Sunday, 23 September 2012

Aspirin as good as amantadine for fatigue? Or not?

Epub: Shaygannejad et al. Comparison of the effect of aspirin and amantadine for the treatment of fatigue in multiple sclerosis: a randomized, blinded, crossover study. Neurol Res. 2012 Sep 12.

OBJECTIVES: The purpose of this study was to compare the relative efficacy of acetylsalicylic acid (ASA) and amantadine for the treatment of fatigue in MS.

METHODS: A 10-week, randomized double-blind crossover clinical trial conducted from October 2009 to September 2010. Fifty-two MSers presenting fatigue at 21 to 53 years of age were randomly allocated to the two treatment groups. The first group received amantadine (100 mg twice daily) for a total of 4 weeks. The second group received ASA (500 mg once daily) for four weeks. After a 2-week washout period, they crossed over to the alternative treatment for 4 weeks. MSers were rated at baseline and the end of each phase with the Fatigue Severity Scale (FSS).

RESULTS: ASA appeared to be equivalent in efficacy and safety to amantadine. A significant decrease in FSS occurred in both groups. Of the 26 MSers treated with amantadine, the mean (SD) of FSS decreased from 4.8 (1.4) to 4.0 (1.4) (P<0.001). In the 26 MSers treated with ASA, the mean (SD) of FSS decreased from 4.6 (1.4) to 3.5 (1.5) (P<0.001).

DISCUSSION: This study demonstrates that both ASA and amantadine significantly reduce MS-related fatigue. Both ASA and amantadine have previously been shown to reduce fatigue, and we postulate that treatment with ASA and amantadine may have similar benefits.


"Why was there a placebo phase? A lot of people are unconvinced about the effectiveness of Amantadine. How would aspirin work? It could lower body temperature or work as a an anti-inflammatory agent. Clearly more work needs to be done. On the upside aspirin is very cheap, but the down side it is associated with an increase risk of bleeding; the latter is not insignificant. Would I prescribe it? Not on this evidence. "

10 comments:

  1. Do you mean 'why wasnt there a placebo phase'?

    When people with heart problems are prescribed daily aspirin is that despite the risk of bleeding or is the risk different for them?

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  2. Personally, I think more work needs to be done on Modafinil - both for its impact on fatigue and its possible neuro-protective qualities. I made some inquiries as to how to raise money for you guys to do such work - approaching MSRC to see if under their charitable and fund raising banner I could raise some focused funds. Sadly, my suggestion fell on deaf ears and phone calls were never returned. I am still looking at ways to advance this.
    In the meantime, I take modafinil - it helps with my fatigue and, I hope, will keep me walking for longer.

    http://linkinghub.elsevier.com/retrieve/pii/S2211034812000429?via=sd&cc=y

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    Replies
    1. Why not contact the guys (Cris Constantinescu) in Nottingham to find out if they are intending on following up their interesting study.

      Maybe Prog G has some thoughts

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  3. I've tried both, Amantadine did not agree with me. And yes I agree with Iain O, Modafinil is the only thing I've found that really works. Since Teva now 'own' Modafinil no doubt they could be encouraged to do research if they thought there were dollars in it.

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  4. Low dose aspirin is considered safe for millions (should i say billions) of people with cardiovascular issues with mean age MUCH greater that the mean age of MSers. It is a least laughable to reject it because of the bleeding risk(!?) and prefer the OFF LABEL use of amantadine with "nervousness, anxiety, agitation, insomnia, difficulty in concentrating" as possible side effects. To be doubtful is another thing, but to regard aspirin as a risky choice for the whole MS population is clear pretext.

    There are much more in MS that the immune system, and aspirin is mainly used for its anti-platelet properties, not the anti-inflammatory ones. Of course, for you to accept this would equal accepting a blood circulation problem in MS. That's why you don't mention it. But since you are a man of science dedicated into making the life of MSers easier, you shouldn't leave a stone unturned when the is a hint for benefit. Under this perspective I ask you to carefully read the following study and see HOW can aspirin be beneficial in relieving neurological symptoms in patients with nutcracker syndrome:

    http://www.ncbi.nlm.nih.gov/pubmed/17161550
    "From the nutcracker-phenomenon of the left renal vein to the midline congestion syndrome as a cause of migraine, headache, back and abdominal pain and functional disorders of pelvic organs"

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    1. VV you should do due diligance before you make such sweeping statements regarding aspirin. It is probably more dangerous than natalizumab; the risk of dying from a fatal haemorrhage in the drug is about 1 in 500 and you only need to treat 73 people with the drug to harm one person. I suggest you digest the following meta-analysis:

      Seshasai SR et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Feb 13;172(3):209-16.

      BACKGROUND: The net benefit of aspirin in prevention of CVD and nonvascular events remains unclear. Our objective was to assess the impact (and safety) of aspirin on vascular and nonvascular outcomes in primary prevention.

      DATA SOURCES: MEDLINE, Cochrane Library of Clinical Trials (up to June 2011) and unpublished trial data from investigators.

      STUDY SELECTION: Nine randomized placebo-controlled trials with at least 1000 participants each, reporting on cardiovascular disease (CVD), nonvascular outcomes, or death were included.

      DATA EXTRACTION: Three authors abstracted data. Study-specific odds ratios (ORs) were combined using random-effects meta-analysis. Risks vs benefits were evaluated by comparing CVD risk reductions with increases in bleeding.

      RESULTS: During a mean (SD) follow-up of 6.0 (2.1) years involving over 100, 000 participants, aspirin treatment reduced total CVD events by 10% (OR, 0.90; 95% CI, 0.85-0.96; number needed to treat, 120), driven primarily by reduction in nonfatal MI (OR, 0.80; 95% CI, 0.67-0.96; number needed to treat, 162). There was no significant reduction in CVD death (OR, 0.99; 95% CI, 0.85-1.15) or cancer mortality (OR, 0.93; 95% CI, 0.84-1.03), and there was increased risk of nontrivial bleeding events (OR, 1.31; 95% CI, 1.14-1.50; number needed to harm, 73). Significant heterogeneity was observed for coronary heart disease and bleeding outcomes, which could not be accounted for by major demographic or participant characteristics.

      CONCLUSIONS: Despite important reductions in nonfatal MI, aspirin prophylaxis in people without prior CVD does not lead to reductions in either cardiovascular death or cancer mortality. Because the benefits are further offset by clinically important bleeding events, routine use of aspirin for primary prevention is not warranted and treatment decisions need to be considered on a case-by-case basis.

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    2. Of interest is the data reported here http://www.cancer.gov/about-cancer/causes-prevention/research/aspirin which refers to aspirin lowering the risk of dead from cancer by 20%, in contradiction of the analysis above. It is also a meta-analysis. I guess it is like all meta analysis, what controls the answer you get are your filtering criteria at the beginning, and that can easily end up being biased. If you filter selects, for example, only random control trials but it fails to check the quality of those trials then the answer you get may be junk. But without carefully reading all the included papers we do not know if it is junk. Meta analysis really should be banned, you cannot make a silk purse out of a bag of pigs ears.

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  5. "It is probably more dangerous than natalizumab". Try giving tysabri for 6 consecutive years (as was the mean follow-up for aspirin patients) and see what happens. (285/62 the latest tysabri news)

    Your are comparing apples and oranges.
    - What was the mean age of the patients treated with aspirin? Probably >> of the mean age of an MS patient.
    - Do the risk results apply to the general population? No, the apply to people with diagnosed CVD or at great risk of getting it.

    And then, where does the bleeding risk come from? Surely not from the anti-inflammatory properties of aspirin. Well, then maybe the same goes for the benefit. Why are so afraid to say that aspirin is above all A BLOOD THINNER?

    Then again, some disagree with the conclusions of the met-study you posted:
    http://archinte.jamanetwork.com/article.aspx?articleid=1108689

    Again then again, you can easily adjust or even cease the aspirin dose, when bleeding is suspected. Most MSers are already SP when they reach the risk age for CVD.

    I could wait some more for a reply on the study i posted earlier. I hope you'll spend some time.

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  6. "I could wait some more for a reply on the study i posted earlie"

    Yep I think you will be waiting a long long long time

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