Speaker 1 00:00 Lange, welcome to Rosalind Franklin University, College of Pharmacy, top 200 drugs podcast. Speaker 2 00:12 This podcast is produced by the pharmacy faculty members to supplement study material for students learning the top 200 drugs we're hoping that our real life clinical pearls and discussions from practicing pharmacists will help you study for your next drug quiz. Dr. Sean Kane 00:28 And now on to the show. Welcome to week three of Rosalind Franklin University's top 200 drugs podcast, spring edition. I'm your co host, Dr. Kane and I'm Dr. Holmes, and this week we're talking about antidepressants. We have a number of different antidepressants, but most of them make up the SSRI category. Could you just tell us a little bit about what an SSRI is, why it works, why it's important. Speaker 3 00:53 So SSRIs work in the treatment of depression and all kinds of anxiety disorders such as OCD and generalized anxiety disorder by controlling the amount of serotonin in the synapse of the neuron. So basically, we're keeping enough of the neurotransmitter serotonin where we want it to be in the brain to really help alleviate symptoms of depression and anxiety. Dr. Sean Kane 01:18 So in the term, it says selective. What does that mean? Or why is that important? Speaker 3 01:23 That means that we don't have as much what we like to call dirty pharmacology, where we're hitting other neurotransmitters, so we're specifically using serotonin to alleviate these symptoms, and not hitting a lot of the other neurotransmitters that may be responsible for a lot of side effects. So in general, it's supposed to be more of a clean profile, just looking at serotonin not having some of the bad side effects associated with others. Dr. Sean Kane 01:49 Now I know that the FDA has released a boxed warning for all SSRIs about suicidal risk and suicidal ideations. What is something that you would tell a patient who brought that up to you? A lot Speaker 3 02:00 of patients are going to ask about the suicidal ideation box warning on their antidepressant because it comes in the med guide given with all prescriptions. And it's important to tell patients that there has been an increased risk of suicidal ideation, especially in younger patients and adolescents. When initiated on antidepressant, it's important that they're having routine and regular follow up care with their mental health provider or the prescriber of the medication, so they need to be monitored on a regular basis, and that they're aware of any changes or disruptions in mood or behavior. They need to contact their providers immediately. Great. Dr. Sean Kane 02:40 So as I understand it, for the most part, because we have a really clean drug, we don't see a lot of side effects, but we still see some, like the typical nausea, vomiting, things like that, other side effects that kind of stick out in your mind. Yeah. Speaker 3 02:53 So a lot of patients will complain of sexual dysfunction associated with SSRIs, specifically ejaculatory disorders, but we also see it in women too. So it's not specific to men necessarily, although some of the older antidepressants and SSRIs will be specific to men in the prescribing information. But we now know with newer studies that sexual side effects affect men and women at a similar rate, Dr. Sean Kane 03:19 and I know at least in the ICU, there's three things that aren't very common but do sometimes come up. One is platelet inhibition, or bleeding disorders that can happen with SSRIs. Two is a lot of times we can't give patients their SSRIs if they have to be intubated. We don't have oral access in them, so we worry about things like withdrawal symptoms. And then finally, every once in a while, we will see patients who present with hyponatremia or low sodium level, usually, this is in conjunction with other medications that can also cause low sodium levels. But it's my impression these are fairly rare adverse events. Speaker 3 03:50 They're pretty rare. And another kind of scary warning that we see on SSRIs is that of serotonin syndrome, and it does exist, but again, it is a rare kind of drug drug interaction, and usually we see this when combined with other drugs that can cause serotonin syndrome. So we think about the tryptans can increase serotonin, and there would be a drug drug interaction with tryptans and SSRIs, leading to potential for serotonin syndrome, which could be fatal if not treated. Dr. Sean Kane 04:20 And also, as I understand it, we have a lot of patients who can tend to get depressed in the ICU, sometimes it comes up that maybe we should start an antidepressant. But I think one thing many providers don't understand is that it doesn't have its antidepressant effect very quickly, right? Speaker 3 04:35 So generally, we tell patients that the antidepressant will take at least, at a minimum four to six weeks to even start having an effect. For depression, patients might initially get a little bit more energy. Their sleep might improve. But if we're treating depression, it's going to be at least a month into therapy. And for anxiety disorders, it's even longer, and this needs to be also at an adequate dose, so it's going to. Take a while for patients to have a response, and it's important to remind them to continue taking the medication, even though they don't feel better. One thing to mention with SSRIs is that they all have a very similar efficacy profile, so it's a very patient specific response. There's no right or wrong answer of which specific SSRI to try initially in a patient, but patients do have sometimes a predisposition to responding to one over the other, and we don't know how they're going to react. So we pick the one with based on what are going to be the most tolerable adverse effects, usually, and see how they do. And it's a bit of a trial and error situation, but in looking at the profile, they're very similar in terms of efficacy. They just differ mostly in the side effects. Dr. Sean Kane 05:42 Well, let's go ahead and get started with some of the specific SSRIs that are on our top 200 drug list this week. So we'll go ahead and get started with citalopram or Celexa. And I remember the brand name because both the generic and the brand name start with C, Celexa, citalopram. That's a great way Speaker 3 05:58 to remember it. So one unique warning with citalopram or Celexa is that recently, they have issued a warning, a box warning on QTc prolongation with this medication, which is new from when the drug first came out. Dr. Sean Kane 06:13 So the next agent is s citalopram or Lexapro, and I think the generic name is kind of interesting, because it deals with the chemical structure of it, right? Speaker 3 06:22 So the s citalopram is actually just the s enantiomer of citalopram, instead of having both the racemic mixture of S and R. So s citalopram s enantiomer. So it's supposed to be a little bit more selective for that component of this agent. Dr. Sean Kane 06:40 And I've heard some pretty interesting pronunciations of s citalopram, but it's really the letter S and then citalopram, Speaker 3 06:47 that's right. So this also does contain an FDA warning about QTc prolongation. Dr. Sean Kane 06:53 So our next agent moving along is sertraline or Zoloft. Speaker 3 06:57 So like the other agents, pretty similar efficacy with sertraline or Zoloft, but with this one, we do tend to see more GI disturbances, discomfort and diarrhea compared to the other, SSRIs. It's nice to use sertraline in certain patient populations that have difficulty swallowing, because it is available as a solution as well. So sometimes we will see this used in pediatric patients, Dr. Sean Kane 07:19 so kind of moving backwards in time to two of the older SSRIs. The first one is fluoxetine, or Prozac. This is available as a capsule, which is called Prozac, and then also a weekly capsule called Prozac weekly. Speaker 3 07:33 That's interesting that it's a weekly capsule. Dr. Kane, why is that? Dr. Sean Kane 07:36 We don't see it very much, but because the half life of fluoxetine is so long and it has so many different active metabolites, patients can get away taking it weekly, as opposed to the other SSRIs that tend to only last about a day. Speaker 3 07:49 Of course, remind patients that they need to take it as was prescribed for them, but in certain patient populations, the recommendation might be made that we could dose it weekly, or if patients miss a couple doses, they're actually not going to feel any of the withdrawal symptoms that they might with other agents. So really important point that, in terms of pharmacokinetics, fluoxetine does have an extremely long half life compared to other agents Dr. Sean Kane 08:14 and Dr. Holmes, when do you typically tell patients to take something like fluoxetine? Speaker 3 08:18 So without a doubt, we always tell patients to take fluoxetine or Prozac in the morning because it tends to be more activating or causing a little bit more energy than some of the other SSRIs, which, if we dose it too late into the evening or around bedtime, we could cause a lot of insomnia. Dr. Sean Kane 08:36 So kind of the other old SSRI that was one of the first of the market is paroxetine or Paxil. And for me, at least, it's difficult to keep the brand names of Paroxetine and Paxil straight from fluoxetine and Prozac. One way I do it is Paxil and paroxetine both start with pa whereas fluoxetine and Prozac don't couple Speaker 3 08:56 clinical pearls regarding paroxetine or Paxil. This is the SSRI that we know has the shortest half life. So patients tend to have serotonin discontinuation withdrawal symptoms. Sometimes when they miss doses, even one dose of this medication, they can feel really crummy as a result of not having the medication on board anymore. So this medication, paroxetine or Paxil, is very important to always taper upon discontinuation. We also associate paroxetine or Paxil with the highest incidence of sexual dysfunction, again, both in men and women, and a variety of different effects from ejaculatory disturbances to low libido to lack of interest, paroxetine or Paxil tends to be a little bit more sedating, so we would generally want to dose it at that Dr. Sean Kane 09:46 time to kind of backtrack and review the SSRIs that we discussed. It sounds like citalopram or Celexa, and S citalopram or Lexapro, kind of its nuance is this QTC prolongation from the FDA, a warning from. Speaker 3 10:00 The FDA, right? And other than that, pretty well tolerated. Dr. Sean Kane 10:03 Then we have Zoloft or sertraline, and we worry maybe a little bit more about diarrhea, but for the most part, pretty well tolerated. Yep. Speaker 3 10:10 And then we have the solution available for certain patient populations. Dr. Sean Kane 10:16 Then we move to our two older SSRIs, fluoxetine or Prozac, which has a long half life. We can even take it weekly, Speaker 3 10:22 yep, and it tends to be a bit more activating than other SSRIs. We typically dose it in the morning, Dr. Sean Kane 10:28 and then finally, paroxetine or Paxil, shortest half life, most sexual side effects, and it may be a little bit more sedating than some of our other SSRIs, but again, pretty well tolerated. Speaker 3 10:38 Yep. That's a good summary of the SSRIs. All right, so Dr. Sean Kane 10:42 moving on past the SSRIs. The next drug class is SNRIs. These are serotonin slash norepinephrine reuptake inhibitors. Speaker 3 10:50 And Dr. Kane mentioned a great way to remember why SNRIs affect two different neurotransmitters. So in French, do like duloxetine, our first SNRI means two so it's hitting two neurotransmitters, serotonin and norepinephrine. Dr. Sean Kane 11:07 So do you see that duloxetine or Cymbalta is used for indications that maybe we don't see Speaker 3 11:12 SSRIs used for, yeah, because of the norepinephrine component and activation, and in this class of medications, we do see SNRIs used for neuropathic pain and other pain disorders where we don't use SSRIs, typically for pain disorders. Dr. Sean Kane 11:28 So as far as the dosage form, it's really only available as a delayed release capsule, so we can't crush it, but we can sprinkle it on something like applesauce, but then you can't chew the applesauce. It has to be swallowed whole, right? Speaker 3 11:41 The adverse drug reaction profile is very similar to SSRIs. We may see a little bit of hypertension, however, because of this norepinephrine component with SNRIs, so due to that activation, you could see a slight increase in patient's blood pressure. Always important to monitor, Dr. Sean Kane 11:59 and as far as some of the Warnings and Precautions, they're pretty similar to what we'd see with the SSRI, so the suicidal ideations, the boxed warning, platelet inhibition, serotonin syndrome, hyponatremia, all of those things that we kind of saw with our SSRIs are also rarely but can be seen with our SNRIs like duloxetine or Speaker 3 12:19 Cymbalta, yep. And one important adverse effect related specifically to duloxetine or Cymbalta would be liver injury associated with this medication, so hepatic enzymes do need to be monitored upon initiation of therapy. Dr. Sean Kane 12:35 The next agent is amitriptyline or elibill. Now this is a totally different drug class. This belongs to the tricyclic antidepressant drug class. Really, that name tricyclic comes from the chemical structure, which is three different rings. Speaker 3 12:47 So structurally, the TCAs inhibit the reuptake of both serotonin and norepinephrine, but they also have some other receptor involvement. So they have some anticholinergic effects, Alpha One blockade and many, many others, histamine, for example, which is why we see a lot of the side effects that we do with TCAs, Dr. Sean Kane 13:08 Dr. Holmes. If a patient asked you, is amitriptyline as effective as something like an SSRI? What would you tell them? Speaker 3 13:15 I would tell them that amitriptyline and other TCAs are absolutely as effective as SSRIs or SNRIs. However, what differs is the safety profile. So these are a higher risk class of medications Dr. Sean Kane 13:30 and kind of piggybacking along that amitriptyline is one of the few medications that in Toxicology is a one pill can kill medication where, if a young toddler were to take a very high dose of amitriptyline that could be enough of a dose to kill them. And then as far as the other non depression indications, we can see amitriptyline for something like neuropathic pain, maybe even migraine prophylaxis, maybe even sleep. Yeah. Speaker 3 13:55 So we can use amitriptyline for a variety of indications. We're using them off label, though, because this medication is old and was never originally studied for these indications. Dr. Sean Kane 14:06 So given the fact that we're hitting a lot of different receptors, I bet an astute pharmacy student would be able to predict some of the adverse effects that we might see because of the receptors that it hits. Speaker 3 14:16 That's right, all of our pharmacy students know the receptor binding profiles very well, I'm sure. But if they forgot, they can always remind patients that they might have effects such as drying up, so anticholinergic effects, which we know as dry mouth, dry eye, constipation, in addition to orthostasis or kind of that dizziness when they stand up, and sedation. Dr. Sean Kane 14:38 Moving on to our next agent, which is chemically unrelated to the drug classes we've talked about, is trazodone or Desyrel. Now I pretty much only see this in the hospital as a sleep aid, but I know it's approved or used for a number of different indications, right? Speaker 3 14:52 So originally, trazodone was approved as an antidepressant, but it's most commonly used as only a sedative. Or hypnotic or sleep aid, as Dr. Kane mentioned, we typically don't get a good antidepressant effect from this medication. Therefore avoid its use for the treatment of depression. However, we may use it as an adjunct therapy in addition to an SSRI or an SNRI, and Dr. Sean Kane 15:16 as far as its adverse effect profile, it's actually fairly similar to our TCAs, so we see antihistamine and alpha one blockade, which we would associate with side effects like orthostasis, dizziness and even sedation, Speaker 3 15:30 and patients can attest to the risk of priapism with trazodone, very rare but serious side effect. Dr. Sean Kane 15:37 Moving on to our over the counter agents, the first is fexofenadine or Allegra. And I actually like this brand name a lot, because Allegra is Italian for Speaker 3 15:45 joy, wow. So Allegra is used for allergies. It's available as a tablet, an orally disintegrating tablet, and the suspension for children, we Dr. Sean Kane 15:54 classify fexofenadine, or Allegra as a second generation antihistamine, which means that it doesn't penetrate into the blood brain barrier, so we don't get some of the antihistamine sedative qualities that we would with a first generation like diphenhydramine or Benadryl. So the next over the counter product has a number of different brand names under the flagship of Visine. The generic products that are available are oxymetazoline, naphazoline, tetrahydrozoline. Speaker 3 16:21 I'm glad Dr. Kane had to pronounce all those. So these medications work by relieving red eye by vasoconstricting the blood vessels within the eye, Dr. Sean Kane 16:30 and it works using the Alpha One receptor. So it's an alpha one receptor agonist. Speaker 3 16:35 When we talk to patients about using these eye drops, as with most eye drops, we definitely tell them to remove their contact lenses before use, and you can replace the contact lenses after about 10 minutes. Dr. Sean Kane 16:46 It's important for any eye drop that the tip of the eye drop bottle should never touch the patient's skin or eye to prevent contamination of Speaker 3 16:53 the bottle, and always wash your hands before and after use. In addition to Dr. Sean Kane 16:57 the ophthalmic formulations, many of these products are also available as intranasal formulations for things like nasal congestion, Speaker 3 17:06 and with those nasal decongestants that are used locally within the nose, usually they have a five day limit on use due to the risk of rebound congestion associated Dr. Sean Kane 17:16 with them. And it seems intuitive, but just to throw it out there. You shouldn't be sharing your intranasal products with a friend. So the final over the counter agent is pheniramine and ketotifen. And both of these are over the counter products. They're in a number of different Visine related products, but they aren't under a specific brand name. Speaker 3 17:35 So these medications prevent histamines from causing vasodilation, which is responsible for a lot of the irritation associated with allergy it also blocks other mechanisms that are responsible for the itching and watering of the eyes. So pheniramine and ketotifen work a little bit different than medications like oxymetazoline, because they work for the allergic conjunctivitis on the antihistamine component where the oxymetazoline is a vasoconstrictor, so it's only working on the congestion or dilation of vessels Dr. Sean Kane 18:08 to kind of summarize the agents that we've discussed today. The first was citalopram Speaker 3 18:13 or Celexa, the next was es citalopram or Lexapro. Then we moved on to sertraline or Zoloft, and we have fluoxetine or Prozac, then paroxetine or Paxil, duloxetine or Cymbalta, the SNRI. Dr. Sean Kane 18:27 And then we talked about a TCA, amitriptyline or Elavil. Speaker 3 18:31 Next we moved to trazodone or Desyrel then Dr. Sean Kane 18:34 for our over the counter agents, the first one was fexofenadine or Allegra, Speaker 3 18:38 then oxymetazoline, naphazoline and tetrahydrozoline. Dr. Sean Kane 18:43 And then finally, we discussed pheniramine and ketotifen. So that concludes week three of Rosalind Franklin's top 200 drugs podcast. I'm your co host, Dr. Kane, and I'm Dr. Holmes. Study hard. Speaker 1 18:57 This has been an educational production by the Rosalind Franklin University College of Pharmacy. Dr. Sean Kane 19:01 This podcast is copyright Rosalind Franklin University of Medicine and Science. Speaker 1 19:06 No participants have any conflicts of interest to disclose. This podcast is for educational purposes only and is not intended to treat a particular patient. This information should not be used in lieu of the judgment of a health care provider. Theme music for this podcast is an excerpt of Metro mass by seesaw released on the Creative Commons. You.