- Hi I'm Dr. Tracey Marks
and I make mental health education videos.
I got a question from a long time viewer, Rory,
on the issue of whether or not
you can build a tolerance to antidepressants.
Rory says, "If I could request the topic for the new video,
"that would be Medication Resistance and Tolerance Build-up
"or something along the lines.
"I recently got prescribed Zoloft
"to help with my anxiety and depression,
"and it works pretty great.
"However, I'm afraid I might build up
"tolerance to it someday.
"I would love to learn more about this,
"especially if you can give stories
"or examples from your own practice."
Thanks Rory for this question.
The short answer is yes you can.
It's estimated to happen in about 25% of people.
Here's the longer explanation.
This medication tolerance issue
was first noticed in the early 1980s
when we were using monoamine oxidase inhibitors
called MAOIs.
And these were very effective drugs,
but you had to adhere to a really strict diet
of no cheese and other things
or you could have a dangerous hypertensive crisis,
meaning that your blood pressure
could shoot up dangerously high.
Then in 1988,
we got Prozac or fluoxetine
as the first selective serotonin reuptake inhibitor.
And this was innovative
because now we had another option
that promised to have less side effects,
but it didn't take long
before we started seeing the same problem.
The term was called Prozac poop-out.
The classic way this looks is that you take the medication,
then you get a full remission of your symptoms,
meaning that your symptoms resolve
and you're back to where you were
before you started taking the medication.
Then somewhere around four months to a year
you start feeling bad again,
even though you made no change to the medication.
The medical term for this is antidepressant tachyphylaxis,
which is defined as rapid development
of tolerance or immunity to the effects of a drug.
Why isn't this talked about more?
Because it's complicated
and for a while,
we weren't sure if this was a true tolerance build up
or a return of symptoms that was due to other reasons.
And here are five other reasons
that you can have a change
in your response to your medication.
Number one, changing generic medication.
Different generic brands of the same medication
can have different side effects and different effectiveness.
I did a video explaining how generic medications
can work differently
and I'll put a link in the description
and in the corner of this video.
In my own experience,
I've had patients who were doing well on their medication,
and then they noticed that their pills changed color
from like yellow to blue.
Then sometime later,
they started feeling worse.
What I did was change them to brand necessary
or write that they can only take
a certain generic brand that we know worked.
And I would have to actually write that on the prescription.
By taking the original brand name drug,
you at least know what you're getting each time
and you don't have to factor in any differences
and how the drug is packaged.
Second reason, not being on enough drug.
Some doctors choose to keep you
on the lowest possible effective dose,
and other doctors will overshoot
and you have a dose
that may be a little higher than you need.
The reason to be on the minimum is to reduce side effects
because sometimes as you increase the medication,
side effects can show up
that you didn't see at the lower dose.
But it could be that your low dose
is just keeping your head above water
and if you start to have worsening symptoms,
the dose that you're on
doesn't keep you from slipping beneath the surface.
So that's the reason to overshoot a little bit
so that you have more room for your depression
to fluctuate in intensity
without noticing much difference
because the medication is covering you.
Third reason, having another medical issue.
You could have something else that makes you worse
like having a low thyroid functioning,
or low testosterone or even chronic pain.
Yes, there's a connection
between chronic pain syndromes and depression.
People with chronic pain
are more susceptible to developing depression.
Another medical issue to think about
is that if you have an undiagnosed bipolar disorder,
in this case,
antidepressants can, but not always,
make you cycle between episodes
and make you have mixed states.
I did a video on the effect of antidepressants
and how they can affect your bipolar disorder treatment.
Fourth reason, you could be put on another medication
that interferes with your antidepressant
or even causes depression.
Some medications can interfere
with the metabolism of your medication.
Most of the antidepressants
are metabolized by enzymes in the liver.
Here's a simplified illustration.
Let's say you're taking sertraline
that's metabolized by enzyme B in the liver.
Then you see your primary care doctor
and your started on metoprolol for your blood pressure.
Metoprolol is metabolized by enzyme A,
but it speeds up the metabolism of enzyme B.
The medical term for this
is that it induces the metabolic process of B.
Now your sertraline
is burned up quickly in your body
and you don't get the full effect of it
because it's not around long enough.
It could take a few weeks or to a month
to really see this difference in this change.
So you and your doctor may not make the connection
that adding this new drug affected your sertraline.
But all is not lost here.
You and your doctor can check
for these kinds of drug interactions.
That's why it's important to keep a list
of all of your medications
and give it to your doctors,
so that they can know what else you're taking
and can check for the interactions
before they add another medication.
But if this stuff was missed,
like you forgot to tell your doctor
what medications you were on,
you can check for the medication interactions
using the medication interaction checker on WebMD
and I'll put a link in the description for this site.
It's very easy to use,
you type in the medications that you're taking
and press enter
and it tells you if there's any interactions.
If there are,
you can print the information from your computer
and take it to your doctor to review.
I use Medscape's tool which is designed for physicians
and gives more medical information about the interactions.
But listen up if you have chronic pain
and take opioid medications like hydrocodone or oxycodone,
long term opioid use is associated
with developing or worsening depression
because it alters the connections
between the neurons in your brain
and that's a whole other topic of discussion,
but just keep that in mind.
If you're interested neuroplasticity
and how it's related to depression,
check out this video.
Fifth reason is dopamine depletion.
And this is the experience of feeling blunted or apathetic
after you've been taking the antidepressant for a while.
I talk about this in a video
that I did on emotional blunting and antidepressants.
So there's a lot in my back catalog to see on this topic.
With this, you can feel dull
or like you just don't wanna do things
but this effect is different from having all
or most of your depression symptoms return.
In other words, you get better
then you have this low motivation,
no emotions thing creep in,
but you're not crying every day like you were,
or you're not irritable
like you were when you were fully depressed.
So this is still thought to be different
from the full poop-out or tolerance effect.
So those are some other reasons
why you can experience a decline
in how you feel while still taking your medication.
All those reasons aside,
we still do believe that there are some people
who become less responsive to the medication over time
and develop a true tolerance to the medication.
Some studies have suggested
that this may be what's behind treatment resistance,
when we can't get someone to get better
on a single medication or even multiple medications.
We don't know exactly why this happens
but one thought is that in the brain,
prolonged exposure to the antidepressant
changes the serotonin receptors
and how sensitive they are to medication,
so you lose sensitivity to the medication.
What can you do about this?
Here's four suggestions.
The first is to increase the dose of the medication
if you can.
Sometimes this takes care of the problem,
but it can be temporary
and you can have the same tolerance problem
later on down the road.
The second is to decrease the dose or take a drug holiday.
In a 2014 paper the author Steven Targum,
said that the drug holiday may need to last
about three to four weeks,
and this holiday allows the receptors
to become sensitive again.
Now this can present withdrawal issues if you suddenly stop.
So your doctor would probably need to do a quick taper
to wean you off the medication over a couple of weeks
depending on your dose,
then you would stay off the medication for several weeks.
Third suggestion is to change to an antidepressant
that works differently.
So if you're taking a selective
serotonin reuptake inhibitor,
you may try a serotonin norepinephrine reuptake inhibitor
like duloxetine also known as Cymbalta.
Medications like mirtazapine or vortioxetine
which goes by the brand name Trintellix, enhance serotonin
but do it by a different mechanism
of activating receptors directly
rather than inhibiting the reuptake of serotonin
at the receptor site.
The fourth option is your doctor can give you
an add-on medication like aripiprazole or lithium.
I talk in more detail about medication augmentation
in my video on treatment resistant depression.
So there's a lot of information here to chew on.
I think the takeaway here is that
a minority of people develop tolerance to antidepressants.
However, if this is your first
or second episode of depression,
we generally recommend that you take medication
for six months to a year before weaning off
and then waiting to see if it returns.
So it could be that you get off the medication
before tolerance becomes an issue.
That's a little different
if you're taking the antidepressant for anxiety
because anxiety can last longer than six months.
But there are other behavioral ways to treat anxiety
and other medications as well.
So you don't need to live in fear
that you're gonna run out of treatment options.
Check out this video that I did on the depression diet.
It's great information about how the right kind of diet
can improve your depression.
I think it's a big deal
that you can improve your mood with what you eat.
Don't miss it.
See you next time.