Swollen ankles due to Amantadine

Amantadine can cause Livedo Reticularis

In Brain Injury by Emerson Jane Browne23 Comments

Amantadine can cause livedo reticularis and severe ankle edema in some cases.

Photo of legs showing mottling

Livedo Riticularis mottling on my legs

This is not well known and often not recognized.

Livedo reticularis often gets misdiagnosed as part of an autoimmune disorder.  

In this case it is not.  It is a reaction that some people get from Amantadine after a period of use.  The reaction takes time to build up.

What is Amantadine?

Amantadine is a medication that was originally developed as an antiviral to treat the flu.  

In the past 10 years it has come to the forefront as an excellent medication for treating traumatic brain injury and Parkinson’s.

Amantadine is a good medication!

There are numerous studies that have proven Amantadine’s effectiveness in speeding functional and neurologic recovery in severe brain injury.1,2,3 

It is also widely used to treat cognition problems following mild traumatic brain injury (MTBI) and post-concussive syndrome.

Amantadine is a good medication!  For most TBI survivors it works well and is a huge aid to recovery.  I encourage people recovering from a brain injury to ask their doctors about it.

Do not suddenly stop Amanatdine.  

If you think you may be having an adverse reaction, contact your doctor.  

You need to do a gradual reduction for the least side effects. 

Close up of the Livedo Riticularis

Close up of the Livedo Riticularis on my inner thigh

What is Livedo Reticularis?

Livedo reticularis is a coloration of the skin consisting of purplish web-like mottling that occurs most often on the thigh. (Reticularis means “marked like a net or network.”)  

The discoloration is caused by swelling of the medium veins (not small) in the skin, which makes them more visible. It can be caused by any condition that makes venules swell.4

What was my Reaction?

I usually do not write about such intimately personal things on this blog.  And, I want to be clear that I think Amantadine was extremely beneficial to me and  helped me in my recovery.  

However, when I started having a serious “undesirable response” it was misdiagnosed for almost 5 months.  I hope that this blog post will be useful to others.  That is why I am sharing this story and these photos.

I took Amantadine for 5 weeks before the symptoms became extreme. The reaction was diagnosed correctly a little over 4 months later.

Swollen ankles due to Amantadine

My very swollen ankles! Walking for 3 – 4 miles would get the swelling to go down, but it would come right back.

In hindsight I realize I was showing small symptoms that led up to the full blown reaction.  I had noticed an occasional hand jerk when writing and the frequency of the hand jerk was increasing.  

My finger tips had also become hypersensitive; hypersensitive to the point that it was painful to use the touchscreen on my iPhone and the touchpad on my computer.

Soon I started notice what I called “purple webbing” on my legs, (livedo reticularus). I usually noticed it when I was getting ready to go to bed.  It would be gone by morning.

Quite suddenly, my feet, ankles, and lower leg became swollen with non-pitting edema.  The swelling was the worst right around my ankles but even my toes “felt fat”.  

At the same time I developed a pink mottled (blotchy) coloration on my lower legs.  Over time the pink mottling spread up my legs to mid-thigh.

(Note: I did not photograph the edema at it’s worst.  By the time this photograph was taken I had figured out that if I walked over 3 miles at a fast pace I could get the swelling to reduce significantly. To keep it down, I was walking 2 to 3 times a day.)

How was it diagnosed?

Ankles slightly less swollen

Ankles after 5 weeks off Amantadine — Showing slow reduction in swelling

The important point to my story is that this side effect / reaction to Amantadine is not well documented and therefore it gets missed.

Stephen King, ND, an excellent naturopathic physician practicing in Seattle, is the doctor who finally diagnosed the problem correctly after five MDs had missed it. I was seen by five excellent MD doctors, none of whom realized that the symptoms were a reaction or side effect to Amantadine.  

Even though there are quite a few research papers that document it is not even listed as one of the possible side effects on the National Institute of Health page for Amantadine.  (Both my prescribing doctor and I are submitting reports to NIH.)

What does the Research Show?

In regards to developing livedo reticularis during treatment with amantadine; “This reversible side effect of amantadine has been most often seen in women and is frequently associated with persistent ankle edema. We discuss the signs and symptoms, pathogenesis and treatment of amantadine-induced livedo reticularis.” http://www.ncbi.nlm.nih.gov/pubmed/9565792.5

In this second paper they mention “Livedo reticularis is a common side effect of treatment with amantadine . . . Investigation of 40 such patients suggests that the livedo is a physiological response provoked by depletion of catecholamine stores in peripheral nerve terminals.”   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796527/.6

How has it resolved?

Update: The symptoms did finally resolve but it took many months.

Well, hopefully it is not done resolving.  It has been almost 5 weeks since I stopped taking Amantadine.  You can see the improvement between the two photos, but I also have a ways to go. The livedo reticularus is pretty much gone from my thighs.  The pink mottling that had been on my legs up to mid thigh has receded down to just above my ankles.  The mottling on my feet and ankles has turned brown and seems slow to dissipate.

The swelling is still a problem but is greatly reduced.  I was wearing Dansko clogs today and when I first took the shoes off there was quite a ridge where the swelling stopped at the top edge of the shoe. It shows up in this last photo as a whitish line across the top of my foot.  (I think Danskos may have prevented some swelling of the toes and forefoot today.)  Still, the reduction in swelling is a big improvement.  I could not even wear my Danskos for about 4 months. I will update this section as needed; hopefully to report a full recovery.

What has your experience been with Amantadine?

Please comment below


  1. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366(9):819-26. http://www.nejm.org/doi/full/10.1056/NEJMoa1102609
  2. Meythaler JM, Brunner RC, Johnson A, Novack TA. Amantadine to improve neurorecovery in traumatic brain injury associated diffuse axonal injury: a pilot double-blind randomized trial. J Head Trauma Rehabil 2002;17:300-313
  3. Schneider WN, Drew Cates J, Wong TM, Dombovy ML. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo controlled study. Brain Inj 1999;13:863-872
  4. Livedo reticularis. (2012, October 26). In Wikipedia, The Free Encyclopedia. Retrieved 08:33, November 6, 2012, from http://en.wikipedia.org/w/index.php?title=Livedo_reticularis&oldid=520015923
  5. Löffler H, Habermann B, Effendy I. [Amantadine-induced livedo reticularis]. Hautarzt. 1998;49(3):224-7. http://www.ncbi.nlm.nih.gov/pubmed/9565792
  6. Vollum DI, Parkes JD, Doyle D. Livedo reticularis during amantadine treatment. Br Med J. 1971;2(5762):627-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796527/
Emerson Jane Browne
I am Emerson Jane Browne. I write about Brains, Apps, & Productivity, and many other aspects of Life. I speak to TBI support groups, speak and teach workshops at tech, music, and writer conferences. I consult with organizations on strategic planning and building a strong community.
  • Michele


    I was on Amantadine for probably 7 years before the Livedo Reticulartis showed up. I took it to give me energy due to the fatigue caused by Multiple Sclerosis. My primary care provider diagnosed it but confirmed it by sending me to a rheumatologist. I stopped taking the medication and within a year it was gone. My doctor said he had found one research article about this side effect of amantadine so I am glad to see your post regarding it!

  • Lucy Lee Her

    I am not on Amantadine currently but have received flu shots annually, sometimes skipping a year or two. I developed livedo reticularis in October 2016. My primary doctor diagnosed me with livedo reticularis but had little knowledge about it so referred me to a dermatologist. I found one of the best dermatologist in the Twin Cities. She took blood tests and said everything in my blood level looks fine and that the condition should go away once summer comes around. It’s now 2018 and my reticularis has not gone away. I have no idea what caused this condition since it is apparently not an underlying issue of lupus. Anyone have any ideas as to what may have triggered it?

  • Ginece Jackson

    I am currently on Amantadine and I have severe swelling of my ankles and feet. I am contemplating asking my doctor if I can discontinue the medication. How long did it take for your swelling to completely go away?

    • @ginecejackson:disqus Read through the comments below and I may have said how quickly the swelling went away. It has been a while since I took the medication and I do not recall the specifics. My memory is that the extreme swelling abated pretty quickly – especially because I was taking a 3 mile walk every day – but that I had some residual low-level swelling that took a while to fully go away. I also think my feet have swelled a bit easier ever since I had this reaction, but that may have more to do with aging than the medication reaction.

      • Ginece Jackson

        Thank you.

  • Kristen

    Why didn’t I find this 10 months ago!ive been to urgent care, ER, PCP, vascular surgeon, dermatologist and the Neuro who prescribed the Amantadine and not one of these MDs could tell me what was causing the mottling and edema. I had an appt the other day with my neuros NP, and as soon as she walks in the room she says “oh wow! Look at your Livedo Reticularis! Can I show it to a medical student?”. Unbelievable! How long did it take for the mottling to go away?

    • Kristin, so sorry you had to go through all that!! I am trying to remember about how long it took. I know the swelling stopped within a few days to a week. I know the Livedo Reticularis took a little bit longer to lighten. Then there was a residual mottling that took a long time. I remember wondering if it was always going to be there but it faded away over time and I have no shadow of it at all now.

    • cyberties

      Time to get a different (and better) Neurologist.

      The first thing mine told me when I reported the swelling was that the Amantadine caused it. He had mentioned it as a possible side effect. The dosage was being gradually increased from 1 a day to 3 a day over a 6 week period ( 1 a day for 2 weeks, then 2 a day for 2 weeks, then 3 a day for good). I noticed some edema the during the 5th week of regimen. So, I called my Neuro and told him about the edema and that I would be taking a trip which required air travel. He told me to stop taking the Amantadine immediately. Two weeks later and I still have the edema. I’m wearing compression hose at night and that seems to help. But the swelling comes back during the day while I’m sitting at my desk all day.

      If no improvement by end of 3rd week off of the drug, I will see my primary care physician.

      • Cyberties, one thing that I did that helped was that I walked – a lot!

        After I stopped the Amantadine I walked about 3 miles every day. I had been doing that while on the drug too because 3 miles seemed to be the magic number to get the edema to recede some.

        It actually sounds like you have a good neurologist if he identified the cause of the edema to be Amantadine. If there are other problems, then yes, it may be time. But if it is just over the Amantadine . . .

  • Kristen

    Why didn’t I find this 10 months ago!! I’ve been to urgent care, ER, Vascular surgeon, PCP, Dermatologist and Neurologist (who prescribed the Amantadine) and not one MD knew what this was or where it came from! Had an appt with the NP at Neuros office the other day, and as soon as she walked in the room she says “Oh wow, look at that livedo reticularis. Can I have a medical student come and see it?” How long did it take to go away once you stopped Amantadine?

  • Stacy, thank you for your comment. I am envious that you were able to stay on Amantadine for as long as you were. It is a good medication if you do not react to it. Unfortunately there does not seem to be a real good alternative. If you are not already on Buproprion (Wellbutrin) you could ask your doctor about that one. I am not sure if it is used for MS. It is frequently used for TBI.

    (Ps. Due to some tech problems I had the Disqus plugin temporarily turned off during the time your comment came in. When I turned it back on I had quite a bit of difficulty getting your comment to sync into Disqus comment system. That is why your comment only finally showed up today – two days late.)

  • Stacy

    Thanks so much for the info. I’ve been on amantadine for over 12 years for MS related fatigue. These side effects are not well documented. Thanks for explaining them. Now I have some reading to do and informed decisions to make.

  • Heather Steele

    I want to say THANK YOU so much for writing about this. My son is on Amantadine and the Dr was concerned. We have tried to figure out what this was and because of you my special needs son will not be traumatized by trying to get blood work. There are not enough words to say how thankful I am!

    • Heather, Thank you so much for your comment! That is exactly why I wrote this article. And comments like yours keep me going on this blog.

  • LisaDF

    You have described exactly what is happening to me. I have been on Amantadine, 200 mg per day for about 6 weeks. The webbing start around week 4 and the swollen feet and ankles just yesterday, week 6. The webbing is on all of both legs and the backs of my arms, above the elbows. I live in Florida and so this unsightly webbing is not something I want to continue. I take the Amantadine in combination with 50 mg of Primidone, for essential tremor. They are working beautifully together, so I am sorry to have to drop the Amantadine. Thanks for the post, it has helped me nail down the reason for the foot and ankle swelling very quickly. And your links gave a good time frame to expect reversal of the webbing, 6-12 weeks.

    • I am so happy that this post helped you Lisa. That is exactly why I wrote it. It has already received hundreds of views so this must be a common problem.

      • Just

        so your livedo reticularis resolved on its own when you stop taking the medication? I’ve had mines since 2006 🙁

        • It did take a long time for the livedo reticularis to resolve. How long have you been off Amantadine?

          Take long walks and walk briskly, if you are able. Getting your blood pumping through the area helps it to resolve. Being sedentary will cause it to take a lot longer.

          • Just

            I didn’t take Amantadine, so do you think taking brisk walks would still help me get rid of my livedo reticularis?

            • Livedo Riticularus can be caused by other medications and health issues too; not just Amantadine. Taking brisk walks to get your blood pumping will help it resolve if the source of it is resolved. And it is likely important that you are eating well too.

              • Just

                Thanks for the reply 🙂 Would you recommend I walk everyday? Is that what you did? Also are there certain foods you avoid, like greasy food, sweets and fast food?

                • Just, I really cannot go into a whole dietary thing here. Of course avoid the ones you list. Eat lots of raw vegetables, organic if possible. Same for meat – organic if you can. Stop eating processed foods entirely. If it comes in a package and has more than two ingredients – consider it processed. If you smoke – get help stopping so you can stay stopped. (That is a big one because affects blood flow.) All of that will help your health overall. And thus it will likely help with the livedo reticularis. But again, unless you have stopped whatever caused it in the first place it will not resolve. Wishing you all the best with this.

  • Dr G

    Thank you for the clear and instructive explanation of the symptoms and the information for patients and their doctors!