Hi I'm Dr Tracey Marks, a psychiatrist and I make mental health
education videos.
If you've ever been prescribed an antidepressant medication
like fluoxetine or Escitalopram for either depression or
anxiety, you had to notice that it took a while to work like
weeks. This is different from medications that you take for
pain, high blood pressure, or even sleep.
You can see the desired effect of those medications within
an hour or even sooner.
Antidepressants can take anywhere from two to 6 weeks to
see a therapeutic effect.
You may notice a little improvement sooner than that, but
it's usually weeks, and there's a couple of reasons for this.
The first is due to the way that the drug works.
Medications have to reach steady state in your body before
you can get a reliable effect.
When you initially take the medication, it peaks at a certain
level. Then it drops.
You can take the medication the next day, and then you get
another peak and a drop.
It takes approximately five half lives to reach steady state.
If you have a medication that has a half life of 24 hours,
then it takes five days to reach steady state.
So you take the antidepressant.
Let's say it's s Citalopram brand name Lexapro. Lexapro causes
an increase in serotonin in the nerve synapse, which is a
small space between the nerves.
That increase doesn't fix everything.
The nerve then has to react to the increase in serotonin.
By creating a downstream effect of changing the way the nerves
behave, the nerves go through a process of downregulating
and upregulating receptors to adjust to the artificially
increased serotonin.
These changes happen at a genetic level.
Think of it as the nerve having people in the control room
rewriting computer code that controls the nerves behavior.
It's a complicated process, but suffice it to say that the
rewriting of code doesn't happen in an hour, but it's a domino
effect. The steady state level of the serotonin knocks the
first domino over, and you have to wait until you get all
the way to the end to see the result.
Here's what that looks like on a diagram.
This is the current accepted view of the delayed effect of
antidepressants. You have this increase serotonin, then a
delay. Then you have the downstream neuro adaptive effect,
which is reducing an increasing various receptors.
Then you have a change in mood that causes a change in emotional
bias. What is emotional bias?
A cognitive model of depression is that negative thinking
both causes and perpetuates depression.
That it's not just the thoughts that pop into your head.
It's a negative view of the world.
Depression affects what you pay attention to.
You're more likely to notice facial expressions or negative
facial expressions or spot negative cues in your environment
and draw negative conclusions about things.
This is referred to as a negative bias or negative valence.
There are several psychological questionnaires that have
been developed to assess a person's thoughts, and they're
called scales.
One such scale is the Dysfunctional Attitude Scale, developed
by Arlene Weissman and Aaron Beck, who is considered the
father of cognitive therapy.
Dr Beck developed the Cognitive Triad, which, according
to this view, are key elements behind your depression.
These elements are having a negative views about the world,
negative views about yourself, and negative views about the
future. It's a triangle of thoughts that build on each other.
So the Dysfunctional Attitude Scale is one way to measure
how many of these thoughts you have and what domains they
affect. The actual scale is 80 statements and the statements
address different attitude themes.
For example, my value as a person depends greatly on what
others think of me.
This looks at your tendency to measure yourself esteem based
on how other people react to you.
Here's another one, If I cannot do something well, there's
little point in doing it at all.
This is a measure of perfectionism and rigid thinking.
High scores in this subscale suggests you've set the bar
so high for yourself in the world you're doomed to feel like
a failure.
And this is a setup for feeling hopeless.
So back to the antidepressant, your depressed mood is closely
connected to your thoughts.
Antidepressants ultimately reverse negative biases, but that
doesn't happen immediately.
Neuroimaging studies using functional MRI have shown changes
in areas of the brain like the amygdala, which affects threat
perception in the limbic region, which corresponds to memory
and frontoparietal regions, which affects attention and problem
solving. What researchers have seen is antidepressants produce
a more immediate effect in these regions, which corresponds
to changes in your emotional regulation.
So changes in your Amygdala can result in less threat awareness,
so you're less on edge and maybe less irritated by things
and changes in your attention in memory areas mean you focus
more on positive faces and experiences.
So all of this is to say when you first start the antidepressant,
the early improvements are more likely to be related to your
emotions and less related to your thoughts.
But your negative thinking is the big elephant in the room
that continues to weigh you down and takes weeks to reverse.
So Here's a proposed revised diagram of how antidepressants
work, and this revision is based on the neuro imaging studies
showing the initial emotional response in the brain.
And Here's what it looks like.
First, you get increased serotonin, then after delayed, the
serotonin increase directly causes the domino effect of downstream
nerve receptor changes and directly changes emotional bias
from negative to positive.
Then there's another delay before you have improved mood
due to the positive emotional changes that transform your
thoughts. Now you may say, What about things like sleep and
appetite in depression?
How do thoughts affect that?
Well, the mind is powerful, what you pay attention to and
how you judge a situation determines how you experience the
physical symptoms.
We call this your attention and appraisal.
For example, one study treated a group of depressed people
with fluvoxamine, the people reported improvement in their
sleep. But objective testing showed that their sleep was
worse. But these people felt like they were sleeping better.
Even though they weren't so, thoughts and feelings and behaviors
are all connected.
There is a model still of what we call endogenous depression,
where you develop depressions solely based on brain changes.
But we still believe even that depression affects your thinking.
So which came first, the depression or your thoughts that
might be debatable.
But the mind and the body or one, and the best approach to
depression is to address them both equally.
The mind approach would be through therapy or self help measures
that address your mindset.
And the body approach would be diet, exercise, sleep hygiene,
and medication.
If appropriate, watch this video on psychological flexibility
for more on how your thinking affects how you feel, including
how it's connected to anxiety disorders.
See you next time.