Tag Archives: placebo

Exploiting the Placebo Effect:  Legitimate Practice or Chicanery?

On June 13, 2014, Psychiatric Times published an article by Steve Balt, MD.  The article is titled Assessing and Enhancing the Effectiveness of Antidepressants, and is a good deal more candid as to the efficacy of antidepressants than one normally encounters from psychiatry.  Dr. Balt is a private practice psychiatrist in California.  He is the editor-in-chief of The Carlat Psychiatry Report.

The article opens with the observation that despite the large number of antidepressants on the market, and decades of clinical experience, no particular product seems to have emerged as substantially better than the rest.

“As a result, most psychiatrists choose antidepressants not on the basis of efficacy, but rather on the basis of insurance coverage, adverse-effect profiles, or particular clinical features of depression (eg, melancholic, atypical, anxious features), for which some differences in efficacy do exist.”

The author refers to a number of studies, including NIMH’s STAR*D trial, and states:

“Despite the scope and initial aims of the study, no single antidepressant strategy or combination appeared more advantageous than any other.”

And:

“Effectiveness trials, therefore, seem to confirm the conventional wisdom that no single antidepressant works better than—or worse than—any other.”

And:

“Findings indicate that there were no significant differences in effectiveness of antidepressants, although individual drugs did differ in terms of onset of action and ease of dosing.”

In studies that did detect differences between products, Dr. Balt expresses the view that they “…were slight and of questionable clinical significance.”

Then the author makes this surprisingly candid observation:

“Because a meta-analysis is only as good as the data on which it is based, these meta-analyses must be considered in light of the very real problem of selective publication. This is the tendency for favorable results to be published, while negative or neutral results are not. In an analysis of 74 antidepressant trials registered with the FDA between 1987 and 2004, Turner and colleagues found that nearly half (36, or 48.6%) were negative, and the vast majority of these were either not published or were published in a way that made the drug seem favorable. Likewise, industry-sponsored studies are more likely to favor the manufacturer’s drug, often because of nuances in experimental design. While most researchers make every effort to include unpublished results in their meta-analyses, the “file-drawer” phenomenon of unpublished negative results may bias the conclusions of analyses that exclude the inaccessible data.”

Dr. Balt summarizes all of this with what he calls:  two “stark truths about antidepressants.”

“First, there seem to be no significant differences among them; although future research may uncover patient-specific biomarkers that favor one medication over another, none has yet done so. Second, and somewhat surprisingly, antidepressant effectiveness is quite low.”

And he concludes:

“Thus, in the absence of data that can predict the best antidepressant regimen for a patient, enhancing the effectiveness of an antidepressant seems to be the best strategy.”

Dr. Balt mentions two possible strategies for enhancing the effectiveness of an antidepressant.  The first is to recognize that depression is not a single condition, but rather  “…multiple conditions, each deserving of its own unique treatment approach.”  He states that  “…much of the antidepressant response in mild to moderate depression may be due to the placebo effect”, and that anxious individuals may do better with psychotherapy.

Dr. Balt’s second suggestion for effectiveness-enhancing might be to combine antidepressants, or to supplement them, with what he calls “augmentation agents”.  But he acknowledges that while there might be some “intuitive appeal” to these strategies, there is little in the way of supporting evidence for their effectiveness.

Then:

“The more important question may be more about whom we are treating rather than what we treat with.”

Which, of course, is close to what we, on this side of the debate, have been saying all along – that effective help must be tailor-made to the personal characteristics and context of the individual, and that the facile labels which psychiatrists optimistically and misleadingly call “diagnoses” are counterproductive.

For the sake of thoroughness, Dr. Balt dismisses the relevance of genetics:

“In reality, however, the genetic contribution likely involves an impractically large number of variants, each having a very small effect, that together contribute to the very complex phenotype of antidepressant response. Indeed, 2 meta-analyses, using genome-wide analysis to identify polymorphisms to predict treatment response, found only a 1.2% contribution or no contribution at all.”

And metabolism:

“With few possible exceptions, no evidence exists that blood concentrations influence antidepressant outcomes, and there are multiple nongenetic factors that influence drug metabolism, such as diet, other medications, and adherence.”

This last assertion – that antidepressant blood concentrations have no effect on outcome – is a truly extraordinary admission from a psychiatrist, and could even be interpreted as the (psychiatric) baby going out with the bathwater.

But then, just as Dr. Balt appears to be morphing into a psychotherapist, he slips back into psychiatric mode:

“Not surprisingly, we can take advantage of patient preferences to enhance treatment outcomes.” [From the context, it is clear that he means drug treatment]

“…the quality of the therapeutic alliance between prescriber and patient is sometimes a better predictor of patient outcome than which drugs are prescribed.”

The last quote sounds positive, but watch where Dr. Balt goes with it:

“One study found that ‘effective’ prescribers obtained better outcomes with placebos than ‘less effective’ prescribers with active antidepressants.  Asking ‘which’ medication may be less important than the ‘meaning’ of medication to both clinician and patient.”

So what Dr. Balt is describing and suggesting is to use the therapeutic alliance, not to connect to the individual, and to provide real support in the resolution of personal concerns and problems.  But rather, to enhance the effectiveness of psychiatric drugs.

“The recent emphasis on personalized antidepressant prescribing seems warranted, but rather than taking a combination or pharmacogenomic approach to medication selection, clinicians should focus more on a personalized approach, establish realistic (but hopeful) expectations, and use patient preferences and beliefs to optimize outcomes.” [Emphasis added]

And:

“Even when patients’ preferences do not have any bearing on outcome, matching treatments with patients’ preferences increases their willingness to initiate and adhere to a treatment plan.” [Emphasis added]

So if a client believes that Zoloft, say, will be helpful, because it seemed to help a family member, perhaps, or even because the TV ad made the product seem attractive, the psychiatrist should prescribe Zoloft?  That feels a little bit like a con.  It’s an admission that although the drugs aren’t much good, we can sort of trick the client into enrolling, adhering, and perhaps even becoming happier.

And why is “adherence” so important, if the drugs aren’t much use to begin with, and often bring a host of additional problems?

I can appreciate Dr. Balt’s honesty concerning antidepressants, but, in my view, his recommendations entail a good measure of condescension and disrespect.  They also have the potential to encourage increased prescribing of drugs, despite his assertions of their limited efficacy.

. . . . . . . . . . . . . . . .

And incidentally, besides his recent critique of antidepressants, Dr. Balt had earlier gone on the record with some biting and revealing criticism of a psychiatric clinic where he worked from about 2009 to 2012.

In August 2014, Dr. Balt was taken to task on Twitter for being a top prescriber of Seroquel (quetiapine), a neuroleptic, in California in 2009 (1,000+ prescriptions).  In a subsequent interview with William Heisel of William Heisel’s Antidote, Dr. Balt is quoted as writing:

“More than 1,000 new prescriptions in one year is hard to fathom. Given my part-time schedule there, it would have meant six to seven new prescriptions each day, which is impossible. However, if it includes each month’s refills for patients who took the drug all year long, that does not seem at all unreasonable for that clinic. Given the volume of patients (and their specific requests for Seroquel, a medication in high demand), automatic refills were frequently given.”

And:

“That was my first full year at a clinic where quick visits, busy schedules, and knee-jerk prescribing were the order of the day. Over time, I became quite disappointed — if not angry — at what seemed to pass for ‘treatment’ and the overwhelming emphasis (on the part of patients and doctors alike) on the use of psychotropics to manage what were, most of the time, sociocultural stressors in our largely indigent, population.”

And:

“I’d estimate that 50% to 70% were for ‘schizophrenia.’  Keep in mind, however, that a schizophrenia diagnosis is freely given in these settings, e.g., for otherwise healthy people who say, ‘I talk to myself sometimes,’ or ‘I sometimes see shadows at night,’ or ‘I’m always looking behind my back when I’m outside,’ etc.  As for the rest, those prescriptions were probably given for bipolar disorder or off-label for sleep.  As I learned more about the metabolic effects of Seroquel I tried to use less of it.”

And:

“I have worked at other clinics, and my experience tells me that overprescribing is rampant in the Medicaid setting and apparently accepted as the standard of care. I have seen the same over-reliance on psychotropics, over-diagnosis and waste of resources in other parts of the state, although the volumes were not nearly as high as what I experienced in Oakland.”

So Dr. Balt is describing a psychiatric practice in which:

  • “automatic” refills for a neuroleptic were frequently given
  • “knee-jerk prescribing” was the order of the day
  • psychosocial stressors were “managed” with psychotropic drugs
  • diagnoses of schizophrenia were “freely given”
  • and overprescribing for Medicaid recipients (i.e. poor people) was “rampant”

Dr. Balt is now in private practice, and on his Psychology Today bio page he tells us that he offers “both medication management and psychotherapy” and that his “…approach to medications is a conservative one.”

And then he writes:  “… I am willing to help patients taper or discontinue medications that provide little benefit, or which cause harm.”  I have no reason to doubt Dr. Balt’s sincerity in this matter, but the fact that he felt the need to issue such a statement implies, I think, that it is not standard practice in psychiatry.  In other words:  psychiatrists routinely leave people on  “…medications that provide little benefit, or which cause harm.”  This, of course, is something that we on this side of the debate have been saying all along, but it is interesting to see these ideas coming from within psychiatry itself.

Mood Disorders and Stem Cells

Thank you to Tallaght Trialogue for drawing my attention to Blue Horizon Stem Cells (you can see their website here) and a recent article they’ve written titled Mood Disorder (here).

The article contains a very brief discussion of the term mood disorder, including a mention of “major depressive disorder” and “bipolar disorder.”  It then goes on to say:

“To find out more about how you may benefit from stem cell therapy, please complete our Contact Us form and one of our physicians will reach out to you for a private consultation.”

Interestingly, it never actually says that stem cells can help with depression, but the implication is clear.  Blue Horizon Stem Calls is based in New York, and they list two phone numbers.

THE FACTS

In January of this year Neurology Today ran an article titled “Legal Ruling Puts the Brakes on Unlicensed Stem Cell Therapies.”  You can see it here.

Here are the first three paragraphs:

“Blue Horizon Stem Cells of New York City claims to offer stem cell treatments for heart disease, arthritis, diabetes, Alzheimer’s disease, sports injuries, spinal cord injuries, stroke, and many more conditions. The Stem Cell Rejuvenation Center of Phoenix, AZ, charges patients a flat $7,600 fee to receive stem cell treatments for “a variety of conditions” — their Web site doesn’t get any more specific than that. And the Stem Cell Institute of Fort Lauderdale, FL, promises treatments for multiple sclerosis, spinal cord injury, osteoarthritis, rheumatoid arthritis and other autoimmune diseases, autism, heart disease, and cerebral palsy. The price tag: between $15,000 and $20,000 — except for spinal cord injury, which one assumes costs more.

One thing these “stem cell clinics” all have in common: none of their treatments are approved by the US Food and Drug Administration (FDA). The operators argue that, since the stem cell treatments are simply “minimally manipulated” versions of the patient’s own cells, these therapies don’t constitute a drug or biologic that the FDA could regulate.

But a decision by a US District Court judge made last July could put the brakes on what several neurologists with expertise in stem cell research have likened to a “wild West” atmosphere. In U.S. v. Regenerative Sciences, Judge Rosemary Collyer declared that, contrary to claims made by Denver-based Regenerative Sciences, the stem cell treatments it offers for injuries and degenerative joint conditions, which it calls the “Regenexx” procedures — are subject to regulation by the US FDA.”

The article goes on to discuss the difference between genuine stem cell work (slow, careful, scientific and appropriately regulated), and the other sort (unscientific, no demonstrated efficacy).

It’s also pointed out that, given the media coverage and the strong expectations of healing associated with stem cells, the field is particularly open to placebo effects.

Now what does that remind me of?

 

 

More about Antidepressants and Placebos

The debate is over.  Antidepressants are only very marginally more effective than placebos.  And yet the “depression-is-an-illness” lobby continues to grasp for straws.

Fiona Godlee, editor of the British Medical Journal, recently cited “evidence” of the efficacy of antidepressants.  For a critique of the Godlee article go to Duncan Double’s website “Critical Psychiatry.”

Surprise finding! – Antidepressants are only very marginally more effective than placebos.

What this means in effect is that people are “curing” their own depression (gasp), and perhaps don’t really need the mental health practitioners (double gasp).

Drugs, Placebos, and Life

I have recently read a very interesting book by Irving Kirsch, PhD. It’s called The Emperor’s New Drugs, and the central theme of the work is that antidepressants are only very slightly more effective than placebos (i.e. sugar pills), and that the difference is not clinically significant.

The logic is cogent and the research is rigorous. Read the book and decide for yourself.

Dr. Kirsch argues in favor of psychotherapy as a substitute for pills. And certainly talking is usually helpful. However, as long as depression is conceptualized as an illness, I don’t believe we will see real progress in this field.

Depression is not an illness. Depression is not an instance of something going wrong in an organism, but rather something going right. It is an adaptive response – a warning system (analogous to pain), alerting us to a need to make some changes in lifestyle.

The fact is that each person has within him or herself the resources needed to generate and maintain positive feelings. This is the essential point of the placebo research. It wasn’t the sugar pills (or the antidepressants) that generated the positive feelings. It was the individuals themselves starting to take appropriate corrective action in their lives.

The six natural antidepressants are:

– good nutrition

– fresh air

– sunshine

– physical activity, with frequent successes

– purposeful activity

– at least one good, open, honest relationship

When these factors are present in our lives to a significant degree, we feel generally positive; when one or more is largely absent, we feel down. These ideas are developed more fully in my post of July 28, 2009: Depression is not an Illness.

If you’re taking antidepressants, you owe it to yourself to read Dr. Kirsch’s book.

Cover of Kirsch's Book Irving Kirsch, Ph.D,
The Bodley Head, 2009