ROBUST Placebo Effect

Medicating depressed TBI-patients is both medically and morally negligent--commentary on a medical publication

Well, we've all certainly heard the above before, haven't we?

When my feelings got hurt as a young person, my mother used to always say, "Consider the source."

In other words, if someone says or does something that hurtful, then it's on them, not you. Their issue, not yours.

But what if the offending person had the power to make it my issue? Your issue? Our issue?

An issue that involved our actual health, safety, lives?


So, let us consider the source, then, BMC (Biomed Central) Psychiatry, when we consider their publication of an article that's accessible to every family practitioner, every primary health provider (PCP), every Tom, Dick, and Mary, M.D., when they see patients in their clinical practices who present with depression after a mild-to-moderate brain injury.

The source, BMC, and the article's headline, authors, below:

Antidepressants for depression after concussion and traumatic brain injury are still best practice
Noah D. Silverberg & William J. Panenka BMC Psychiatry volume 19, Article number: 100 (2019) Cite this article 22k Accesses, 17 Citations, 11 Altmetric, Metrics

Please note the number of times the article has been accessed. Twenty-two thousand times. Did 21,000 people accidentally stumble on the article while seeking a recipe for 'Keto-friendly bran confections?'

Or is the likelihood greater that this article has been read by PCPs and family practitioners, thus determining their courses of action, their treatment plans, for patients seeking clinical intervention for depression after a TBI?

I'm sickened and afraid to even consider the answer to that question.

Still Best Practice

I'd like to dissect the first paragraph within the main body of the article. I encourage you to read it in its entirety. It makes me too angry to think straight, so it's been a minute.

Caveat/disclaimer: I'm not a doctor, and I'm not a researcher, but I am, by all accounts, proficient and well-versed in the use of language. That said, I'm going to break this paragraph from the BMC's site down into smaller, more digestible chunks./End caveat

(Bold, and CAPS for emphasis.)

"Selective serotonin reuptake inhibitors are recommended as FIRST-LINE TREATMENT for depression in contemporary expert consensus clinical practice guidelines for management of TBI. This recommendation is based on multiple prior meta-analyses of clinical trials in depression after TBI as well as depression in the general population. The evidence is mixed. A recent clinical trial and new meta-analysis including that trial found no benefit of antidepressants for depression following TBI. WE ARGUE THAT THIS FINDING SHOULD NOT CHANGE PRACTICE, i.e., patients who present with depression after TBI should still be considered for antidepressant treatment, because they may (1) benefit from ROBUST PLACEBO EFFECTS, (2) benefit from an alternative or adjunctive medication if the agent prescribed first does not achieve a depression remission, and (3) make improvements that are not captured well by traditional depression outcome measures, which are confounded by TBI sequelae."

So, the very first paragraph asserts a lack of new evidence to suggest that using medication to treat head-injury patients who are experiencing severe depression—a consistent and common complication after head trauma—may be "no more effective than placebo" in this extremely vulnerable population. Please read it again:

A lack of evidence suggesting SSRIs or SNRIs could help these patients.

However. Everyone else is doing it…

If you read the first sentence/portion closely, the authors assert that the reason SSRIs should be used by clinicians after a patient presents with post-TBI depression is because it's still part of the professional/"expert" consensus—meaning, it's the current practice.

That's why. They're already doing it.

Well, if everyone else jumps off of a cliff, would you want to do that, too? asked my mother when I used that logic. Of course, I remember being petulant enough to say, "Maybe!"

So, would they? Jump?

Maybe, if it's still within the clinical practice guidelines for management of TBI. Which, apparently, it is.

It's In The (a) Book

Yes, the clinical practice guidelines. But what are those? Clinical practice guidelines, or "Development of Evidence-based Clinical Practice Guidelines (CPGs)" are, according to the American Academy of Family Physicians, (AAFP):

a. Definition: Clinical practice guidelines are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Rather than dictating a one-size-fits-all approach to patient care, clinical practice guidelines offer an evaluation of the quality of the relevant scientific literature, and an assessment of the likely benefits and harms of a particular treatment. This information enables health care clinicians to select the best care for a unique patient based on his or her preferences.

Again, I bolded part of this because where, in the previous article, do these authors address the potential harms of medicating TBI patients with SSRIs?

What I conclude from the definition of CPGs is that they're in place to advise and guide clinicians, making sure their treatments are based on the patient's needs and a thorough overview of all possible benefits and potential harms in order to 'optimize patient care.' They even list it twice—benefits and harms.

Where are the potential harms for TBI patients and SSRIs in your publication, Drs. Silverberg and Panenka?

Where are they.

Dead people
Clinical trial exhibit, Dolin v. GSK

Clinical Trials Happened

They also recommend SSRIs for TBI patients based on clinical trials—trials that have long-since been debunked by actual, non-industry-funded trials and medical researchers without financial incentives tied to the outcomes.

So, the recommendation is based on the many clinical trials themselves—not from any kind of overwhelmingly positive outcomes from the trials. Just based on their own research of other researchers, which is what they mean by prior meta-analyses—and don't let those fancy statistician words scare you.

'Prior,' of course, means 'studies done before 2019' when the article was published.

'Meta-analyses' simply refers to the method these particular authors used to arrive at their conclusions.

So, this is how that works. They gathered all the clinical trials that treated depressed patients AND TBI patients with SSRIs and their findings? Confirmed. Those clinical trials exist.

That's it.

There's nothing in the article to indicate any positive outcome in either population using SSRIs. How do I know that? They tell us in the main body of their paper.

"The evidence is mixed."

And yet, from the CDC's website:

Suicide? Isn't that a common side effect of SSRIs? It sure is. I wonder why the rise? Could it be causal, or correlational? Perhaps in direct proportion to the "first-line treatment" of TBI-related depression and the medical profession's "...still best practice" assertions?

Mixed Evidence = Inconclusive

At the very best.

How many times have you asked someone if their antidepressant is helping them, and they answer, "Oh, my GOD, I'm a new person! I have my life back!"

It's never happened to me, personally. I'm not saying antidepressants haven't helped people, I'm saying, more often than not, their answers run the gamut from "Eh," to, "Kinda."

But my anecdotal "data" doesn't matter. OUR anecdotal evidence doesn't matter. However, the term "contemporary expert consensus" is medical code for just that. So could a patient-doctor relationships ever get tainted by biases in a clinical setting? Hm.

They are authority figures, and we want to be 'good.' If we're having a good day that day, we'll be biased by that, and we know they want to hear that their "first-line" treatment is providing some benefit, no matter how modest, and—"give it time."

So, do SSRIs work in these populations? Eh. Kinda. Maybe. However, the 'kinda' might be explained in the following. Remember what your grandmother used to say?

"Only believe half of what you see, and none of what you hear."

Because We Say So

The more redundancies, the better, because we all know when a lie is repeated enough times, it finds a foothold in the collective psyche. Here's the latter portion of the first paragraph again.


  1. Placebo effect means NO EFFECT

The authors state here that SSRIs don't work—antidepressants have zero-ability to impact the physiology of the patient and they proffer no pharmacological effects. Well which is it, guys?

So, SSRIs are basically like sugar pills? If that's true, why not give TBI patients sugar pills? Oh, this is why:

2. SSRIs are gateway drugs

Once on an SSRI, once the "placebo" wears off and the adverse reactions and side effects kick in, the patient is ready to kick it up a notch to be prescribed even more brain damaging, brain scrambling drugs such as SNRIs ( an incredibly harmful, yet disturbingly underestimated and underreported drug-class that could be described as the older, meaner version of SSRIs), benzodiazepines, and eventually, the re-branded "booster" drugs, atypical antipsychotics, for when the "sugar pills" give you diabetes.

Only much, much worse.

3. Patients WILL get better because we can't prove they'll get worse—they're brain damaged, after all

Sequalae. What a fun word. Here's what it means. From Dictionary.com:

sequala/sequalae (pl). Pathology.

1. an abnormal condition resulting from a previous disease.

Brain injuries are so incredibly difficult to manage, let alone diagnose, and the conditions that arise from brain injuries are so diverse and complex, "…traditional depression outcome measures are CONFOUNDED…" by brain injuries. Which again, are incredibly difficult to manage, let alone diagnose, and the conditions that arise from brain injuries are so diverse and complex, how utterly arrogant and depraved would a doctor, a family practitioner, have to be to presume to understand the pathophysiology of clinical depression, let alone adding TBI-induced depression into the mix?

It's absolutely unfathomable to me.

But… it happened to me in just this way by a well-meaning family doc. It happens all. The. Time.

These Docs are trying to do their jobs, folks. But they don't understand the gravity of the phrase "consider the source" here. Pharmaceutical profits are at the helm of this source, but it's couched in medical jargon and professional biases rife with financial conflicts of interest. How utterly naïve medical professionals—the really good ones—are when it comes to their colleagues' "good intentions." The Blue Code's got nothing on the White Wall.

Tell me, why has this "paper" not been flagged?

You know the phrase, "The road to Hell is paved with good intentions." You ever hear that? In this case, the intentions, no matter how grand, kill people.

A Cure for Alzheimer's Disease! A… possible cure for… Alzheimer's disease? Never mind…

In 2020, researchers discovered an energy-elevating neuroprotective compound and neuroprotective treatment for chronic TBI. It also promises huge strides in the prevention, and treatment, of Alzheimer's disease. The compound is called P7C3-A20, and the article still proffers hope to those of us suffering from complications related to TBIs.

It's still being researched for use because you never 'count your chickens before they hatch,' right?

Meanwhile, a drug with similar compounds, "Latrepirdine (INN, also known as dimebolin and sold as Dimebon), is an antihistamine drug which has been used clinically in Russia since 1983."

However, in Phase III of the clinical trials, the push to get FDA approval squealed to a halt in May of 2010. Why?

From the Wikipedia page on the drug, Latrepirdine:

"Research was conducted in both Russia and western nations into potential applications as a neuroprotective drug to treat Alzheimer's disease and, possibly, as a nootropic, as well. After a major phase III clinical trial for Alzheimer's disease (AD) treatment failed to show any benefit, three other AD trials continued. Major industry-based development in this indication essentially stopped after another Phase III trial suffered the same fate in 2012. Latrepirdine failed in the phase III trial for Huntington disease."

Again, some sections, bolded by me. So, what does "failure" mean in terms of clinical trials? From the same source:

"A Cochrane meta-analysis of the three pivotal phase III efficacy trials found no significant effect of latrepirdine on cognition and function in mild-to-moderate Alzheimer's patients, though there appears to be a modest benefit for overall behavior disturbances."

So, it didn't help. One could even posit that "the evidence was mixed" because there were some modest benefits.

What about harm? Screenshot taken from NIH/ ClinicalTrials.gov:

So… no worsening of Alzheimer's disease, then.

No worsening of Huntington's disease, then.

No worsening of the conditions THE DRUG WAS PURPORTED TO HELP, THEN.

A modest benefit for overall behavior disturbances sounds promising—placebo effect? Perhaps, with a new medication and actual care, patients just feel better.


Despite the drug being well-tolerated and having no known long-term side-effect, lifting the spirits of Alzheimer's patients and patients with Huntington's disease just doesn't seem to be of the utmost value and importance to these researchers, no matter how "robust" the "modest" benefits are.

JACW Photography Copyrighted material not to be used w/o proper attribution

Old Wives' Tales

If you're wondering why I've inserted antiquated little axioms and "homegrown wisdom" into this article, it's because the article to which I refer throughout could be effectively reduced into a series of banal platitudes and trite-isms, told again and again, to justify immoral behavior from medical professionals who have used their positions and medical training to pull the wool over their colleagues' eyes. It's shameful. It's criminal, or it should be.

And they did it and do it, not because 'money is the root of all evil.' Get it right, it's in the Bible. While I'm not much of a church-going gal, truth is truth is truth.


And it's time for you to consider the source of this article, now. Me. My professional livelihood is not dependent on the veracity of the information, here. I gain nothing, and in fact, spent an afternoon on this nonsense because unlike these two MDs, I care, deeply, about whether certain treatments for TBI-related conditions are helpful or harmful.

My life depends on the research continuing, rather than screeching to a halt because "In for a penny, in for a pound" mentality has made repurposing harmful medications on vulnerable populations a whole new level of evil I can't believe we didn't see coming. And their profit-losses due to failed drug trials doesn't just mean they drop within the black one or two quarters. It means my life.

My life.

My fucking life.

(To be honest, I worried about this last bit, losing credibility and all that, but then again, I considered the source-material, the original paper by two MDs, and you know what? I'm not worried about my credibility. Not anymore. I've got everything to lose. But this source can't sleep at night knowing this is "standard practice" for people fresh from a brain injury, being tortured. As if they don't have a difficult enough road ahead. As if WE don't.)

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