Methotrexate and depression – methotrexate side effects

mtx prefilled syringe

Ok, I have to face it.  Methotrexate and depression.  Methotrexate causes depression. Serious depression.  After three or four weeks of 0.8ml injections (equivalent to 20mg oral) I start to spiral down.  I don’t want to accept it.  I want to tell myself that its mind over matter. And I can overcome these feelings. They are just feelings. Feelings mean nothing without action.

But you can’t control your feelings.  You can’t just stop feeling something, much as you might want to. And it’s a constant battle fighting my own negative emotions.

I am completely anal. I have spreadsheets where I document my medications, dosages, possible side effects and my pain levels.  And I have documented my life with methotrexate many times.  My life with methotrexate and depression.  When I took the tablets, it caused immediate depression. Entirely dose dependent, I could sort of tolerate 7.5mg.  But after a few weeks of only 10mg the depression, anxiety and suicidal ideation took over and I had a psychotic break.  I spent time in the psych ward.  I was given heavy duty anti-psychotics and my GP didn’t think I was coming back from there.

Two weeks later, once the methotrexate was out of my system, I was fine.  All the doctors were astounded. They thought my mental state was due to prednisone.  Psychotic breaks are a well documented side effect of prednisone.  It’s also a known side effect of methotrexate, its just considered very rare.

I don’t believe the link between methotrexate and depression is that rare, its just under-reported, and perhaps disbelieved.  Now I am sure it is absolutely a side effect, and as I search google, I find more and more people reporting same.

I was under a lot of emotional pressure at the time.  Methotrexate can’t create emotions, it acts more as an amplifier.  It brings negative emotions to the fore.  My normal state of being is to be a ridiculous optimist.  I am usually positive and happy.  Genuinely happy.  I tend not to dwell on things I can’t change.  I focus forward and keep moving.

Methotrexate turns that around.  Every morning I wake with a crushing pain in my chest. It feels like grief.  My heart races, I have panic attacks and this sense of impending doom.  I want to cry all the time, and just curl up in bed and hide from the world.

Of course I can’t do any of that, so I just tell myself that it’s mind over matter, and force myself to get up, keep going, get things done.  But it’s exhausting.  And it’s a lie.

I switched to injections, because the side effects are far less, and the drug is better absorbed. I am now taking the equivalent of 20mg, and have been for four weeks.  But I have to stop.  The mood crashes are getting too much.  I can’t live this way.

But I don’t want to stop, because methotrexate gives me 30-40% improvement. That’s the best response I’ve gotten from any drug.  There’s a reason why methotrexate is the gold standard treatment. Most people do get benefit from it.

And 40% might not sound like much, but when it’s the difference between between being mostly bedridden, or having a few functional hours a day, being able to do light workouts at the gym, taking 5mg less of prednisone daily, and 10mg less of oxycodone daily, on average, that’s a pretty big deal.  So I keep trying to take it.

I am one of the most determined people you are ever likely to meet.  The same determination that allows me to work out through the pain allows me to get up and keep faking it and pushing the depression and anxiety to one side.  No one can tell from my behavior what I am feeling.  I appear completely normal.

But I don’t feel normal. I don’t feel OK. It’s getting too exhausting dealing with these feelings.  And it’s getting worse, I’m struggling to keep going.  Even though my pain levels are lower, I don’t want to go to gym.  I don’t want to see people. I’ve almost completely stopped eating,  I just drink wine. Which I shouldn’t be doing AT ALL.

Downward spiral. I recognize it.  But I don’t want the crippling pain to come back. For the pain to be constant again.  The knives in every joint, the screwdrivers prising my joints apart, the deep, aching pain that never, ever stops.

I’m afraid of the pain.  The pain IS that bad.

I spent most of last year on my couch.  I don’t want my life to be that again.

Right now my pain level is about a 4.  I used to live at 7s and 8s, and that was a good day.  I still have those days, but only one or two a week rather than every day.  Most nights are still bad, but some nights I sleep.  I still have fatigue, but that body-made-of-lead-wading-through-a-swamp feeling happens less often.  My hair has thickened up.  My muscles don’t feel like they are going to melt down when I ride a spin bike. I have some strength and stamina.  I can lift light weights.  I can do yoga.  I can have a life.

But the signs are all there.  It wouldn’t take much to tip me over.  And there’s no one here to watch me. No one here to catch me if I start to fall.  And sometimes other people get hurt.  I definitely hurt myself.  I can’t think clearly and I become self-destructive.  And people get caught in the fall out sometimes.  I never hurt people intentionally.  Except myself.

And I only do this when I’m on methotrexate.

My blood work came back yesterday. My liver has recovered, but my doctor told me yesterday my white cell count is getting too low.  I had already taken my shot. But I should lower the dose for that reason alone.  Or maybe stop it completely for a few weeks. Let my immune system recover.

So it can attack my joints again full force.

Maybe there’s a balance point.  Where I can tolerate the side effects, and still reap some benefits.  But 20mg is definitely too much.  So I’ll try 10mg for a few weeks.  And wait and see.

And hope.


  1. Very interesting to hear someone else had an issue with methotrexate causing depression. Like you I’ve some pretty good success with it controlling my joint pain but was confused and unprepared for the “little dark cloud of depression” rolled in. Seems slightly better after lowering my dosage but would have been more prepared if my rheumatologist would have at least mentioned that this could be a possibility. Now I’m learning how to cope and deal with secondary Sjogrens. I never thought parotid glands would end up being such a big deal. But I’m staying positive and moving forward in search of a doctor in Georgia open to exploring the anti-biotic protocol that I’ve read about in Henry Scammells book “The New Arthritis Breakthrough”. Wishing there was a local, monthly support group in metro Atlanta just for RA specifically! If you’re in Georgia and want to chat and share experiences don’t hesitate to contact me at 404-242-5607. I’m determined to beat this thing! Cindy

    • Good for you Cindi – you have the right attitude to beat it, that’s for sure! Wish I was in Georgia. I’ve tried the antibiotic protocol, and while it didn’t work for me, its definately worth a shot. I’m glad you’re aware that methotrexate can causes or intensify depression. The more I post about it, the more people I find who DO experience the same thing. Doctors need to accept this. And prepare us for the possibility, and not just keep blaming it on the disease. Ten years ago if you googled ‘does methotrexate cause depression’ there was nothing. Now there is lots more information. So I’m very glad that the word is getting out. There are many other options. All the best to you, and let me know how you go with the antibiotic protocol!

  2. Hi, I just found your page. I was diagnosed with RA about 2 years ago. I started taking methotrexate 15 mg pills once a week for about 6 weeks. The doctor increased my dosage to 20 mg when the inflammation wasn’t decreasing much. I hated taking it. The depression, fatigue, the bone pain, basicly entire body pain, became too much for me to stay on the medication and I ended up discontinuing it after 6 months.
    I was put on arava, which worked pretty good. I lost a lot of weight which I needed to but the doctor was concerned about it so after a few months he put me on Enbrel. So far the Enbrel is working. I had that fear of giving myself injection once a week but it isn’t bad at all with the injection pen. But the depression had gotten seriously bad. I’m a happy, love life type of person and when I started having suicidal thoughts I knew something was terribly wrong. My regular doctor prescribed me Lexapro antidepressant and I feel like a new person. The pain has decreased considerably, going from a 9 down to about 5. Depression will make the pain a lot worse and cause nerve pain.
    I just wanted to share my story with you. Thank you for sharing yours.

    • Hi Karen, I’m sorry I didn’t reply sooner! I’m so happy that you’ve found a combo that works for you! Depression is terrible, and you’re so right, depression makes pain worse…which makes depression worse. Horrible, vicious cycle thats so hard to break. Congrats on persevering and finding your new life. Love a happy story. Take care xx

  3. I will be on it soon.I’m already depressed so ill take all YOUR stories and keep them in my thoughts blessings not you ALL!???? I’m seeking to be pain freeeeeeee!

  4. I will be on it soon.I’m already depressed so ill take all YOUR stories and keep them in my thoughts blessings not you ALL!???? I’m seeking to be pain freeeeeeee!

  5. I have been taken methotrexate injections for about 10 months. I could start to see a decline in my mood but put it down to having kids and work but over the last 2 months things have for so bad I have lost a stone in a month o have constant knots in my stomach I’m never away from the toilet and I’ve been having suicidal thoughts. I am in a very dark place and don’t see a way out anymore.

    • Please talk to your doctor, GP or rheumatologist ASAP. Most doctors realise that methotrexate can cause severe depression but only once you are ‘there’ so to speak. tHey don’t warn you, because that might be self-fulfilling. Please see your doctor right away, about changing medications. Anti-depressants did not help me with this depression, and it can quickly become life threatening. Please take care. There are so many other medications for RA, you don’t need to go through this, but its very hard to pull out of that state of mind when a medication is causing it. Please keep in touch and let me know how you go. My thoughts are with you Xx

    • I started taking it. My husband swears I’m crazy and on drugs. I’m suicidal I don’t feel right. I told my doctor,then she boosted up dosage of folic acid. Not helping! I feel any moment I’ll be dead! I am so depressed. What hurts is my husband tells me I’m so full of shit. Never been alone in a very dark place. Methotrexate ruined my marriage!

      • I’m so sorry Sharon. I hope your husband can try to understand this is NOT you. Not your fault. There are so many other options, medications for RA. Methotrexate is NOT The one for you. Can you go back to your doctor again, and tell her you want to try another medication? Depression is deadly. Some people have luck with taking an anti-depressant. I have now found a lower dose, and injectable mtx is tolerable and really helps me. But please, stop taking mtx, and see your doctor. You shouldn’t have to suffer this way. I’m really worried for you, message me any time if you want to talk privately.
        sending all my love xx

  6. I just saw this after calling my mom and telling her “something is seriously wrong”. Started MTX 6 w is ago. Can’t stop crying, definitely feeling it’s all in my head. I’ve been on antidepressants for years. I know this feeling. It’s a spiral and I’m already going down.
    Thank you so much for this post. It is healing to know it’s not me going crazy. I don’t want the pain to come back either, but this cannot continue. Bless you for sharing. You helped me validate what is happening and I can’t begin to tell you how much that means.

  7. Wow ditto . Thanks for sharing. I thought I was just reacting to some post dramatic stress from a skin condition lymphamatiod papulosis that I was told could become lymphoma. I was exhausted from the papulosis sores that have been like chicken pox 24/7. While waiting to start methotrexate I had a manic episode and I to spent time in the psych ward. Ha ha and sadly my mental health struggled more under those conditions. I start on the methotrexate when I got out after 3 days and ended up having a massive psychotic episode. I’ve never experienced such insanity before .It was so heart breaking for family and friends and a lover who was burnt out by the drama.( eg police search) With a so call history now of bipolar and L.P. sodium valproate( for bipolar) and methotrexate (for LP). I had terrible flash backs of this time. But finding your post today is such a comfort. I think it will be for my psych dr too( who has been worried his meds are not kicking in). But I think the methotrexate is the big bully here. and I too have always been a sunny person and an encourager to others. All I want to do is sleep my life away and hide from crying in front of people. So I can’t thank you enough for the honesty on this page. THANK YOU ALL

  8. i had the same issues with mtx made my life hell……hated myself hated the condition that i was in,i just used to lock myself in my room and cry and feel sorry for myself i couldn’t make it stop. Till the day i decided it was enough and went to my rheumatologist and told her i cant take it anymore and we decided to stop mtx and just take prednisone and went to see a psychiatrist who gave me meds to help with the depression,anxiety and suicidal thoughts. It has been more than a year now i do have the anxiety but not as much,sucks mostly when i get bad news…… i get really bad which i was never like this before mtx came in. I regret taking mtx.

  9. I’m so grateful I read this. I started this med 3 weeks ago and am stopping it. I hate it. I feel miserable, depressed and on the verge of crying every second. I rather have the pain from Sjögren then feel this way.

    • How much melegramms yoi were taking per week ? I’ve started methotrexate a month ago 7.5 mg/week and i start feeling like things are getting out of control..

  10. I have been taking it 2 years and 6 months, I didn’t experience any mood swings or depression in the beginning but now suddenly everything changed. You guys are literally describing my situation from A to Z I couldn’t add more but my other problem is that my doctor think that im exaggerating and “google” affects my thoughts and as I failed all Crohn’s disease medications i have no other choice. Because even with mtx im still not getting any better but as my doctor said at least im not getting worse. It’s very hard to go through all this and im still physical health isn’t getting better and in addition my mental health. If you guys recommend anything any good medication that will help nausea please don’t hesitate to write it down and thank you for the post I felt that im not alone here.

  11. I just want to say a couple of things: 1) Thank you for sharing your stories. I’ve just really started to realize what mtx has been doing to me. 2) Meds didn’t ruin the marriage; they exposed issues in that person. Don’t blame yourself.

  12. Hey y’all!

    Hope everyone is well. I too struggle with these autoimmune Therapies!! It suppresses your immune response but seems to decrease the neurotransmitters 🤔.
    After a few years I noticed but here recently after going back on the mthx injections; I could count the hours down until the depression kicked in- then a couple days and it would level back off. Crazy just like a period 🤷🏼‍♀️
    Thank y’all for sharing

  13. I am so glad to have found this. I have AS and have been taking Simponi Aria for 3 years with a lot of success. The past few months I could tell that it hasn’t been working that well. After the treatment I had two weeks ago the doctor had me take methotrexate again. I took it yesterday and woke up in the middle of the night from a panic attack. I had been on a smaller dose before and don’t remember feeling this way. Thank you for posting this! My doctor says it’s not related but I know it is. This was confirmation for me. I am not sure what comes next for me but I know I can’t do the methotrexate.

  14. Thanks for writing your story, I have been on 20mg Methotrexate for over a year now. Helps with the pain, but when I’m typing methotrexate and Depression into Google, something is clearly wrong.
    Thankfully, I’m going onto my first biologic soon, so hopefully I can stop or at least reduce the Methotrexate.

    Thank again for sharing, Phil

  15. Glad this blog post is still up. MTX changed my life in both good and bad ways. It took 8 months and a transition to the injectable to manage symptoms and start to get my life back. I agree with Jessica above (re the relationship flaws become impossible to work around… Not your fault.) My rheumatologist added folic acid once I called his office about “dark thoughts” That helped the depression. I also experienced a “break” and wish I had been more prepared for this rare side effect. Now I tell everyone I know about this possible side effect since it can be life altering.

  16. Glad this blog post is still up. MTX changed my life in both good and bad ways. It took 8 months and a transition to the injectable to manage symptoms and start to get my life back. I agree with Jessica above (re the relationship flaws become impossible to work around… Not your fault.) My rheumatologist added folic acid once I called his office about “dark thoughts” That helped the depression. I also experienced a “break” and wish I had been more prepared for this rare side effect. Now I tell everyone I know about this possible side effect since it can be life altering.


Please enter your comment!
Please enter your name here

This site uses Akismet to reduce spam. Learn how your comment data is processed.