Doesn't that long half-life also mean fluoxetine takes longer to reach steady state? Yes, but that doesn’t matter like you’d think. You'll sometimes hear that fluoxetine has a slower onset than other SSRIs because it takes longer to reach steady state. But that's a theory, no fact behind it. In clinical trials, fluoxetine takes effect at the same steady pace as other SSRIs. I guess the brain doesn’t need round-the-clock fluoxetine coverage to treat depression, any more than a garden needs constant watering to grow. Plants do worse when we water them all day long. The roots get soggy and mold, and lithium is safer for the kidneys when they get a little reprieve in the levels by dosing it all at night instead of twice a day. So why should we assume the brain needs a constant flow of medication?

KELLIE NEWSOME: SSRIs have FDA approval for premenstrual dysphoria, but they're not the only option — and they're not safe in bipolar. Another way to address premenstrual dysphoria is through natural therapies. Last night, Dr. Aiken just turned in what he hopes is his final manuscript on the upcoming Carlat Complementary and Alternative Medicine Psychiatry Fact Book. In it, he sorted through around 2,000 randomized trials to rank each one by the quality of the evidence.

CHRIS AIKEN: If the treatment worked in at least two large randomized trials, I give it the top rating, “confirmed,” in line with what the FDA requires for approval, at least, what they used to require. While I was writing the book, they lowered their standard to one trial, but I’m old school.

KELLIE NEWSOME: OK, only one supplement earned Dr. Aiken’s approval for premenstrual syndromes: Chasteberry, which is backed by nine large and three small placebo-controlled trials in premenstrual syndrome, where it improved irritability, sleep, mood swings, headache, bloating, and breast pain, but it’s a little better for physical than mental symptoms. Moving down a step, where the trials are smaller, these earn a “probably effective” rating. So the evidence is decent, kinda like when you use medications off label. They are: omega-3 fatty acids, zinc, calcium, and ginkgo. Eleven other treatments earn a "possible" rating based on smaller studies, and these are rarely worth using so we won’t mention them here.

CHRIS AIKEN: But, you know, whether a treatment is likely to work depends on the patient, so we can personalize this by checking blood levels – not of hormones but of iron and vitamin D, those are the two with the highest yield. Iron is often low in menstruating women, and correcting it improves mood and fatigue. Vitamin D has a more specific link to premenstrual dysphoria, and this nutrient treated the disorder, but only when levels are low. L-methylfolate may also work; it hasn’t been tested, but we know that abnormal folate metabolism genes, the MTHFR, double the risk of premenstrual dysphoria.

KELLIE NEWSOME: What about vitamin B6? I often see that one used for premenstrual dysphoria.

CHRIS AIKEN: Yes, that one has a fascinating history. In the 1970’s, it was promoted for women’s health and menstrual symptoms in the groundbreaking book Our Bodies Ourselves. The book was an instructional manifesto, urging women to take control of their own healthcare in a male-dominated medical world. The impact was profound, and helped moved the field from paternalism to collaboration, but there are risks on both sides of that balance. The early editions encouraged vitamin B6, and some women started taking more and more. In the 1980s, case reports came out of neuropathy on high-dose vitamin B6. Doctors were quick to pounce on this wayward vitamin, and the book Our Bodies Ourselves toned down their recommendations. Here’s where the research stands today. Vitamin B6 has 11 randomized trials in premenstrual syndromes, and although only 45% were positive, it did pass in a meta-analysis. Now, that is better than the FDA’s scorecard for Gepirone, which they just approved for depression after it worked in 15% of its trials, but to me, the glass is only half full on vitamin B6, so I gave it a lower rating of “possible."

KELLIE NEWSOME: But the story doesn’t end there. There’s emerging evidence that we can avoid this neuropathy risk by using the active form of vitamin B6 instead of the synthetic pyridoxine, kinda like how we use methyl-folate instead of folic acid. One of my favorite parts about the book was the new research on using vitamin B6 to reduce antipsychotic side effects like high prolactin, akathisia, EPS, tremor, and possibly tardive dyskinesia.

CHRIS AIKEN: We could probably write a whole book on menstrual changes and psychiatric treatment, because it’s so relevant to patients, but this would be a hard book to write because the research is so thin. Many women say that ADHD worsens before their menstrual cycle, and observational studies confirm this, but there are no treatment studies to tell us what to do. It's intuitive to raise the stimulant in the two weeks before menses, but that carries cardiac and psychiatric risks. Hormonal treatments may be a better option, or some of the CAM therapies we mentioned earlier. Some natural therapies improve both ADHD and premenstrual syndrome, like zinc and omega-3 fatty acids, and one improves cognition and premenstrual syndrome: ginkgo. If your patient says their psychiatric symptoms worsen before menses, don’t just assume it’s the psychiatric disorder. It could be premenstrual syndrome, so ask about those symptoms.

KELLIE NEWSOME: On the psychological side, there are mood swings, irritability, tearfulness, anxiety, insomnia, fatigue. On the physical side: hot flushes, night sweats, palpitations, bloating, food cravings, joint pain, breast tenderness, vaginal dryness, pain on intercourse, and urinary frequency or urgency.

CHRIS AIKEN: Around 40% of women with ADHD have premenstrual dysphoric disorder. Those symptoms are distracting in themselves and are treatable with oral contraceptives, SSRIs, Chasteberry, omega-3 fatty acids, zinc, and Ginkgo.

KELLIE NEWSOME: What about bupropion?

CHRIS AIKEN: Bupropion helps ADHD a little, but not premenstrual symptoms. It failed in the only randomized trial that tested it in premenstrual dysphoria.

KELLIE NEWSOME: Most psychiatric disorders can worsen in the 2 weeks before menses: depression, bipolar, borderline personality, psychosis, ADHD, OCD, and anxiety disorders, including PTSD. Also, binge eating and bulimia, because premenstrual hormonal changes cause food cravings. Alcohol use rises, too, though we don’t know much about other substances. The cause of all this premenstrual worsening is poorly understood, but likely involves heightened sensitivity to normal fluctuations in estrogen and progesterone, which have downstream effects on serotonin and GABA. And for most disorders, the treatment is unclear. Should you treat the underlying psych disorder, or treat the premenstrual syndrome? In depression, we often raise the serotonergic antidepressant, as that addresses both problems, but outside of depression, we don’t know which, if any, of these roads to take.

CHRIS AIKEN: A large Swedish study published last May gives a clue. The design is a little complex, so let’s start with the bottom line: Premenstrual syndrome causes psychiatric disorders to worsen, and having a psychiatric disorder causes people to have more premenstrual syndrome. The causes are bidirectional; each one roughly doubled the risk of the other. That means you may be able to make a difference on either end, with one exception. Schizophrenia. The study was huge. They followed psychiatric and premenstrual symptoms in just over 100,000 women for eight years. For comparisons, they used a case control design, where psychiatric patients were matched with similar healthy controls — they were also matched with their biological siblings, to account for shared genetics and environment.

KELLIE NEWSOME: They found this bi-directional causation held up for nearly all psychiatric disorders: Bipolar disorder, depression, anxiety disorders, ADHD, and personality disorders. The one exception was schizophrenia, where premenstrual syndromes did not predict psychotic worsening. Schizophrenia does tend to worsen before menses, it’s just that this worsening is not connected to any premenstrual symptoms. Why is schizophrenia the lone exception? The authors speculated that psychotic symptoms may be so florid that we miss the more subtle premenstrual ones, so the link may still exist. But I'd at least avoid Chasteberry in psychotic disorders. It can raise dopamine, and there's a case report of psychosis on it. Pearl Number 5: Oral Contraceptives and Mood in Younger Women.

CHRIS AIKEN: There's a paradox with prescription hormones. Estrogen can improve mood during perimenopause, when hormone levels are falling. But estrogen can worsen mood in younger women with normal estrogen levels when it is given as an oral contraceptive. The risk is small, and here’s who you need to look out for: Teens are more vulnerable, and so are women who’ve had painful menses or have a history of perinatal depression. And some oral contraceptives carry more risk than others.

KELLIE NEWSOME: The oral contraceptives that are least likely to disrupt mood are those containing drospirenone and ethinyl estradiol — Yaz and Yasmin are the common brands. This is a lot to remember, so here’s a mnemonic: Say YES to Yaz and Yasmin. Intrauterine devices are also lower risk, because they deliver much smaller doses of hormones. The contraceptives with a greater risk of worsening mood are triphasic preparations, where hormone levels fluctuate across the cycle, and also the progestin-only  formulations. Progesterone is more destabilizing. Here's a practical option for women who want to reduce premenstrual mood symptoms while taking oral contraceptives: the OB-GYN can extend the cycle by skipping the placebo week. With this strategy, the patient will menstruate every 6 months instead of monthly. This smooths out the hormonal swings that drive premenstrual symptoms, both physical and emotional ones.

CHRIS AIKEN: Another option is a little off the beaten path. Lavender oil, marketed as Silexan, is a prescription medication for generalized anxiety in Germany and other countries. It modulates glutamate and serotonin. Many of our listeners know of lavender for its large effect in anxiety. It’s also the only “medication” I know of that improved mood symptoms caused by oral contraceptives in a controlled trial. The study was small — 60 women aged 15 to 49, but the idea is backed by large studies in anxiety and depression. The dose for anxiety is 160 mg per day, but for mood symptoms on oral contraceptives, they used 80 mg per day. Lavender is well tolerated, with lavender-flavored burps the main side effect. In the US, it’s available as CalmAid by Nature’s Way, which uses the same patented extract available by prescription in Europe. People sometimes ask why I'm interested in natural therapies. I'm not interested in them for their own sake. I'm interested in getting patients to full recovery, and medications alone don't get them there enough. Most disorders have full recovery rates around 30% with meds, and rotating meds doesn’t move those recovery rates much further. So I believe in using all options: Therapy, lifestyle change, neuromodulation, and natural supplements. Sometimes, the non-pharmacologic pathways are more effective than medications. In the case of neuromodulation, it’s almost always more effective.

KELLIE NEWSOME: But are there supplements that have an edge over medications?

CHRIS AIKEN: Most do for tolerability, and some have additional medical benefits, but in terms of beating out meds on efficacy… that’s a short list. Lightbox for depression, lavender in generalized anxiety disorder, Ginkgo in vascular depression, zinc in anorexia, and maybe a few more. It’s a tough call and depends on the patient. Like, if they have folate deficiency, l-methylfolate is probably going to be more effective than an SSRI in depression.

KELLIE NEWSOME: Number 6: Watch for drug interactions with contraceptives.

CHRIS AIKEN: Estrogen-containing contraceptives lower lamotrigine levels significantly — by 30 to 50 percent. Hormone replacement therapy lowers lamotrigine too, but to a lesser degree. For most people, lamotrigine maxes out around 200 mg a day. Studies have compared 200 mg to higher doses, but it didn’t make any difference for depression. But women on oral contraceptives are an exception, where you may need to push lamotrigine to 300 or 400mg a day.

KELLIE NEWSOME: What about middle-aged women on hormone replacement therapy, HRT? Should you push it there?

CHRIS AIKEN: HRT doesn’t lower lamotrigine as much, so raising the dose is optional, and I usually don’t because of their age. Older adults tend to respond to lower doses of lamotrigine and are more sensitive to side effects, especially cognitive ones, so I’ll usually stick in the 100-150 mg range for patients over 60. If they're on HRT, I may push to 200 mg, but not higher. Oh, and don’t forget pregnancy. Lamotrigine levels fall 30-50% in the third trimester of pregnancy.

KELLIE NEWSOME: But this contraceptive interaction doesn’t go the other way. There's a myth that lamotrigine lowers oral contraceptive levels. There's no evidence for that. But several psychiatric medications do lower oral contraceptive and HRT levels: carbamazepine is the most potent, followed by oxcarbazepine, topiramate, the modafinils, and St. John's Wort. These drugs induce CYP-3A4, accelerating estrogen’s clearance. If you prescribe any of them, recommend another method of contraception, like condoms or barrier contraception. Transdermal and implant formulations of contraceptives bypass this interaction, but only partially, so the risk is still there. Today's research update covers an unpublished study that led to a new FDA approval. On May 26, 2026, the FDA approved the first at-home neuromodulation device for PTSD. The device is called Modius Spero, made by Neurovalens — the same company behind a similar device for insomnia. This is an approval, not just a clearance.

CHRIS AIKEN: Modius Spero is the third at-home neuromodulation device approved in the past year, following Flow, a tDCS device for depression, and ProLivRx for depression that has failed an antidepressant. Modius Spero resembles ProLivRx in that it stimulates cranial nerves rather than stimulating the brain directly. It delivers low-level electrical current to the skin behind the ears, activating the vestibular nerve — the nerve that handles balance and position. The signal then travels to the brainstem and hypothalamus, areas that regulate sleep, circadian rhythms, and the stress response.

KELLIE NEWSOME: The trial behind the approval was a randomized, sham-controlled study of 383 adults over 12 weeks. Patients wore the headset 30 minutes daily. Reportedly, two-thirds had a meaningful improvement — but the trial hasn't been published yet, so we can't say anything about its validity. The study was funded by Neurovalens, the manufacturer. Modius Spero is approved for adults 22 and older. Starting in July, it should be available by prescription through the VA health system. VA clinicians can sign up on the Neurovalens website. Outside the VA, access is unclear — the retail cost is just over two thousand dollars. Dr. Aiken posts brief research updates on his blog. Go to chrisaikenmd.com and click on RESEARCH UPDATES, or in the menu, click LEARN. If you're short on time, filter the list to just the TOP STUDIES. And join the conversation on social media — search ChrisAikenMD on LinkedIn, Twitter, Facebook, Bluesky, or Threads.