00:01
Treatment with antidepressants
is a very important topic.
00:05
So let’s look at some
of the highlights here.
00:07
Some of the most commonly prescribed
antidepressant medications
include the tricyclics, MAOIs, SSRIs, and
there are also atypical antidepressants.
00:18
So we’ll take a moment to
review the highlights of each.
00:21
When it comes to tricyclic antidepressants,
there are a lot of different
examples as you can see;
imipramine, amitriptyline,
the list goes on and on.
00:30
So the mechanism of action here
is that these medications will
actually block the reuptake of
both noradrenaline and serotonin.
00:39
Some of the major uses include depression,
enuresis, OCD, and fibromyalgia.
00:45
So as you can see, these
medicines can actually
be used for things other than depression,
although they are labeled
as antidepressants.
00:53
Some side effects are anticholinergic
problems like urinary retention.
00:58
And also, you get some alpha-adrenergic
side effects, including sedation.
01:03
So the toxic effects can be
fatal when it comes to TCAs.
01:09
So you’re going to be very careful
to not use these medications
in the very elderly patient.
01:16
And also, you won’t use it in somebody
with suicidal ideation or a plan
because overdose on only a small
amount of these medications
can actually be highly lethal.
01:26
So it causes the three Cs:
convulsions, coma, and cardiotoxicity.
01:33
The mechanism of action again, it’s
inhibiting noradrenaline and serotonin,
increasing their amounts
in the synapse.
01:40
Now, here’s a pearl of information.
01:42
These are rarely first line agents.
01:44
And again, that’s due to
their cardiotoxicity.
01:48
With TCAs, you always want to start
a patient on a very low dose.
01:54
They can get anticholinergic
side effects,
and this may lead to them not being
compliant with the medication.
02:01
Now, if you’re a visual learner, we
listed out the side effects here again.
02:06
So sedation, hypotension,
tachycardia, arrhythmias,
dry mouth, and constipation,
urinary retention, blurry
vision, weight gain,
and again, that ever most important
side effect of lethality,
something to keep in mind.
02:21
The reason that there are
potentially so many side effects
with tricyclic antidepressants is that as
their name indicates, they’re tricyclics.
02:31
So they work at a number of receptors.
02:33
They have antihistamine potential,
they have antiadrenergic potential,
as well as antimuscarinic properties.
02:41
So they really lack specificity, and
therefore, you can get a lot of side effects.
02:45
Let’s move on now to talk about the MAOIs.
02:48
These are monoamine
oxidase inhibitors.
02:51
So here are some drug examples:
phenelzine, tranylcypromine, for example.
02:56
The mechanism of action is
to decrease MAO activity
resulting in a decrease
in amine degradation,
and therefore, increase levels
of amine neurotransmitters.
03:09
There are a lot of different
uses for this medication,
and very importantly, MAOIs, are
used for atypical depression;
something to keep in
mind for your exam.
03:18
They’re also very useful in the treatment
resistant, patient with depression.
03:23
Some of the side effects, very important
to know is the hypertensive crisis,
and also, overexcitation,
CNS stimulation.
03:33
So if you’re a visual learner,
you can check out this graph,
depicting the mechanism
of action for MAOIs.
03:41
And the problem is that these really
prevent inactivation of biogenic amines.
03:46
One really important one
to note is tyramine.
03:50
So therefore, people can actually get an
overload of tyramine in their symptoms.
03:56
And the link between MAOIs and tyramine is
very important to keep
in mind for your exam.
04:02
Note again that MAOIs are useful
for refractory depression,
but they’re again, not first line
because of safety and tolerability.
04:12
The side effects include
orthostatic hypotension,
drowsiness, weight gain,
sexual dysfunction,
dry mouth, and sleep dysfunction.
04:22
Now, the hypertensive crisis is a
potential side effect of MAOIs,
and this can be
potentially deadly.
04:31
And again, this is where that link between
tyramine and MAOIs comes into play.
04:36
So the hypertensive
crisis risk elevates
when people who are taking this medication
eat foods that are rich in tyramine.
04:44
They end up with an
overload in their system.
04:47
And so a lot of patients
won’t tolerate this medicine
because they hardly want to eliminate
from their diet their favorite foods
including wine, cheese, cured
meats, chicken liver, et cetera.
05:00
The hypertensive crisis
comes from tyramine,
which is found in
these favorite foods.
05:05
And MAOs, monoamine oxidase, would
usually degrade the tyramine.
05:11
But because it’s being
inhibited by this medication,
again, people who are
eating tyramine reach foods
end up with an overload and
a hypertensive crisis.
05:21
There’s also another potential drug-drug
interaction for patients who take MAOIs.
05:27
If they’re on any other compound that
increases serotonin in their systems,
such as an SSRI or an SNRI,
then these patients are going to be
at risk for the serotonin syndrome,
and you treat serotonin syndrome by of
course discontinuing the offending agents.
05:46
And you can also use
cyproheptadine as an antidote.
05:51
Let’s talk now about SSRIs.
05:53
Let’s talk now about SSRIs.
05:55
These are very commonly
prescribed medications
and really important to know about
for your exam and clinical practice.
06:01
So, SSRIs decrease the
reuptake of serotonin,
thereby increasing the
neurochemical in the synapse.
06:09
And SSRIs can be used for whole host
of things, not only depression,
but they can also be used for anxiety
disorders, binge eating disorders, panic.
06:19
The side effects are actually
quite mild with SSRIs.
06:22
This makes them a very commonly
prescribed medication.
06:26
There can be weight gain, however,
and QTC prolongation on the EKG.
06:31
There can sometimes be GI distress,
and also sexual dysfunction,
which will lead some patients
to discontinue the medication.
06:39
Again, if a patient is on too
much of this medication,
or it’s overlapping with another
medicine such as an MAOI,
they’re going to be at risk
for serotonin syndrome,
so too much serotonin
in their system.
06:54
And people can also get something called
an SSRI discontinuation syndrome.
06:59
This occurs when somebody has
been on a higher dose of SSRI,
and then abruptly
stops the medication.
07:05
Here’s a visual graph of how serotonin
is being increased by use of SSRIs.
07:12
And note that SSRIs really
have similar efficacy.
07:15
You saw that there are a lot of
different choices you can pick from.
07:19
Well, when you’re choosing the
right medication for a patient,
you’re really going to be thinking about
the side effects profile, and also cost.
07:26
So there are some distinct advantages for
using an SSRI over other medications.
07:31
There’s a low incidence of side effects,
there are no food restrictions, and
it’s fairly safe even in overdose,
although you do have to monitor a patient
for serotonin syndrome in overdose.
07:44
There are a lot of different
uses as we talked about before
that are even beyond
depression uses.
07:51
And then again, a list of some of the
side effects that we talked about before,
noting that in addition to sexual
dysfunction and GI disturbance,
some patients can have trouble
sleeping or get a headache.
08:02
They may have weight changes
on the medication as well.
08:07
When a patient is having a
sexual side effect from an SSRI,
it can be very dissatisfying,
obviously, to their lives.
08:14
And there’s a way to treat that.
08:15
So of course, you could consider
reducing the dose of the SSRI
or switching to another agent.
08:21
But let’s say you have a patient who’s
been severely depressed for a long time
and they’re doing really
well on their SSRI.
08:27
Let’s say they’re taking fluoxetine
and their depression has really
lifted and they’re feeling great
and they don’t want to change
to a different medicine because
they of course don’t want their
depressive symptoms to return.
08:38
Well, you have other options.
08:39
So, two antidotes to the side effects
that cause sexual dysfunction in SSRIs
are things like bupropion
and also mirtazapine.
08:48
They tend to reverse
that sexual dysfunction.
08:51
Now, let’s look at another class
of antidepressants, the SNRIs.
08:56
There are a couple of
examples listed here,
and the mechanism here is that
serotonin and noradrenaline,
and sometimes dopamine are being
increased in a synaptic cleft.
09:06
There are a lot of difference
uses for the SNRIs,
including diabetic
peripheral neuropathy.
09:12
So these medicines have really
great anti-pain properties,
something to keep in
mind for your exam.
09:18
And the side effects are
notable for hypertension.
09:21
That’s something that might
come up on your exam.
09:23
It can also cause
sedation and nausea.
09:26
Here’s another visual
list of the side effects:
possibly, sexual disturbance
again and GI upset,
headache, and keeping in mind
that hypertension can occur
and so can the
serotonin syndrome,
especially when this medicine is mixed
with others like in SSRI or in MAOI.
09:46
So let’s talk about
withdrawal from SNRIs
because this is actually
pretty important as well.
09:51
There is a potential withdrawal syndrome,
and it can be seen after only
one or three missed doses.
09:56
So, a patient taking an antidepressant
who missed their dose or two
and starts complaining of
a feeling like they’re
getting electrical shocks
or zaps in their brain,
that’s probably a patient who’s taking an
SNRI and they’re going through withdrawal.
10:11
There are also atypical
antidepressants.
10:14
There is bupropion, which is an NDRI,
meaning it increases
noradrenaline and dopamine.
10:20
And it has a bit of a stimulating effect
because of those two
chemicals being increased.
10:25
There’s mirtazapine, which
is an alpha 2 antagonist
that can cause weight
gain and sedation.
10:31
And also, trazodone; this
inhibits serotonin reuptake,
and the major side effect of
it is that it causes sedation.
10:38
For this reason, trazodone is actually
frequently used as a sleeping aid,
and that’s because the side effect
of it is, in fact, sleepiness.
10:48
When it comes to atypical
antidepressants and trazodone,
keep in mind that a negative
side effect is priapism.
10:55
So it’s a very prolonged and
painful erection in a man.
11:00
So if you hear about that on your
boards or in the clinical wards,
think about trazodone being the cause.