Human Subject: An Investigational Memoir

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9. It’s the Serotonin, Stupid

“Dans les sciences expérimentales, la mesure des phénomènes est un point fondamental, puisque c'est par la détermination quantitative d'un effet relativement à une cause donnée que la loi des phénomènes peut être établie. Si en biologie on veut arriver à connaître les lois de la vie, il faut donc non-seulement observer et constater les phénomènes vitaux, mais de plus il faut fixer numériquement les relations d'intensité dans lesquelles ils sont les uns par rapport aux autres.”

Toward the end of my Paxil washout period, I finally got a call about the breast-cancer-and-stress study, the one that promised to teach participants ten relaxation techniques. By then I was feeling much less stressed, but I was still willing to take part, if they would have me.

The study coordinator asked me several screening questions, including “Do you have any infectious diseases?” I wasn't entirely sure that herpes would qualify as infectious if it's suppressed by drugs, and I was in a public place where saying the word “herpes” might itself be stressful enough to cause an outbreak, so I said, “Not currently.” If they called me back to say I qualified for the study, I figured I would come clean about my shameful secret.

A week later, after I had started taking the depression study medication, the research assistant did call me back, with apologies for taking so long. She had some more questions about my physical and mental health: Do I think people don't like me? Do I think life isn't worth living? Do I have trouble “getting going"? Not only did my answers expose me as a flagrant depressive, but I had to confess that I was probably taking an antidepressant. I was sure that either the disease or the cure would disqualify me. And I’m sure it didn’t help my cause to admit that I didn’t find the idea of getting breast cancer all that stressful.

This was supposedly a study for women at high risk of getting breast cancer. During the first call, the screener had asked if I had any relatives with breast cancer, but she didn't seem to care who or how many had the disease. Thinking that this information was relevant, I had used the assessment tool at to calculate my risk of getting breast cancer. Sure enough, the questionnaire asked how many first-degree relatives (mothers, sisters, daughters) had been afflicted. I had one sister and a maternal aunt who'd both been diagnosed in middle age, but apparently only the sister was relevant. The online risk calculator gave me an 18 percent chance of developing breast cancer before age 90 and a 2.4 percent chance of getting it in the next five years. This was close to twice the average woman's risk.

At the end of the second call, the study coordinator said it might be another week before they would know if I qualified for the study. Apparently I didn’t qualify, because I never heard from her again. I was on my own with my cancer risk and my anxiety, probably because they didn’t overlap enough.

The benefits of modern antidepressants usually take several weeks to kick in, but side effects can strike at any time. By the end of the first day of the drug trial, I suspected that I was taking some sort of drug and not a placebo: I had gotten so sleepy that I needed an afternoon nap. The next day I felt a strange combination of stupor and mania. My mouth was sort of dry, with a sort of metallic taste. I've never been very good at describing my symptoms. “It hurts” is about the best I can usually do.

Apparently this is a deficiency I share with the Hmong people. Because they rely on traditional, spiritual explanations and cures for whatever ails them, they have no words in their own language for most Western medical concepts. To the great frustration of American medical personnel, Hmong patients are frequently unable describing an illness or injury, even when there’s an interpreter present. (Fadiman, 1997)

By the fourth day I was convinced that my grogginess was due to medication, and I was resigned to an 8-week nap. By the seventh day, the sleepiness had subsided a bit. However, I had pretty much lost interest in sex, so I was able to take advantage of my few waking hours to get a lot of work done.

High levels of serotonin in the brain are correlated with low levels of sexual desire. Since most antidepressants prescribed today are designed to increase the level of serotonin, it’s no surprise that many formerly depressed patients suffer from “sexual side effects,” a euphemistic catch-all term for lack of desire, anorgasmia, impotence, etc. It was clear that, as long as I was in the antidepressant study, I would never win any prizes in the herpes study for having the most sex.

It’s pretty much accepted, by patients as well as mental health practitioners, that serotonin has a big role to play in regulating our moods. Lately, however, a few people from both groups have been questioning the whole notion of a chemical basis for mental illness. Many claim that the drug companies invented the connection between depression and serotonin in order to “sell” the disease. Ironically, some people making this claim are themselves selling a cure for depression. For instance, Satellite Corporation ( offers an article called “7 Facts about SSRIs the Pharmaceutical Companies Don’t Want You to Know.” They also offer a guaranteed drug-free solution that works by “subconsciously re-programming the destructive negative thought patterns that cause episodes of depression and replacing them with positive new perceptions.”

Dr. David Healy, a more mainstream critic of the medicalization of mood disorders, writes: “There has never been any evidence for a lowering of serotonin levels in those exhibiting any nervous disorder, or indeed anything wrong with the serotonin systems in anyone affected with nerves or moods.” (Healy 2006) I wondered about this statement, so I looked for the evidence, and I found some brain imaging studies that seemed to support the theory that depression lowers serotonin levels. One such study concluded: “Subjects in a major depressive episode have lower serotonin transporter binding potential in the amygdala and midbrain, compared to healthy subjects.” (Parsey et al., 2006, p. 52) I don’t pretend to know what “transporter binding potential” is, but it sure sounds to me like the evidence that, according to Dr. Healy, doesn’t exist.

Now that drugs are being tested and marketed in many countries, there are global implications for the accusation that the pharmaceutical industry is selling diseases. Regulatory agencies and pharmaceutical companies in Europe, the United States, and Japan are working together to make it easier for drugs that are approved in one country to win approval elsewhere without extensive additional testing. An organization called the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (abbreviated simply ICH) publishes Good Clinical Practice standards to guide its members in their “harmonisation” efforts.

Most clinical trials in the U.S. and abroad are run by U.S.-based contract research organizations (CROs). I think PsychoPharm is in that category, although they don’t use that term, describing themselves instead as a “medical research organization.” According to at least one author, the reason that CROs must look outside the U.S. for subjects is very simple: We Americans are overmedicated. We already take so many drugs that it’s hard to find anyone who meets the criteria established in the protocol for a clinical trial. (Petryna, 2007) Knowing this, I could see why the staff at PsychoPharm did everything they could to ensure that I qualified for—and stayed in—the study.

I returned to PsychoPharm after a week of taking the mystery pills. First I saw Nurse D, who obtained my vital signs. The blood pressure and pulse had to be taken four times, twice while I was on my back (“supine”) and twice after I stood up. The protocol required that the same person take these readings each time, so I spent a lot of time with Nurse D’s chubby hand around my wrist. Before the initial reading, I had to lie down for several minutes, but after the first day we met she avoided instructing me to do so, and she always left me alone in the dark during that rest period.

Next it was time to talk about how I was feeling, which wasn’t much different from the week before. Nurse L and Dr J each asked me many questions about my symptoms and side effects. They also gave me a form to use for rating three aspects of the side effects I’d experienced in the last week:


No Side Effects Present 10% of the Time Present 25% of the Time Present 50% of the Time Present 75% of the Time Present 90% of the Time Present all the Time


No Side Effects Trivial Mild Moderate Marked Severe Intolerable

Degree to which side effects interfered with day-to-day functions

No Impairment Minimal Impairment Mild Impairment Moderate Impairment Marked Impairment Severe Impairment Unable to Function Due

The last entry was grammatically offensive, but fortunately I didn’t have to linger there very long, because I was still able to function despite my impairment.

I returned a week later, on the fourteenth day of the study, feeling about the same. That week there was another fasting blood draw (I’d been told not to eat anything for 12 hours before I came in, but to drink plenty of water) and the taking of vital signs. When I saw that I had gained a pound since the previous week, I felt a brief twinge of the anorexia that should have excluded me from the study.

When the blood-drawing nurse (that seemed to be her only responsibility) asked me which arm she should use, I elected to have the blood taken from my left arm, for no particular reason. Only later did I realize that there was a particular reason why the right arm would have been a better choice: The protocol required that the blood pressure be taken each time not just by the same staff member but also on the same arm. Since the arm used at the baseline visit was my left, that was the one Nurse D would always have to use. I was a bit apprehensive about this, having read recently about someone whose arm spurted blood from the puncture site when the blood pressure cuff was inflated.

There was no embarrassing bleeding incident, but even after drinking plenty of water, my blood pressure was extremely low: about 85 over 60. This was so low that Nurse D said she was worried, even though my normal BP isn’t much higher than that. She told me she would have to take it again before I left.

Next I filled out the same side-effects questionnaire from a week earlier. Then I discussed my symptoms and side effects with Dr. K (thoroughly) and with Dr. J (briefly). There had been no change in my symptoms and almost no change in the side effects.

I never thought to ask which instrument they were using to assess the severity of my depression. It could have been the Hamilton Rating Scale for Depression, which is available in lengths of 17 and 21 questions. The study that had originally brought me to PsychoPharm used the HAMD-17, so that was probably the one in use for the desvenlafaxine study, but I never counted the questions they asked me.

When Dr. K asked if I had felt guilty during the past week, I said, “Constantly.”

Had I felt guilty about the past, the present, decisions made, family issues . . . ?

“Yes.” I told her that whenever anyone I knew seemed to be having any kind of difficulty, I would ask, “What did I do wrong?”

She told me that her years of monitoring patients on psychiatric medication had taught her that, much to her amazement, guilt seems to have a chemical basis. That is, she had seen formerly guilt-racked study subjects become virtually guilt-free when on medication that worked for them. Since guilt feelings are really just a sub-species of worry, which is a symptom of anxiety, this didn’t surprise me, but it gave me a little hope (not much though, because hopelessness was something else I felt almost constantly).

The day before, someone had called from UniVir to ask if I could come in for a one-time blood draw. It was for a different study from the one I was already in. Since I would be in the neighborhood anyway, visiting PsychoPharm, and since I would get paid $25 for my blood, I had readily agreed. So as soon as I’d gotten my new batch of overpackaged pills, I walked the six blocks from PsychoPharm to UniVir.

A research study coordinator whom I hadn’t met before was going to draw my blood, but first I had to sign another consent form. This study would require nothing of me but my HSV-2-positive blood, which, the study coordinator explained, would be used to test a new vaccine.

Before sticking a needle in me, she got out a form that she called a “follow-up” questionnaire.

“Follow-up to what?” I asked.

She said that whenever I came in for any reason unconnected with the study I was in, they needed to ask me the questions on that form. This made no sense to me, but I obediently answered all the questions, which were about my sexual practices and other intimate details of my life. I again asked for the reason for this interrogation, and I found her answer so illogical that I can’t remember what it was.

“Did the questions make you uncomfortable?” she asked.

“No,” I lied. “They just seem kind of unnecessary.”

While she prepared to draw my blood, she made small talk, asking me if I had weekend plans and telling me about her unusual and irrational desire to garden (irrational because she lived in a city apartment with no balcony). Then she asked me what I did with my life, either for work or for fun.

“I’d rather not say,” I said.

She seemed only slightly taken aback. Still, I felt bad, so I went on to explain, “I’m between jobs, between careers, between lives . . . ”

“That’s a hard place to be,” she said sympathetically.

Then she stuck in the needle, and she missed the vein.

“Do you want me to get Donna to do it?” she asked.

“You mean you think she’s better at it than you?”

“No,” she said. “I just always give people that option.”

Always? So venipuncture failure was a habit with her? I said, “That’s OK. I trust you.”

So she tried again, and missed again.

“OK,” she said, “that’s my limit.” And she went to get Donna.

The two failed attempts had been in my right arm. Donna decided to try the left arm, despite the fact that it had been tapped just an hour earlier at PsychoPharm. She had no trouble finding a vein. She asked if I was left-handed, and I said no. She explained that veins are usually easier to find in the dominant arm.

Donna always tried to give me useful information like that, because she thought I had a lot of scientific interest in the research they were doing. She’d gotten that idea two weeks earlier when I had asked if I could see the study protocol. I didn’t tell her that I only wanted to see how the response to my request would compare to the ordeal I had gone through to see the protocol for the oxycodone study.

She had seemed a bit surprised by my request, but had said she would ask the PI about it. The next time I went in, she brought me the protocol and said that I could look at it, but that they couldn’t give me a copy. “For proprietary reasons,” she had said. This explanation didn’t really make sense, but I accepted it. Anyway it was a fairly short protocol, and since I had only a casual interest in it, it took about 10 minutes to look through it.

Reading the protocol was a good refresher for me on the goals of the research. I had forgotten that a main point of the study was to demonstrate that viral shedding varies with the time of day. That was the reason for the incessant swabbing.

Donna frequently praised me for being conscientious and compliant, at one point even calling me a “stellar subject.” One day I told her about my fanciful idea that subjects could get letters of recommendation from their investigators. To my surprise, she said that she had occasionally offered a recommendation to a subject who might not make a good first impression at a screening. I could certainly empathize with anyone in that category, since I tend to make a really lousy first impression in almost every situation (but especially in job interviews).

The studies at both UniVir and PsychoPharm not only paid $25 per visit, but they also reimbursed for parking or bus fare. When asked, I would always say that I rode the bus, and they would give me bus tickets. What I didn’t reveal was that the bus I rode was the free shuttle that carried people between the main Big U medical center and its satellite in the hospital district. “I can always use more bus tickets,” I would say honestly, and then I would pocket the tickets and use them for a later, unrelated trip.

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