Fluoxetine (Prozac) & Sertraline (Zoloft) for Depression: UNDERSTAND the Benefits & Side Effects

Updated: Jan 5

This article is a transcribed edited summary of a video Bob and Brad recorded in April of 2021. For the original video go to https://www.youtube.com/watch?v=SKo2JtGBz8c&t=110s

Chris: We’re going to talk about a couple different antidepressants. One is call fluoxetine; the brand name is Prozac. And the second one is call sertraline under the brand name of Zoloft. So, we’re going to use that for depression and we’re going to talk about the benefits and side effects and what to watch for over time when we’re taking these medications.


Brad: And the goal is so that you understand what these meds are, how they work, how to take them, and things that maybe you don’t feel comfortable about. I think once you learn what Chris has to say it’s going to open a lot of information. When you’re educated on something, everything can change.


Chris: Hopefully we’re going to help a lot of people.


Brad: Exactly. So, now we’re going to run this as a format. Chris being the pharmacist, I’m going to be the patient. I come in with my prescription on paper from the doctor. Obviously, I can’t read it because you can never read those prescriptions. He says I got some depression things. I’m not excited about this. I am a little apprehensive that I want to start taking these meds because I don’t know, I heard bad thing about them, and Chris is going to address this. This is something that Chris does very well professionally as a pharmacist, better than other pharmacists I’ve been to for sure. So, I think it’s going to be helpful. So, here we go, Chris, I need this medication.


Chris: All right, hey Brad. I see you had a visit with your doctor, and I guess just for the quick purposes of the conversation, fluoxetine and sertraline are antidepressants, they’re serotonin reuptake inhibitors, which that’s the class of drug they’re in. The consult that I’ll perform on both is the same for both medications.


Brad: So, wait, the fluoxetine and sertraline, I’ve heard those called other names.


Chris: Zoloft and Prozac. Prozac is fluoxetine and Zoloft in sertraline.


Brad: You know, I've got a little gray hair and stuff and those terms I do remember. So, what you’re saying is they’re the same medication but different names?


Chris: They do the same thing. I would consider them kind of like Coke and Pepsi. So, how they’re cola’s, they have little nuances that are a little bit different, but for the most part they’re generally used for the same type of thing. So, for depression, anxiety, there’s certain thing that woman take for their menstrual cycles. There are a couple differences, but we’re going to focus on depression exclusively.


Brad: Okay. So, these two things because the doctor talk to me about both and he decided I’m going to go on this one, but he/she will look at my history.


Chris: The doctor is going to diagnose the patient. So, you went in, and you visited your doctor, Brad. You had some sort of conversation to the amount of where, “You know, I’m just not feeling right. Things aren’t going my way, I’m just down. I’m sleeping all the time, but I don’t feel like I have any rest. I just, I feel really awful.” And really, this season right now with COVID, and this pandemic that we’re dealing with, there’s a lot of people in this boat. We’re in the holiday season which also brings out more depression. So, a lot of people are hopefully going to see their doctors because mental health is tricky to deal with. And there’s 40 million adults that are out there that are really struggling with it. So, if you think there’s even a question, reach out to a friend, but more than likely, go see your doctor. They’re trained to help you. They’re going to come up with a diagnosis which will probably generate a prescription and they might even suggest counseling and other tips, some lifestyle changes, getting more active, trying to get a little bit of better sleep.


Brad: So, with these two medications, either one, am I on this for life? Is this a lifetime prescription?


Chris: No, it’s kind of interesting. When these drugs first came out on the market, Prozac came out in the late 80’s, I believe a little bit before my time and then basically, sertraline followed and then there was Paxil and then there was Celexa.


Brad: I don’t even know what they are.


Chris: Whatever. Yeah, but they’re all just, “me toos.” Basically, from the standpoint, these medications when you’re starting to use them, we use them to create an effect to try and help to alleviate your symptoms.


Brad: So, it’s not a feel-good thing. It’s not like an opioid where you get the buzz.


Chris: No, no. It’s going to take time to improve. You know, when your doctor comes up with this, the original guideline, you’re only going to take this for six months. Now we find that people take this indefinitely. It comes down to you, the patient, and what your doctor, your clinician, decides is ultimately best. Maybe you only need it for 18 months, maybe you only need it for 8 months. Maybe you need it for 5 years. Maybe you need it for 20 years. The set guideline was six to nine months when these drugs were initially invented and brought out on the market. But we’re finding that when people come off the medications, sometimes the depression relapses or comes back. There are some strategies that we’ll talk about too when maybe it’s time for you to go off the drug and we’ll touch on that as we go through this. We’ll pretend that you came in and today we’ll talk, and it doesn’t matter if it’s fluoxetine or sertraline. The points that I make are going to be the same because the side effects and their benefits are generally similar.


Brad: So, how do they work? They go into the nervous system through your brain?


Chris: So, you take the medication, it absorbs into your body, gets into the blood, and it builds up into your brain. What it does is it helps to allow there’s a neurotransmitter called serotonin.


Brad: That’s some nerve stuff in my brain.


Chris: Yeah, and most of it is in your gut, which is one of the side-effect things we’ll talk about at that point. It bathes these nerves and allows them to get some more sertraline and so what that does is helps improve mood. Oddly enough, exercise can raise a certain amount of serotonin as well. There’s a lot of things that do occur from other benefits and we’ll talk about that as we go through this as well.


Brad: Okay. So, what you’re saying, regular exercise could improve my mood?


Chris: Yes. Very much so. That’s something that’s often overlooked and a lot of times when people go down this pathway of depression, they kind of lose interest in things that they may have enjoyed. They kind of stop and they shut down and suddenly, they’re just sitting in their house and maybe they’re just watching TV because they can’t find any excitement or any type of joy or satisfaction. So, at that point you visit the doctor, and this is a lot more involved than what I would deal with, with the patient. You get to this point, and you say, “Hey Chris, I have this prescription. My doctor just sent it to you. I’m going to take the drug fluoxetine today.” And so, I’d be, “Well, Brad. What did your doctor tell you this is for? Did he talk to you a little bit?”


Brad: Yeah. He said I should take one, but I can’t remember how often, and I can’t read his handwriting. So, if I take one a day or two, I don’t know.


Chris: Sure. Well, the way the doctor designed this prescription he’s going to give you a fluoxetine 20-milligram capsule. It’s a normal starting point for a lot of people and we’d like you to take it first thing in the morning, after breakfast. You heard me say first thing in the morning and after breakfast. Those two points are important. Most of the serotonin receptors are in our gut. So, what makes our gut move.


Brad: Stomach.


Chris: Yep, your stomach. Basically, it makes you feel either nauseous, queasy, or can even give you loose stools. So, we want to be careful of that. I want you to eat something first because that slows down stomach transit time. That wave slows down and so it slows down the absorption and kind of eases the gut.


Brad: Put the brakes on a little bit.


Chris: Exactly. That’s not why we’re taking the medication, but that’s one of the first things you’ll notice in that first week while you start it. So, food first, in the morning. Now, you heard me say in the morning. Most of us experience somewhat of an activating effect from these medications. I don’t want to feel like it’s you had a cup of coffee and it’s that spark like you get from a little bit of caffeine. It’s once the drug starts to kick in, you notice more of an alertness. Like “Hey, I’m going to get up. I’m going to brush my teeth, comb my hair, take a shower, and I’m going to get out and get on with my day.”


Brad: But this won’t happen for a week or so?


Chris: Yeah, it’s going to be a gradual build up. Particularly with fluoxetine, Prozac and sertraline, Zoloft. These drugs take about four weeks to really kick in. So, it’s a very gradual process. A lot of times, many doctors tell patients that, but there’s so many things going through your mind when you meet with your doctor, “Oh I’m depressed. Oh my God, what am I going to do?” You feel, “Now it’s even more despair, and I feel even worse.” So, it’s always nice to come and see us, and then we’ll spend a little extra time to make sure you understand it. We’re taking it in the morning, and we’re taking it with food. Well, one of the side effects that can occur is dizziness, and/or drowsiness. That’s something that’s like, “Oh. What’s up with that?” Well, there’s about 10% of the people who get more tired on either drug. So, what we suggest, instead of taking it in the morning, that 10% would be better off taking it at bedtime. So, we just make that simple switch from bedtime or in the evening and suddenly you sleep through that side effect, and you wake up and everything’s just a little bit better. Again, you also heard me briefly say, it takes about four weeks for these drugs starting to work. I mean, some people will report in about two or three weeks that they start to feel some benefits. Interestingly, one of the things that seem to stabilize with depression, specifically is, your sleep seems to get better. Many of the chief complaints when people are depressed are so much that when they’re down and low, they feel like they’re sleeping for 12-13 hours a day, but not feeling restful. They’re just tired, they’re exhausted. Suddenly, you start taking this medication and it gradually gets better. It’s going to be very gradual. There’s an important appointment that comes up in about four weeks for most of these patients that are on these medications. In about a month’s time, you’re going to meet back with your doctor, sometimes they’ll do a Zoom call or even a phone chat, depending upon how COVID has affected the situation. It’s very important to talk to this doctor now because they’re going to ask, “Brad, how are you feeling on this medication?” And we hope the answer is, “I’m starting to feel a lot better. I’m more engaged at work. I’m doing a lot more. I really enjoy the patients I’m seeing. With my videos, I’m way more effective, more effusive. Things are going a lot better for me. Julie, my wife, says things are going well.” I mean, these are things that sometimes people around you notice before you do even. So, your doctor’s listening for a lot of things that you’re saying to them, and they’re going to say, “Okay, Brad. I think this 20-miligram dose of fluoxetine is appropriate for you. I’d like to continue this for a few more months and we’ll touch back in about six months, but if there’s any questions, I’d like you to call me.” So, you go back to your pharmacy to get your refill, because it seems like it’s the right choice. Now, what if it’s the other end? “You know, my stomach is upset, I’m dizzy all the time, I have a headache.” These are side effects that can happen with these medications. A lot of these side effects for most people on any of these drugs, typically get better in about a week, but sometimes they linger and sometimes it’s just not the right choice for you. When a doctor meets Brad and says, “Hey, I think you’re depressed, and I’d like to address that with some medication.” They had an empiric thought, but there’s some companies out there now that can take a saliva swab and will look at your DNA and say, “Brad, fluoxetine is a great choice for you.” When we start with fluoxetine after we have the DNA testing that shows it’s the most appropriate choice, you’re like, “Oh, wow.” Maybe it should have been sertraline, which is the other drug that we’re hitting on here. So, there’s nuances between the two. Like I said, it’s like Coke and Pepsi. They’re colas and they’re the same, but Coke tastes a little different than Pepsi.


Brad: Personal choice. Maybe a genetic component in there.


Chris: Yes. It says your body accepts that molecule, and it helps to raise more sertraline more effectively than the other one. So, that’s kind of what we’re starting to see at least with some of these things that we’re unlocking with genetic codes.


Brad: So, the saliva thing, they’re checking the DNA and they have all these statistics that show one works for me and one doesn’t.


Chris: Basically, it’s a very fancy company and they read the result and then they spit out the answer. It’s like if you do 23andMe, where you’re finding out your genetics, your family history, where you came from, what you could be susceptible to. It’s the whole nine yards, but they’ve done that with medications.


Brad: So, that just narrows it down and probably you’re going to be on the right medication?


Chris: Yes, so this is where we get the right choice the first time. It’s somewhat expensive. I think it’s about $300 and it’s only offered to physicians. It’s not offered to the lay public now. With genetic testing, they show that this is the right choice right out of the gate. It narrows it down. I do know that at least Mayo Clinic in La Crosse, in their psychiatric department, they were using this for a time. I don’t know if they’ve continued with it or not, but it was interesting literature with it.


Brad: But I could ask the doctor.


Chris: If it’s offered.


Brad: But it’s not.


Chris: It’s not offered, and a lot of doctors are into it. The nice thing about these medications, is there’s so many different ones that ultimately, they can make another selection for you that maybe the things that you decided that were affecting you negatively and they can come up with another more positive, more effective choice for you.


Brad: So, the doctor, with their experience and their knowledge, they probably have a pretty good idea on what to give you. They’re going to send you down the right path, but the saliva thing is going to help.


Chris: Absolutely. Again, it’s not standard, it’s expensive. It’s just something that’s more of a sidebar, but if it’s offered to you, I think it’s worth its weight in gold. Most insurance companies are not going to pay for a service like that. It is about $300 so, it’d be something to be aware of, it could be an additional cost, but it might be well worth it. Moving forward, we made that appointment, everything’s going well and, “Ah, great, Brad. Well, I think we’re going to continue with this medication. How are you feeling?”, “I’m starting to feel a lot better”, “Well, that’s great. Here’s your refill Brad. Do you have any questions that you’ve notice about things that have happened to you since you’ve started this medication?”


Brad: Are there any red flags out there?


Chris: There are some things, because with all drugs, there’s risks. So, two things that exceedingly rare, would be serotonin syndrome which would be brought on by taking other medications with this. You pharmacist and doctor would be looking at your profile to make sure we’re not going to get you into trouble. Most commonly see it with the painkiller tramadol, but common is the wrong word because you’re talking an infinitesimally small chance for this to occur, but it’s life-threatening. It’d be things like serotonin syndrome, since we’re going to sidebar it, it’d be something that you feel hot, 104-degree fever, but you didn’t have an illness that brought it on. You can have muscle pain, rigidity, twitching, just not right. You feel agitated, unwell.


Brad: So, you’re saying less than 1%.


Chris: It’s less than 1%. It’s something else that we want to be careful with, but it’s not something that I would necessarily lose sleep over. If suddenly you wake up, you’re on these medications may have triggered it, yeah, you need to have a conversation with your doctor ASAP or go to the ER. Along with that 1% side effect, the other thing is, a lot of times, young kids will be prescribed these medications now, although there may be off label, but you’ll see particularly the age for male patients, particularly from 18 to 24, 1% of the time, they have suicidal ideation, where they think that they want to hurt themselves or end it all. It’s a big deal and we see it more with male patients than female patients. It’s something I think, if a parent comes in, and let’s say they have a 14-year-old or a 16-year-old young male, I’m going to be like “Hey, did your doctor talk to you about the possibility that your son may have suicidal ideations?”


Brad: So, you’re talking statistically, right?


Chris: Yes. Statistically speaking that you have a higher risk for suicide in that first 7-10 days of taking medication. A lot of times when we’re depressed, our thinking is not very clear. You can’t connect the dots. So, when we get on the medication, everything becomes more linear. Everything’s just a straight line. It’s like, “I feel miserable. I’m awful. I’m going to end myself.” And they connect those dots and it’s very tragic. The medications for whatever reason, in this small percentage, can lead to it. If you’re a young male, it’s something that, as a pharmacist and certainly as a doctor, they’re going to hammer that home because even though it’s so rare, it’s about as serious as it gets. So, it’s something we want to be careful with. The other thing would pregnancy. So, for our female patients that are either on sertraline or fluoxetine, they can be used during pregnancy, but during that last trimester, it can create some issues for the baby. In a perfect world, if it comes down to being depressed, and everything is awful, or not being depressed, your doctor may weigh out the benefits versus the risk. They may tell you to take it throughout the pregnancy or they may suggest, “Well if you can get off it, we can get through this and then we can get you started at the end of the pregnancy, when postpartum kicks in, to kind of reestablish it. It could be conceivably healthier for the baby.” There’s risk and benefit there.


Brad: There’s going to be a lot of conversation between the doctor and the patient.


Chris: There’s going to be a lot of clinical decisions there that’s best for you, but it’s certainly something you want to disclose with your doctor. We’re pregnant or we’re trying to get pregnant, just things to be aware of.


Brad: To finish this out, with these two meds, you say they’re very similar. What’s the success rate? Are they, in general, because there’s some negative things that aren’t very common?


Chris: I think in general, they’re very successful medications. We have millions of Americans, that successfully used as medications. Some is for a short period of time, and many is for much longer periods of time. I can tell you firsthand that I know people that use these things that have been on it for years, decades.


Brad: And living a successful life.


Chris: Yeah. It’s managing quite well versus not being on it. There are still things that you can do with certain foods and certainly exercising. That’ll go a long way to helping you and we encourage that at every step along the way. I think that’s something that will pay full benefit to it as well. Then there’s always the exit strategy. You’ll say, “When is it time to come off this drug?” Well, it’s something that we want to taper off. You don’t just stop taking it, you go off slowly. So, in the case of a 20-miligram capsule, you’d maybe drop down to 10-miligrams for 2-4 weeks.


Brad: And that happens with the doctor?


Chris: Yes. The doctor will make that determination and fluoxetine and sertraline have different half-lives. So, fluoxetine, you can stop, and it just goes away. Sertraline, not so much. So, one of the things we look at is adherence or how consistently people take medications. With a drug like sertraline, if you skip a dose, you’re going to feel it. You’re going to feel weird. You’re going to have headache, agitated, you can just not feel right. Some people describe it like an electrical sensation in the brain, they call them “brain zaps.” It’s something that with these drugs, the key is to use it consistently, to use it about the same time every day. When you and your doctor decide it’s time for you to come off it, there should be a tapering process. Then we talked about relapse briefly, but s