Once is Never

May, 31, 2012 | 10 Comments


  1. Bravo! The mantras “RCT is the gold standard, “Case reports are just anecdotes”& “Once is never”are like slogans- a good one can stop progress for 50 years! I’d like to see a 4th article, or the Epilogue, titled : “A conclusions just marks the place where one has decided to STOP thinking”

    I think you have been kind enough in suggesting a rationale for the ease by which pharmaceutical companies have misled doctors. I happen to believe that it is mostly due to a gross lacking in the understanding of and having no experience in the practice of the “scientific method”- or “medical model” that produces MDs who are capable of calling a toxic side effect from a drug a symptom of severe mental illness that the drug has “unmasked”.

    You use analogies from baseball, like “step up to the plate”, which are visually stimulating. I think football (as it is played in America) offers another equally motivating visual. The FDA and doctors alike should have been throwing “Red Flags” on PHARMA’s playing field 20 years ago. A Red flag means : Play stops. Penalty announced along with punishment- like “15 yards and loss of down”- An early instituted behavioral modification program would have firmly established the rules of play- and inspired PHARMA to think more about patients if they were dreaming of big profits.

    One more thing. When RCTs are relying a great deal on subjective data that is taken by an interviewer, using a standardized scale for assessing , say- depression (The Beck’s scale, for instance), how many factors of personal bias- that could influence the result are taken into consideration- ? I am thinking about the main aspect of ‘truth’ telling- just because that seems to come up throughout the analysis and publication of the data on adverse effects. It could account for any seemingly positive result as well. There are three opportunities for lying :the subject in the RCT, the interviewer who rates the symptom that is targeted and the data analyzer. The other truth tampering occurs in places we have already examined.

    Time to spread the word to academic medical centers- EVERYWHERE-

      • Altostrata,

        I’ve lost faith in the umpires. At every major academic medical center, the department of psychiatric is part of the medical school. Any first year resident should be able to employ rudimentary scientific analysis to establish a link between a new variable and the emergence of a new symptom. If the new variable is a drug, the automatic response is to withdraw the drug. If the new symptom happens to be a documented adverse effect of the drug, withdrawing the drug would be sufficient treatment of the symptom. The unmitigated gall of any academic affiliated MD to begin a course of new drugs , calling this treatment of a disorder, which amounts to calling an adverse drug effect a disorder, should warrant the attention of any professor in that medical school who values the reputation of his/her medical school/institution. This practice was publicized in medical journals, raved about in the elite circles of psychiatrists at HMS- and not a single professor of Medicine at HMS bothered to scrutinize this bizarre means for creating a new disorder. There has been no oversight of psychiatry within medicine even amidst their mockery that pervaded the early years of biomedical psychiatry. You’d think this would have been a top priority as psychiatrists back in the 70’s were notoriously medical knowledge compromised.

        I can’t contain my outrage enough to appropriately engage the ‘umpires’ on these matters, but I am inspired to engage those still in training and newly graduated from their psychiatric fellowships at Harvard affiliated hospitals. Dr. Healy’s work is of paramount importance for this endeavor. A rather good fit at the most crucial moment, I’d say. The upcoming generation of psychiatrists are of the age to use the eleventh hour atmosphere pervading psychiatry today as a spring board for their professional development.

        The task at hand is devising strategies for slipping Dr. Healy’s work past the umpires and the under the noses of the ruling class of full professors. I have no doubt that the critical thinking skills and the passion to revitalize the ethical honorable aspects of the medical profession are ripe in this youthful group. They need a mentor to the same extent that Dr. Healy needs successors.

        • Agree again.

          I was pondering the extremely common practice of prescribing an antidepressant and, when adverse effects demonstrating excessive stimulation emerge — sleep disturbances, akathisia, jitters, etc. — a benzo is added, masking the adverse effects of the antidepressant.

          These people then go on to years of misery on the drug combination — which never seems to work very well — and then have difficulty tapering off both drugs, the iatrogenic perturbation of normal functioning having done its work below the surface, not to mention inadvertent addiction to the benzo.

          Certainly many PCPs are involved, but psychiatrists don’t seem to know any better. Clinicians are using the antidepressant-benzo combination widely as a panacea to keep people on antidepressants when, if the world worked in a reasonable way, they should be discontinued due to obvious adverse effects.

  2. I admit at the outset to having a very strong bias against using “tests” of various kinds for reasons that are too numerous to describe here. The reference above, to the Beck (not favourable I infer) reminded me of my particular objections to this “Inventory”.
    The standardization sample was inadequate and potentially misleading. The average age of the outpatients in the sample was 37.20 years, however, the range was from 13-86years. Caucasians made up ninety-one percent of the sample, while African-Americans and Asian-Americans made up only four and one percent, respectively and were the only minority groups included at all. Together, they comprise only five percent of the total sample. Containing only 500 individuals, the standardization sample is too small. There is no information regarding socioeconomic status or residential location (urban, suburban, rural) compared to US census data. A brief scan of the reported means and standard deviation raise some concern about the variation of a client’s scores on the BDI and clinical severity estimates. For example, the manual reports that clients clinically diagnosed as severely depressed obtained a mean of 32.96 (SD = 12.0) on the BDI. The manual, however, states the cutoff for the severely depressed range is 29-63. These data really only lead the clinician to conclude that higher scores on the BDI serve to indicate that a significant level of depressive symptoms is being reported.
    A crystal ball would be much less expensive.

  3. Dr. Healy, what about tying in the adverse events databases of countries other than the US?

    I believe the Netherlands has one, and the UK has its Yellow Card system http://yellowcard.mhra.gov.uk/. I know this would be a substantial undertaking but the more data points the better; this would be a way to accumulate them fairly quickly.

    I was looking at the FDA results and found them kind of sparse, which is no surprise because doctors don’t take reporting adverse events seriously and patients don’t know it’s there.

    • Rxisk when launched in the next few days will take reports globally. We hope to recruit teams of patients and doctors on a global basis to report.

      • I looked at the Yellow Card report on duloxetine and couldn’t make head or tails of it. Seems those reports are keyed to body system (“Cardiac disorders”) rather than symptom (tachycardia), which makes them hard to interpret.

        There were 52 “Fatal ADR reports,” though.

  4. I fear this is going to sound pedantic but it is important to distinguish between an adverse drug reaction (ADR) ( any undesirable effect of a drug beyond its anticipated therapeutic effects occurring during clinical use) and an adverse drug event (ADE) an untoward occurrence after exposure to a drug that is not necessarily caused by the drug. An example would be a medication error in wrong dosage, wrong drug, etc. A review of the literature shows that often the terms are confused or are used as synonyms.
    The reasons that physicians don’t report adverse reactions include, but are not limited to the following:
    1.The perception that it would appear that he/she has made a treatment error.
    2. Failure to believe the patient unless the adverse event is something like a rash that can a) be identified and b) written off as an idiosyncratic response.
    3. Time involved in filling in forms, the bane of any physician’s life.
    4. Belief that it is the manifestation of a separate disorder.
    Many adverse events are not reported because they involve mainly giving the wrong drug or the wrong dosage which may result from confusion of drug names or accident in writing the order by the physician e.g. 0.5mg instead of 0.05mg or misreading by the nurse. Name confusions are common e.g risperdal vs ropinerole and, of course, there is the notoriously poor handwriting to deal with – of which I must confess, I am so guilty that it is not unknown for me to be unable to read what I have written myself.
    Fear of malpractice litigation governs many decisions especially in locales that are particularly litigious.

  5. Addendum:
    In Canada, manufacturers of medical devices and drugs must report adverse reactions under the Food and Drug Act.
    Consumers may fill in a form (that is postage paid) and mail it to the requisite authority.


    Of course, none of the above carries any guarantee of appropriate action.

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