Thought Experiments in Cosmetic Pharmacology

In order to draw attention to some ethical concepts regarding cosmetic pharmacology, here are a couple thought experiments regarding hypothetical drugs and philosophical issues they bring up. Consider the following drugs while asking yourself the following questions: Should any of the above drugs be able to be acquired by anyone over the counter? With a prescription? Should any of them never be used by anyone?

1) A drug that makes people extremely productive, happy, not "emotionally-flattened" without any side effects, except for once every two years at an unexpected time, send user into a fit of violent rage. It cures a subset of dementias completely.

2) Consider a drug that completely suppresses sexual desire without any side effects, with long-term safety established.

3) Consider a drug that completely flattens all emotions with no side effects and established long-term safety.

The first case I think brings up the issue of giving someone a drug that could, due specifically to the drugs action, endanger the health and well-being of others in society. SSRIs have been accused of this in the past due to such things as association with school shootings and violent criminal acts. Even if a drug has a massive benefit, with such great risks should it be completely suppressed? Should the drug be allowed to circulate but only under intense supervision such that the negative effects could be negated? Could such purported violence be curbed? Where do you draw the line with regard to negative side effects? If it simply makes people verbally aggressive, would it be an infringment upon their rights to refuse them its other benefits? What if it cures the dementia but makes them not want to integrate into society or work at all? Would you let the individual decide how much a drug alters their personality by simply drawing the line at risk of violence toward others? Should the individual, medical establishment, or government have the last say in the usage of such a drug or similar drugs that lie across the spectrum of possessing side effects? I'd argue that unless a drug has a proven risk of making an individual significantly more of a direct risk to society or themselves (direct and significant here indicating interpersonal violence or suicidal tendencies), then the individual should ultimately have the decision of whether to use the drug. A possible counter-example to this argument would be: what about heroin addicts? Can a caveat be defined where disallow blatantly self-destructive tendencies without infringing upon individual rights? This seems to tap into existing drug debates involving the DEA/FDA with regard to the use of such recreational drugs as marijuana. More on these ideas later.... (in subsequent posts)

The latter two examples bring up the idea that was is natural is good and what is unnatural is necessarily bad. Much debate against emerging technologies has revolved around the technologies being "unnatural" and that their use is therefore unethical. Possibly some of the most "unnatural" side effects of drugs could be an abolishment of sexual drive or flattening of emotions, two purported side effects of SSRIs. Personally, I see these concerns as asinine knee-jerk reactions, but they seem deep seated in the contemporary status quo. Traditional counter-responses to the "unnatural is bad" mentality include the fact that pacemakers, much of contemporary medicine, antibiotics, contraception, are all unnatural. Any form of technology is likewise as unnatural from telephones to calculators, from preachers via tv to orbital satellites. What cosmetic pharmacology brings to the table as new in this regard revolves around the fact that it could much more blatantly alter who we are. I believe that the modulation of the substrate of cognition and the direct alteration of personality coming into the purvey of scientific analysis constitutes a significant paradigm shift.

How should all these concerns guide drug development and evaluation of purpoted cosmetic pharmaceutics?

Apologies for the stream of consciousness writing style, trying to get as many ideas on the table as possible for greater cohesion on this site later on.... More soon.

"Better than Well" Variability and Dr. Healy's Let Them Eat Prozac

To follow up on Chris' well written post on Listening to Prozac, I thought I'd introduce another author who's written on the subject of antidepressants. A simplistic view of Dr. David Healy is that his opinions are somewhere in between Dr. Breggin and Dr. Kramer. Like Dr. Breggin, he's extremely outspoken against the practices of the pharmaceutical industry with regards to antidepressants, even losing a job to his opinions on Prozac's suidicial risk (see http://www.pharmapolitics.com). Unlike Dr. Breggin and more towards Dr. Kramer's outlook, he recognizes the usefulness of antidepressants in psychiatry and even presents an interesting arguement for their Over the Counter status (see The Antidepressant Era and Let Them Eat Prozac).

In terms of Healy's relationship to the idea of cosmetic pharmacology and the better than well effect, in his book Let Them Eat Prozac, he shares the result of a very interesting (albeit small) experiment he conducted at his hospital in the UK (Primary Care Psychiatry, 2000). Utilizing 19 healthy hospital employees, including psychiatrists, nurses, and administrators, Healy performed a 2 week cross over study with the SSRI Zoloft and the SNRI (Selective Noradrenaline Re-uptake inhibitor) Reboxetine. The findings? There was indeed a "better than well" effect, meaning these "normal" individuals felt good on drugs that are usually reserved for depressed individuals. The kicker comes in when we see that this effect was split down the middle: half the group like Zoloft and half the group liked Reboxetine. While the unliked drug usually only resulted in expected side effects, there were a couple individuals who had a negative response to either drug. It made their mood worse.

The results of Healy's small experiment speak to 2 very important ideas. The first is a rather old idea that is utilized by psychiatrists today: individual temperment can often predict response to an antidepressant with a particular mechanism (for more information on this, do a pubmed search for Joyce PR). While the exact details of this phenomenon have yet to be worked out (what types of people will respond to which drugs?), even non-depressed individuals might have specific responses to seroternergic or noradrenergic drugs. The second idea is that for any given drug, it appears there are always going to be three main groups of people: 1 group who responds well to the drug, 1 group who doesn't respond, and 1 group who responds adversely.

Listening to Prozac by Dr. Kramer

First published in 1993, "Listening to Prozac" by Dr. Kramer contains the origin of the term "cosmetic pharmacology." It is derived from Kramer ascertaining the future sub-clinical use of SSRI antidepressants like Prozac in the general population. That is, based on his experience with Prozac with his clinically-diagnosed patients, he argues that individuals without any serious psychiatric problems could benefit from the use of the drug.

Kramer refers to case reports of patients of his that were either not responsive or minimally responsive with traditional psychotherapy, but upon treatment with Prozac underwent transcendental metamorphoses that alleviated their clinical symptoms. In addition, a number of these patients purportedly felt "better than well" and aspects of their lives completely independent of those being psychiatrically treated were bettered. Kramer attributes some of the effects of Prozac to it altering the neural substrate of personality, which traditionally has been (strangely) considered outside of the domain and capability of psychopharmacology.

I personally am very skeptical of the widespread use of SSRI's under the umbrella term of cosmetic pharmacology. As we shall address in the future, their popularization and ubiquity is a result of being firmly pushed by large pharmaceutical companies with mass marketing campaigns for both individual patients (TV ads) and medical professionals (free food, insurance benefits, etc. by catering via pharmaceutical representatives). At first glance I immediately dismissed concerns over this as conspiracy theories. However, Dr. Breggin, possibly the most direct counterpoint to Kramer, draws attention in his works (I read The Antidepressant Fact Book, but his related popular work is Talking back to Prozac) to how the majority of all the basic clinical research done on SSRI's and Prozac in particular are in serious question. Suicides are written off under "depression not cured" and not reported. Participant pools have weeded out individuals unlikely to give favorable data for the drugs. The double-blind portion of a number of the studies is easily broken via the identification of well-known side effects of SSRIs. In short, there have been a number of violations of both scientific ethics as well as the basic principles of the scientific method. In addition to concerns over the basic research, there is very little long-term data on the safety and efficacy of SSRIs. Contrary to popular belief, just because something has "been around for a long time" (here, only a few decades) or just because "a billion people have taken something" doesn't mean a drug is safe or efficacious. In a nutshell, a plethora of work is necessitated before SSRIs can be considered safe for clinical pathologies, let alone as cosmetic pharmaceutical agents. However, I don't think this means they aren't good candidates for cosmetic pharmacology; the data just isn't there yet to ascertain one way or the other.

Despite my skepticism over SSRIs as cosmetic pharmaceutics, Kramer paves a lot of philosophical groundwork for this emerging concept. He ties in his SSRI treatments with Dr. Mark Sullivan's suggestion that patient autonomy is the ethical yardstick to replace the contemporary standard of risk-to-benefit ratio. Kramer writes "In judging whether the use of a medicine is for good or ill, Sullivan proposes we ask whether it promotes or retards a person's capacity to run his or her own life. An addicting drug may make a well person happier, but, by virtue of the compulsion inherent in addiction, it compromises autonomy. Illness also compromises autonomy, so an addicting drug might be used in the treatment of illness and on balance meet the ethical guideline. The standard of autonomy makes us rethink what our objections might be to a mood brightener, a drug that is by definition not addicting." (p. 256)

I believe the above excerpt applies as well to cosmetic pharmacology as it does to contemporary medicine, in no small part due to the lack of a good alternative yardstick of efficacy. The majority of workings of the brain are still an enigma to modern science, the mechanistic fashion with which antidepressants specifically "work" foremost in relation to the current discussion. Because of this, brain imaging technologies and neurochemical analyses cannot yet prove sufficiently guiding in ascertaining whether or not a pharmaceutical is "working" for a patient. We therefore have to substitute the absurdly crude and arbitrary criteria of the DSM-IV and similar clinical evaluation tests to guide medical treatments. This notion of autonomy as an ethical yardstick partially resolves these "shooting in the dark" attempts to ascertain the efficacy of pharmaceuticals. While still crude and abstract, it seems to me a more concretely positive criterion than the aforementioned ones. Combined with sufficient clinical data for the efficacy and safety of pharmaceuticals, I hope that this concept of autonomy receives greater focus when applied to candidate cosmetic pharmaceutics.

"Listening to Prozac" is a great place to start with regard to exploring the topic of cosmetic pharmacology. It identifies well the potential scope of pharmaceutics' ability to alter a wide array of individual attributes both within and outside clinical pathology and addresses the knee-jerk reaction that "cosmetic pharmacology" evokes in within the medical ethics status quo. It also provides guidelines for evaluating cosmetic pharmaceutics and less explicitly (perhaps indirectly) illuminates how we should be more critical of candidate cosmetic pharmaceutics with regard to efficacy, safety, and how research data regarding them is acquired to ensure high quality and lack of bias.