In terms of the new class of drugs called the serotonin/
norepinephrine reuptake inhibitors. Take a look here.
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.
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.
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.
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.
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.
This results in great antianxiety activity and great
antidepressant action with minimal peripheral symptoms.
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.
They are shaking like a leaf if they overdose. And they
sometimes can also develop extrapyramidal side effects.
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.
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.
And in terms of the gastrointestinal system, you can get
increased bowel sounds and complaints of diarrhoea.
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.
Myoclonus is M, and shivering. And in terms of tips there is
tachycardia, increased reflexes, pyrexia and sweating.