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SNRIs, Serotonin Antagonists and SSRIs – Antidepressants

by Pravin Shukle, MD
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    00:01 In terms of the new class of drugs called the serotonin/ norepinephrine reuptake inhibitors. Take a look here.

    00:08 So now these drugs are getting more and more specific to act on either norepinephrine or serotonin, and this group of drug acts on both relatively equally. So in terms of the profile, they are similar to the tricyclic antidepressants but because they are more specific, we have fewer side effects peripherally. Now SNRI's do not have a blocking effect on the peripheral tissues and in particular they don't have blocking effects on the post-synaptic neuron like the other drugs.

    00:38 The classic SNRI is Cymbalta. It's a very widespread drug used almost everywhere in the world. It's used in major depressive disorders. It's also interestingly used in neuropathic pain. So many of my patients who are diabetic who have neuropathic pain are on this drug. The most popular antidepressant in Canada is venlafaxine or Effexor or Effexor XR.

    01:08 It is a heavily prescribed drug because it has relatively few side effects and it has less affinity for norepinephrine than duloxetine. The side effects, it do include a decrease in blood pressure which sometimes is a benefit because a lot of our patients have high blood pressure. The side effect profile is similar to the newest class of drugs which is called the SSRI's which we will talk about later. There are some withdrawal symptoms. So if a patient misses even one dose you can see withdrawal symptoms develop. So the drug company developed Effexor XR which is the extended release version of this drug which somewhat mitigates that disadvantage but it's still there. So it's important that this drug be used in those patients who are very compliant or very adherent to medication regimens. Let's talk about the serotonin antagonists.

    02:12 The acronym is SA or 5-HTA but we use SA's more now. Now you can notice here that we are no longer talking about the norepinephrine receptor system right. We are now focusing on serotonin. So this is a relatively targeted activity against the serotonin receptor which is a G-protein mediated event. These are located in the neocortex of the brain. This results in better antianxiety activity and better antidepressant activity as well. So the SA's block the serotonin 2A receptor. As I said before it's a G-protein coupled receptor. It's located in the neocortex. It's a short acting drug.

    03:01 So we often have to prescribe it 2 or 3 times a day. These are some of the examples. Now this particular drug, I'm not even gonna mention it because it's not used because of it's severe interaction with cytochrome system. But trazodone is a very commonly used SA. It's used as a sleep aid. Many of my patients are on it. It's quite effective and it seems to be a lot better than the benzodiazepines which it replaced. Let's move on to the newest group of drugs. The selective serotonin reuptake inhibitors or the SSRI's. Sometimes these are called serotonin specific reuptake inhibitors with the same initials. Now it causes allosteric inhibition of the serotonin receptor itself. It has minimal or zero effects on the norepinephrine uptake and it binds at a different site to the serotonin receptor, than the serotonin itself does. The nice thing about SSRI's are the minimum side effects.

    04:05 This results in great antianxiety activity and great antidepressant action with minimal peripheral symptoms.

    04:15 These are a list of the SSRI's. And if you only want to remember one, you can remember the top one but in general all of these will come into your hands at some point during your practice. Now in terms of the effectiveness, these drugs have the same effectiveness as the tricyclic antidepressants and fewer almost minimal side effects. In terms of toxicity and overdose, you will see patients develop headache, nausea, anxiety and agitation. They often complain of jitters.

    04:50 They are shaking like a leaf if they overdose. And they sometimes can also develop extrapyramidal side effects.

    04:57 This means akathisia, dyskinesias, dystonic reactions, and we are going to be talking a little bit about dystonic reactions in our Parkinson's disease lecture. And we also mentioned dystonic reactions in our autonomic nervous system lecture.

    05:15 In terms of drug interactions with the SSRI's, with fluoxetine which is commonly known as Prozac, it inhibits the cytochrome system and so therefore you are going to have interactions with multiple drugs. So this fluoxetine will increase the level of dextromethrophan, of propranolol, of tamoxifen and of the tricyclic antidepressants. Now fluvoxemine, also called Luvox inhibits the 1A2 subunit of the cytochrome system. And citalopram which is Celexa affects the cytochrome system as well, but it affects fewer drugs because it actually acts on a more rare isoenzyme. While we are talking about the SSRI's I want to talk about something called serotonin syndrome. Serotonin syndrome was first described as a reaction between monoamine oxidase inhibitors and the SSRI's. It is a life threatening condition. Here's how it presents. In terms of the central nervous system, it's stimulation. So there is severe muscle rigidity, myoclonus and hyperreflexia. You get hyperthermia And you get seizure and mydriasis. In terms of the cardiovascular symptoms, you get tachycardia and an unstable blood pressure.

    06:42 And in terms of the gastrointestinal system, you can get increased bowel sounds and complaints of diarrhoea.

    06:49 The serotonin syndrome has a mnemonic called MADAM'S TIPS. So I'm just going to go through them for you. M is mental status change which I have mentioned before. A is agitation. D is diarrhoea. A is ataxia or the inability to walk properly.

    07:07 Myoclonus is M, and shivering. And in terms of tips there is tachycardia, increased reflexes, pyrexia and sweating.


    About the Lecture

    The lecture SNRIs, Serotonin Antagonists and SSRIs – Antidepressants by Pravin Shukle, MD is from the course CNS - Pharmacology. It contains the following chapters:

    • Serotonin/Norepinephrine Reuptake Inhibitors
    • Selective Serotonin Reuptake Inhibitors

    Included Quiz Questions

    1. Duloxetine: withdrawal symptoms
    2. Venlafaxine: withdrawal symtoms
    3. Duloxetine: neuropathic pain treatment
    4. Duloxetine: diabetic neuropathy
    5. Venlafaxine: decreased blood pressure
    1. Improved sleep quality
    2. Lowers blood pressure
    3. Improves erectile dysfunction
    4. Assists with smoking cessation
    5. Lowers the seizure threshold
    1. Sedation and dry mouth
    2. Headache and nausea
    3. "The Jitters"
    4. Akathisia and dyskinesia
    5. Anxiety and agitation
    1. 34 year old with depression, currently being treated with a Monoamine Oxidase Inhibitor (MAOI).
    2. 25 year old with depression and is interested in smoking cessation.
    3. 75 year old with depression, currently being treated with a TCA.
    4. 42 year old with depression who enjoys aged cheese and red wine.
    5. 31 year old with depression who failed a trial of SSRI's in the past.

    Author of lecture SNRIs, Serotonin Antagonists and SSRIs – Antidepressants

     Pravin Shukle, MD

    Pravin Shukle, MD


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    By Tinashe M. on 09. June 2017 for SNRIs, Serotonin Antagonists and SSRIs – Antidepressants

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