Much of U.S. Healthcare Is Broken: How to Fix It (Chapter 2, Part 7)

Editor’s Note: Over the next several months, Mad in America is publishing a serialized version of Les Ruthven’s book, Much of U.S. Healthcare is Broken: How to Fix It. In this blog, he addresses antidepressants versus CBT, the buzz around ketamine and esketamine, and the new frontier of drugs for postpartum depression. Each Monday, a new section of the book is published, and all chapters are archived here.

When antidepressants fail bring on cognitive behavioral therapy (CBT).

There are several dozen research studies on CBT and depression; a number of these studies involve a combination of drugs and CBT in treating clinical depression, and there are fewer studies in which CBT is brought in when patients relapse during drug therapy, which happens very frequently. Giovanni A. Fava et al¹⁴ conducted one such study. Ten patients who relapsed on ADM therapy were randomly assigned to dose increases or CBT and continuing clinical management. Four of five patients responded to the larger dose but at a one-year follow-up four of these five patients had relapsed again. However, four of the five patients responded to CBT, and only one of the five relapsed by the one-year follow-up.

One of these studies, sponsored of course by a pharmaceutical company, was conducted by the Kansas University Medical School, Wichita branch, and I attended, along with a group of local psychologists, a presentation of this study in progress by one of the staff psychologists who was one of the researchers and CBT therapists. Drug-treated depressed patients were given CBT along with continuing drug treatment and there were positive effects of the CBT intervention vs. drugs alone. Of course, at the discussion period I asked the obvious question, “Why don’t you just start with CBT and add drugs for the ones who fail to respond to CBT or the ones who relapse during or after CBT?” The psychologist presenter just smiled because he knew the answer as well as I did, that a drug company would not fund such a study, which would pit CBT versus drug therapy.

The Fava and other such studies demonstrate the superiority of CBT over drugs in treating depression, yet none of the results of these studies point out the obvious—that drug treatment of clinical depression is ineffective and that one should start with CBT or other proven forms of psychotherapy before considering other treatments.

In view of the above, over the years I have come across many examples of people and groups who have deeply held beliefs on a variety of matters that are completely impervious to any scientific or other evidence to the contrary. I have seen this occur in all walks of life and the phenomena has no respect for intelligence, education or economic position in society. I have often pointed out that many “normal”, non-psychotic individuals entertain “delusions” that do not differ in degree or kind from schizophrenics undergoing an acute episode! There are a number of people who still hold onto the idea that the earth is flat, that our earth is only 6,000 or so years old, that some people need to be purged of the Devil inside of them, that fluoride is harmful to humans in drinking water and perhaps hundreds of other “delusions”.

The vast majority of psychiatrists and non-psychiatric physicians still hold onto the belief, despite overwhelming scientific evidence, that behavioral health disorders are diseases of the brain and for most of these “diseases” the primary and, for many of physicians, the sole treatment is pharmaceuticals! Psychiatry has been going down this mental disease road for 75 years or more, and I doubt, for psychiatry, that there is any turning back.

2017: The latest psychiatric depression drug “breakthrough”: “Here we go again”.

The avant-garde in psychiatry is now promoting what one psychiatrist called the greatest breakthrough in depression drug treatment in the past two decades, the street drug called ketamine. Ketamine, a general anesthesia drug, in lower doses is better known as a psychedelic club drug that causes hallucinations. This occurs within the context of psychiatry telling the general public and physicians for over 50 years that antidepressants restore a chemical imbalance in the brain (unlike the effects of street drugs such as ketamine) and can we believe that such a hallucinogen as ketamine restores a brain disease to normal brain function?

I have found these “miracle drug breakthroughs” have in common a consistent pattern, one of which is a major cover story in a national magazine, in this case Time magazine. The Time magazine cover story reads “Depression afflicts 16 million Americans. One-third don’t get better with treatment [meaning drug treatment]. A surprising new drug may change that”. The text of the article tells us that traditional antidepressants (ADMs) take too long to work (let’s forget for the moment the fact that traditional ADMs do not work very well at all), and the new ketamine derivative drugs work almost instantaneously, report several users who have had years of failure on ADMs (what else would one expect?).

Anesthesiologists and psychiatrists/nurses have set up several hundred treatment centers across the country (one in Wichita, KS) for treating drug resistant depression with ketamine injections. To me, the Time article suggests it is another street hallucinogenic, “feel good” drug that does not treat depression. In the Time article one depressed, suicidal patient after the treatment reported he still wanted to kill himself as much as ever, but it didn’t bother him anymore! Ketamine was used off-label, but I knew that the FDA would soon begin giving their approval for this new “breakthrough” drug and other street drugs to follow.

FDA approves esketamine nasal spray for resistant depression and acute suicidality.

I am inserting this section after the above ketamine discussion after I predicted that ketamine-like drugs for treating drug resistant depression would gain FDA approval. The esketamine spray (brand name Spravato)^16b was the first of several more ketamine type and other street drugs to gain FDA approval and to come to the market to treat a variety of behavioral health disorders.

For the life of me I cannot get excited about another “breakthrough” drug in treating drug resistant depression, especially esketamine nasal spray with the following side effects: dissociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk. With those brain- and other organ-impairing side effects, it is not even justified to look at any efficacy data as far as I am concerned, but let’s look at Spravato’s efficacy.

With Spravato we have the usual caution against driving and operating heavy machinery with use of this drug. As with so many other drugs that compromise brain functions we do not know if the brain impairment is reversible after drug discontinuation or if permanent brain damage ensues. At the very least the FDA should require that all proposed drugs be evaluated for any brain-impairing adverse side effects, although with the drug under discussion (Spravato is the brand name) the long list of major adverse side effects are enough to know that the brain has to be severely compromised.

One should be extremely cautious about using a variant of a street drug such as ketamine, which is a hallucinogen, but also an FDA approved drug for anesthetic purposes in general medicine and surgery. The Spravato drug is a variant of ketamine and I suspect it is the first of many other similar drugs to come for addressing treatment resistant depression, which should be referred to as drug resistant depression.

In reading about this new “breakthrough”, because of its addictive qualities and potential for abuse, much is made of the attempts to curtail abuses. The patient self-administers the esketamine nasal spray under the supervision of a healthcare provider in a certified doctor’s office or clinic. In addition, patients must be monitored by a healthcare provider for at least two hours after drug administration. After each treatment the provider is required to check the patient and determine when the patient is ready to leave the office along with a designated driver. Patients are cautioned not to drive or use heavy machinery on the day of treatment (what about the next day and days thereafter?). If you think the Spravato drug is expensive you are quite right. The patient has to come into the hospital or clinic twice a week for four weeks. The initial charge for the standard care will range from $4,700.00 to $6,785.00 depending on dosage and follow-up treatment will cost an additional $2,360.00 to $3,540.00 according to the maker. We are told that these prices compare favorably with the cost of electroconvulsive therapy (ECT) in a hospital at $25,000.00 per treatment, which for some reason does not make me feel better about the cost of the Spravato spray.

In the esketamine nasal spray study I can’t understand why the drug was combined with “a new oral antidepressant”? Even if the combination drug proves effective (it doesn’t) how much of any improvement was due to the antidepressant and how much was due to the Spravato? I don’t think the defective experimental design or the researchers can give an answer that question to anyone’s satisfaction.

With regard to questions of efficacy of Spravato in this flawed study in treating drug resistant depression and acute suicidality, it is difficult to say at this time except for the data described in the FDA and the maker’s announcements of the FDA drug approval. Thus far the efficacy seems less than impressive and much the same as the outcome from other antidepressant drug clinical trials. There was improvement in depressive symptoms in the esketamine and placebo groups from baseline to four hours after the first dose but greater improvement in the esketamine patients, although the effect size of less than a standard deviation (-0.6) of improvement in favor of esketamine was not very impressive as far as I am concerned for the treated group. I believe the FDA would do better to insist upon at least one standard deviation or more over placebo improvement in any proposed treatment in order to gain FDA approval.

The improvement of depressive symptoms of the esketamine patients over placebo at 24 hours favored the treated group but not at day 25! There seems to be slight short-term benefit of the drug but from the trial data there seems to be no long-term benefit! Spravato sounds to me like another expensive “feel good” and distracting drug, a drug that makes you feel better but does not address the causes of your health problem.

With regard to suicidality, intranasal esketamine demonstrated a rapid and statistically significant effect on suicidal ideation at four hours after initial dosing but not at 24 hours or at day 25. Moreover, there were six deaths of esketamine treated patients during the study, including three from suicide! From the latter I would have a problem calling esketamine an anti-suicide drug or that the drug is safe.  How in the world and why did Spravato get FDA approval?

[Editor’s Note: Further information critical of Spravato’s FDA approval, including the fact that it failed to beat placebo in five of its six clinical trials, can be found on Mad in America, Medscape, and in the peer-reviewed research literature.]

“Toad venom psychedelic may rapidly improve depression and anxiety”.

How about toad venom as the new psychedelic kid on the block to treat resistant depression? The psychedelic toad venom¹⁷ was selected because it is relatively short acting (it fits within a 50-minute hour) versus 7 to 10 hours for some other psychedelics. In this toad venom pilot study the drug is used in conjunction with “psychotherapy”, in this case groups of 5 to 12 people in which 1 to 2 participants administer and guide the sessions which last 35 to 45 minutes.  This is not what one thinks of as traditional group therapy because it is described as a group “ceremonial” environment in which subjects describe “mystical” effects, a sense of meaning and anticipated improvement in well-being and increased life satisfaction. Of the 350 participants, 80% reported improvements in depression and anxiety. Almost 73% of the subjects claimed it was one of the top five most important personally meaningful experiences of their lives! Yes, I grant you that this experience may well be the single most meaningful experience in their lives but does it have anything to do with treating depression or does one have to take the toad venom every day to maintain the high and for the rest of one’s life? But of course we have many other street drugs that will do that for the person, although these drugs can cause a very serious addiction.

The problem in treating depression has never been to make it go away temporarily (often a fortunate life event, exercise or any pill will do that in many cases) but the difficult part is to keep the depression from returning! Will one shot of toad venom in a 45-minute group ceremony keep the depression (or the anxiety) from returning or is it only good for the one day? I don’t think one needs to be a trained psychologist to answer that.

In the toad venom study, did the “life changing” transient high have anything to do with treating depression or anxiety even though many participants said so? I seriously doubt it, but the psychedelic effect did indeed mask the mood and stress problems of the participants, at least temporarily. However, if we did away with any prescription drugs that mask or cover over underlying health problems I am sure we would lose a very large proportion of current healthcare treatment today. In this class of “feel” good drugs I would put SSRIs and some other antidepressant drugs, the benzodiazepine and related drugs for the treatment of a host of the anxiety disorders and insomnia, perhaps the steroids and opioids for pain and I am sure there are other feel-good drugs not mentioned here. In this same vein one must remember that Sigmund Freud for a time believed he also had discovered a wonder drug to treat a variety of mental disorders and the drug was cocaine!

In healthcare as in other life endeavors one should think that we should be able to learn from past history but, apparently, we do not.

A new low in FDA’s approval in the supposed treatment of postpartum depression (PPD) with hormone replacement therapy.

This FDA approval¹⁸ for treating PPD is symptomatic of what is wrong with large segments of U.S. healthcare today, which typically looks for bio-physical solutions for major health problems that often arise from stress and other psychosocial and life difficulties of the individual, in this case pregnancy and childbirth. PPD is a physician’s dream of those who want to believe that there is a drug or other bio-physical answer to all of our health problems, in this case ascribing PPD to the reduction of a hormone due to pregnancy, and the cure is simply the replenishment of the hormone! The reduction of a hormone to explain PPD is a naive hypothesis and not an established fact! All pregnancies are stressful for all women. While these physicians are bent on finding bio-physical health solutions, the vast majority of our health problems as we shall see arise more from behavioral and psychosocial factors of the patient rather than their biology.

Before going further let’s see what we get for the 60-hour infusion of the hormone at an approximate cost of $66,000.00 ($36,000 for the hormone drug and $30,000.00 or so for the hospital costs). For such costs I think we should expect not just a little superiority of the drug over placebo but a robust superiority such as a permanent remission! However, in the several PPD drug-placebo trials the superiority (i.e., the reduction in Hamilton depression scale scores) of the hormone replacement in the several trials was 15% better, 22% better, 30% better, 29% better, and 20% better than placebo, which averages to the hormone superiority of 23.2 percent per trial! The “superiority” of hormone replacement therapy is really no better than antidepressant drug effectiveness in the FDA clinical trials in reducing depressive symptoms!

How does this efficacy compare with antibiotics in treating various infections? One should be aware that these announcements of such “breakthrough” treatments often “forget” to include important facts relating to efficacy and safety. With regard to efficacy, we are told in the PPD trials how many of the depressed patients reduced their symptoms but not how many remitted their depression, a score of 8 points or less on the Hamilton Depression Scale. If the depression in PPD is due to the reduction of the hormone shouldn’t this drug cure or remit the problem of some treated patients?

As a psychologist in looking at women with PPD I suspect that the patient’s core problem is anxiety and the depression is secondary to the women’s anxiety and fear about the demands of motherhood or an additional child and fear of perhaps not being up to the demands.

Rather than replacing hormones, I think we would do better with PPD in understanding this depressed birthing woman’s fears, provide her with emotional support, education and for the first child teaching her mothering skills. Such a program would help the pregnant woman overcome her fears about motherhood and fear of social (and self) sanctions if she does not master these new life demands and I believe such therapy/education would cost substantially less than $66,000.00.

With regard to safety of this FDA approved hormone treatment, shouldn’t the researchers of the infusion therapy be at least a little concerned by the six deaths of the treated patients, three of whom committed suicide?

I don’t want to be accused of being an alarmist, but would anyone in their right mind submit themselves to such a treatment even if approved by the FDA?

Gwyneth Paltrow and her turning to “alternative” treatment for her postpartum depression.

It is interesting that psychotherapy as the principal treatment for a variety of behavioral disorders goes back as far as the late 19^th century. Since then, psychiatry and Pharma have “educated” the public that psychotherapy is now thought of as alternative treatment! In addition to Sigmund Freud, dozens of other psychoanalysts and in the 20^th century scores of eminent psychologists and some psychiatrists contributed to the theory and practice of behavioral and psychosocial treatment of a variety of mental health conditions. Especially in the second half of the 20^th century psychiatric drugs have almost completely taken over the field of mental health treatment in both psychiatry and in the mind of the public at large.

The movie star Gwyneth Paltrow announced, through the media, her mental health problems, including her physician’s recommendation of antidepressant medication to treat her PPD. The media said that Paltrow rejected the offered antidepressant medication and selected “alternative” therapy including psychotherapy, exercise, and a plan to stop alcohol use and to get more sleep. The Paltrow story shows how far psychiatry and society at large have come to accepting psychiatric drugs as the preferred treatment and that psychotherapy is now a part of “alternative” treatment, which is often a code word for unscientific or unproven treatments!

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To see the list of all references cited, click here.