Much of U.S. Healthcare Is Broken: How to Fix It (Chapter 2, Part 4)

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 sexual dysfunction on antidepressants, increased suicidality on antidepressants, and explores a ghostwritten study claiming effectiveness of antidepressants for children and adolescents. Each Monday, a new section of the book is published, and all chapters are archived here.

Sexual dysfunction side effects of modern antidepressants.

Is this what psychiatry means by “restoring the chemical balance in the brain for those with major depression”?

There are reports by a number of women treated with SSRI antidepressants (ADMs) having unexpected orgasms while taking these drugs. One woman while shopping alone in a store experienced an orgasm, which seemingly came out from nowhere. Needless to say, it must have been startling and the woman reportedly stopped using the drug immediately even though she said she did enjoy the experience!

A psychiatrist and other colleagues of the Department of Psychiatric Medicine at the University of Virginia conducted an observational study of the frequency of antidepressant-induced sexual dysfunction at 1,101 primary care clinics in the U.S.⁷ The researchers (Clayton et al.) studied the incidence of sexual dysfunction on eight of the most widely used current generation ADMs. Of a target population 6,297 patients, the researchers selected 802 patients who were least likely to have sexual dysfunction from non-drug causes and who had never been on psychiatric drugs other than ADMs. Patients had to have been on one of the eight antidepressants for at least three months for inclusion in the study. The researchers found the prevalence of sexual dysfunction in the study group to be 37%, ranging from 22% in bupropion induced sexual dysfunction to 43% for Paxil.

Prior to the study, the participating physicians had estimated the incidence of antidepressant sexual dysfunction to be about 20%, which is a little more than half the rate the study found. Some researchers estimate the rate to be from 50 to 70% in the real world. This estimate is made because patients are often on more than one psychotropic drug, unlike the Clayton study. Moreover, some of the study subjects may have been switched from another antidepressant because of drug induced sexual dysfunction. The researchers also noted that PCPs tend to use lower doses of ADMs than psychiatrists, resulting in a lower incidence of sexual dysfunction than in patients of their psychiatrist colleagues.  With such critical, pervasive adverse side effects how can the FDA justify approval of ADMs for treating depression?

Antidepressants are not the only culprit for drug-induced sexual dysfunction. In another study by Salerian, et al.^7a the researchers retrospectively looked at 31 women and 61 men with psychotropic-induced sexual dysfunction. Of these patients, 64 were on SSRIs, eight on TCAs, 36 on non-SSRI antidepressants, 20 on benzodiazepines, 20 on mood stabilizers, four on stimulants, four on narcotics and nine on atypical antipsychotics. Interestingly, 62 (68%) of these 92 subjects with drug-induced sexual dysfunction were receiving more than one of these drugs. As an aside, when one sees patients on multiple psychiatric drugs it is very likely that the drug treatment of the behavioral health problem is not working, and the prescriber is looking for the exact drug combination that will fix this patient’s brain!

None of the commentators on the problem of drug-induced sexual dysfunction ever recommend the rational solution to the problem, i.e., of tapering the patient off the antidepressant (or another drug) and discontinue the drug treatment! Even if the physician does not refer the patient for behavioral psychotherapy, the return of the patient’s sexual capacity and sexual pleasure should help the depression or other MH problem, everything being equal. Is this a case of the propaganda disseminated by the drug companies to physicians that depression is a brain disease and the only possible solution must be to find the right drug for this person’s brain?

Cost of treating the drug-induced sexual side effects

In several articles on Viagra to treat treatment-emergent sexual dysfunction, no authority brought up the cost of Viagra to treat these cases or even the desirability of using Viagra in this way. One pharmaceutical journal berated some managed care companies for not paying for Viagra for drug-induced sexual dysfunction. I wrote a letter to the editor of this journal agreeing with a policy of disallowing payment for such Viagra use and I was surprised when my letter was published.

Let us say there are about 15 million of us on SSRIs for a year; approximately 5.25 million of us would have drug induced sexual dysfunction. At $10.00 a pill for Viagra, therefore, I would estimate the costs at about $15 billion a year, which may be more than the cost of the SSRIs themselves! I suspect that Viagra is more effective than an SSRI in treating depression and in a head to head FDA clinical trial Viagra would beat the SSRI quite handedly! However, I doubt that a pharmaceutical company would market Viagra as a treatment for depression; to do so one would have to diagnose depression as caused by an “insufficient blood supply to the genitals”!

Certainly, the accepted conviction that antidepressants have very tolerable side effects cannot be supported by the facts, yet this conventional wisdom prevails. Moreover, patients are not told that these drugs are addicting and there are major problems getting off these drugs and that often the primary drug requires one or more drugs to address side effects. I fear that most physicians prescribing these drugs to patients stress the benefit side to the patient and downplay serious risks.

Celexa and the notorious antidepressant drug, double-blind, placebo-controlled treatment study of child and adolescent major depression.

The above study, funded by Forest Pharmaceuticals, quickly boosted the sales of Celexa to depressed children and teens. This was a large multi-center, placebo-controlled study with some six researchers involving efficacy and safety of Celexa in treating depressed children. The “researchers” concluded that Celexa was both safe and effective in treating these children (see below). However, later it came out that Forest Laboratories had paid a ghostwriter to analyze the data and to write the research article for publication! It is very difficult to believe that all parties to this transaction, including the six investigators, would go along with such a ruse, and many would say a fraud—including me. At the very least, one should be a little skeptical of drug maker funding of any health research and the study under discussion is a case in point. First, let’s look at the study results and later I will go on with the Celexa story started above.

This was an eight-week inert placebo-controlled study comparing the safety and efficacy of Celexa (citalopram) for the treatment of depression in children (ages 7-11) and adolescents (ages 12-17) with MDD. The major conclusion was that treatment with Celexa reduced depressive symptoms to a significantly greater degree than placebo treatment and was well tolerated. However, let’s look at the results, which were reported in the publication by the ghostwriter.

The major finding was that the ADM group outperformed the placebo group by 36% to 24%, a difference of 12% in favor of drug treatment. In similar studies with depressed adult patients, there was an 18% superiority of the drug over inert placebo, which means that one has to give a drug to six depressed patients in order for one of the six patients to do better on the drug than if the six were all on placebo! The efficacy difference in drug versus placebo in the child-adolescent study would mean that one would have to give the drug to eight depressed youth to be sure that only one of eight would have a better outcome on the drug than if all eight had been on placebo! Would your physician prescribe blood pressure medication to you if in prescribing the drug to eight hypertensive patients he knew that only one of the eight would benefit from the drug over placebo? Of course not.

Moreover, in the Celexa study the investigators had to fudge the data in order to come up with any drug-placebo difference. First, the investigators in the eight week study allowed in the fourth week a drug dosage increase for some of the drug treated trial subjects, apparently for those drug-treated subjects who were not responding well to the drug. I suspect to make the two groups “equivalent,” the placebo dosages were “increased”! Also, the drug dosage increase could have acted as a placebo in these depressed subjects, perhaps the dosage increase raising the subject’s expectation of a future drug benefit. The investigators authorized the drug dosage increase for the drug non-responders, which was certainly a major breach of even the appearance of any adequate scientific control in the study.

In subsequent litigation, the judge ordered Forest Pharmaceuticals to turn over all of the child-adolescent Celexa study data, including pertinent facts that did not appear in the publication. The ghostwriting team included in their data analysis eight subjects who had become aware because of a packaging error that they were taking Celexa. The blind was broken for these eight Celexa patients and these patients should have been removed from the data analysis, but the ghostwriter included these subjects in the data analysis in order to report “positive” findings for the drug.

A reanalysis by a third party of the outcome data with these subjects removed found no statistically significant difference in improvement between drug and placebo subjects! The study reported that nausea, runny nose, and abdominal pain were the only adverse side effects reported in over 10% of the Celexa treated patients. The study did, however, mention—almost as an aside—that two Celexa treated patients (no placebo treated patients) had the side effect of agitation. Agitation, however, is a very serious side effect since many behavioral health professionals believe that agitation/akathisia could play a role in both suicide and homicide. As one who has specialized in clinical neuropsychology, agitation to me implies that the brain (and person) is unable to maintain any specific cognitive focus in order to guide one’s behavior and thinking.

I am sure the investigators in the Celexa study (one or all) had to approve the write up by the ghostwriter and of course these investigators must assume responsibility for the final draft. I assume the three PhDs were psychologists and being trained scientists, they should have known better than to attach their name to such a flawed study. For example, in the subjects selected for the study 20% of the patients in the Celexa group and 18% of placebo patients received previous antidepressant treatment (these subjects should not have been included in the study), and approximately 15% of the Celexa patients and 16% of the patients in the placebo group had a history of nonresponse to antidepressant treatment. This means that 36% of the depressed youth had been on ADMs previously and 31% of those were antidepressant drug failures! We know from these numbers alone that there is no rational reason to even conduct the study since these numbers indicate that ADMs are not an effective treatment of childhood depression.

Celexa had finally broken into the large adolescent and child depression market, which had previously been rightly closed to the pharmaceutical drug industry because of the risk of cases of suicide ideation and suicide attempts during the adult antidepressant/placebo controlled FDA clinical trials. Celexa broke through the FDA Black Box warning about the risk of suicide events associated with antidepressant drug treatment in adults and the ban of such medications for child and adolescent treatment. I believe it is safe to say that in general the pharmaceutical industry in submitting ADM drugs for FDA approval has been less than candid in describing their drug’s adverse side effects.

To continue the Celexa story, after full disclosure that the published study seriously misrepresented the effectiveness of the medication and safety of the drug, 16 doctors, researchers, and academics, sent a letter to the president of the American Psychiatric Association pressing her to retract the tainted study promoting the benefits of Celexa for treating depression in childhood and teens, which had of course been widely distributed to physicians and the general public through the media.

The letter included the ghostwritten charges; however, thus far the president of APA and the association have taken no action on this matter. Borrowing a phrase of our current president, this fake study caused tens of thousands of children being needlessly prescribed ADMs and exposed these children to adverse side effects and possible long-term harm and, for some, violent behavior. If many in psychiatry are not in bed with the Pharmaceutical Industry, then at least the Celexa study shows that they may at least be next of kin.

The higher suicide events associated with Celexa is patent evidence that Celexa is cognitively impairing, which is something school children do not need. I have not looked into this, but I would not be at all surprised to learn that the largest funding source of the American Psychiatric Association comes from the pharmaceutical industry, which certainly seems to have shaped American psychiatry for the worse.

The above Celexa story was scandalous and terrible news for the pharmaceutical industry at large. The industry went on developing ADMs for children and adolescents despite knowing full well that ADMs are cognitively impairing drugs! Why would anyone with any ethics at all—or concern for children in the least—agree to market a drug that is impairing of the child’s ability to learn? I know the industry’s defense, but I don’t buy it: “Depression impairs learning in children as well as adults and if we can cure the depression we improve learning ability over all even if our drug is slightly cognitively impairing.” However, remember you also recommend life-time treatment with your antidepressant drug!

Why is the suicide rate for both adults and children continuing to climb?

Having been pretty much stable for many years, the Center for Disease Control (CDC) reports^8a the suicide rate for the population as a whole from 2007 to 2017 increased by 30% while the teen suicide rate (age 10 to 24) increased by 56%! While the suicide rate was climbing, that decade saw attempts at prevention with the growth of suicide prevention centers, the growth of antidepressant drug prescriptions for adults, children, and youth, and the growth of school programs to identify at-risk students to see that these youths received help.

Apparently none of these, and probably other measures, were effective in stemming the tide of suicide. So, isn’t it time to try something else? Moreover, would the increasing rate of suicide have anything to do with the increased prevalence of psychiatric drug use in society during the period of increasing suicide, especially with depressed youth? I am sure psychiatry and Pharma would have a “good” explanation for why there is no causal relationship between the two. Add to it, despite the sound research on the connection between ADMs and suicide, the FDA continues to suggest that we need more data to determine any relationship between suicide and psychiatric drugs!

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