Tolerance – When Psychiatric Drugs Stop Working

May 14, 2012 Natasha Tracy

There is an interesting, if perhaps disturbing, phenomenon in psychopharmacological drug treatment. It is the instance where a person initially has a satisfactory response to a medication, getting well, and perhaps staying well for years, only to have the illness come back at a random time in the future. The medication just “stopped” working. We have known about this for a long time with many drugs including antidepressants and anticonvulsants (mood stabilizers) and it’s sometimes referred to as antidepressant “poop-out” (I kid you not).

But this phenomenon goes against even the most basic understanding of medication, so why is it happening?

Tolerance to Medication

More scientifically, this is seen as tolerance to the medication. Tolerance induces a state where the same dosage of a given drug will no longer produce the desired effect and more of the drug, or a different drug, is needed. This is a physiological process and not necessarily indicative of addiction. This will happen with every substance you consume from sugar to coffee to fluoxetine (Prozac).

Tolerance happens because your body adjusts to the drug. Your body actually starts to produce more, or less, of chemicals in response to a drug in an attempt to keep your body at a neutral point (homeostasis). For example, one cup of coffee might have once given you energy, but now, you need two cups of coffee to feel any difference. This is tolerance thanks to the magic of your body. (The same thing can be said of tequila shooters.)

Tolerance is frequently seen to the side effects of medication. For example, when you start an antidepressant, you may get headaches, but after three weeks of being on the medication, that side effect goes away.

Developing Tolerance

And this example with antidepressants and headaches makes sense. When you introduce the drug to your body, your body compensates, and you see tolerance gradually over time. But this is not the case when medications work for prolonged periods of time such as months, or years, and then spontaneously stop working. This prolonged wellness followed by spontaneous tolerance is something we just don’t understand.

No one knows exactly how many people suffer from spontaneous tolerance, but in my experience the number is quite high over long periods of time. It can happen to anyone and does not indicate anything is wrong with the patient or the medication.

What to Do About Tolerance

No one really knows what to do about tolerance either. Sometimes switching to another medication in the same class or another medication in a different class is successful. Sometimes it isn’t. Sometimes a dosage change helps. Sometimes augmentation with another medication is the way to go. Unfortunately it puts people in the position of grasping around in the dark for another medication or medication combination and this can take months to find, all the while the person is suffering from their illness.

The one thing I can say is that an interesting piece of research suggests that spending some time off the medication and then restarting the medication can make it effective again. Do not take this as a recommendation – I recommend you work with your doctor to find the right solution for you. But if you are suffering from spontaneous medication tolerance, I recommend you read or talk to your doctor about this article. (It’s probably too scientific for some, but that’s OK, that’s what doctors are for.)

You can find Natasha Tracy on Facebook or GooglePlus or @Natasha_Tracy on Twitter.

APA Reference
Tracy, N. (2012, May 14). Tolerance – When Psychiatric Drugs Stop Working, HealthyPlace. Retrieved on 2024, July 24 from

Author: Natasha Tracy

Natasha Tracy is a renowned speaker, award-winning advocate, and author of Lost Marbles: Insights into My Life with Depression & Bipolar. She's also the host of the podcast Snap Out of It! The Mental Illness in the Workplace Podcast.

Find Natasha Tracy on her blog, Bipolar BurbleTwitter, InstagramFacebook, and YouTube.

May, 14 2012 at 11:29 pm

Thank you <3
I never really felt any improvement with medication, but I do feel worse after I stop?
I wasn't well while taking them, but I am worse without them, but that is not enough for me to convince me to keep taking them. I need to feel OK, not good, but at least OK.

May, 15 2012 at 7:58 am

Hi Natasha:) I've only experienced one "poop out" of seroquel, I'd been on it for a year. I'm now on symbyax and it is working well, hopefully it doesn't stop. My husband has depression and has had several instances of meds that stopped working. It took awhile but adjusments seem to be helping, not completely,but he is getting somewhat better.

June, 4 2013 at 1:53 am

It took me a few tries on google to find this, I suddenly after 2 years on lamictal started slowly then rapidly cycling. I had no idea what was going on... I am scared... It started with the insomnia and then over sleeping, then with huge bouts of agression... and finally and most concerning self mutilation. I am scared to tell my docter because I dont want to be hospitalized...

Natasha Tracy
June, 4 2013 at 5:45 am

Hi Chelsea,
Please, please call your doctor immediately. I don't know what your doctor will do, of course, but I can tell you that mine wouldn't hospitalize me in that situation - but it's _important_ you deal with it now before you get to the point when you _really_ need the hospital.
Ignoring the problem will just let it get worse and not make it better.
- Natasha Tracy

Paul Ritter
January, 28 2015 at 7:38 am

I realize I am a little late to the party on this thread, but wanted to throw in my two cents. I have a science background, all be it an earth science one, and have spent some time learning amateur psychiatry/psychopharmacology. I just finished a 19 month run with Parnate, an antidepressant in the MAOI class. Worked wonderfully for the first 12 to 15 months, then started the "poop-out" phase. Dose increase brought more side effects with no real relief from the returning symptoms. Doc and I tapered off and are now looking at other options.
The point here is that all these things are, as they state, "treatments". They are not cures. Through my amature studies I have drawn a very strong but humble opinion: there will not be a 'cure' for psychotropic issues (and other illnesses for that matter) until we find a way to safely and effectively understand and then rewire the individuals genetic makeup. It is in fact our genes that tell the CNS how much serotonin, dopamine, etc. to produce. Introducing an outside agent to modify it will last until the genetic programming readjusts the amounts to get everything back in back in balance.
Unfortunately I don't think the above hypothesis will be proven in my lifetime (I am 41 now, 42 on March 28th), but I can see no other way to permanently modify the neurochemicals that take away the depression-anxiety-OCD, etc. I am personally just happy we have some things that help us for a while before having to look elsewhere.

January, 21 2016 at 5:25 am

I was on Lamictal for 4 years. It would work great, then an episode would hit so we would increase it. Then it worked great again for a while. Finally after being on it for 4 years or so and finally maxed out, it just all of a sudden quit working. Pdoc didn't think that was possible and wouldn't change my meds all the while I continued to get worse and finally ended up overdosing and back in the hospital. Hospital pdoc let me try lithium and so far it is working great. i just wonder how long I have till it quicks working for me.

March, 31 2016 at 11:47 am

It has taken me years to find this I have BPD and am taking antidepressants to combat some of my particularly volatile symptoms, the problem I have is it seems my body builds a permanent tolerance for them and most recently my welbutrin/buspirone combo has stopped I've been on "every thing" and I can't function without them my Dr treats me like I'm an idiot/looking for drugs and getting a second opinon isn't really an option. Do you know of any scientific articles about anything related to this that I could perhaps bring to him?

Larry Kinder
May, 19 2016 at 8:12 am

I have experienced the phenomena in the past. My current AD med is Cymbalta. It has served me well for several years but it, also, has a high instance of sexual side effects that viagra and cialis were unable to compensate for. I have attempted to try others but I have found out I have severe withdrawal symptoms. My Dr. has tried weaning me off over time but even that didn't work. I guess as long as I'm not wishing to die I should count that as a win.

May, 19 2016 at 6:19 pm

There is potentially misinformation in this article because stopping your medications can cause a tolerance to grow that can hinder their effect when started again.

August, 26 2016 at 7:04 am

I was taking Paxil for panic disorder and agoraphobia for 15 wonderful years. Finally, it stopped working. I've yet to find anything that works as well. I wonder how long you have to be off before you can go back on it again and it will work.

October, 9 2016 at 12:06 pm

I have taken lithium from 18 years old I have always been well I'm 56 years now had no support from family but managed to have a beautiful daughter a wonderful husband I only worked part time retired at 54 years seroquel lamactoltablet are great too I have had 13 lots of EAT that helped me so much my reasons for bipolar my father has it and my sister abused me at the age of between 5 years to 7 years the pain of keeping that a secret was an enormous feeling of losing my childhood she went on to having anorexia 5 stone and my dad was drinking heavy too it was so difficult to cope but my advice is NEVER drink and take tablets good luck friends xx

November, 14 2016 at 8:17 pm

I am schizoaffective, lamictal keeps my mood in check for the most part but I'm struggling to find a good antipsychotic. Haldol worked wonders for years then I started to get the tardive dyskinesia symptoms so I had to stop it. Over the course of 20 years I've been on basically all the atypicals, I'm trying Fanapt right now and I hate it. I want to try and go back on one or another med that had stopped working in the past. I'm very frustrated, the haldol is out of my system but the Fanapt hasn't kicked in yet and I'm experiencing psychotic episodes. Between this and some medical issues, I'm just glad I have things to live for or else I'd just end it.

In reply to by Anonymous (not verified)

Rochelle Dawson
March, 7 2018 at 1:55 pm

hang in there sweety-we know its not easy

December, 27 2016 at 8:28 am

Nobody can answer the question of if the drug poops out and you go off of it how long do you have to wait before you can go back on it?

In reply to by Anonymous (not verified)

September, 22 2017 at 10:06 am

It depends on the type of drug you are using and how long you've been using it.

April, 21 2017 at 3:31 pm

Built tolerance to neurontin after 14 yrs. After stopping how long should I stay off to loose some of the tolerance?

April, 5 2018 at 4:59 pm

i started feeling depressed in 2002. 2 years after my one and only and much needed baby girl came after having 5 wonderful boys. I thought I should have been the happiest mom in the world. I began seeing a script doctor but each and every single anti-depressant just made me feel more depressed. I don't remember how long this went on, "trying new things" but it seemed forever. The last time I went to see him, he told me that we were out of options. There was nothing left. As I got up to leave, he said that he would give me a call if something new came on the market. That raised no hope concidering everything else made me feel worse. I cried all the way home but didn't give up there. When I got home, I pulled out my laptop and started reading every page about depression and medication. I came across "Lamotrogine" and when I read what it was for and side affects, I felt like I was reading my own Biography. I answered every question that placed me as a "Bipola, OCD and ADHD patient" When I brought this medication to my doctors attention, he right away gave me a prescription. I don't remember how long it took but it felt like an angel reached down into my dark cold lonely hole and pulled me out. I couldn't believe that I started enjoying life all over again. In 2013, I was rushed up to the hospital for severe headache and vomiting. They diagnosed me with a very ugly " doc's words", ruptured brain aneurysm. I had a blood clot in my brain, which he had to abandon surgery to get the clot that caused a very small unnoticeable stroke. "He completedthe aneurysm the next year." 5 month's later, I had to uthenize my favorite maincoon cat, "Ralph". The mouring lasted unusually long. Ever since that, I stopped feeling relief from my medication and fell right back into that dark cold lonely hole. 5 years later, "I'M STILL HERE!!!" Come to realize that Bipolar patients shouldn't take anti-depressants. Lamotragine is a mood stabilizer. I seriously don't know how much longer I have. I'm not getting better and a new symptom to my depression and anxiety is a pounding heart. Starts up in the morning and lasts all day. I don't know what to do with myself anymore. I go from room to room, up and down the stairs, sit for awhile then just cry the rest of the time, swearing at God for not taking me when I was "supposed to die from that aneurysm. I cry all day and feel like it's never gonna change. Lately, I've been thinking about just doing it. I can
t live like this anymore. I hope every night I ho to bed, I don't wake up. I think about ending it so often now, it scares me. I even think about when would be a good time to do it and keep telling myself, I need to be here for my daughter's high school graduation. I use to think that people who killed themselves were selfish, but lately, my thought's are who are really the selfish ones here. Your loved ones should never want you to be in such pain 24-7, but they still call you selfish if you were to do it. I call it "ending your suffering" I love my family and I don't want to die. I want this back under control so I can enjoy the rest of my mom and dad's lives and embrace life with my children and husband. Is there anyone out there that can help"? maybe has heard of successful meds? I really don't know how much longer I can live with this. Every morning my thoughts tend to be pulling me towards the negative.

In reply to by Anonymous (not verified)

Natasha Tracy
April, 6 2018 at 7:44 am

Hi Sandy,
I'm so sorry you're in that situation. I've been there, more than once. There is hope and there is help. I would recommend you try a new doctor. The fact is, there are many options out there aside from lamotrigine, not to mention many cocktails.
I am very familiar with this as I wrote about all the evidence-based options in my book. I highly recommend you look it up. (It's not, in any way, affiliated with HealthyPlace.) It's here:… (You'll find the medication options outlined in the appendix. Discuss those options with your doctor.)
Also, please know there is always help for your suicidal feelings. Reach out. There are many hotlines and numbers listed here:…
I understand wanting not to wake up. I have felt that feeling for years at a time. But it _can_ get better.
- Natasha Tracy

In reply to by Anonymous (not verified)

December, 17 2018 at 3:15 pm

What about seeing a counselor?
Being able to talk about your feelings with someone could help.

In reply to by Anonymous (not verified)

March, 5 2019 at 6:20 pm

Are you still here?

In reply to by Anonymous (not verified)

August, 15 2019 at 12:46 pm

Talked to your doctor about TMS and ketamine infusion

Brad K
May, 31 2018 at 5:50 pm

Seroquel stopped helping with sleep after eight years...I take 450 mg. It was great when it worked but now it’s really hard. Almost seems like it keeps me awake now. I would caution people who take it...not trying to scare anyone.

June, 6 2018 at 5:39 pm

I was on Prozac about 20 years ago. It Worked great for eight years then I became immune to it. Nothing is quite worked his good sense. Do you think if I tried the Prozac now 20 years later it would work again?

December, 17 2018 at 3:35 pm

It seems with certain types of depression medication won't work because it's situational and sadness and medication can only cover up feelings not chemistry issues for so long. I think one might need to consider counseling because no amount of medication can erase traumatic life events or feelings about current life events that one is not happy with. I
Vs chemical depression that one would think that would need a prescription. But is there a way to change the brain chemistry if the medication is not working without medication. ..??
What is the root of the depression??
How, when and why did the depression start?
Is it thinking certain thoughts that fuel that depression?
I'm sure there is not a one size fits all solution but I def think medication is overused these days.
It seems like everyone is medicated these days and that's not the way it always was. It seems there are more side effects on a medication and problems then then initial first problem...that started one thinking about seeking medication.
There are def people who need medications and can't live without it and need medication to stay stable. (bi-polar,schizophrenia..others)
But if one is trying to coverbad feelings with a medication when there is a source that needs to be looked at and possibly dealt with the depression could be the side effect of not dealing with what is actually depressing you....

March, 20 2019 at 6:42 am

I get this... but it happens really quickly. Like, within a month or two of starting the medication. I get really bad panic attacks frequently, and have not found a mood stabilizer/anxiety med/anti-depressant that works, or works for very long.
I'm not suicidal or anything, but my brain is in a constant cycle of feeling nothing to feeling too much, which is so exhausting. I just want something that works.

May, 25 2022 at 10:05 am

I can relate to this. I have been on so many medications over the last 10years I've been in Therapy. I either have bad reactions or if it does work, it's for a short amount of time. A couple of months at the most. My Therapist is going to see about getting me an appointment for Genetic testing to see what will and won't work for me.

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