Human Subject: An Investigational Memoir

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13. Luck of the Blood Draw

“À l'état normal le sang veineux du rein est à peu près constamment rutilant, parce que l'organe urinaire sécrète d'une manière à peu près continue bien qu'alternativement pour chaque rein.”

Starting to take a new psychoactive drug is a lot like getting to know a new love interest. During the courtship phase, as you gradually increase the intensity of the relationship (i.e., the dose), you grow to appreciate your new partner’s positive aspects, and you try to accept the less beneficial traits, like the tendency to cause headaches, nausea, or dizziness. Once you find a drug that works well, you experience all the mixed feelings that come with entering any committed relationship: You hope that the two of you will continue to get along well for years to come, but you’re still a little leery of commitment. At the same time, you wonder if you’ll become too attached to your new partner.

I had stuck with Paxil for ten years, my lifetime record for pharmaceutical faithfulness. Recently we had drifted apart, when I decreased my dose, but I was afraid that if I completely broke off the relationship, I would begin having “panic attacks” again. Now, as I read up on the various antidepressants and their capabilities, I began to wonder if my fear of relapse could have been at least partly manufactured by the manufacturer of the drug, GlaxoSmithKline. I’m pretty sure that Paxil was the first SSRI to win FDA approval for treatment of panic, and it was heavily marketed for that indication, but now there are at least two others, Prozac and Zoloft (both of which I had taken in the past), that have been approved for treating panic disorder. Other types of drugs, including tricyclic antidepressants, are also prescribed for that purpose. So presumably I had lots of choices for keeping my demons at bay.

After doing some research on the history of psychiatric diagnosis, I even began to doubt that I ever had panic attacks at all. Beginning with the third edition of the Diagnostic and Statistical Manual of Mental Disorders (APA, DSM-III, 1980), the formerly vanilla-only concept of anxiety was available in multiple flavors, including social phobia, panic disorder, and posttraumatic stress disorder. Taking advantage of this change, the drug companies sought FDA approval for treating the new diseases and then promoted their existence to doctors and, beginning in the 1990s, to patients. (So far, New Zealand is the only other developed country that allows direct-to-consumer advertising of drugs, although the idea is being considered in Europe.) For several years clinicians had been telling me that what I probably had was “just” severe anxiety, not panic, but the line between them seemed pretty blurry to me.

Not only is it hard to distinguish among the different types of anxiety, but recent research suggests that anxiety and depression are basically two manifestations of the same biological tendency. That is, they have the same genetic basis, with a person’s environment determining which condition becomes more prominent. (Sussman, 2007) This discovery refutes another assumption codified in the DSM-III: Depression and anxiety were considered to be totally separate categories, with a different committee assigned to study each. Any connection between them was considered “comorbidity,” that is, the simultaneous presence of two separate conditions. As one critic has pointed out, “The firewall between anxiety and depression ignores the fact that the commonest form of affective disorder is mixed anxiety-depression.” (Shorter & Tyrer, 2003)

The manual is now in its fifth incarnation, DSM-IV-TR, with a new edition currently being planned for publication in 2011. Interested parties can follow the new volume’s progress, and even make suggestions, at As part of the planning process, the American Psychiatric Association, in conjunction with the World Health Organization and with funding from the National Institutes of Health, organized a series of ten conferences on “The Future of Psychiatric Diagnosis: Refining the Research Agenda.” As of this writing, the only conference that has not been held is the one called “Comorbidity of Depression and Anxiety.” The fact that they saved this one for last—and, as of July 2007, have yet to schedule a date for it—may reflect the contentiousness of the topic.

The International Classification of Diseases, 10th revision (ICD-10), which is used worldwide for labeling all types of diseases, recognizes a condition called “mixed anxiety and depressive disorder” (F41.2). This diagnosis, appropriately abbreviated MAD, is to be used when both conditions are present, neither one predominates, and neither is severe enough to justify separate diagnosis. If both are equally present and severe enough to warrant individual diagnoses, the patient should be diagnosed with the two separate conditions. This classification is problematic both for clinicians who believe that the two conditions are totally separate and for those who believe the criteria should allow for the coexistence of full-blown manifestations of both diseases.

I used to wonder whether my real disease was anxiety or depression. It’s a relief to be able to say that it’s both, and it’s somehow reassuring to know that the psychiatric community is currently in turmoil over the commingling of these two diseases.

My penultimate appointment at PsychoPharm was scheduled for two hours before my fifth visit with Donna. The day before, she had left a message asking if I could donate some more blood while I was there. I called back and left a message saying that, for 30 bucks, I certainly could. I planned to ask the nurse at PsychoPharm to use my more challenging arm, figuring that it would give less trouble to someone who pretty much spent her whole day drawing blood from an assortment of arms.

My elevator ride to PsychoPharm was once more educational. I got in a freight elevator (it was in the same bank of elevators as the three others, so I had probably ridden in it before), which had a button for the 12th floor and a key switch labeled “12TH FLOOR ACCESS.” There was also an extra set of doors at the back of the elevator. So apparently the 12th floor was the nerve center of the building, to which only authorized people were allowed access. I guess if you were given the choice between making the 12th or the 13th floor the one where you had all your climate-control equipment and sensitive electronic components, and if you were the superstitious type, there was really only one choice.

That day I met first with Dr. J, who wrote me a prescription for a month’s worth of 60 mg Cymbalta capsules. Then he read through a checklist of 42 possible symptoms of withdrawal. Withdrawal from duloxetine? Or from desvenlafaxine? I wasn’t exactly sure, but the whole concept of withdrawal didn’t seem applicable, since there was a good chance I had gone right on taking the drug I’d had during the study, assuming that I’d been taking any drug at all, which neither of us knew for sure. Still, we went through the list, and I had none of the symptoms (nausea, headaches, bursts of anger, irritability, sweating, etc.), or at least not to any extent I deemed worth reporting.

Dr. J found the list more tedious than I did, because he was the one who had to read it to me. I asked him if it wasn’t possible to have the subject just check boxes on a form, and he said no, but in some studies subjects were able to call in and listen to an automated list, pressing a button each time they heard a symptom they were having. That would have been preferable, he said, to having to read the list himself hundreds of times (three times for each of 70 or so subjects at the end of their time in the study). I thought about Lisa, in the oxycodone study, who had to read the same lists of words at least six times for each of 60 or more subjects, not to mention the lists of symptoms to be rated repeatedly. Of course, Dr. J probably got paid more than $13 per hour, so perhaps he thought it was a poor use of his costly time.

Next I went to the blood-drawing nurse, who seemed more perturbed than flattered when I asked her to use my right arm. “It’s because I know how competent you are,” I explained lamely. She remained unappreciative, but after a few moments of probing with her expert fingers, she found a vein and sank the needle on the first try.

This was the last time that Nurse D would be taking my blood pressure. She had accepted a full-time job with the county, specifically the county jail. The benefits would be much better than with a private company. She had been working at the jail part time for a while, but it would still be quite a change to go from taking routine BPs to caring full time for people with AIDS, GSWs, TB, and the DTs.

My blood pressure was even lower than it had been the week before. At least there were no consequences this time, since I had already been kicked out of the study. Either of the study drugs could have caused my “orthostatic hypotension” (low blood pressure occurring when you stand up after lying down for a while), so it still wasn’t clear which drug I’d been on. But my money was on the duloxetine (quite literally, now that I had to buy it myself). Later I read that increasing the dose of duloxetine can cause blood pressure to fall. I hoped that by the time of my last visit, the following week, I would have stabilized at 60 mg.

I walked the six blocks to UniVir, where Donna gave me my last seven days’ worth of Valtrex. After that I would have my washout week, to be followed by 7 weeks of acyclovir. Just in case I had a herpes recurrence during the washout period, Donna gave me six doses of Valtrex from her stash of free samples. Each pill was in its own blister pack, inside its own cardboard box. She emptied five boxes, crammed all six blister packs into the sixth, and tossed the other five.

I asked Donna if the blood she was drawing today was for a different study from the previous one.

“No,” she said. “It’s the same study. They had to throw the blood out.”

She explained that UniVir had gotten incomplete instructions from the company conducting the study. They hadn’t realized that the blood had to “keep moving,” i.e., be shipped off immediately. So they’d had to throw everyone’s blood away and start over. Luckily, there was no trial and error this time: Donna easily extracted two tubes of blood from my left arm.

I got my usual $30 check, plus $35 for the extra blood draw, plus two bus tickets to add to my growing collection.

When I got home, I looked at the record of my PsychoPharm vital signs (which I’d been given by mistake—more on that in chapter 16). The “criteria for withdrawal” for orthostatic hypotension were given at the bottom of the form: “a decrease of 40 mmHg or more in systolic BP or a decrease of 20 mmHg or more in systolic BP associated with moderate to severe clinical symptoms or below the absolute value of 90 mm Hg but a change of more than 10 mm Hg from baseline after at least two minutes standing compared to the previous lying BP will be withdrawn.”

After puzzling over this bloated and comma-deprived clause for several minutes, I finally came up with this translation of the part that applied to me: You look at the difference between the lying and standing BPs for the baseline visit, and then you look at the difference for the current visit, and then you compare the two differences. At baseline my BP was 92 lying and 91 standing, a difference of 1 mm; at the last visit it was 91 lying and 80 standing, a difference of 11 mm. The difference between the two differences was 10. In other words, it appeared to me that I’d been wrongly withdrawn from the study, because the criterion was “more than 10” and my change was exactly 10.

Not that I was likely to complain about being booted out, but I did mention it to the PI when he checked in with me by phone a few days later. He assured me that, contrary to the apparent intent of the sponsor’s criteria, the difference that mattered was the one between the current measurement and the baseline measurement, not the difference in the differences between lying and standing. I still think that he and whoever he talked to at Wyeth were wrong, but I decided that it just wasn’t worth it to pursue that argument.

Meanwhile I did some more research on hypotension and was disturbed, but not at all surprised, to learn that blood pressure that’s chronically as low as mine can cause problems with cognitive functioning, especially attention and memory. But there is disagreement on just what constitutes low blood pressure. One source I found defined low blood pressure for a woman as anything below 100 mm systolic (that’s the number on top in the blood pressure reading). For a man, it was 110 mm. The diastolic reading, this source said, is insignificant. Other sources said that either the systolic or diastolic reading could be too low, but they disagreed as to whether the cutoff measurements were at 90 and 60 or 100 and 65 or some other combination. It didn’t really matter to me, because I was hypotensive by anyone’s definition.

By anyone's except Donna’s, as it turned out. One day, after I’d learned about the cognitive consequences of hypotension, I asked her to take my blood pressure. According to her, it was something like 110/63. Not only is that not considered low, but she said that the various cutoffs I’d found weren’t necessarily low either. She was also extremely skeptical that low blood pressure could have anything to do with cognitive impairment. Admittedly, the evidence for that was kind of skimpy, so I figured the jury was still out on where to place the blame for my hampered cognition.

No one ever told me the results of that second blood test at PsychoPharm, and I never asked. I assume that my potassium level was normal, just as my blood pressure had gone from barely there to merely inadequate. Only days later did I remember (perhaps confirming, after all, what I’d read about hypotension and memory) that potassium lowers blood pressure. On further reading, I learned that the hormone aldosterone, secreted by the adrenal gland, is what regulates potassium and sodium levels in the blood. Something about the study drug, which I was pretty sure now was desvenlafaxine and not duloxetine, must have interfered with aldosterone production. But I didn’t spend a lot of time trying to understand this possible connection, because I couldn’t concentrate on what I was reading and figured I wouldn’t remember it anyway.

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