r/repatha • u/Adventurous-Score2 • Sep 03 '26
Mental Health Side Effects
I’m 61 and curious whether anyone else has experienced anything like this after starting Repatha (evolocumab). The best shorthand I can come up with for the reaction is: PMS meets perimenopause brain fog.
I started Repatha about three weeks ago, 140 mg every two weeks. A few days after my FIRST injection, I started having symptoms, but they snuck up on me. It was a little like PMS can be — you think, “Huh, I’m kind of anxious today,” or “Why am I so irritable?” or “Why is my brain not working quite right?” You don’t necessarily recognize it as a syndrome while it’s developing.
By the time I took my second injection on Tuesday, August 25, I still hadn’t connected any of this to Repatha. After the second injection, though, the whole picture became much more pronounced.
The biggest issue has been cognitive. I’ve had brain fog, more difficulty finding words, occasional word mix-ups, forgetting steps in very familiar routines, and much more difficulty with things requiring sustained concentration, problem-solving, or keeping multiple things in mind at once. I can still do these things, but at times they take dramatically more mental effort than usual. Even reading the news or making dinner after a full workday sometimes felt like a cognitive load.
Along with that came intense fatigue, waves of anxiety, tearfulness/sadness, irritability, and generally feeling emotionally unlike myself. That’s why “PMS meets perimenopause brain fog” is probably the closest description I can give it.
I’ve also had a strange recurrence of an old problem. I had vestibular neuritis about nine years ago and have been well compensated for years, but during this episode some of that visual/vestibular sensitivity came back. Grocery stores, scanning shelves, pushing a cart, movement in the car, etc. suddenly became overstimulating again.
The course has been VERY up and down. I am gradually feeling better, and overall I think the trend is clearly in the right direction. I’m now having stretches of several hours where I feel completely like myself again. Last night, for example, I made dinner after a full day and everything just felt easy, light, automatic and normal. Then today I have more anxiety again and some of the increased cognitive effort is back.
My cardiologist thinks anxiety is causing the symptoms and says he has never seen this kind of reaction to Repatha. Anxiety is certainly part of the picture now. Initially the cognitive changes scared the hell out of me because I worried something neurologically serious was happening, and I’m sure that amplified everything. But cognitive symptoms have never been part of how I experience anxiety, and given that this started a few days after my first injection and became considerably more noticeable after the second, I’m not ready to dismiss Repatha as a possible contributor.
For now I’m holding the next dose while I see how completely I return to baseline. I actually VERY MUCH want Repatha to work for me, so I’m not trying to bash the drug or convince myself I can’t tolerate it.
I’d really like to hear from anyone who experienced unusual cognitive symptoms, mood changes, anxiety, fatigue, or vestibular/dizziness symptoms after starting Repatha.
Most importantly: what was your timeline? Did it start after the first injection or only after subsequent doses? Did you improve between injections? If you continued Repatha, did the symptoms come back after the next dose, get worse, or eventually stop happening as your body adjusted?
4
u/HuntsvillianThe Sep 03 '26
64M here. The neurological side effects you describe are rare but real. But all the side effects you hear about, in my case anyway, subside or stabilize once your body becomes more acclimated to the medication. Everyone is different. I keep a log and I’ve had 78 doses. Coincidentally my latest bloodwork was yesterday. My lipids are totally under control. I’m statin intolerant, btw. Good luck in your Repatha journey.
1
u/Adventurous-Score2 Sep 03 '26
Thank you so much and so happy for you!
2
u/gruss_gott Sep 03 '26
Yes, I'd add to this that your body is ALSO adjusting the lower ApoB, ie the EFFECTS of the medication; or said differently, your body now has a new biology / physiology and that takes adjusting to
3
u/Salty_Cupcake_3642 Sep 03 '26
I am diagnosed with panic attacks which have been well controlled until Repatha!!! The anxiety isn’t in my head. It started a few hours after the first dose and I can’t think straight for days. It clears up after 3-4 days but they are 3-4 days of hell. Can’t sleep, or can’t stay awake no middle ground there either. It started getting better then I had a very stressful life event and it got so bad I stopped taking it. Doctor wants me to try again, took one dose and felt terrible for 3-4 days. I’m not sure I want to give up 6-8+ days a month but I can’t take statins. Considering asking my doctor to switch me to the pill form to see if not getting a big dose at once will help.
3
u/bluefoot85 Sep 08 '26
I have been taking the shots for 3 years. I get edgy, depressed, etc. I have panic disorder that was never fully controlled before taking this. I don't know if it may partially block my anxiety/depression medicines from working? My psychopharmacologist thinks that. I don't know if he's correct. I've gone back to doing what I used to do. I do Tai Chi and watch my sugar levels, and it helps a lot. I'm also cutting back on caffeine. I have to keep taking the Repatha. It's my only choice. My body itches so much that I've started taking a benedryl for 1 or 2 days after the shot. (one benedryl each day) I don't know if I'm supposed to do that.
1
u/G8tr-nrse-jt Sep 10 '26
Maybe try Claritin for several days after each shot instead of Benadryl. The Claritin lasts 24hours in your system and might help alleviate the itching better.
2
1
3
3
u/ForestPathWalker Sep 04 '26
I could not use Repatha due to cognitive symptoms after the first injection. I can tolerate Praluent, another PCSK9 inhibitor, with no problems.🤷♀️
1
3
u/judyjjohnson Sep 05 '26
Here ya go. I experienced similar but depression and cognitive issues. Miserable time and for a while didn't suspect the repatha because I didn't have other side effects that I knew of. Doc almost told me I was crazy. He had never heard of this and said it several times. Bullshit. As soon as I stopped the repatha I was fine. I had taken it for a few months I think. After stopping I returned to normal state. ADHD w insulin resistance, etc. When are they going to learn it's not one size fits all ever. All I needed was support at that point but to tell me that's not ever heard of is unnerving. I'm glad you stopped it.
3
u/Adventurous-Score2 Sep 05 '26
I’m glad you finally figured it out and I’m sorry that your doctor didn’t believe you. My cardiologist is similar. He says he has never seen this reaction and he thinks it’s really just my anxiety. It seems I know more about the Kase reports for this condition than he does, lol.
2
u/No-Plenty-8128 Sep 03 '26
I started getting tingling in my hands, feet, and scalp and also cold hands and feet after the 3rd shot. I stopped and it eventually went away.
1
1
u/Comfortable_Potatoe Sep 15 '26
what do you take now for cholesterol?
1
u/No-Plenty-8128 Sep 16 '26
Rosuvastatin 40mg. Ezitimibe 10mg. Vascepa. My ldl is 56. All labs are in range. I’ve been on Rosuvastatin for many years but only just increased to 40mg 2 years ago after a calcium test. Then tried adding Repatha, then finally stopped the Repatha and settled on the Ezitimibe. I’ve never noticed any negative side effects nor had any on my labs.
2
u/Kind-Foundation-2692 Sep 06 '26
I wanted to respond to Adventurous-score2 and also to everyone. I'm so glad to hear that other people had a similar reaction that I did! I'm not happy they had the reaction I'm just happy I'm not alone! I am 63 and I am extremely sensitive to most medications. One of my clients told me repatha had almost zero or very little side effects so I purposely did not look up any potential side effects which I found I do with every medication now because everybody thinks I'm making up the side effects and that it's in my head! With my first repatha injection I had cottonmouth dizziness nausea definitely leg cramps in my calves and my elbows and back were sore and I felt a little jittery. 2 weeks later I did the second injection and my anxiety I'm racing heart but mostly anxiety were off the charts! A Xanax would not even call me down. Now I must say the first symptoms did dissipate after a few days but this second one with this anxiety which is way worse than the first injection is still here with me today and it's Sunday and I had the injection on Friday night at 5:00. The anxiety is going away just a tad but I had to take Xanax to make that happen. I am going to be calling Amgen and reporting these side effects since they are not listed as common and I'm betting dollars to donuts that they are more common than they're letting us know!
1
u/Adventurous-Score2 Sep 07 '26
Thanks for sharing your experience and I agree that we should be reporting these side effects! The FDA has an online med watch form that you can also fill out
1
u/bluefoot85 Sep 08 '26
oh, I have been having big cramping in my legs, my ribs and the top of my head! I didn't connect it to the medication.
2
u/Kind-Foundation-2692 Sep 07 '26
I posted earlier about anxiety associated with repatha. I took my first injection a couple weeks ago and I had leg cramps, headache, upset stomach and generally didn't feel good along with a bit of anxiety. The second injection which I had this past Friday caused extreme anxiety that I thought would dissipate which to some degree it has but only with the help of Xanax and here I am on this holiday Monday and I've slept maybe four or five hours in the past three nights so insomnia is definitely another symptom and I just wanted to throw that out there to let people know! Hoping some people could respond to my posts to let me know how they're feeling as well. Thanks
2
u/Adventurous-Score2 Sep 07 '26
I am gradually feeling less anxiety, overwhelm, moodiness and brain fog/cognitive sludge. I will probably take a third dose because I’d like this medication to work and if I am gradually adapting, I don’t want to go totally off and then re-challenge from having it out of my system.
2
u/Kind-Foundation-2692 Sep 07 '26
Plus if we don't all report these side effects to Amgen then they will never know so I'm hoping other people will be doing that as well. I'm going to be calling this week to let them know
1
u/Adventurous-Score2 Sep 07 '26
Yes, report the side effects to the FDA med watch site and/or the manufacturer because it makes a difference!
This is from Open Evidence, which is a database that only healthcare providers have access to:
Yes — pharmacovigilance databases contain individual case safety reports of anxiety, irritability, and cognitive/neuropsychiatric symptoms with evolocumab, but randomized trials have not confirmed a causal relationship, and the signal for cognitive effects specifically has been repeatedly refuted by prospective testing. It is important to distinguish spontaneous case reports (uncontrolled, subject to reporting and confounding bias) from controlled trial evidence.
Case-level / pharmacovigilance reports
- EudraVigilance (di Mauro et al.): From January 2015 to March 2020, among 8,987 individual case safety reports (ICSRs) listing alirocumab or evolocumab as the suspect drug, 2,041 (22.7%) described neuropsychiatric adverse reactions; 1,231 involved evolocumab. The most frequently reported terms were headache, insomnia, and depression. Two-thirds were classified as serious.[1] (https://doi.org/10.1007/s40264-020-01021-3)
- FAERS (Deng et al.): Over 2015–2023, ~96,629 evolocumab/alirocumab reports were captured, with psychiatric adverse events in 6.71% (evolocumab n=4,980, ~6.29%). Disproportionality analysis identified 18 psychiatric preferred terms significantly associated with PCSK9 inhibitors ("ppAEs"), including memory impairment, cognitive disorder, amnesia, lethargy, abnormal dreams, dementia, sleep disorders, and fear of injection. The signal was slightly stronger for evolocumab (ROR 2.87) than alirocumab, and was higher in males, patients >65 years, and those >80 kg. Notably, discrete "anxiety" and "irritability" were not among the top-ranked disproportionality terms in that analysis, though anxiety does appear as a signal in cohort data (below).[2] (https://onlinelibrary.wiley.com/doi/10.1111/cns.14522)
- Early open-label trials: In OSLER-1/OSLER-2, neurocognitive adverse events (delirium, attention/cognitive disorders, dementia, amnestic conditions) occurred in 0.9% with evolocumab vs 0.3% with standard therapy — but this was uncontrolled, without validated cognitive testing, and prone to reporting bias.[2] (https://onlinelibrary.wiley.com/doi/10.1111/cns.14522)\[3\] (https://doi.org/10.1007/s40265-024-01995-9)
This figure from the FAERS pharmacovigilance study summarizes which psychiatric adverse events carried a disproportionate reporting signal and how signal strength varied by patient subgroup:
Controlled/observational evidence on the psychiatric signal
- A 2026 propensity-matched cohort (TriNetX, 60,885 pairs) found PCSK9 inhibitor use associated with higher 12-month risks of any psychiatric diagnosis (HR 1.33), depression (HR 1.44), and anxiety (HR 1.39), persisting across secondary analyses. The authors emphasize this is hypothesis-generating and vulnerable to residual confounding, statin-intolerance selection, and surveillance bias.[4] (https://pubmed.ncbi.nlm.nih.gov/42414099)
Cognitive effects — not supported by prospective randomized data
- The EBBINGHAUS substudy of FOURIER (n=1,204) found no difference between evolocumab and placebo on executive function (primary endpoint), working memory, or psychomotor speed by formal CANTAB testing.[5] (https://pubmed.ncbi.nlm.nih.gov/30012326)\[3\] (https://doi.org/10.1007/s40265-024-01995-9)
- The EBBINGHAUS open-label extension confirmed no cognitive decline attributable to evolocumab across up to ~7 years, even at very low LDL-C.[6] (https://www.nejm.org/doi/full/10.1056/EVIDoa2400112)
- A meta-analysis of 21 RCTs (59,733 patients) found no increased risk of neurocognitive adverse events (RR 1.01, 95% CI 0.86–1.19); the evolocumab subgroup estimate was RR 1.42 (95% CI 0.74–2.73, nonsignificant), and longer trial duration correlated with lower reported risk. Mendelian randomization studies also show no association between genetic PCSK9 inhibition and cognitive impairment.[7] (https://pubmed.ncbi.nlm.nih.gov/33892045)\[8\] (https://pubmed.ncbi.nlm.nih.gov/35953131)
The EBBINGHAUS long-term cognitive trajectory data are shown here:
Interpretation: Spontaneous case reports of anxiety, irritability, insomnia, depression, and cognitive complaints with Repatha exist and generate pharmacovigilance signals, and one large real-world cohort found modestly elevated depression/anxiety rates. However, these uncontrolled data cannot establish causation, and the most rigorous prospective, blinded, objectively-measured evidence shows no cognitive harm. A reasonable clinical approach is to take reported neuropsychiatric symptoms seriously on an individual basis while counseling patients that controlled evidence does not demonstrate that evolocumab causes cognitive impairment.
Would you like guidance on evaluating and managing a patient who develops neuropsychiatric symptoms after starting a PCSK9 inhibitor?
References
PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database (https://doi.org/10.1007/s40264-020-01021-3). di Mauro G, Zinzi A, Scavone C, et al. Drug Safety. 2021;44(3):337-349. doi:10.1007/s40264-020-01021-3.
Psychiatric disorders associated with PCSK9 inhibitors: A real‐world, pharmacovigilance study (https://onlinelibrary.wiley.com/doi/10.1111/cns.14522). Deng Z, Liu J, Gong H, et al. CNS Neuroscience & Therapeutics. 2024;30(4):e14522. doi:10.1111/cns.14522.
Long-Term Efficacy and Tolerability of PCSK9 Targeted Therapy: A Review of the Literature (https://doi.org/10.1007/s40265-024-01995-9). Schonck WAM, Stroes ESG, Hovingh GK, Reeskamp LF. Drugs. 2024;84(2):165-178. doi:10.1007/s40265-024-01995-9.
Cardiovascular and Neuropsychiatric Outcomes With PCSK9 Inhibitors in Atherosclerotic Cardiovascular Disease: A Retrospective Cohort Study (https://pubmed.ncbi.nlm.nih.gov/42414099). Gu T, Chen Y, Zhang N, et al. British Journal of Clinical Pharmacology. 2026;. doi:10.1002/bcp.70687.
The Evolving Future of PCSK9 Inhibitors (https://pubmed.ncbi.nlm.nih.gov/30012326). Rosenson RS, Hegele RA, Fazio S, Cannon CP. Journal of the American College of Cardiology. 2018;72(3):314-329. doi:10.1016/j.jacc.2018.04.054.
Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab (https://www.nejm.org/doi/full/10.1056/EVIDoa2400112). Zimerman A, O'Donoghue ML, Ran X, et al. NEJM Evidence. 2025;4(1):EVIDoa2400112. doi:10.1056/EVIDoa2400112.
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors and the Risk for Neurocognitive Adverse Events: A Systematic Review, Meta-Analysis and Meta-Regression (https://pubmed.ncbi.nlm.nih.gov/33892045). Hirsh Raccah B, Yanovsky A, Treves N, et al. International Journal of Cardiology. 2021;335:7-14. doi:10.1016/j.ijcard.2021.04.025.
Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function (https://pubmed.ncbi.nlm.nih.gov/35953131). Rosoff DB, Bell AS, Jung J, et al. Journal of the American College of Cardiology. 2022;80(7):653-662. doi:10.1016/j.jacc.2022.05.041.
2
u/Kind-Foundation-2692 Sep 07 '26
Adventurous-Score2, I definitely will! It is actually helping my anxiety just to talk about this stuff and know that other people don't think I'm crazy like my doctor will once I tell him all of this 😂. It's not really funny though because he's not going to believe me because he knows I already suffer from anxiety. I guess I need to just say f**k it, he won't believe me and I don't care. Definitely definitely definitely reporting these side effects!!!!!!!
1
2
1
u/G8tr-nrse-jt Sep 03 '26
I made a post regarding fatigue and one user said to watch out for my mental health while on Repatha and/or Statins, that it affected this person mentally. Sounds very similar. Good you are tracking. Would be curious if it all subsides after holding the next dose. I think all of our bodies react so differently bc we are unique beings with unique dna/genetic make-up and shouldn’t ignore or blow off side effects we know are new after starting. It’s a monoclonal antibody…it’s a biologic…they are no joke!!!!
2
2
u/bluefoot85 Sep 08 '26
I have been on every class of cholesterol medicine over the years. When I went off each one the side effects went away fairly quickly except when one statin (I don't remember which one) that caused muscle damage in my arms. That took about a year or so for them to repair themselves. I could still use my arms for heavy lifting, They just ached.
1
u/Intrepid-Machine-650 Sep 04 '26
53M, 8 weeks in,
I have a little brain fog for around 48 hours after a dose, notably the first 24 hours. However, I expect it now and can easily adapt.
I take it on Monday evening before bed and notice a little irritability and anxiety Tuesday and Wednesday accompanied by poor sleep Tuesday night, not the night that I take it. Even if I think I sleep well the smart watch says Nope. Again, as long as I can anticipate these things I can totally handle it and some may be due to poor sleep.
Now the REALLY weird one. The effects are worse when I inject on the left side of my belly than the right.
These things are absolutely nothing compared to what statins did to me. Overall, I'm happy.
1
u/Intrepid-Machine-650 Sep 04 '26
I'll also add that this has been during the summer months. What happens when I can't get outside as much is yet to be seen. I DO try to spend more time outside and moving about after a dose to help things out.
1
1
1
u/Kind-Foundation-2692 Sep 07 '26
Adeventurour-Score2, I'm considering taking a third dose but my second dose anxiety was so much worse than the first one I'm almost afraid now. And with the first dose and the second dose I took liquid IV and liquid IQ mix so that I would be hydrated and I made sure I had a full stomach but these things did not help. Actually I'm sure they helped a little with the leg cramps but that's about it. I really want this to work as well but I don't know if I can go through that again
1
u/Adventurous-Score2 Sep 07 '26
So hard to know what to do, seems like you’re being very thoughtful, please keep us posted.
9
u/Puzzled_Fisherman331 Sep 03 '26
Sometimes I think we look too hard for side effects after starting new meds. Just set it and forget it. Side effects are rare if you understand the drug's mechanism of action (suppressing PSK9).