Can Antidepressants Stop Working?
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Can Antidepressants Stop Working?

October 9, 2019

– 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.

Only registered users can comment.

  1. Thank you for posting this, I've been wondering about this interaction with my sertraline and it feels great to be educated!

  2. I was on 27 pills a day…high BP… and severely over weight. I had 13 major surgeries that took 5 organs… stroke.. severe stomach problem. Today…on NO pills! Lost over 40lbs.. walk over seven miles a week.. and i feel great!! What did I do? I stopped listening to Drs!! Got off the pills and as of now i haven't seen a Dr in 4 years 😊. Stop listening to pill pushers!! Drs are the exact same thing as a drug dealer in the local bar. I actually feel like I did when i was in my 20s and I'll only go to the er if i have an accident..i will no longer be listening to Drs… they lie!!!!

  3. Thanks for another great video. Prozac Poop Out! Sooo funny! It's even funnier because you said it with a straight face. :)))
    I tried Prozac and it gave me BLINDING headaches. I heard Prozac isn't prescribed much anymore because it gave a lot of people migraines. Is that true?

  4. Thanks for this information. Your videos are always well produced and accessible.

    You suggested bringing medication conflicts to your doctor’s attention. Should you stay with a doctor who did not notice a conflict with your medication? I don’t think I should have to notice conflicts and advise my doctor. I’ve had a doctor mess up my prescriptions. He’s at the top of his field as a specialist; however, he can be sloppy, careless, uncommunicative and unprofessional.

  5. So many variables. That in itself is depressing! Thanks for laying it all out for us, Dr Mark's. Knowledge is power! – dj

  6. If I could request a topic for the new video I would like to know how bad the consequences are for a person who is schizophrenic or has schizoaffective disoder like I do to go withdraw from their antipsychotic medication

  7. Excellent information. I LOVE that you mentioned diet and how it can effect your moods. We are living in a nation that eats food-like substances and expect our brains to function normally. You can't supplement yourself into health! Eat the food!! Real food, as it comes out of the ground! I have bipolar disorder and learned from a good friend, that wrote a book about using nutrition to combat mental illness, that nutrition matters. I do like QSciences supplement for when I am going through a bad spell with the bipolar. But, it loses its effectiveness if I take it all the time. The real challenge is to remember to start it before I decend into what I call the outer darkness…LOL Gotta laugh about it, crying doesn't help! Thanks again.

  8. Great video, thank you.

    Speaking of MAOI’s, can you give your opinion on them? I was on Nardil and it took away all of my depression and anxiety, but within a month, everything went back to normal.

    What is your opinion on Tranylcypromine? How does it compare to amphetamine, or if it does at all? Does it work on dopamine?

    Thank you! Love your videos.

  9. I take drugs holiday to reduce tolerance, also tricyclic antidepressants work fine and no tolerance but the side effects is not worth it

  10. Loved this new video Dr. as always! I have bipolar disorder and I couldn’t stop wondering if this is the same for bipolar disorder medications, aka, mood stabilizers such as Lithium and Quetiapine. Would love to hear your thoughts about this. Great week!

  11. Thank you dr. Tracey
    I have 2 questions please,
    Can treatment resistant depression happen to bipolar patients? Even when given for example Lamictal?

    Are there SSRIs or antidepressants considered contraindicated for bipolar patients? Even when given with a mood stabilizer?

  12. Doc I'm taking Cymbalta 60mg BID here recently I've noticed if I don't take my Cymbalta everyday that's a I take it today and tomorrow I don't take it right away I noticed there's a changing me did I go a little bit further down but if I take it as soon as I feel that I go back to feeling a little bit better it's just possible to happen like this? I've been taking Cymbalta since it came out on the market of course I'm taking the generic now. 1 other question. Why don't all ADHD medications work the same ? For an example I started out back in 2006 taking Ritalin that didn't work so the psychiatrist I was seeing it put me on Compazine and that medication didn't work either so he put me on Strattera but that medication didn't work either so I tried Adderall and that medication worked ADHD medicines work the same? I will say this about the pain medication it has no effect on whether I feel any better with my Bipolar. And I got one more question for you doc can diazepam stop seizures? Because 2016 I had emergency room in Madison Wisconsin tell me that diazepam stop seizures but in May 2019 a neurologist said that that has a pain can cause seizures why would he tell me that when two other medical professions told me the opposite? I greatly appreciate you answering these questions I would like to send me an email with the answers let me know and I will give you my email address.

  13. Thank god i reduced my dosage now….I skip antidepressant now day by day and felt normal but did not completely stop…

  14. I am fairly confident that I had this issue with the medication called Effexor. I was using it from 2017 until March 2018 and it worked really well at the beginning but slowly started to increase my symptoms back to how they were before taking it. Now I am at a point where I do not even need to take medication 🙂 Effexor was my last one.

  15. Psychiatrists are not scientists … some are not even doctors … since no one understands what SSRI do or how they do it how can they possibly explain why the same drugs are no longer exhibiting the same response?? About 50% of patients improve without drugs if given the opportunity why could it not be that something else changed unrelated to the drugs ?? Psychiatry is built on a belief system based on accepting whatever the Pharmacy reps and pill pushers tell you … if the psychiatrist can't baffle you with brilliance they just befuddled you with bull excrement …. the truth is SSRI drugs do not treat your problem at all … these drugs create a new problem that may mask your current brain illness until it goes away or increases. SSRI drugs are not a cure so much as a competing illness created by the drug. It's like trying to right a listing ship which is taking on water through a hull breach by flooding other compartments. Initially the ship is righted but then the breach is repaired and the ship is permanently at a disadvantage because it is carrying half a cargo capacity of water. Perhaps the breach is repaired ( your brain can repair itself or recover ) and the leaking compartments are pumped out … now the drug flooded compartments are causing the ship to list in another direction ( need to stop the drugs not add more ). Another possibility is the breach continues to add ballast in the affected compartments so the treatment is to add more ballast in the unaffected compartments which can lead to the ship performing a more balanced sinking. Psychiatric drugs are not curative and they do not balance out brain chemistry … the cure these drugs offer is as bad as the problem … it's like putting a cast on a broken arm and just leaving the cast on forever because you might break your arm again … despite the fact that with the cast you lose 50% of the function in that arm

  16. Different brands of medication can make a difference. I take tramadol for pain and I've notice that some brands have a more stimulating effect while others a more calming effect. So now I keep the different brands for different points in the day, ie I dont use the more wakefulness brand at night.

  17. Great video. Very interesting and informative. Thank you so much Dr. Marks. I'm using Lyrica (pregabalin) for chronic pain for already about 5 years. I did take recently a medication holiday and stopped for about a few weeks in using this medicine. So when I started after that holiday again with this medicine it really does work much better again. I'm having less pains now. I think the brain gets a time out and can 'reset' again. It's like, when your computer is working slower after a time, you use a program to scan the PC well and after that it works faster again.
    So I think it's true, that my brain first got used to the medication and it didn't work not so well anymore after using it for 5 years.
    I like to do this medicine holiday time more often in the future.

    My question to you Dr. Marks is do you have any idea what might be a good time to take such a holiday? After one year maybe or so?
    Thanks again for this professional video. I have learned a lot I didn't know of. You explained it all very good doctor Tracey.
    Greetings from Ben in the Netherlands 😃🇳🇱

  18. Pls make a video about selfharm.thanks🌹
    And how to know what i feel its the effect of meds or my high or low of bpd or its normal. im confiuse about my feeling are heathly or not

  19. Thanks as always, Doctor. I was on a minimum dose of escitalopram for several years, and it mostly worked, but when I recently discussed my situation with my own doctor, he simply doubled the dose. Voila!

  20. Isn't this the story of life generally speaking? When it comes to drugs, you can have your dose upped to a more effective level, but what about people. If you get sick of your wife, it's not like you can get 5 extra milligrams of wife. We constantly quit jobs, move to new cities, and get divorced because maybe the magical things we were taught to think of as inexhausatable are not all that different from drugs. How many times can you ride a rollercoaster until you are scrolling through your phone upside down? Is completing each other's sentences true love, or is that an expiration date?

  21. I don't have 'episodes'. My depression never leaves. I'm in bed all day. Sad everyday. I've been on over 30 medication. Nothing works, or works 20% like ssri, or side effects too hard like snri.

  22. I’m going to do all of your tips. I need all the help I can get. It seems I’m fine for the first few months then everything comes back again.

  23. Can you do a video on building tolerance to adhd meds (mostly stimulants) I've been on vyvanse for nearly a year after taking a couple years off meds (having taken ritalin and concerta in school but getting nasty side effects). The vyvanse worked amazingly to start with but i think ive developed a tolerance because ive noticed myself falling into older less healthy patterns and becoming less focused

  24. I love your videos and find them really helpful! I was wandering if you could do a video on forming a relationship/friendship and supporting someone with ptsd. I recently met someone who has severe ptsd from a previous abusive relationship (physical and mental) but we had to break it off because it got too much for her when she found out I had feelings for her. She is terrified of men and finds it hard establishing trust. She also suffers anxiety, depression, derealisation and has seizures. I would really like her to be apart of my life, even if it's just a friendship. How do I prove myself to her? I also suffer from severe anxiety which hasn't helped. Thankyou for any advice/help 🤗

  25. Thank you for posting, mine stopped working awhile ago,I'm having trouble finding the right one but I hope to get the right one soon. God bless.

  26. I have been diagnosed as bipolar disorder type 2 rapid cycling also i take wellbutrin for about 3 months or maybe even more now i am developing tolerance or lower reaction to it, i take one tablet every day once i mean, should i take it twice or what? knowing that my psychiatrist prescription at first was twice daily and he decreased it because it induced hypomania

  27. I had reverse tolerance to parnate I took it for two months and had to stop my depression was better but side effects were severe this was back in 1981

  28. Great video. I'm schizophrenic and worry one day I might develop a tolerance to anti psychotic drugs. What is the percent of people with schizophrenia develop a tolerance to their medication, if any? ….Thanks

  29. @ Dr. Marks.. How are you happy Wednesday.. ' I was amazed about with video this was a excellent breakdown it's so well needed as always . YOU deliver wonderful presentation of diagnosis about how the body works with medications ) will share video with family & friend's as all ways .) Thank you again stay bless🙏

  30. Good day Doctor. Tracey! I was just wondering, what if a psychiatrist develops depression, anxiety, PTSD or any other mental illnesses, can they prescribe themselves their own medications or can they treat their own selves? Psychiatrists are human beings after all. It is possible that they can also experience mental illness themselves…

  31. do you advise or endorse the use of hemp supplements by any of your clients for the possibilities of mood elevation doctor ?

  32. I developed ototoxicity, tinnitus, and "snow vision" from taking SSRI'S. And I was told I can no longer take an SSRI. Are you familiar with this side effect? Unfortunately this side effect has made me have horrible insomnia..and panic attacks. I've ended up in the ER probably 5 times in the last couple months thinking I was having cardiac issues or a stroke. In the end it all seems to pointed at panicking episodes.. usually induced by these awful symptoms.
    I'm at the point where I just dont know what to do. My depression and anxiety is pretty much out of control. My quality of life is pretty pathetic.
    Have you ever done any videos or research on this?

  33. i am on zoloft for anxiety. i stayed 5 weeks at 100 mb and 6 weeks at 75 mg, instead of getting less anxious i get agitated, ringing in the ears, eyelid twiching, muscle spams and tiredness, it seems that either the dose is too much or this drug is not for me. while i was feeling better in 50 mg before reaching the 100 mg the doc prescribed, u think that my dose is too much or too low ? i will ask the doc to go down to 50 mg or find a more relaxing med. i also take lyrica 75 mg x 3 and it doesnt do much, what do u think doc ?

  34. I've been on Paxil for about 28 years. I don't feel like it's working anymore & maybe I should have it changed. Thank you for the great info!

  35. I suffer from Anxiety Disorder. I have been prescribed prozac 20mg and etizolam 0.5 mg twice a day(short term)… but i am too scared to take them. However my anxiety is making my life more miserable day by day….what shud i do ?

  36. I was on Effexor and had the worst depression I ever had while still taking the medication. I wonder if it was tolerance or just that the medication wasn't working for me. I was on Effexor for almost two years.

  37. Tracey love to know… How do u know when lexpro had a bad reaction in person from first dose… As first time i took it 5mg dropped stuff and had like overstimulation had to cover eyes…… Question is antidepressants how we know normal response to first dose or when to say check with doctor..

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