Recent

% | $
Quotes you view appear here for quick access.

Avanir Pharmaceuticals, Inc. Message Board

  • onlyfactsplease onlyfactsplease Jan 17, 2013 11:33 AM Flag

    Nuedexta and impulse control

    This AAN abstract is important not just for the extra use for N but in what may be an expanded thought process about what PBA is, what disorders are clinically, and the mechanism by which it's produced:

    [P04.029] Dextromethorphan/Quinidine Attenuates Compulsive Shopping Behaviors and Pseudobulbar Affect in Individuals with Traumatic Brain Injury

    Christine M. Zakrzewski, Flanders, NJ, Phillip A. DeFina, Flanders, NJ, Jonathan Fellus, Flanders, NJ

    OBJECTIVE: These retrospective findings were described in order to broaden clinical awareness and understanding of pseudobulbar affect and the comorbid occurrence of compulsive shopping secondary to traumatic brain injury. The effective treatment of both conditions with a single pharmacotherapy hints at a broader syndrome of post-traumatic impulsivity. BACKGROUND: Pseudobulbar affect (PBA) comprises transient, involuntary paroxysms of affective lability resulting from various neurological conditions. Dextromethorphan/quinidine (DMQ) has been shown to effectively suppress PBA in diverse neurological populations. DESIGN/METHODS: The medical records of 12 patients with traumatic brain injury (TBI) were examined following the clinical observations of one of the authors (JLF). All 12 patients had a stable history of PBA and frequently displayed impulsive behaviors post-TBI. Treatment with DMQ was indicated in all 12 patients for paroxysmal outbursts of laughing and crying classically associated with PBA. RESULTS: The results of this case-series highlight DMQ as a potent pharmacotherapy for various neuropsychiatric behaviors secondary to TBI, including PBA. Treatment of PBA with DMQ in all 12 patients had the unexpected, salubrious benefit of decreasing the frequency of compulsive shopping behaviors. CONCLUSIONS: DMQ deserves consideration for the management of various neuropsychiatric behaviors associated with TBI, including PBA and impulsivity. Initiation of DMQ therapy holds the promise to significantly enhance the quality of life for individuals with PBA and poor impulse control. The co-occurring inhibition of compulsive shopping behaviors in this sample further supports a recently suggested hypothesis that the operational definition of PBA secondary to TBI be expanded to formally acknowledge the primary impairment of impulse control within which these episodes of affective lability frequently occur.
    Category - Neural Repair/Rehabilitation: Clinical: Traumatic Brain Injury

    SortNewest  |  Oldest  |  Most Replied Expand all replies
    • further proof that nuedexta effectively manages impulsivity: in patients with acquired brain injury, treatment with nuedexta rapidly eliminates suicidal ideation and also relieves chronic depression--within hours of the first dose. these patients had previously been treated with a dozen different conventional antidepressant medications. the definition of pba, specifically in patients with tbi, will soon be expanded to include a spectrum of disinhibited behaviors. this includes anger and agitation, which nuedexta also effectively diminishes. the market potential for this drug is seemingly ENDLESS!

      Sentiment: Strong Buy

    • nuedexta is an amazing drug abd these scientists are brilliant. i hear the first author is a patient with pba secondary to tbi and her life was dramatically turned around after taking dmq.

      Sentiment: Strong Buy

    • "This AAN abstract is important not just for the extra use for N but in what may be an expanded thought process about what PBA is, what disorders are clinically, and the mechanism by which it's produced: "
      No disrepect but I must strenuously disagree that this study is not the least bit "important" for any of those things.
      I think it is important that we realize (1) how medically unimportant this study is and
      (2) how it reeks of commercial bias.

      • 1 Reply to rayonman1
      • Ray, it all starts with it being just an abstract and your expectations. It is an entirely appropriate observational retrospective study. Like any similar case series it helps to form hypotheses that can be tested. I'm not sure what you expect out of an abstract but this one is just fine (would have been improved if they hadn't overstated their claims). You can't not expect ANY study that is limited to an abstract or has the words "retrospective" to be profound.

        It's importance comes from the fact that it may lead to experiments/findings that support a more expanded idea and understanding of how the brain controls emotions, anger, and impulses. You've been pretty clear that you reject any theory that expands the idea about the clinical spectrum of PBA beyond laughing/crying. You base that rejection on theoretical reasoning that IMO is not at all convincing.

        For those still open to the idea of an expanded spectrum, it's an important observation because it opens one more avenue of possibility and evaluation. Does it prove anything? - NO. Is it interesting? - To that group, yes. Are the authors so biased they just made these cases up? - NO. Is the area of impulse shopping disorder fraught with insanely high placebo effects and studies of other drugs thought to be useful and subsequently proven not to be? - YES.

    • "If this were presented at a medical meeting" - It's about to be presented at the AAN meeting

      "it would fail the audience question of whether there was evidence of commercial bias" - but hopefully this highly speculative finding would be interpreted with the consideration that that bias may be present. That being said, I expect this is a poster presentation and there will be no pass or fail criterion.

      As is true with most abstracts, the methods used need to be picked apart. Esp. how the 12 patients were chosen (consecutive unselected series vs. chose because they had an effect) and how the "salubrious" effect was determined.

      As for conclusions they are only saying this unexpected finding deserves further consideration. They didn't say they found a "cure" for compulsive shoppers. That being said, I do think a positive bias is present in their wording. But I also think that the link to a possible effect should be pursued as should the entire concept of what may be an expanded/linked disorder of impulse/emotional control of which PBA may be one component.

      • 2 Replies to onlyfactsplease
      • "The scientific method requires formation of hypotheses based on observations. Those hypotheses are then experimentally tested. The present study includes relevant observations that absolutely support a hypothesis that PBA may be a wider spectrum of disorders. Not sure why you'd call this aspect unscientific."
        Because the "support" you are referring to above is so small as to be effectively lacking.
        The wording of the abstract, the way they ignore the junk science they are presenting (12 patients, uncontrolled, retrospectively being treated, (presumably successfully) for PBA, with a soft endpoint of how much impulsive/compulsive shopping they are doing and talking about changing the very definition of the condition is all unscientific.
        I can tell you have read many abstracts and research papersin your career so just allow me to remind you to read the abstract from a purely professional scientist point of view (I'm just trying to help here) and be overridingly mindful of how conservatively scientific papers and abstracts are usually worded (and appropriately so).
        Scientific papers and abstracts discuss the limitations of the study (although in this case, the "limitations" are so huge that to talk about them would be much bigger than the abstract itself :-) and they don't talk about a garbage study redefining the definition of the illness or recommending it be tried as management of the condition or as is "potent pharmacotherapy".

        There are so many flashing red signals here that no benefit of the doubt should be given about "ambiguous" wording. The wording about "management" is inappropriate enough that it just does not belong there. I agree with you that they were trying to be "purposefully ambiguous" with their "management" wording and I hope you agree with me that they crossed the line to inappropriateness and it was because of commercial bias. In my opinion, their abstract crossed lines to being unprofessional and unscientific and I suspect it was not unwitting. I suspect it was for the serious MOTIVE of commercial off-label promotion of the drug as a hired doctor.

        I am sure you would agree that they should have commented that treating PBA itself could lessen depression and thereby lower obsessive/impulsive shopping. But if they had done that, it would have diminished their calls for redefining the disease and using the drug and I suspect that is why they omitted this obviously necessary commentary as well as other obviouisly necessary commentary about the myriad severe of the "study".

        I think it is fair to surmise this clinical abstract, while barely appropriate to even present at a medical meeting, is being used as a little advertising booth for inadvisable off-label use of Nuedexta at the American Academy of Neurology meeting.
        In my opinon, I can only surmise Avanir management is too greedy and unethical to realize these commercial efforts by physician proxy diminishes Avanir's credibility amongst physicians and investors.
        As an example, I suspect the same greedy, unethical and unscientific thinking prevents the CEO from ever mentioning that about 30% of the severe PBA in the STAR trial had a complete remission with placebo when he crows about how something like 51% in the Nuedexta arms had complete remission. Before anyone jumps to say how the CEO is not a scientist, he has at least two physicians working for him and surely he would run his presentation by them for medical comments. I can only surmise it has been pointed out to him by at least one of his physician employees that he should mention this placebo efficacy but he does not and instead always clues his audience that he is a conniving stock promoter. It is just foolish.

        A scientific approach would have been to acknowledge how poor quality this clinical data is and to have a brief suggestion of doing a small prospective randomized placebo controlled Phase 2 study in traumatic brain injury patients with impulsive or compulsive shopping problems but who do not have PBA (but definitely NOT with Avanir's money, PLEASE) and that study would have to see if there is an efficacy signal.
        That is all that is warranted mentioning here by the "study" authors.
        But I'm sure Avanir's CEO is "delighted" with the abstract.

        OnlyF, I think especially after being burned by accepting Avanir's huge expansion of claims of the PBA population that you would be more careful touching anything Avanir influences, like this "study" and what you basically acknowledge is its inappropriate suggestions and conclusions.
        This "study" is not the least bit "important," to use your word.

      • "As for conclusions they are only saying this unexpected finding deserves further consideration."

        This thing exudes unwarranted conclusions and bias.
        Note, for just one example, they are saying that dex/quin deserves "consideration for "management" of various neuropsychiatric behaviors associated with TBI" This is an unwarranted conclusion based on really poor "'data".
        Consideration of a Phase1/small Phase 2 study would be okay, but consideration for management is nonsensical given the extemely poor quality of the data presented.

        They say the "results" highlight dex/quin as potent pharmacotherapy for various neuropsychiatric behaviors secondary to TBI" I'm sorry, but this statement is just an affront and shows how biased they are. They seriously underestimate their audience.

        These 12 retrospective cases don't "support" any "hypothesis" about expanding the definition of PBA. This is really unscientific and inappropriate, in my opinion.

        "The results of this case-series highlight DMQ as a potent pharmacotherapy for various neuropsychiatric behaviors secondary to TBI, including PBA. Treatment of PBA with DMQ in all 12 patients had the unexpected, salubrious benefit of decreasing the frequency of compulsive shopping behaviors. CONCLUSIONS: DMQ deserves consideration for the management of various neuropsychiatric behaviors associated with TBI, including PBA and impulsivity. Initiation of DMQ therapy holds the promise to significantly enhance the quality of life for individuals with PBA and poor impulse control. The co-occurring inhibition of compulsive shopping behaviors in this sample further supports a recently suggested hypothesis that the operational definition of PBA secondary to TBI be expanded to formally acknowledge the primary impairment of impulse control within which these episodes of affective lability frequently occur."

    • This is all way overstated. If this were presented at a medical meeting it would fail the audience question of whether there was evidence of commercial bias.
      Thank you for providing an example of why medical presentations are required to ask attendees if there was evidence of bias. Sometimes, apparently, presentations are just covered with it!
      Unbiased medical researchers would pick these totally unwarranted statements to shreds:
      "
      The results of this case-series highlight DMQ as a potent pharmacotherapy for various neuropsychiatric behaviors secondary to TBI, including PBA. Treatment of PBA with DMQ in all 12 patients had the unexpected, salubrious benefit of decreasing the frequency of compulsive shopping behaviors. CONCLUSIONS: DMQ deserves consideration for the management of various neuropsychiatric behaviors associated with TBI, including PBA and impulsivity. Initiation of DMQ therapy holds the promise to significantly enhance the quality of life for individuals with PBA and poor impulse control. The co-occurring inhibition of compulsive shopping behaviors in this sample further supports a recently suggested hypothesis that the operational definition of PBA secondary to TBI be expanded to formally acknowledge the primary impairment of impulse control within which these episodes of affective lability frequently occur."

    • "This AAN abstract is important not just for the extra use for N but in what may be an expanded thought process about what PBA is, what disorders are clinically, and the mechanism by which it's produced: "
      I think you should reconsider how important this abstract is. I think it is not important.
      This is a retrospective account of only 12 patients by Dr. Fellus who has disclosed he has been paid $20,000 by Avanir.
      When patients have PBA due to traumatic brain injury, they will frequently have depression.
      If they have a shopping disorder, treating their PBA effectively is likely to improve their mood
      and to lessen their impulsiveness and shopping disorder.
      Rather than jump to the conclusions put out by the authors, they should do a prospective, randomized, placebo controlled, multi center study of a much larger group of patients with traumatic brain injury who do not have PBA and see if there is any signal of effectiveness.
      This is the same deficiency in approach that led to Avanir doing their ill-advised agitation in dementia study.
      This uncontrolled retrospective account of only 12 patients confounded by PBA is relatively meaningless.
      PBA is thought to be a condition of the lack of inhibition of the motor response to emotion.
      PBA is therefore not likely to be related to agitation or impulsivity.
      It looks like we are in for countless false starts on other conditions because of a lack of scientific rigor.

    • Interesting read, many thanks.
      Regards

    • Just think of all the patients who have impairment of impulse control, addictions etc. Amazing!

    • Interesting sleuthing zack...maybe he stopped posting once he became a consultant?

      Would expect he'd be prohibited if he's a consultant.

      • 1 Reply to onlyfactsplease
      • Said sleuthing was done as soon as I saw him post where he worked. I remember thinking how odd it was that he was posting, since I think he was already known to be involved with the company. (Don't really care enough to go back and check, lol).

        IIRC, it was Ray who kept asking him if he was in any way paid by AVNR, and he wouldn't answer (again, iirc). I also think that badgering led him to eventually stop posting, but it's a little hazy in my memory.

    • Onlyfacts – Great thanks for posting the additional information, as your rightly point out very interesting. In the event you post further extracts from the AAN and I do not reply immediately please excuse me as I have an appointment to attend to.

      That is not an excuse for you to relax and not post any further relative details ;-)
      Catch up with you later.

      Best regards
      Sr Falconi

      Sentiment: Hold

    • View More Messages
 
AVNR
16.960.00(0.00%)Jan 12 4:00 PMEST