Can Antidepressants Stop Working?


– 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.

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