Methotrexate for Rheumatoid Arthritis and the side effects


Today is post methotrexate day.  The day after I take my methotrexate dose, to treat my rheumatoid arthritis.

I take it just before bed, as advised by many who know the effects only too well, so that I can sleep through the initial side effects.

Unfortunately the side effects are severe, and they persist well beyond the 8 hours after popping the little yellow pills.  They include nausea, headache, dizziness and a delightful ‘I’ve just been kicked in the guts by a black belt’ feeling.

And they have mood altering effects. I have been tapering up on methotrexate very slowly.  I have tried to tolerate this drug four times before.  Each time the side effects have dropped me.  The worst side effect?  Depression. Not mild depression.  Major depression.  At times, suicidal depression.  A complete hijack of my mind and feelings.  Total deadening of every positive emotion,  leaving nothing but a void of despair and misery.  A complete inability to see anything light, to see anything changing, so see a way out of this life of constant pain and disability. This is not me.  This is methotrexate.  This is what it can do.  This is what it does do to me.

So why am I taking it again?  I am in Australia, and here access to newer, TNF blockers and biological treatments is very tightly regulated.  If you’ve read other posts you’ll know I have seronegative rheumatoid arthritis, and my acute phase reactants and inflammation markers are seldom raised.  So I don’t quality for these drugs.

I have tried all the other options open to me, except Arava.  My rheumy thinks Arava (leflunomide) would be A Very Bad Idea, based on his experience.  I tend to agree.  I have tried Salazopyrin (sulfasalazine) twice and failed.  I have tried Imuran – the mood symptoms were worse than methotrexate.  So those are all the drugs available to me for moderate to severe RA.

I take plaquenil, but it’s only for mild RA, so no surprises that it doesn’t control my symptoms.

Methotrexate is the gold standard treatment for rheumatoid arthritis.  It is cheap.  Many people respond very well to it, and have few side effects.  And from all I’ve been told, the side effects lessen with time. I have been back on methotrexate for 9 weeks.  It’s a pill you take once per week.  My rheumy wants to get me to 15mg per week.  He will be happy if I can get to 10mg per week.  The lowest possible therapeutic dose is 7.5 mg per week.  Again, this is usually for people with mild disease.  Or children and teenagers with JIA. I can tolerate 5mg with few problems.  At 7.5 mgs I start to feel the depression kick in.  At 10mg I start to feel like life is not worth living.

So to combat this, I have been tapering up the dose very, very slowly.  I started on 2.5 mg for two weeks.  Then 5mg for five weeks.  I have just taken my second dose of 7.5mg. Side effects?  They are what you would expect.  For the last few weeks I have been plagued with negative emotions.  Thoughts come into my head and get lodged there.  Not nice thoughts.  Stupid thoughts.  Nasty thoughts.  Sad thoughts.  I try to push these away, and remind myself they are just thoughts, but the methotrexate is amplifying them. Everyone has these kinds of thoughts hundreds of times a day, but somehow the methotrexate makes me hold onto them.  So I have to make a concerted effort to let them go.  Don’t give them a place to dwell.  Do not allow them to grow.

This is not easy.  I am already fighting my body every day.  Now I am fighting my mind as well. I am also still taking prednisone – tapering down.  I am at 12.5mg per day now.  As I taper down, the pain is increasing, the fatigue is returning.  I have always fought depression with hard exercise…as the prednisone decreases, my ability to exercise hard also decreases.  The constant catch-22 of rheumatoid arthritis, and its treatments.

But I need to persevere.  Thank the gods no one can read the thoughts stomping around in my head!  I will continue to paste a smile on my face, and force myself to go to the gym, get some design work done, work on my blog, care for my children.  All the day to day mechanics, that will keep the cogs of my life turning. I must never let them stop. I must not fall in a hole.  Because it is so much harder to climb back up once you have fallen down.

I have been there before, and learned this the hard way.  Even if I am only going through the motions right now, my life appears to be travelling as normal to everyone else.  A few friends might notice I am not as social as usual.  That’s fine. Because if I persevere with methotrexate, at least I have hope.  It may help my symptoms, reduce my pain, in time.  I am cheered by others’ assertions that the side effects will fade.  I just need to stick it out.  And it if doesn’t help, failing methotrexate for once and for all will at least open more treatment options to me.  I can then try the next drug. And maybe the next one.  Until the day I find my magic bullet, my combination of drugs that will return my life to my control, and no longer the control of Rheumatoid Arthritis.


  1. I also take Cymbalta for the fibro, which helps tremendously with my depression. They reported last night on the news about this new medication. I don’t know yet if it is available there, but it is for people that don’t respond well to other meds. I too have seronegative RA, it is really ashame that we are treated still as though it is a lesser disease…I wish too that something could help without causing all the horrible side effects. Praying that you find that magic bullet.

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    • Hi Claudia,
      Thanks for the link – I have been following some of the stories about Tofacitinib with interest. New treatments give us hope!

      Good point about the seronegative RA – I know several people who have seronegative RA that is severe, and they have endured multiple surgeries and damage to their joints. I also know a few people who are seropositive and yet clearly have mild disease. Its certainly a misconception – and a post for another day!

      I should also have mentioned in my post that I have tried a few antidepressants, but they weren’t effective. So glad that Cymbalta helps you! I think we wouldn’t be human if we didn’t experience depression at some point. Thanks for your comments, and take care.

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  2. Hi there. I too have severe RA. Have you tried changing your diet to a more plant based diet? I’ve just started this myself, so I’m not sure the results yet. I hate drugs too, and have bad side effects as well. Changing what I eat is my last resort, but not sure why it wasn’t my first. Try it! :)) Good luck.

    • Hi Jojo, I have played with my diet. For three months I was a gluten free vegan, and I must admit I had much less pain! It was unsustainable though, so I experiemented and stuck with the gluten free, but introduced a bit of meat, eggs and dairy. Over time the pain has gotten worse, but I still try to eat lots of veg, a bit of meat and very very few processed foods. I feel its just healthier on the whole. Good luck with your diet changes – its not easy! Please let me know how it goes? Every little bit helps, I think!

      Arthritic chick signature

    • Thanks Christy – you’re a huge inspiration to me the way you keep your sense of humour and keep smiling, in spite of everything.

      Arthritic chick signature

  3. Many times, these medicines affect us because they deplete the body of vital minerals and nutrients. We with RA, must be sure that we are taking vitamin/mineral supplements, and the folic acid, yes, especially our B vitamins, and omega 3’s.

    Also a raw vegan diet and staying away from chemicals in our foods. I have been contemplating all of this with my new diagnosis. Its definitely a long road ahead.

    My prayers are with everyone, and I am really grateful for this informative blog site.

    • Thanks for your comments, Helen. Are you following a raw vegan diet? Please let us know if it helps you. I was vegan/gluten free for many months, I found it so hard to maintain. Hats off to you! Good point about the vitamins – I take those, and vitamin D as well. Always seems to be low! It certainly is a long road…best of luck.

      Arthritic chick signature

  4. Hi there,
    What a relief to know that it could be the mtx that’s making me feel so down and depressed. I have suffered with depression on and off for year and last year it came back with a vengeance after nearly losing my hubby through ill health. I had been taking citalopram 40 mg and it had made things so much better that I reduced my dose a couple of months ago to 20 mg. I have recently been diagnosed with RA having had years of pain in my limbs but more recently a flare in which my ankles swelled and stiffened so much that I could hardly walk and getting out of bed in the mornings was so painful. My rheumy has started me on 15 mg mtx which i started last Wednesday evening. Thursday afternoon I started to feel nauseous but coped. Friday morning I still felt nauseous and struggled to get toast down but I needed to have food to take my NSAID. This nausea lasted all of Friday and at lunchtime got so bad I had to leave work early as I also felt dizzy. Saturday was the worst day by far. The nausea had gone only to be replaced by the overerwhelming feeling of sadness and depression. I cried on and off all day and could not tell anyone how I felt. The nausea came back and I was sick. It’s now Sunday and to be honest I don’t feel much different today . I’m now counting down the days til I take my next dose of mtx and am dreading these feelings continuing or getting worse.

    • I’m so sorry Helen – I know what those feelings are like. It is truly terrible to be severely depressed. Please be careful on the methotrexate – my rheumatologist admitted the second time I complained of it as a side effect that yes, it DOES cause depression. But often doctors right it off as the Rheumatoid Arthritis causing the depression. He finally listened, and after my last episode, will never push me to take it again.

      Can you increase your dose of citalopram again? I hope that will help some. Is your husband there to support you? Please let the people around you know how bad you’re feeling. And if you can, call you rheumy and tell him/her. Perhaps a smaller dose will be effective? I found that 7.5mg gave me some improvement in my joint pain. I completley fell apart at 10mg. Perhaps you could take a smaller dose, and then taper up?

      In the end the only way to know if its the methotrexate causing the depression is to stop it, and see if it lifts. Then start the mtx again and see if it returns. I did that four times – slow learner. Please just make sure there are people around you watching out for you. Take care.

      Arthritic chick signature

  5. Wow, I thought my life was falling apart, on 10mg metho for the last three months and lately have been more and more sad, anxious and depressed. My new partner has been living with me temporarily, now bought his own house and will be moving there soon and I have been having some terrible feelings of abandonment, thinking the worst will happen and that it’s the end of the road for us although he treats me like gold. I am hating my job I had always loved, and just want to crawl into a little dark cave and stay there. Last night I had my shot for the week and burst into tears as soon as I was out of the surgery. This is the opposite of me, and it’s so convincing I feel like these thoughts are all real.
    Thank god for you posting this, now I know I am not necessarily going down the path of the end of my life where everything will go bad. Just don’t know what to do from here because without the metho I can’t walk for at least half the day.

    • Mel, I’m sorry that meth is affecting you badly as well! Its not that uncommon, but doctors don’t like to admit it. Please see your rheumy! There are other medication options. Depression is awful, and it can sneak up on you and make you behave in ways you never would otherwise. What other meds are you taking? And what else have you tried? Its irony that meth helped my pain and inflammation levels, but the side effects made it untenable. There will be something else that works for you, without sending your emotions on a downward spiral. I’m glad you have a wonderful partner. Maybe you should tell him about your feelings, so that he knows its the methotrexate? And he can give you some support. Please see your rheumy, and let me know how you go? Take care xx

  6. I’m so glad I found this site! Thank God it wasn’t just me! I previously was on methotrexate yet it was too strong and now I’m on Arava and cymbalta and feel like it’s not helping. I recently experienced a major break down I don’t know what came over me? Day before my birthday I just wanted life to be over with. Everything in my life felt overwhelming. I cried and screamed like a child. I definitely want to join a support team I too have seronegative RA and fibromyalgia something I thought my mother used as an excuse for attention until the day I was told why I have been experiencing pain stiffness for so long. I’m glad I’m not alone it’s the worst feeling to not be able to explain to my fiance and kids why I look the way I feel day to day.

    • Hi Diana, I’m so sorry you’ve had such a terrible time. When I first started on methotrexate, all the doctors told me it does not cause depression, that it was the RA causing the depression. Now, many years later, doctors are more aware. More of their patients are telling them that mtx can mess with your moods and bring on terrible depression. I hope you’re doing better now, but finding a support group is a great idea…other people who understand what you’re going through. And also help explain it to your fiance and kids..having their support is everything. There are many support groups on facebook. Whearabouts are you located?


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