        
                              GENERIC DRUGS FOR ADD
        
             Generic drugs can offer substantial cost savings for ADDers,
        but reports of their effectiveness vary significantly, and
        none of the literal seems to state authoritatively why this
        should be.  The following is a transcript of messages on this 
        subject between members of the ADD Forum on CompuServe, including
        
             Several people who've bought both the brand name medication 
        (e.g. Ritalin or Dexedrine) and generics (methylphenidate) and a 
        real specialist in the field, a psychopharmacologist.
        
             This document may be copied and distributed freely without 
        modification. It is not, however, medical advice, which can only 
        be given by a physician who's familiar with a specific 
        individual's case.
        
             Have you heard of any problems with generic Ritalin?
        
             I think I saw a thread on the forum not too long ago in
        which people were expressing concern about generic Ritalin 
        (methylphenidate).  I have no personal experience of patients 
        reporting problems.
        
             At one time, the pharmacy where I _USED_ to get my son's
        prescriptions filled substituted generic Ritalin for brand name;
        the substitution was immediately noticable, and so, I always
        stree that I want brand name when his precription is refilled.  
        Also, they have increasingly had problems in filling his 
        prescription, telling me that their suppier is "holding back" on 
        the Ritalin.  I mentioned this to the neurologist the other day 
        and he gave me a look as if to say, "What are they talking 
        about?"  I go to another pharmacy to fill a prescription that I 
        use that is not easily obtainable, and they have reassured me 
        that, to date, they do not have problems getting the medication 
        and, since my son will be away at school next year, they will 
        fill the prescription, and send it directly to my son.
        
             Sometime, I guess, you just have to find the right pharmacy,
        once everything else is in place!
        
             Glad to hear you found a pharmacy that would give you the 
        straight scoop.  I remember hearing your tales of getting 
        obstacles from the first one.
        
        To briefly recap the thread on the generic of Ritalin:
        
         - Some people find it works fine, others don't
         - Some say "increase the dosage 20% because it's weaker"
         - Everyone seems to agree that one should get stabilized on the
           brand name stuff first, because it's got known potency, then
           try the generic and see what happens.
        
             I'm on the east coast, but there aren't too many
        manufacturers of Dexedrine, so I'll comment from personal
        experience.
        
             My wife and I have always insisted on name-brand quality for
        our son's dexedrine.  We are convinced we saw inconsistent
        dosages on the rare occasions that he got generic drugs. 
        Sometimes he zombied, sometimes he came off the drug with a
        crash.  Fortunately for us, our medical plan is limits our co-pay
        to $12 for name-brand drugs.  It's $6 for generic, but $6 more is
        worth it for consistency.
        
        
             Yes, there is a difference in the generic. It does NOT work
        as well.  Also, It's better to take it more often than using the 
        sustained release kind. 
        
             There definitely doesn't seem to be a concensus on this
        issue.  I know there may not be a definitive one way or the
        other, but I hoped to get a majority on one side or the other.  I
        will continue to experiment.  I got the 20mg generic this time.
        But I was taking 2 10mg of the "real" so I don't think this is a
        fair comparison due to disolving times and the like.  I will get
        the "real" next time.  The pharmicist told me he sells 80%
        generic and for what it is worth, he said he never heard any
        problems or differences. The physician said he has only heard of
        a few problems such as shorter duration or fluctuating
        effectiveness, and he wasn't sure whether it was due to concerns
        from patients or the drug. Can you relay your experience in more
        detail?
        
             I have no idea why the name brand is better, unless there
        are fewer quality control checks for generic makers. I would
        think that most children using Ritalin do not have the maturity
        to speak up about the difference. I am taking three 10 mg a day.
        I don't take them unless I know I will need them. I have had no 
        problems with Ritalin, but I would rather use Dexedrine because 
        the dosage is about half and it's CHEAPER! 
        
             There are those who say that for them it does work as well;
        I guess different folks respond differently.
        
             To those working with generic drugs.  I couldn't help but to
        notice this thread.  Just to let you know about a couple of 
        things I have been reading about currently.  In the field of 
        generic drugs there are different companies that make the same 
        drug all across the country.  So some of it can be because of the
        area you live, that and the fact that the standards set for 
        controlling generic drugs are considered weak at best.  
        
             In this field there are very few on the site inspection of
        where the drugs are made. All the drug company has to do is turn
        in a  couple of bottles for testing. Also from what I have been
        reading the drugs can vary upwards of 20% - 30% of the strength
        of the name brand drug.  In one book it said the standard was
        50%.  So you can get a generic lot of drug that is 20% weaker
        than the name brand and then go acrosse the street to another
        drug store and get a generic that is only 10% weaker. 
        
             It all varies on the company that makes the generic drug and
        what there standards are. There have been several groups out
        there pushing for better standards amoung the drug companies that
        make generic.  However these groups keep running up against drug 
        companies that put up millions of $$$ to keep the standards right
        where they are now.
        
             Do you happen to recall the name of the book that discussed 
        standards for generics?
        
             My impression, from previous conversations with docs here,
        is that a generic must have the same mix of active ingredients,
        no question about that. (Correct me, you knowers out there!)  The
        variation can come in how well the active ingredients make it 
        into your system.  For instance, some mentioned seeing generic 
        pills that were crumbling right in the bottle, which gives good 
        reason to think they wouldn't have consistent potency.  And the 
        mixture of inert ingredients could affect how well it gets 
        absorbed into the system.
        
             But then, recently, someone (don't remember who) said "The
        FDA has been much more on top of the generics recently, making
        sure they actually work like the brand names."  
        
             Current federal regs require equivalence within 20% of the
        innovator's product, either way. Bioequivalence is defined
        basically as the area of the time vs serum concentration curve.  
        On a graph on which the vertical axis is serum concentration of 
        the drug and the horizontal axis is time, points are plotted and 
        connected until drug can no longer be detected.  A generic is 
        considered "bioequivalent" as long as the area under the curve 
        (AUC) is 80%-120% of the product originally marketed.
        
             If this seems to be a large range, I agree, unfortunately. 
        To make matters worse, the shape of the curve doesn't have to be
        the same.  This means that a high peak concentration with a
        shorter duration can have the same AUC and still be considered 
        bioequivalent.  If the generic product causes problems with 
        toxicity, however, then it would have to be reformulated, in 
        theory.  My opinion, however, is that generic manufacturers are 
        much less closely supervised by the FDA than the larger research 
        centered companies.  So, problems may exist for quite a while 
        before regulatory action is actually taken.
        
             In spite of the above, I do want to say that I think there
        are many more "good" generics out there than bad.  The advice of
        stabilizing on the brand name and then trying the generic should
        be gospel here, as far as I'm concerned.
        
             The 20% rule is correct.  The generic manufacturer is
        required to comply with what are known as good manufacturing
        practices as well.  The generics don't have to be within 20% of
        each other, but do have to be within 20% of the innovator's
        product.  That means one generic could be 80% of the original and
        another could be 120%.  Both meet the 20% rule, but the two
        generics are more than 20% different.  This is why people
        shouldn't switch frequently from one generic to another.
        
             Another point I probably should make is that once the drug 
        reaches systemic circulation, rates of metabolism are the same 
        regardless of source of delivery.  There are a few exceptions to 
        this, but very few.  Side effects and therapeutic effect 
        differences among generic drugs have more to do with rate of 
        release/absorption.  
        
             If drug is released too fast, higher peak levels will be 
        achieved, thus potentially more side effects for a while, but 
        more drug is available for metabolism, so duration of effect is 
        shorter.  If drug is released too slowly, sufficiently high 
        levels may not be achieved in order to maintain a therapeutic 
        effect, but enough may float around to cause side effects for a 
        relatively long while.  This is especially important with 
        antibiotics.  Again, if a product causes significant toxicity, 
        the gov't is supposed to step in, but this is usually very slow 
        to occur.
        
             I should have realized that once the stuff's in the blood,
        it metabolizes at the same rate regardless of where it came from. 
        Sorta like booze, right? Once you've got 1ml of ethanol in your 
        blood, it'll take a certain amount of time to clear out, no 
        matter how it got there; same with meds, generic or not. Right?
        So then the questions would become:
        
         - out of a given dose, how much "active ingredient" actually 
           gets into the blood, and how fast?  In other words, what does 
           the start of the curve look like?
        
         - is the start of the curve steep enough to "jump-start" the 
           response? (I mention this because some doc said he gives 5mg 
           of regular Ritalin along with the SR, or else it never seems 
           to "kick in", so I speculate the same might happen with a 
           slow-delivery generic?)
        
                  With most drugs, however, the amount of drug 
            metabolized per unit time is expressed as a *percentage*.  It
        
            takes the same amount of time to eliminate, say 50%, of drug 
            on board no matter how much is present.  So, once the drug 
            gets in, the same amount of time is needed to get it out.  If
        
            the drug is absorbed very slowly, it takes longer to get rid 
            of all the dose taken than if it is absorbed rapidly only 
            because delivery of the drug to the site of metabolism is 
            delayed.
        
        2.  Re how much "active ingredient" actually gets into the blood 
            and how fast: The upslope of the blood level vs time curve 
            may vary somewhat from generic to generic of the same drug.  
            The whole idea of a "generic equivalent" is that the drug 
            "behaves" the same as the innovator's product.  Variation in 
            absorption *rate* can yield the same total amount of drug 
            available, but a different clinical profile.  Too much 
            difference in *extent* of absorption, on the other hand, 
            would be much more likely to make the drug fall outside of 
            legally acceptable limits; i.e., 80%-120%, as well as 
            different therapeutic effects.
        
        3.  Re "jump starting" the effect with rapid absorption, if you 
            can do it with Ritalin, you should be able to do with a truly
        
            equivalent generic methylphenidate.  A generic which is more 
            slowly absorbed would be less likely to have such an effect.
        
             Since we don't clearly understand how Ritalin (for instance)
        works in the first place, nor exactly what ADD is for various 
        people, it really does come down to that same principle: if a 
        generic works for an individual, fine, but if it doesn't, it's no
        huge surprise.  Another generic might, or might not.
        
        Two final questions (anyone out there, feel free to answer):
        
        1. how much less expensive are the generics, roughly? Half, or 
           not that big a difference?
        
        2. Given that different generics behave differently, the next 
           question is, is each generic at least consistent?  Or will the 
          same "brand" of generic be consistent from month to month, 
           year to year?
