SSRIs, SNRIs and NDRIs: Understanding Antidepressants with Josh Maline, PharmD

Podcast Transcript

John Horton:

Hello, and welcome to another Health Essentials Podcast. I'm John Horton, your host.

The use of antidepressants has climbed in recent years as folks seek out solutions for increased stress and anxiety. These medications are first-line treatments for a variety of mental health issues, and they're now used by more than 1 in 10 people in the United States and many other countries. Today, we're going to take a closer look at the more common types of antidepressants while exploring how they work and the differences between them.

Board-certified clinical pharmacy specialist Josh Maline is with us to break it down. Dr. Maline is one of the many experts at Cleveland Clinic who pops into our weekly podcast to help us better understand the way our bodies work. So with that, let's talk about SSRIs, SNRIs and NDRIs to make sense of this alphabet soup of antidepressants.

Welcome to the podcast, Dr. Maline. Thanks for stepping away from the pharmacy for a few minutes to chat.

Dr. Josh Maline:

Hey, John, thanks for having me on the podcast. Happy to be here.

John Horton:

We're glad you could stop by. And I'd like to kind of start things off by talking about how common antidepressants have become as a form of mental health treatment and just how usage has been on a steady rise, particularly among young adults.

Dr. Josh Maline:

Yeah, absolutely. I think, it kind of really all started with COVID, really increased the prevalence of prescription prescribing for antidepressants. I know there were a couple of recent studies last year that said that about 64% of prescriptions had increased from 2020 onward and stuff.

John Horton:

Wow. Well, it was a rough stretch. That's understandable.

Dr. Josh Maline:

It was a rough stretch. Absolutely. Yeah, and I think just from COVID, kind of being in isolation, I know some of us had to keep going in the hospital and things like that, and got a little bit of that social interaction, but a lot of people missed out on that during that COVID time. So obviously, financial stressors, relationship stressors, all kinds of came about from that.

John Horton:

It has been, I mean, these have been some stressful years and we see that in just about every aspect of life. Are there other things being done as far as to help people deal with some of the stress and just handle it a little better?

Dr. Josh Maline:

Yeah, there's some great organizations out there. One that really comes to mind is the National Alliance on Mental Illness, as well as some other public health campaigns that are really trying to reduce the stigma around mental health, as well as just provide some more online resources to really emphasize the importance of treatment.

John Horton:

And one of the things we want to emphasize here is, obviously, that these antidepressant medications are available, but it's not necessarily the only way to go at these issues.

Dr. Josh Maline:

Yeah, absolutely. I think these organizations have done a great way just to overall, just provide better access to care, whether that be online resources, growth in areas like telehealth and virtual appointments to gain access to providers to get medications, but also to increase access to therapy as well.

John Horton:

And it's all part of the solution. And obviously, medication is kind of in there. So that's kind of what we're going to focus on a bit today. So in the most, I guess, basic sense, what is an antidepressant medication?

Dr. Josh Maline:

Yeah, absolutely. Basically, an antidepressant medication is a type of medication that is used to treat depression, as well as other mood disorders by helping balance certain chemicals in the brains that we call neurotransmitters — and those include serotonin, dopamine and norepinephrine. And all of these chemicals play a role in regulating our mood, our emotions and just overall mental well-being. And by influencing these chemicals, they can help improve symptoms of depression, anxiety, maybe feelings of hopelessness or lack of interest in hobbies or activities.

John Horton:

It's so interesting because I think when we do think about our mood and just how you're feeling, you don't really tie it to these chemicals that are running around in your brain. It's one of those things you don't necessarily think about a lot.

Dr. Josh Maline:

Yeah, it's definitely not on your mind, right? It's like we eat a good meal or we hang out with friends, and those dopamine or those chemicals sort of increase and that sort of contributes to it, but there's just a lot going around or going on in the background that we're really not aware of.

John Horton:

So if you take an antidepressant, how quickly do these medications work?

Dr. Josh Maline:

That is a great question because when someone is feeling down or depressed, we want to feel better as soon as possible. Unfortunately, these medications do take a little bit of time to work. Really, the studies and research that we have seen can take anywhere upward of four to six, maybe all the way up to six to eight weeks to really see the maximum efficacy of these medications.

John Horton:

Wow, I had no idea it was that long. So there's no just instant happiness pill that somebody can take?

Dr. Josh Maline:

Unfortunately not. But there are things early on when you do start taking antidepressants that we do start to see improvements in. So that could include improvements in appetite, sleep, and just overall improvements in energy and sort of motivation. It's really kind of around week two or so where we really start to see improvements in mood. But there are cases where people do start taking antidepressants and they do start to feel better relatively quick.

John Horton:

Well, let's start with what the most common type of antidepressant is.

Dr. Josh Maline:

I would say probably the most common antidepressant people may be prescribed are what we call SSRIs — get into a little bit of that alphabet soup you talked about earlier. But that essentially stands for “selective serotonin reuptake inhibitors.” And some common ones you might hear of are going to be like Prozac®, Zoloft®, Celexa®, Lexapro®. Those are the brand names of those. That can be a little bit confusing with the generic versus brand names, but that's kind of where those medications initially start with.

John Horton:

So what are these SSRIs? What do they do?

Dr. Josh Maline:

Yeah, so an SSRI — it's kind of in its name — it's a selective serotonin reuptake inhibitor. What does that mean? What does that complicated word mean? Well, essentially, it works by increasing the amount of serotonin — again, that chemical in the brain that helps regulate our mood, our emotions and mental well-being. And essentially, these medications, essentially, when serotonin is released through brain cells, it causes a signal to be sent and then the brain sort of reabsorbs that. So this medication essentially stops that reabsorption, which means more serotonin is allowed to stay in that brain to help improve our mood and reduce those feelings of anxiety and help with depression.

John Horton:

And serotonin is always, I mean, that's kind of the happy chemical that's up in your brain, right?

Dr. Josh Maline:

Yeah, it's definitely one of them. So serotonin, again, is kind … that chemical that helps with our mood and our emotions, all of that. And then, dopamine is the other big one that really is more of our pleasure or reward pathway, but our SSRIs don't really target dopamine. They're mainly targeting the serotonin.

John Horton:

So when would you be prescribed an SSRI? For what sort of mental health issues?

Dr. Josh Maline:

Yeah, SSRIs are our first line for depression, anxiety and post-traumatic stress disorder. And they could also be beneficial as well for those suffering with OCD [obsessive-compulsive disorder].

John Horton:

All right. Well, now let's switch over to another antidepressant, which are SNRIs. I'll let you handle what the letters stand for there, but how are those different than the antidepressant we just talked about?

Dr. Josh Maline:

Yeah, absolutely. So an SNRI or a “serotonin norepinephrine reuptake inhibitor”-

John Horton:

…Easy for you to say.

Dr. Josh Maline:

Right? I've had a little bit of practice, a little bit of practice, but these work really similar to our SSRIs, but they affect two chemicals in our brain instead of just one. Like an SSRI, an SNRI stops the brain from reabsorbing serotonin, but also blocks the reuptake of norepinephrine, which is another chemical that plays a role in our mood, our motivation and our energy levels.

John Horton:

So is it prescribed for similar things as an SSRI?

Dr. Josh Maline:

Yeah, these are also first-line, as well for depression, and then they can also potentially be used for anxiety disorders as well as PTSD [post-traumatic stress disorder]. But because of that norepinephrine component, we do just need to be a little bit more cautious because that is kind of our fight-or-flight response. So having too much norepinephrine could potentially worsen those anxiety or PTSD symptoms initially until our body kind of gets used to those new levels.

John Horton:

It seems like with all of these, there's really quite a balancing act that has to take place.

Dr. Josh Maline:

Yeah, absolutely. I mean, there are times, too, where it may take more, multiple trials of an antidepressant medication to really try to find the one that works best for somebody, but again, also giving enough time and adequate dosing to make sure that these medications are given a fair trial to work.

John Horton:

All right, so we've talked about SSRIs and SNRIs, and whenever you talk about two things that are similar, first question everybody asks is, "Which is better?" So do we have an answer when it comes to these two types of antidepressants?

Dr. Josh Maline:

So from the studies and things, there really isn't one that's necessarily more effective than another. Both, again, are first-line options for treating depression — it really just kind of comes down to one might be a better option for you based on one specific brain chemistry, as well as kind of the symptoms that one may be experiencing.

As a pharmacist, we're always trying to use the least number of medications to treat as many indications as possible. So there are going to be some circumstances where an SNRI works a little bit better for chronic pain, and if they have depression as well, we can use an SNRI. Whereas SSRIs don't really help with that chronic pain.

John Horton:

And sometimes, are they even used together?

Dr. Josh Maline:

Yeah, I would say not necessarily more with the SSRIs or SNRIs are used together just because they target the same serotonin receptors, but we do often combine an SSRI and maybe bupropion or other different antidepressant drug classes to really kind of target all three neurotransmitters that are thought to play a role in that pathophysiology of depression.

John Horton:

Now, one thing we didn't talk about with both of these would be maybe side effects. So when it comes to SSRIs and SNRIs, are there specific side effects with both of them that kind of make them maybe better for somebody as opposed to the other one?

Dr. Josh Maline:

Yeah, honestly, for really most of all the antidepressant drug classes, they have pretty similar side effect profiles and are generally pretty well-tolerated. Some of those more common side effects might include headache, trouble sleeping and maybe some gastrointestinal side effects like nausea, vomiting or diarrhea. But overall, again, these are pretty well tolerated and should generally improve over one to two weeks as somebody gets used to taking the medication.

John Horton:

Now, let's shift gears. We've been exploring SSRIs ... I'm going to mess them up when I say SSRIs and SNRIs. Now, we have a third one to kind of enter the mix here and those are NDRIs, and I'll let you, again, tackle what those letters stand for.

Dr. Josh Maline:

Yeah, absolutely. So, again, these all have to do with that stopping a reabsorption. So an NDRI is our “norepinephrine and dopamine reuptake inhibitor.” And so really, the most common one out of this drug class is going to be bupropion or Wellbutrin®. Again, it has a pretty similar mechanism of action. Again, stops the reabsorption of dopamine and norepinephrine. Like we mentioned earlier, dopamine is kind of our chemical or neurotransmitter that is kind of part of our pleasure or that reward pathway.

John Horton:

So I'm assuming that the reason why it's different than those other two is that it does not kind of deal with serotonin and that's kind of what sets it apart a little?

Dr. Josh Maline:

Yeah, exactly. So this one really doesn't target serotonin at all. So this one, really, is targeting, again, that norepinephrine and dopamine. And so this is actually one of the more activating or stimulating antidepressants. So if someone is really struggling with low energy levels, lack of motivation, things of that nature, maybe bupropion could be a good option to give them a little bit more energy, more pep in their step to get about their day and help with those depression symptoms.

John Horton:

So once again, since we love to compare things here, how do NDRIs compare to those more common SSRIs? And again, is one more effective than the other, particularly when it comes to treating anxiety or depression?

Dr. Josh Maline:

So I think we'll handle the depression versus anxiety a little bit differently here. So for depression, bupropion is also a first-line option. So the great thing is, we have a lot of options we can choose from that we can prescribe someone when they initially come in or present with depression symptoms.

As far as how it differs, like we mentioned, it doesn't really target serotonin, but we can combine it with an SSRI to target serotonin, norepinephrine and dopamine — all three neurotransmitters that are thought to play a role in those depression symptoms.

From an anxiety standpoint, we can absolutely use bupropion if we want to, but because of how activating and stimulating this medication is, I may be just a little bit more cautious or slowly titrate up on the dose just because it potentially could worsen those anxiety symptoms initially until they get used to it.

John Horton:

Are there some situations where you absolutely wouldn't want an NDRI prescribed? I know you mentioned, I guess, if you had anxiety, maybe it wasn't the best thing. Are there some other issues that might come into play?

Dr. Josh Maline:

Yeah, I think the biggest, I guess, area where we wouldn't want to use bupropion is for those individuals who have a seizure history. So bupropion can lower the seizure threshold, making it a little bit more likely for a potential seizure to happen. So that would definitely be an area where I would avoid prescribing bupropion in.

John Horton:

So from everything you've said, it sounds like all of these are effective and work in various ways, but it sounds like everything works a little different for every person. So with all the options that are out there then, I mean, how do you know that you are getting the right medication for you?

Dr. Josh Maline:

It can be a little bit challenging and, again, frustrating maybe from the patient side of things because, like you mentioned, especially with psychotropic medications, each of these medications can work differently in someone. You and I can both take the same antidepressant and have very different responses to the medications, not only from an efficacy standpoint, but also from a side effect standpoint.

So it is really … the treatment is very individualized when it comes to somebody's depression and how we go about managing it. So it's really important that when somebody is coming in for depression that we get a very accurate picture of what's going on so we can try to use, again, the least number of medications to treat as many things as possible there.

John Horton:

Now, you had mentioned that it can take weeks for antidepressants to really kick in and maybe resolve or ease some symptoms. How quickly will it if they're not working and what kind of things should you look out for?

Dr. Josh Maline:

Yeah, so I think really the earliest when we would sort of reassess if they're working or not, from a provider standpoint, would be kind of at that initial four-week period. From there on, we would just assess how things have been going, how has your mood improved, how have your energy levels been? Has your appetite or sleep improved? Those sorts of things. And then, if someone's getting a partial response to those medications or improvement in those symptoms, we could either go up on the dose or maybe augment with a different medication and then, really, reassessing at that six- to eight-week mark to really see how they're doing.

John Horton:

Are there some red flags that would come up immediately if somebody were having issues with a medication?

Dr. Josh Maline:

Yeah, I think if someone was having just extremely intolerable side effects to the medications or maybe increases in potentially suicidal behavior or ideation or having those thoughts, those are definitely concerning, and you would absolutely want to bring those up to your provider as soon as possible.

John Horton:

Yeah, it sounds like, I mean, as with any medication, I mean, you know it's going to do something to your body, so it sounds like communication and really kind of paying attention to how you're feeling and acting and just going about your day are really critically important.

Dr. Josh Maline:

Yeah, it really is. And I think also, too, I think kind of getting the viewpoint of maybe your spouse or friends and family is a great way to … indicator to how well the medication is working. Sometimes, we're not privy to our own mood sometimes, or if there's improvements and things like that. So getting other people's opinions on, "Hey, how have I been lately?" I think is a really good indicator as well.

John Horton:

Yeah, self-reflection is always difficult for a lot of people. You're right. It is good if you have somebody you can trust who can say, "Hey, listen, I don't know if this is working for you." You should probably make sure it's someone you trust and that you're going to listen to.

Dr. Josh Maline:

Yeah.

John Horton:

So if someone's going to take away a few key points from our chat today, Dr. Maline, what would you want that to be?

Dr. Josh Maline:

Yeah, I think I have three major points that I would try to hit home here. So I think the first one would be is that these medications do take some time to work, and it may take multiple trials of different antidepressants to find the one that works best for you. Everyone's brain chemistry is a little bit different and responds to these types of medications differently.

I think my second one would be that we need to try to utilize a holistic approach when treating depression. While medications alone can be beneficial, combining medications with going to therapy, getting adequate sleep and exercise, a healthy nutrition, as well as using mindfulness and stress management strategies have led to better patient outcomes and remission rates.

And lastly, if you are having concerns or sort of side effects with these medications, it's really important to talk with your healthcare provider or pharmacist before making any changes or stopping it.

John Horton:

Dr. Malin, that's a great way to sum everything up, and I think from everything that you've said, antidepressants can be invaluable to people in, I guess, overcoming some of these issues. But it's also important to remember it's not the only thing, and you can also take advantage of, like you said, therapy and just kind of a healthier lifestyle, and all this together could really help.

Dr. Josh Maline:

Yeah, absolutely.

John Horton:

Well, thank you so much for coming in today. This has been a fascinating talk, and I know I've learned a lot, including what all those letters mean.

Dr. Josh Maline:

Yeah, absolutely. Thank you so much for having me on. It's been a pleasure.

John Horton:

Bye-bye. When it comes to taking antidepressants, you have options. Perhaps one of the different kinds of medications, whether it's an SSRI, SNRI or NDRI, can relieve your symptoms. Work closely with your healthcare provider to see what might bring the best results for you.

If you liked what you heard today, please hit the subscribe button and leave a comment to share your thoughts. Until next time, be well.

Speaker 3:

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