58. Mystery Case: Fluctuating ADHD symptoms

On this MYSTERY CASE episode of Child Mental Health for Pediatric Clinicians, Dr. Elise Fallucco dives into the case of a 12-year-old girl with ADHD whose symptoms are "on again, off again".  Join us to work through a differential diagnosis, discover the history, and most importantly learn about HOW TO HELP!   Let's unlock the mystery together!

00:00 Introduction to the Podcast

00:26 Presenting the Mystery Case

01:13 Exploring Possible Causes

01:56 Investigating the On-Off Pattern

03:51 Discovering the Pattern

05:32 How Hormones Help and Hijack the Brain

09:27 Estrogen and ADHD Symptoms

11:22 Clinical Implications and Recommendations

13:41 Conclusion and Future Research

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Transcript

Dr. Elise Fallucco: 0:21

Welcome back to Child Mental Health for Pediatric Clinicians, the podcast formerly known as Site for peds. I'm your host, Dr. Elise Lucco, child psychiatrist, and mom. We're really excited to return to this case format of a mystery case, which is where we share a brief clinical vignette and then kind of use it to highlight some cutting edge clinical findings that have recently come out. So let's dive in. Today we're talking about a 12-year-old girl who presents to your practice. She has a DHD and no other medical or mental health problems, and she's been stable on stimulants for the past couple of years. When you plot her weight and height, you've noticed that over the past year she's had a very significant growth spurt. And when you ask about how her A DHD is doing, she says overall it seems okay, except it seems like sometimes her medication doesn't work at all. So some days are great, and some days she'll take her medicine and it feels like she completely forgot to take it. What could be going on? Why would she have sort of sporadic times? Where it feels like her medication is not working and other times where it's working fine, what could be going on? Could it be a, she's outgrown her medication and needs some sort of dose adjustment to keep track with her recent growth spurt? Is it B? She's developed one of the comorbidities that we can see with A DH. D. That's affecting her symptom presentation. Is it C that there's some drug or other medication that's affecting the metabolism of the stimulant, or is it D? None of the above. Now without any additional history going through these, what I would say is a, she outgrew her med, could be definitely possible. And we know that we tend to increase doses of stimulants as kids go through major growth spurts. So I'd say that's. Potentially likely. The thing that doesn't make sense is how she says that some days it feels like it's fine, and then other days when she takes her med, it feels like it's not working at all. And if it were really an issue of her outgrowing her medicine and needing a higher dose, you would think that it would be kind of more consistent pattern. Of things not working most of the time, instead of sort of an on off pattern of some days it's great and some days it's not. Hmm. B, could she have another comorbidity? So the things we think about with for A DHD comorbidities would be depression, anxiety, um, or potentially substance use or an undetected learning difference. So we definitely wanna look for those. What about C? We'd wanna ask about any other additional medication or drugs. And D. None of the above is a placeholder for. What else could this be? So thinking about the questions we need to ask, we'll definitely screen for the comorbidities of potential depression, anxiety, and substance use Again, she's 12 years old, so low probability that there's illicit substances and she denies that, so that puts that lower on the list. She denies anxiety and her scared score is unremarkable, but when we talk about mood symptoms, she notices that, yeah, the days that the med doesn't seem to work also seem to be the days when she's more irritable, but she's not quite sure why. We also ask if she's on any other meds or any new changes and we find out she has not had any. Okay, so now we go back to the history and we've got some ideas and thoughts, and here we dig deep. And we try to understand what is with this on off pattern, where some days it, the med seems to work and other days it doesn't. Does it have to do with what subject she's in? Does it have to do with how well she slept? Like what are the things that she's noticed that correlate with the days when it works well versus the days that it doesn't? And then because you are a super astute clinician and you've been following the latest about how A DHD symptoms fluctuate in girls, you think to ask two important questions. One, has she had her period? And two, if she has had her period, has she noticed a pattern of symptoms that fluctuate throughout her menstrual cycle? In other words, is there a certain time in her cycle when it seems like the meds are not working and she has more symptoms and you hit it jackpot? Here's what we find out. Yes. She has had her period, and it's been really since she's had her period about, let's say six months ago. That she's noticed that in the week leading up to her period, it feels like she hasn't even remembered to take her med when she has her A DHD. Symptoms are on fire, and until she has her period and then for the rest of the month, they actually seem to be fairly well controlled. So what we have here in this brief mystery case is an example of premenstrual fluctuation of A DHD symptoms in a girl who has recently developed her period. Now we only know because of fairly cutting edge research that A DHD symptoms in women. And in girls who are having their period fluctuate throughout the month and tend to be worse in the week leading up to your period. So in other words, girls and women with A DHD are not only at higher risk of developing premenstrual syndrome with the irritability. And mood changes, but also are at risk for monthly exacerbation of A DHD symptoms in the week before their period. So now we're gonna do a little brief dive into neurobiology to try to understand how does this happen, and most importantly, what can we do about it? So first step, What's going on in the brain that could explain this change in A DHD symptoms in the week before your period? To answer that, we've gotta go a little bit back to med school and talk about estrogen and why it is such a great hormone. Now we know that estrogen is a reproductive hormone that plays a role in the delicate symphony that leads to ovulation, menstruation, and all the things we associate with our menstrual cycle. But did you know how important estrogen is and how much it affects our brain? in fact, there are receptors for estrogen found all throughout our brain, and most importantly, the ones we care about today are the ones in two different areas of our brain. The first place that estrogen really has a big impact in our brain is in the serotonin headquarters of the brain. Now before I tell you the fancy name for the serotonin headquarters, the reason why we're talking about this is because serotonin itself plays a key role in regulating our mood and our appetite among other things. So the fancy word for the serotonin headquarters is the dorsal RA nucleus, which is actually the largest group of serotonin producing neurons in our brain. Where it promotes the release of our feel good neurotransmitter serotonin. The second place that estrogen acts in our brain, is it the hippocampus and the amygdala, which are these major sites within our brain that are responsible for our learning and our memory. And likewise, estrogen is helping our brain and body produce and maintain high levels of dopamine, which is the neurotransmitter that plays a key role in A DHD. Typically when estrogen levels are high, so our dopamine levels, which is great because that means that A DHD symptoms we would predict would be low. Okay, so if you've not yet fallen asleep with this mini review of neurobiology, let me just summarize it briefly. High levels of estrogen interact with the brain to help us regulate our mood, keep us feeling good, help us learn, pay attention, and memorize things. Excellent. This is all great news. Now, here comes the bad news. This is what we all know, which is that our estrogen levels do not remain super high throughout our lives or even throughout our monthly cycle. In fact, estradiol or estrogen fluctuates like the first big hill of a roller coaster in the month that we get our period. So imagine your favorite roller coaster. I'm thinking about one of the rollercoasters at King's Dominion in Virginia where I grew up, so your first day of your period, which is also considered the first day of your monthly cycle, your estrogen levels are pretty low, and then around day two or three of your period. Your estrogen levels start climbing a gradual steep hill for the next week or so until it reaches the top of the hill or its peak levels around day 14, which is the time of ovulation, and then all of a sudden you start going down this hill, estrogen drops once, levels off, and then in in the last week of your cycle, which is also your premenstrual week, estrogen drops steeply again. Okay? So if you sort of pictured that you have a big uphill and then little downhill leveling off and then a steep downhill, and this rollercoaster analogy represents how estrogen fluctuates in the 28 days of your menstrual cycle. Okay? You're probably wondering why am I getting these elaborate lessons in reproductive hormones? I promise you there is a payoff. Thank you for listening. So now we get. To the second part where we talk about how do our A DHD symptoms fluctuate throughout our cycle related to estrogen changes. So again, let's get back on that rollercoaster. We're starting around day two or three of our period when estrogen is at its lowest and about to climb a steep hill. And as estrogen levels rise, we also see serotonin levels rise. And remember serotonin. Can be oversimplified as kind of a little bit of a feelgood hormone that enhances our mood, our ability to think, and even our ability to tolerate pain. So the week after your period as your estrogen is climbing and rising, this is the time when our mood gets increasingly better up until its peak around day 14 or ovulation when we feel fantastic. So not only does estrogen increase serotonin synthesis and serotonin levels, but we're also seeing an increase in dopamine levels during the week after your period. Which improves our motivation, which is our desire to do things even when they're boring. It increases our productivity and our focus. So as a side note, in the week after your period, this is the time when we're best able to stay organized. Get things done, be super productive. So shortly after ovulation, which takes place around day 14 of your cycle, your estrogen levels start to decrease a little bit, and then they level off for a while until about the week before your period where they drop precipitously. And this is where we see the premenstrual exacerbation of A DHD symptoms. The inattention, the poor, executive functioning, the limited motivation, the difficulty completing tasks and remembering things. And this lasts until about day two or three of your period where it starts all over again. so to think about a clinical implication, definitely ask your girls if they notice worsening of their A DHD symptoms, specifically inattention, executive function concentration in the week before their period, or at any time of their month. You could even consider asking them to track their symptoms on something like the health app available on the iPhone. Or even through sort of old school paper and pencil charts. And for those of you who subscribe to the newsletter, I will include a link to a resource that allows you to track symptoms throughout your period. But most importantly, knowing that there's fluctuation in A DHD symptoms, what can we do about it? How does this change the way we think about treating A DHD? Thinking about a holistic treatment and starting with the basics. Of course, we'd wanna recommend that in this week where there's potential mood changes and definitely changes in attention and concentration. This is the time where we need to double down on sleep. We really need to try to get consistent, regular sleep as much as it's possible. To try to combat these effects on our cognition and our memory and our attention. In addition, movement and exercise is so great for the brain and can be helpful. Okay, so sleep, exercise, of course, proper nutrition. But then the question comes, what about medication? You may be wondering, should we consider adjusting the dose of the stimulant in the week before your period, which is sort of analogous to something that people do for women with premenstrual dysphoric disorder, where they're given a medication around the week before their period to try to treat some of the premenstrual symptoms. So a very small case report showed that the increased dose of stimulants just in the week before their period, helped combat premenstrual worsening of cognitive and emotional symptoms among women with A DHD. So there's still a lot of work to be done with this. If you look at an expert consensus statement that was published in BMC Psychiatry while they acknowledge that there are potential worsening of A DHD symptoms, premenstrually, at this time, they did not find enough evidence to recommend treatment differences. In the week before their period or the premenstrual time.

14:02

Another question that you're probably thinking is, what is the role of oral contraceptive pills or any sort of hormone therapy in this whole puzzle? And the answer is, we do not know yet. And in typical fashion with mystery cases, we come up with lots of questions and some answers that lead to more questions. So hopefully we'll be having ongoing research on A DHD fluctuations in girls and women and what we can do to optimize their treatment.

Dr. Elise Fallucco: 14:31

I hope you found this helpful, that it wasn't too super sciencey and boring. And most importantly, I hope you'll open the door to have these discussions with some of the girls and young women in your practice with A DHD to see how we can better understand their experience and make sure that we're targeting treatment appropriately to help them. Thanks for listening. See you next time on The Child Mental Health Podcasts for pediatric clinicians.