- [Voiceover] One popular way to treat depression is
with antidepressants, and these are drugs
that help to relieve the symptoms of depression.
But before I talk about them, I want to quickly
go over neurotransmission.
So here we have a neuron,
and neurons receive messages through their dendrites,
which are these branching structures here.
Then that electrical signal is sent down the axon
to the axon terminals at the end.
Here it meets up with the dendrites
of the next neuron down the line.
But these cells aren't really touching,
and the electrical signal, the action potential,
it can't actually jump between these cells.
So how does the message get from one cell to the next?
When the action potential reaches the axon terminal,
the electrical signal is actually changed
into a chemical signal, and here's how it works.
The action potential triggers the cell
to release vesicles full of chemicals
called neurotransmitters, and the vesicles,
these kind of cellular sacs,
they dock with the cellular membrane
and the neurotransmitter spills out into the synapse,
which is what we call the space between these two cells.
Once there the neurotransmitters bump around,
and they can dock onto receptors on the next cell.
When they do, this triggers an electrical signal
in that next cell.
The antidepressants that we are going to
be talking about today work on this synaptic level,
as do many other medications.
Because by increasing or decreasing the amount
of available neurotransmitter in the synapse,
medications can make it more or less likely
that a message will be triggered in the next cell.
Depression itself seems to work on this level.
Studies have suggested that depression might
be caused by low levels of certain neurotransmitters
called monoamine neurotransmitters.
This includes serotonin, norepinephrine,
epinephrine, and dopamine.
Different theories disagree about the relative contributions
of each one, but this is something I want you
to keep in mind when we talk about
how these medications work, because all
of the antidepressants we're going to cover
in this video work by trying to correct this imbalance.
They all cause an increase in the levels
of these neurotransmitters, but they do it
using very different mechanisms.
We're going to cover three classes of antidepressants,
monoamine oxidase inhibitors, or MAOIs,
tricyclic antidepressants, or TCAs,
and selective serotonin reuptake inhibitors, or SSRIs.
So let's start off with these MAOIs.
The clue to how these antidepressants work is in the name.
Monoamine oxidase is an enzyme that breaks down
neurotransmitters that isn't stored in vesicles.
So it's kind of like cellular housekeeping.
Monoamine oxidase inhibitors are drugs
that inhibit the actions of monoamine oxidase.
By inhibiting this enzyme, it actually increases
the amount of neurotransmitter that is capable
of being released into the synapse.
More neurotransmitters in the synapse increases
the likelihood that they will dock onto
the postsynaptic cell and cause an action potential.
The next type of antidepressants
are tricyclic antidepressants.
instead of being named for what they do,
these drugs are named for how they look.
I have a few examples here, and you can tell
that all of them have this three-ring structure.
So tri for three and cyclic for the rings.
Tricyclics work by increasing the levels
of two specific neurotransmitters,
norepinephrine and serotonin.
But the way that they do this is very different from MAOIs.
Instead of stopping an enzyme from breaking down
these neurotransmitters, TCAs work by interfering
with a very different housekeeping mechanism
called reuptake.
Much like you, your body likes to recycle.
It likes to be efficient.
This is even true at the neuronal level.
After the neurotransmitter has released into the synapse,
your body doesn't get rid of it, instead it recycles it
by taking it back up into the presynaptic cell
through these reuptake channels.
Then it can be repackaged into vesicles and released again.
TCAs work by blocking these reuptake channels.
The result of this is that the neurotransmitter stays
in the synapse longer, which then increases
the likelihood that it will dock onto a receptor
on the postsynaptic cell and trigger an action potential.
SSRIs, or selective serotonin reuptake inhibitors,
work the same way, they work by blocking reuptake channels.
But instead of blocking them for both norepinephrine
and serotonin like TCAs, they only block reuptake
for serotonin, and only for very specific
serotonin receptors.
So like MAOIs, here we have a situation where the name
of the drug is a description of what the drug does.
I think of all of these antidepressants, SSRIs are probably
the ones that you are most familiar with
because this class of drugs includes fluoxetine,
which is also known as Prozac.
We have three classes of antidepressants,
and the question you might have is,
how do doctors know which one to prescribe?
Your natural answer might be that they should
prescribe the one that works best,
but it turns out that actually all of these medications
are equally effective as antidepressants.
So maybe you think, okay, if we can't differentiate
by effectiveness, maybe we can differentiate
by side effects.
This is where the main differences lie.
MAOIs and TCAs are the oldest antidepressants.
They are what we call "first generation" antidepressants.
But because they are the oldest, they tend to have
more side effects than more recent drugs like SSRIs,
which are considered to be a second class antidepressant.
MAOIs in particular are notorious for having a lot
of side effects, and this stems from the fact
that MAOIs affect a lot of different things.
Remember we said that they affect all
of the monoamine neurotransmitters,
but we also have to remember that these drugs
don't just increase available neurotransmitters
in the brain, they do it in the entire body as well.
This can cause a lot of different side effects.
For example, MAOIs wind up inhibiting a process
in the liver that helps to metabolize medications.
As a result, people taking them need to
be very careful when taking other prescription
and non-prescription medications.
This is something that you might have been aware of
if you have ever paid attention to drug commercials.
Many of them note things like people taking MAOIs
should not take drug "X", or talk to your doctor
if you are taking MAOIs.
The reason behind this is that if your body can't
break down certain drugs, it might lead
to a dangerous buildup of those drugs in your body,
which could potentially be life-threatening.
But MAOIs don't just prevent the breakdown
of certain medications, they prevent the breakdown
of certain foods as well.
I don't want to get too much into this,
but I would definitely recommend that you Google
the list of foods that people on MAOIs can't eat,
because it is pretty long.
It includes all fruits, alcohols, dairy, some meats.
The list is very long, and actually the diet can
be so restrictive that people sometimes stop
taking the medication.
Because of these side effects, MAOIs are no longer
a popular choice for treating depression,
although they are still used when an individual
has not benefited from other treatments.
Before when we talked about TCAs
we noticed that instead working on all
of the monoamine neurotransmitters like MAOIs,
we said that they only work on two of them,
norepinephrine and serotonin.
Because they are more specific in what they affect,
they also have fewer side effects.
However, for some individuals the side effects
that they do have can be severe.
TCAs can sometimes affect things aside
from norepinephrine and serotonin,
things like histamines.
This can lead to fatigue and sluggishness.
Another problem is toxicity.
TCAs are very toxic at higher levels
and someone could go into cardiac arrrest
if they accidentally or purposefully overdose on them.
So individuals taking TCAS need to be carefully monitored
by doctors, especially individuals who might
be at a higher risk for suicide.
Like MAOIs, the severity of these side effects
make it so that TCAs are not always the first choice
when prescribing antidepressants,
although they are prescribed when people aren't
successful with other treatments.
They are also prescribed for individuals
with bipolar disorder, along with other medications
like Lithium, and this is because
other antidepressants, specifically SSRIs,
can sometimes trigger manic episodes
in people with bipolar disorder.
So TCAs are generally a safer option.
But this brings us to SSRIs.
With the exception of very specific cases
like bipolar disorder, this class of antidepressants
are generally the first choice for individuals
seeking treatment for depression.
This is because they are really effective,
like the other antidepressants, but also because
they have fewer side effects.
This has to do with the fact that they are
the most selective in what they act on.
But like the other antidepressants,
they aren't side effect free, because they also work
everywhere in our brain and our body.
So there are some side effects, and these can include
sleeping problems, weight gain, and sexual dysfunctions.
While these are not life-threatening, these side effects
could have a negative impact on a person's quality of life.
There is one exception to this life-threatening clause
though, and that's a condition called serotonin syndrome.
This rarely occurs for people who are taking SSRIs
on their own, but it can become a problem
if they are combined with other substances
that also increase serotonin.
I've talked about these three classes of antidepressants,
but there are other newer substances
that are also on the market now.
Some of them are combined SSRIs and SNRIs,
so they block reuptake for both serotonin
and norepinephrine, but only for very specific
types of each, so I generally like to think about them
as more restrictive TCAs.
They get all of the benefits of TCAs
with fewer side effects.
Another new kind of antidepressants are NDRIs,
norepinephrine and dopamine reuptake inhibitors.
Also NDRAs, norepinephrine and dopamine releasing agents.
One blocks reuptake of norepinephrine and dopamine,
and the other triggers additional release of norepinephrine
and dopamine, but both result in an increase
of these neurotransmitters in the synapse.
Both of these drugs are really promising.
I'm sure that they'll only increase in popularity
as time goes on, but I really wanted
to mention them here because I think
that they challenge our cultural narrative of depression
being caused by a decreased level of serotonin
because these drugs relieve the symptoms of depression
without influencing serotonin levels at all.
That's just something to keep in mind
because as our knowledge of this topic increases,
how we think about depression from both a medical
and cultural standpoint will change as well.