View episode transcript

Featured Guest

Amy VandenBerg, PharmD, BCPP

Objectives

• Identify appropriate selective serotonin reuptake inhibitors for the management of depression in pediatric patients and how they work.
• Identify appropriate serotonin-norepinephrine reuptake inhibitors for the management of depression in pediatric patients and how they work.
• Discuss the black-box warning associated with these medications.
• Identify symptoms of serotonin syndrome.
• Identify symptoms of discontinuation syndrome.

Resources

• Selective serotonin reuptake inhibitors (StatPearls) 
• Demystifying serotonin syndrome (or serotonin toxicity) (Canadian Family Physician)
• Antidepressant discontinuation syndrome (Canadian Medical Association Journal)
• Antidepressants and the FDA’s black-box warning: determining a rational public policy in the absence of sufficient evidence (AMA Journal of Ethics)
• Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison (Innovations in Clinical Neuroscience)

CME

Credits available: 0.5 

To enroll for CME credit, visit our episode activity website. Visit our CME course overview page for details on CME credit, or complete this survey for social work CEUs.

Visit our podcast website for more information about this episode and the Breaking Down Mental Health podcast series.

Breaking Down Mental Health is a part of the Michigan Medicine Podcast Network. You can subscribe to Breaking Down Mental Health podcast wherever you listen to podcasts.

Transcript

Syma Khan: 

Hello and welcome to Breaking Down Mental Health with myself, social workers Syma Khan, nurse practitioner, Dr. Christina Cwynar, and child and adolescent psychiatrist, Dr. Heidi Burns. We're joined today by Amy VandenBerg to talk about medications in the setting of depression management, specifically selective serotonin reuptake inhibitors, or SSRIs, and serotonin and norepinephrine reuptake inhibitors, or SNRIs.

Amy VandenBerg is a clinical associate professor at the University of Michigan College of Pharmacy, and a board-certified psychiatric pharmacist who collaborates with inpatient psychiatry services at Michigan Medicine.

Thank you so much for joining us today.

Amy VandenBerg:

Thank you for having me today.

Syma Khan: 

In episode one, Dr. Arango and Dr. Quigley talked with us about when treatment of depression with medication should be considered. While the gold standard is a combination of therapy and medication for the most efficacious outcomes, this week we are going to focus on medications, and next week we'll talk a little bit more about therapy.

Amy, let's start our talk with a little bit more about SSRIs. What are they and how do they work?

Amy VandenBerg:

So, SSRIs are selective serotonin reuptake inhibitors, which is a mouthful, are the most commonly used class of antidepressants in all age groups. So, from children to adolescents, through geriatrics. This class of medication has been around since the '80s with Fluoxetine being the first one that came to market. And currently we have six SSRIs on the market. These are Fluoxetine, or Prozac, Paroxetine, Sertraline, Fluvoxamine, Citalopram, and Escitalopram. And these medications work by increasing serotonin levels, but it does get a little bit more complex than that.

For almost 75 years, so since around the '50s, we've conceptualized the underlying cause of depression, and some types of anxiety as a decreased activity in three brain chemicals or neurotransmitters. So, serotonin, norepinephrine, and dopamine. Serotonin became the primary target of most antidepressant medications, and I think of it as our content neurotransmitters. So, when serotonin functions properly, we feel content, and when we feel content, serotonin symptoms function properly. So, it's sort of a give and take between these two things.

Depression and anxiety are associated with a deficiency of serotonin, and SSRIs seem to restore proper function and proper balance. They do this by increasing activity. But more recently we've discovered that while they directly increase serotonin levels, that's only part of the story. This happens within days of starting SSRIs, but we know that they take weeks to months to have full effect, and there are further downstream effects that happen after taking these medications for months.

So more recently, we've discovered that directly increasing serotonin as only part of the story, these medicines increase serotonin levels within days of taking the medication. However, longer term use of two or more months has been associated, one with more improvement, but also a number of other changes including increased neuroplasticity. So, when we are depressed or chronically anxious or chronically stressed, it appears that our brains get stuck, in a way. We get stuck in this depressed or chronically anxious or stressed-out state, and our brains are less flexible in how we think, they're less adaptable to change, and this is due to this decreased neuroplasticity or decreased flexibility.

So, what can this do? Well, it impacts motivation, concentration, level of energy, even how we engage in the world around us. And what we find is when we use SSRIs with chronic anxiety or depression and they work, along with therapy like cognitive behavioral therapy, things like exercise, even exposure to nature, changes in diet, all of these things improve this neuroplasticity. They improve how adaptable our brains are. And this explains, in part, why it takes so long for these medications to work. If our brains are stuck and inflexible and we're trying to improve that, I use the analogy of if I break my leg, it takes a long time for me to recover and get strength and flexibility back in my leg. In this case, the medicines are helping that happen.

Syma Khan: 

Thank you very much for the introduction. So, there are a number of SSRIs that are approved for the treatment of depression and others that we utilize for depression in pediatrics, but are actually approved for other indications by the FDA. Can you talk a little bit about which SSRIs are safe for pediatrics, they're indications both on-label and off-label, and which SSRIs should be avoided in pediatrics?

Amy VandenBerg:

Sure. SSRIs are all approved to treat depression in adults. Some are also approved in pediatrics, and some are also approved for various anxiety disorders. The most, well-studied SSRI in pediatrics is Fluoxetine, with indications for obsessive compulsive disorder and depression. Fluvoxamine and Sertraline are FDA approved for OCD, and Escitalopram is approved for depression and generalized anxiety in children. So, this means we have safety data, we have efficacy data in this population for these medications. Celexa or Citalopram and Paroxetine are two agents that do not have FDA approvals in patients under 18. There's some evidence for them, but they're not FDA approved. And because that, we generally avoid those.

Dr. Christina Cwynar: 

Yeah, and I think it's good to remember as providers, there's reasons why we use these medications, and choosing carefully which ones we're using and thinking about that as well. I know I've had patients come in on some of these meds, the ones that aren't approved by the FDA for pediatrics, and did they get themselves into some dangerous situations. So just reminding ourselves that there are some reasons, and they're not completely studied in this population at this time. So just remembering that.

Oftentimes when we're talking about patients and families with starting medications for depression, their biggest concern is that medications will change their personality. Can you speak a little bit to common side effects and about the black box warning?

Amy VandenBerg:

Sure. So, I'm going to tackle those as two different things. We'll first talk about the personality question. So, medications for depression improve symptoms of depression. We talked about neuroplasticity. So, they improve our ability to adapt to change and cope with stress and effectively interact with what's going on around us. This may come across as a change in personality. If I have a child who's depressed, they may be withdrawn and irritable and not socializing, and now on the medication, if it's working, they may seem more outgoing. Or I may have a child who starts a medication and they get adverse effects from it. They have headaches, they have upset stomach with it, and now they're more irritable and maybe more withdrawn or grumpy because they don't feel good. But this isn't a change in their underlying personality. The things that drive development or personality is much more complex than something that a medication could just change.

The other concern you mentioned is about the boxed warning for suicidality. So, this boxed warning is for any medication that is FDA approved for the treatment of depression, regardless of what class it's in. And the warning goes up to patients who are 24 years of age. There's a few caveats to this warning. One is suicidality as the term was used in this warning ranged from everything from superficial self-injurious behaviors, say scratching yourself without any suicidal intent to suicide attempts. So, there's a wide range of what was considered suicidality when they developed this warning.

The studies that were done, if we look at clinical trials of antidepressants in this population, or in any population, almost always exclude patients who have any suicidal ideation. So, these patients are excluded from the trials. We don't have a lot of data there.

The third thing I think about is suicidality is a symptom of depression, and we know these medications take a while to work. We know that they may have physical adverse effects in the first few weeks that make people feel worse even, before they get better. And it's that period of time where we're more concerned. And so, what do we do? Well, we put in place a safety plan. We make sure that things like weapons are out of the homes. But as a pharmacist, I also think about medications. So, can we have somebody take care of the patient's medications, maybe lock them up and administer them? Make sure everybody else in the household who's on medication has their medications locked up. And even looking at over the counter things like Tylenol and Motrin and getting those out of the way and reassessing for suicidality and reassessing that safety plan at every point of contact with a healthcare provider is good as well.

Dr. Christina Cwynar:

I always like to remind patients and families when I'm starting an SSRI or an antidepressant in general that oftentimes we see improvements in things such as energy before we see improvements in thoughts of suicide, or those types of thought patterns. And that's when we get into trouble is when we now have the energy to act on our thoughts. So that's when we need to kind of beef up those safety plans and that watching. But it doesn't mean that that medication is causing that. It just means that we just need to support that patient through that time period a little bit more.

Amy VandenBerg:

Right. And I think at times the suicidality may have been something that somebody didn't want to endorse or it may have been something that was in the background and now that energy is better and some other symptoms are better, it becomes more prominent. But the medications don't magically impart suicidal thoughts into somebody's head.

Syma Khan: 

I really appreciated the reflection about personality, and I think for a lot of adolescents, sometimes they've been depressed or they've been feeling down for so long, it's almost hard to remember what being themself is like. And so, there's an aspect of they feel a little uncomfortable now that that depression is gone. And so, they just need that support to remind them it's okay to feel different and that we want them back to who they are and to be able to enjoy things, because they think there is this degree also of that's almost who they become because they've just felt so bad for so long and they've been coping oftentimes alone for so long that when they get support, it's hard for them to process that. And I think the safety planning piece is essential, because I think we recognize that medications are just one aspect of how we treat depression. And so, making sure we have that solid safety plan is really key as we get them support and treatment for depression.

Dr. Christina Cwynar

Yeah. And thinking about the personality piece of it, I was talking to a young man about starting medications just a few weeks ago, and one of his biggest fear was actually losing his anger. He felt like it gave him an edge. And while his anger was multifactorial, I don't think he fully realized how debilitating it was to his life. So, as we got medication started and stuff, on his terms of course, and with a lot of education and stuff, it's come down quite a bit and he's able to function in his life a little bit better, but he has not lost his edge or his personality. So, I think rest assured, he's still himself.

Syma Khan: 

So, in episode one we talked a little bit about what an adequate trial of an SSRI is. I want you to provide or consider up titration or switching medications, and when should you look at switching classes of medications?

Amy VandenBerg:

So, we talked about you can see some initial benefit with improved energy. I also think of appetite and sleep, depending on the medication we use, as symptoms that improve early on in the first two weeks. Usually when we look at these medications, if I look at a typical clinical trial, it's at least eight weeks long and we have good evidence that we continue to see increasing benefit out to 12 weeks with these medications. So, what I usually recommend is at least four weeks to determine whether or not the medication is helping. If we stop earlier than that, we don't know if that medication was going to help at some point or not.

Now, if somebody's having intolerable adverse effects, they're so nauseated, or they have such a bad headache that they're skipping school, that they can't hang out with their friends, they're missing work, or they're wanting to skip medication because they don't feel good on it, well obviously we would change earlier, but if somebody's tolerating it at least four weeks, we do want to look at what dose we're at. So, if we're starting at a low dose, to prevent some of these side effects from happening, we do want to make sure that we've increased the dose to a reasonable dose before we say the medicine didn't work.

If it does not work, if the patient's not feeling any better, or if they have adverse effects that are intolerable, we can switch to another SSRI. So, it seems odd sometimes. People say, "Well, I don't understand they work the same way. Why would another one work if this one didn't?" And it's interesting, because intolerance or non-response to one does not predict the same with another. And this has to do with what else our bodies do to these medications. So, we have a lot of genetic differences in how we absorb medication when we take it orally, what our liver does to that medication, how it gets into the brain, how it gets out of the brain, and even once it does get into the brain, where does it bind, which receptors does it bind to once it's there?

Unfortunately, we only have tests for a fraction of these genes at this point, and so we can't predict which medication is going to work, but we know there are differences between patients and these things, and that likely explains the differences in tolerability and response. If I have somebody who has not done well on two, or especially three different SSRIs, now we might look at switching to a different class. Especially if somebody has other conditions like migraine headaches or nerve related pain, we may switch to a class called SNRIs.

Dr. Heidi Burns:

So, tell us a little bit more about SNRIs. What are they and how do they work?

Amy VandenBerg:

So, these are now serotonin and norepinephrine reuptake inhibitors. So, they're similar to SSRIs in that they increase activity of serotonin in the brain, but they also increase activity of norepinephrine. So, we have these three chemicals that we think of with depression, serotonin, norepinephrine, and dopamine, and now we're targeting two of them.

Overall, there's limited evidence that targeting two is better than targeting one. They seem to have the same level of response. In adults, there's some evidence that SNRIs may be slightly more effective than SSRIs, but the evidence is pretty variable. What is nice about these medications is they're very effective, in many cases, in treating nerve related pain. So, if patients do have migraines, or if we have somebody who say has some sort of nerve injury or spinal cord injury and they've got nerve related pain, serotonin and norepinephrine work together in those types of pain transmission that's associated with neuropathy, and they help decrease that. We know pain and depression go hand in hand, pain and anxiety go hand in hand. So, if we can improve one, sometimes we can also improve the other.

Dr. Christina Cwynar:

I think that's an important reminder is that these meds can work for one or both of those things, and I know there's some data out there to show that we can use duloxetine specifically just for pain, even without depression on your differential. So, I think you're planning on talking a little bit more about some of this here in a second. So, I'll ask my question and we can move forward, but like many medications that we utilize in psychiatry, some are approved for pediatrics. So, let's talk a little bit about which ones are approved for pediatric, for what indications, and which ones should we avoid in this class.

Amy VandenBerg:

So, as we talked about before, the SSRIs are variably approved in pediatrics for obsessive compulsive disorder, generalized anxiety, and depression, with the exception of Paroxetine and Citalopram. Paroxetine tends to have more adverse effects than some of the SSRIs. It is a little unique. It causes more sedation, it can cause more dry mouth, and because it has a very short half-life, it tends to be very unforgiving for missed doses, which is common in this patient population. So, there's a couple of reasons why we may avoid that one.

Citalopram is very similar to Escitalopram. So, Escitalopram is just a single isomer of this. Escitalopram happens to have the FDA approval, where Citalopram does not. However, we consider the adverse effects and efficacy are likely similar across the two. We just don't have the FDA approval for the Citalopram.

In adults, we use SSRIs for depression as well as these other anxiety disorders, and PTSD, and panic, and seasonal affective disorder. So, while there's variable approval in adults, we tend to consider these things a class effect. So, I would say the same with SSRIs in patients under 18. So, they as a class should work for obsessive compulsive disorder. As a class, they should work for generalized anxiety and depression, even though they have slightly different specific FDA approvals. If we switch over to SNRIs, we have Venlafaxine and Duloxetine are the ones most folks are common with. Venlafaxine is not FDA approved for any indications in patients under 18. There is research with it. There are some trials of Venlafaxine, and it was shown to be moderately effective in some of these studies.

Where we get a little concerned about venlafaxine is in meta-analysis looking at suicidality. It seemed to have a slightly higher marker for suicidality. However, there was wide variation in the data that was included in these meta-analyses, and likely that increased risk is due to a few outliers, and it's really tricky to go back and see where that data came from. So, it may not be preferred because it's not FDA approved and we've got these potential markers, but it can still be used for depression, and in adults it has evidence for anxiety disorders as well.

Duloxetine, we talked about a minute ago, is maybe used. It's FDA approved for fibromyalgia, which is a nerve related pain, in patients 13 or older, and generalized anxiety disorder in patients seven or older, but not for depression. Again, it's FDA approved for depression in adults. We have evidence that it should work for depression, it just doesn't have that specific FDA approval. So, we may use that agent as well.

Then there are two others, Milnacipran, and Levomilnacipran, which are less commonly used in adults as well. They do not have any pediatric indications. So, we typically would not use those.

Generally, SNRIs in this population, I'd say, as well as adults, are not used as first-line options. It's usually a second or third choice unless somebody has a compelling reason to be on it, like migraines or neuropathy or fibromyalgia.

Syma Khan:

I appreciate the overview and review of these different classes of medications. As a social worker, my role is not to prescribe, but I think it's important to be aware of what are the different classes of medications, what are some of the things that people may experience, because that may help guide a patient or family, or may be something that you can just be aware of when you're working with a patient to know, "Okay, they're on a low dose. Maybe we should encourage them to talk to their psychiatrist to check in and say, "Hey, let's move this up," or if a primary care physician may be managing it, that's good background to have.

So, thinking about SNRIs, what are some of the common side effects with this class of medication? Does this class come with similar black box warning as SSRIs do?

Amy VandenBerg:

Sure. So SNRIs tend to be a little more activating, so they may cause more initial anxiety when they're started. So again, they're used to treat anxiety, but because of some of the immediate effects that both SSRIs and SNRIs have, patients can have a slight increase in symptoms of anxiety in the first few weeks. That's transient, and then they tend to trend down over time.

Outside of that, there's a large overlap with SSRI adverse effects. So, the anxiety, some upset stomach, headache. And this isn't about one in four patients that each of those things happen. In adults, this class has been associated with increases in blood pressure, although this doesn't seem to be as much of an issue in children. There are instances of increased heart rate, so tachycardia, in kids. We may watch heart rate. Whether this is due specifically to the medication or due to that sort of transient increase in anxiety and the anxiety driving the heart rate in kids is questionable, but we may watch heart rate in the first few weeks.

The other thing, I think we're going to talk about this a little more later, is patients tend to be more sensitive to discontinuation syndrome with SNRIs than they are with SSRIs. So, SSRIs, if we stop them abruptly, tend to lead to flu-like symptoms. SNRIs, because of their effects on nerve transmission and that nerve pain transmission, if they're abruptly stopped, we can get some additional neuropathic type symptoms. Regarding the suicidality warning, again, all medications with any FDA approved indication for depression have the same suicidality warning.

Dr. Heidi Burns:

I think we can get into the discontinuation syndrome a little bit more, but I think it's also important that we talk about one of the most serious side effects that come with these medications, which is serotonin syndrome.

Let's start with talking about serotonin syndrome, and maybe you can tell us a little bit more about it. What symptoms there are, what causes it, how to manage it, and then maybe we can talk a little bit more about that discontinuation syndrome and what to look for there.

Amy VandenBerg:

Sure. So, serotonin syndrome, or it's sometimes referred to as serotonin toxicity, occurs when there's excessive serotonin activity in the brain. And this is caused by medications in some way, either excessive doses or drug interactions. So, we don't just spontaneously develop serotonin syndrome. It has to be due to a medication. It is exceedingly rare for this to happen with a single medication that increases serotonin. So, there are a few case reports here and there, again, we're talking over 30 or 40 years now since SSRIs have been on the market. There's a few case reports of serotonin toxicity with a single medication at a standard dose, but usually it's multiple medications that increase serotonin by different mechanisms, or medicines that interact in increased levels of medication. So, you're talking about basically medication toxicity.

Older medications like MAO inhibitors had a higher risk of serotonin syndrome when used with other antidepressants, but we rarely use these medications anymore. There are certain antibiotics that are only really used in the hospital or for severe infections. There are certain pain medications that are really only used in the hospital or for severe chronic pain that also increase serotonin. So, if I have somebody on multiple medications that increase serotonin, I become more concerned about it.

To make things more confusing, there's at least six different published diagnostic criteria for serotonin syndrome. So, when we're looking at reports, it's important to see is this the diagnostic criteria that was really more severe case of adverse effects of SSRIs, or was this a toxicity criteria that may have been life-threatening? And that varies in what we find in the literature, but in practice, if we are evaluating somebody for serotonin syndrome, typically we use something called the Hunter criteria based on reports of toxicity of antidepressants, either ... Mostly due to overdose, a few due to drug interactions, but it was mostly an overdose database. So, this is different than what we would expect with, say, somebody who maybe had an interaction and a slight increase in their levels.

So, Hunter toxicology criteria always include some sort of muscle involvement. Typically, myoclonus, sometimes tremor, may involve fever, and may involve altered mental status. So that's the more severe criteria that are used for serotonin syndrome. Again, I've seen other criteria that include things that are more severe adverse effects. Nausea, vomiting, headache, and sometimes fevers. So, we want to be cautious about using the term serotonin syndrome, because not everybody means the same thing.

If I have somebody who's on a combination of medications that I think maybe puts them at risk, one, I know that the risk is highest when they are in the first few days to weeks of being on that combination of treatment. Typically, doesn't present after somebody's been stable on a regimen for months or years. And I'm going to try to put that in patient friendly terms. So, I usually say if you have any strange muscle sensation or muscle tremor, if you get more agitated or confused, any headache, any fever, these would be times that you'd want to present for further evaluation.

Dr. Christina Cwynar:

And I think remembering that while serotonin can present across the spectrum from mild to lethal, it's important that if there's concerns for it, they're presenting to the ER to be assessed for that concern. Because it can quickly progress to some life-threatening complications like rhabdo, and seizures, and coma, and those need to be managed in an ICU level of care.

Dr. Burns, you had mentioned talking a little bit about the management of serotonin syndrome, and I would just comment a little bit about that. But it's really in discontinuing the serotonergic agent and then symptom management from there.

Dr. Burns:

Right.

Dr. Christina Cwynar:

There's not, from my understanding, great evidence for cyproheptadine in these cases. Although that is kind of the default medication that we use.

Dr. Burns:

Right.

Amy VandenBerg:

So, the idea with serotonin syndrome is that it's excessive activity at serotonin 2A receptors, which is blocked by a medicine called Cyproheptadine. If you look at overall outcomes, the overall outcomes are not different, whether I give Cyproheptadine or I don't. However, some patients do feel better sooner with Cyproheptadine. So, if I change ... I'm not changing the overall outcome, but I may change the comfort level for the patient in the first few days of treatment.

Dr. Christina Cwynar:

Thank you. So now that we've reviewed serotonin syndrome, let's switch gears and talk a little bit about discontinuation syndrome.

Amy VandenBerg:

Sure. As the name implies, it happens when we stop antidepressants. This discontinuation syndrome is attributed most to SSRIs and SNRIs of the antidepressants. It occurs on a spectrum. It tends to be more common, and more severe, or prolonged if patients have been on higher doses for a longer period of time. It's not dangerous, but it's uncomfortable for the patients.

I'll get into the symptoms in a minute, but I think sometimes this discontinuation syndrome, or sometimes it's called withdrawal syndrome, gets confused as, well, does this mean I'm addicted to the medication, or my family member's addicted to the medication? What do you mean they're going into withdrawal if they stop it? Doesn't mean they're addicted. It just means that your body has adapted to having this medication on board, you've re-regulated your system with this medication. So, if I take a medicine for high blood pressure and my blood pressure's under control and I stop it, my blood pressure's going to go up because my body has re-regulated to having that on board. It doesn't mean I'm addicted to my blood pressure medicine.

Typically, what happens is within the first couple days, if I abruptly stop one of these medicines, whether it's an SSRI or SNRI, it tends to be flu-like symptoms. People get headaches, they get upset stomach, they can have muscle aches with it. If I get into SNRIs, I mentioned they have some more neuropathic related symptoms, and so patients will talk about having sort of electrical sensations in their hands or feet, or their arms and legs. And then I've also had patients say that they get brain zaps. And that's the best description I've had of them is, "I get brain zaps if I stop my Effexor abruptly," or my Venlafaxine.

So good rule of thumb is if we're looking at stopping a medication, one is why are we stopping it? So if somebody has serotonin syndrome, obviously we're just going to stop the medication. But if somebody says, "Look, I don't want to be on this anymore, I feel fine. I don't think I need it anymore," that's a different discussion. And so, if we have somebody who started a medication for depression, their depression is under control, they've been stable for a year or more, and things are going well, then maybe we do look at is this a time to try to wean off the medication and see how things go? I think it's important to make sure it's the right time to do it. So right before final exams is not the right time to wean off a medication. Right before you move, when there's a lot of family conflict, or other things going on is not the best time to do it. So, picking a time of relative stability where you expect there to be continued relative stability is a good time to start. And then taking off about 25% of a dose at a time, reassess after a few weeks, see how things are going.

What this does, one, is it prevents the discontinuation syndrome, or minimizes it. The other thing is if symptoms start to come back, we can increase that dose back up and we tend to have better outcomes than if somebody has just completely stopped the medication when we're starting back from zero.

Syma Khan:

It's been a really rich discussion of a really big aspect of treating depression. One thought is, are there resources that pediatricians could access regarding education around SSRIs or SNRIs for their patients?

Amy VandenBerg:

Sure, there's a few different resources. I think things like Hippocrates and Lexicomp have general patient information for medications, and the information they have tends to be similar to what you get, say if you go fill a prescription at the pharmacy, it's what the pharmacy gives you. So, there's a handful of databases that have similar information. They tend to, I think, over list adverse effects sometimes in those, which can be scary for patients and family members.

There's another resource which is NAMI, or National Alliance on Mental Illness, which actually coordinates with a group of psychiatric pharmacists to do medication information sheets for patients. They're designed in a little bit different way than what you typically see. So, they include, one, all of the dosage forms, which is nice in this population because then you can see if it's available as a liquid, say if somebody has difficulty swallowing. Also goes into different FDA approved indications and the target symptoms that the medication was meant to treat. They give an idea of how long it takes for the medication to work, questions to ask providers about the medication before you start it, information to give to your providers before you start it.

And then the adverse effects are broken down into these are common adverse effects that are less severe, and here's some rare things that maybe your providers will be monitoring for, but they're unlikely to happen. So, it differentiates those adverse effects instead of just having a laundry list. They also do have some key drug interactions listed in those sheets, which I think are helpful.

Syma Khan:

That's awesome. I didn't know that they offer that resource, so I'll definitely keep that in mind as well. Are there any other closing thoughts or things that you'd like to share?

Amy VandenBerg:

I think ... One of the things I usually close on when I'm talking to patients about medications is that they're part of it, but they're not magic. And so, medications can help treat depression, they can help treat anxiety, but there are other things that can help, and there are other things that can prevent the medications from doing their job, especially if we're looking at teenagers in states that have legal cannabis where it's easy to get it. It may prevent the medications from doing their job, and so if that is something that is in the picture, we want to talk about that really openly and not demonize it, but say, "Look, if we're trying to treat your depression, cannabis may impact the levels of your medication. There's some evidence that it may worsen depression over time." So, what I get is, "Well, it feels good now." It may feel good today, but what seems to be the case is that six months down the line, these things are going to be worse, not better.

And then I end with the things that can help. So, we talked about that neuroplasticity and increasing flexibility of our brain. There's a lot of evidence coming out that things like exercise can improve that. Going into nature. You don't have to go on a 10-mile hike. You can just go sit under a tree and read a book. And that has been shown to improve some of those markers, improve symptoms of depression. And looking at diet. So, we know that high intake of sugar is associated with worsened depression. So, can we cut out one of the Cokes? Can we cut out one of the Starbucks drinks? Can we cut out some of the cookies and add some fruit, or something else in there to get the sugar out of our diet?

None of these things are magic, but I talk about medications may take us 50 or 60% of the way, and if one of these things can take us another 5%, and another one can take us another 5%, now we're starting to get symptoms under control.

Dr. Christina Cwynar: 

Well, thank you so much for joining us today and sharing your expertise. We appreciate your time. Thank you to everybody that tuned in this week. Nurses, social workers, and physicians can claim CMEs and CEUs at UofMhealth.org/breakingdownmentalhealth. You're able to do this anytime within three years of the initial air date. We hope that you join us next time.