Testosterone injections, administered to raise the level of free testosterone in the body, can have some useful effect, but they are difficult to administer and control and their effects are not entirely clear. The brightest ray of hope is Viagra. Because of its psychological and physical effects, it seems to affect three of Clayton’s stages; it falls short only in that it does not stimulate libido. It may as a secondary step help to restore confidence in one’s ability to interact sexually, and this helps one to relax, which in turn helps libido. It is to be hoped that dopamine boosters currently in development may take care of that, since dopamine appears to be strongly implicated in libido. Taken regularly, Viagra will also restore men’s nighttime erections, which are often eliminated by antidepressants. This in turn has a positive effect on libido. It has been proposed that men who are on antidepressants should take Viagra every night as a therapeutic agent, even if they are not having sex each time they take it. It can in effect be a quick and effective antidepressant; high levels of sexual function lift mood like almost nothing else. The research of both Andrew Nierenberg of Harvard and Julia Warnock of the University of Oklahoma indicates that Viagra, while it is not officially approved for women, seems to have good effects on their sexual drive and may facilitate orgasm. This is in part because it helps the clitoris to enlarge with blood flow. Hormone therapies are also useful in women with sexual dysfunction. Keeping up levels of estrogen improves mood, and sudden declines in estrogen levels can be devastating. The 80 percent drop in estrogen that women experience during menopause has pronounced mood effects. Women with low levels of estrogen develop all kinds of complaints, and Warnock stresses that the estrogen levels need to be normalized before Viagra can have any useful effect. Though it is important not to raise testosterone levels too high in women, lest they become hairy and aggressive, testosterone is a necessary hormone for female libido, and it too needs to be kept at appropriate levels.
The tricyclic antidepressants work on several neurotransmitter systems, including acetylcholine, serotonin, norepinephrine, and dopamine. The tricyclics are particularly useful in severe or delusional depression. The acetylcholine inhibition carries a number of unpleasant side effects, including dry mouth and eyes and constipation. Tricyclics can also be somewhat sedating. Use of the tricyclics in people with bipolar illness can precipitate mania, so considerable care must be taken in prescribing them. The SSRIs and bupropion can also trigger mania, but are less likely to do so.
The MAOIs are particularly useful when depression carries acute physical symptoms such as pain, decreased energy, and interrupted sleep. These drugs block the enzyme that breaks down adrenaline and serotonin, thus increasing the level of these substances. MAOIs are excellent drugs but have many side effects. Patients taking them have to avoid a range of foodstuffs with which they have troubling interactions. They can also affect bodily function. One patient I interviewed got total urinary retention from MAOIs: “I pretty much needed to go to the hospital whenever I had to pee, which was not convenient.”
The atypical antidepressants are just that: atypical. Each has its own novel mode of action. Effexor affects both serotonin and norepinephrine. Wellbutrin acts on dopamine and norepinephrine. Asendin and Serzone work on all the systems. It is popular at the moment to try for so-called clean drugs, drugs that have highly specific effects. Clean drugs are not necessarily more effective than dirty ones; specificity may to some degree be connected to the control of side effects, but it seems that the more things you muck around with in the human brain, the more effective the treatment is likely to be for depression. Clean drugs are developed by the pharmaceutical companies, which are enthusiastic about the tidiness of chemical sophistication; but such drugs are not particularly distinguished for therapeutic purposes.
The effects of antidepressants are unpredictable and cannot always be sustained. However, “I don’t believe total poop-out happens nearly as often as they say,” says Richard A. Friedman. “I believe that dosage may need to be readjusted, that the medication may need to be buffered. Psychopharmacology involves a lot of tinkering. And many of those who do have poop-out have it because they have lost a placebo response, which tends to be short-lived.” Nonetheless, many patients do experience medication as only temporary relief. Sarah Gold, who had a history of depression for her entire adult life, had a total remission with Wellbutrin—for a year. She achieved the effect again briefly from Effexor, but that too wore off within eighteen months. “People noticed. I was sharing a house with a few other people, and one of them told me I had a black aura and she couldn’t stand to be in the house when I was up in my room with the door closed.” Gold went on a mix of lithium, Zoloft, and Ativan; now she is on Anafranet, Celexa, Risperdal, and Ativan and she is “less energetic, less secure, but able to cope.” It may be that no current medications could give her the permanent remission that some people achieve, and for someone who will need to be on medication permanently, this darting from one solution to the next is intensely demoralizing.
A number of drugs, such as BuSpar, which acts on certain nerves sensitive to serotonin, are used for the long-term control of anxiety. There are also fast-acting drugs, the benzodiazepines—a category that includes Klonopin, Ativan, Valium, and Xanax. Halcion and Restoril, which are prescribed for insomnia, are also benzodiazepines. These drugs can be taken as needed to allay anxiety immediately. Fear of addiction, however, has led to gross underuse of the benzos. They are marvelous drugs for short-term use, and can make life tolerable during periods of acute anxiety. I have met people who were tortured with psychic anguish that could have been alleviated had their physicians been more permissive in the prescription of the benzos, and I always remember what my first psychopharmacologist told me: “If you get addicted, we’ll get you unaddicted. Meanwhile, let’s assuage your suffering.” Most people who take benzodiazepines will develop tolerance and dependence, which means that they cannot stop them suddenly; but they will not take escalating doses to obtain therapeutic benefits. “With these drugs,” says Friedman, “addiction is a problem mainly in people with a history of substance abuse. The addictive risk of the benzodiazepines is greatly overestimated.”
In my case, Xanax made the horror disappear as a magician makes a rabbit vanish. While the antidepressants I have taken were slow as dawn, shedding light bit by bit on my personality and letting it come back into the known and patterned world, Xanax provided extraordinary instant relief from anxiety—“a finger in a dike at the crucial moment,” as James Ballenger, an anxiety expert, says. For people who are not inclined toward abuse, benzos save lives. “What the general public knows,” Ballenger says, “is largely incorrect. Sedation is a side effect; using the drugs as sleeping pills is an abuse. Using them for anxiety is not. Withdrawing quickly gives you symptoms, but that’s true of many, many drugs.” Though benzos can help anxiety, they do not, by themselves, alleviate depression. They can affect short-term memory. Over the long term, they can have depressant qualities, and long-term sustained use should be closely monitored.
Since that first visit to the first psychopharmacologist, seven years ago, I have been playing the medicine game. For the sake of my mental health, I have been on, in various combinations and at various doses, Zoloft, Paxil, Navane, Effexor, Wellbutrin, Serzone, BuSpar, Zyprexa, Dexedrine, Xanax, Valium, Ambien, and Viagra. I’m lucky; I responded well to drugs within the class with which I began. Nonetheless, I can attest to the hell of experimentation. Trying out different medications makes you feel like a dartboard. “Depression these days is curable,” people told me. “You take antidepressants like people take aspirin for a headache.” This is not true. Depression these days is treatable; you take antidepressants like you take radiation for cancer. They sometimes do miraculous things, but none of it is easy and results are inconsistent.
I have so far not gone in for a full hospitalization, but I know that I may need one someday. In a hospital, one is usually on medications and/or receiving ECT. Part of what can
be curative, however, is the hospitalization itself, the close attention of staff, the systems to protect you from your destructive or suicidal impulses. Hospitalization should not be the very last resort of desperate people. It is a resource like any other and should be exploited when necessary—if only your insurance will allow it.
Researchers are working in four directions toward new treatments. The first is to shift as far as possible to preventative therapies: the sooner you catch mental problems of any kind, the better off you are. The second is increased specificity of drugs. The brain has at least fifteen different serotonin receptors. Evidence suggests that the antidepressant effects depend on only a few of these sites, and that many of the nasty side effects of SSRIs probably go with others. The third is faster drugs. The fourth is more specificity to symptom rather than to biological position, so that the experimentation to choose drugs can be abrogated. If we discover, for example, tags that would allow genetic subtypes of depression to be identified, it might be possible to find treatments specific to those subtypes. “The existing medications,” says William Potter, formerly of the NIMH, “are just too indirect in the way they work for us ever to get much control over them.” Thus this kind of specificity is likely to remain elusive. Mood disorders involve not a single signal from a single gene, but many genes, each one contributing a small increment of risk—which gets triggered by external circumstances to create a sum vulnerability.
The most successful physical treatment for depression is the least clean and specific one of all. Antidepressants are effective about 50 percent of the time, perhaps a bit more; ECT seems to have some significant impact between 75 and 90 percent of the time. About half of those who have improved on ECT still feel good a year after treatment, though others require repeated rounds of ECT or regular maintenance ECT. ECT works fast. Many patients feel substantially better within a few days of having an ECT treatment—a boon particularly striking in contrast to the long, slow process of medication response. ECT is particularly appropriate for the severely suicidal—for patients who repeatedly injure themselves and whose situation is therefore mortally urgent—because of its rapid action and high response rate, and it is used in pregnant women, the sick, and the elderly, because it does not have the systemic side effects or drug-interaction problems of most medications.
After some routine blood work, a cardiogram, often a chest X ray, and some anesthesia-related checks, patients who are deemed fit for ECT sign consent forms, which are also presented to their family. The night before the treatment, the patient fasts and has an IV put in place. In the morning, he is taken to the ECT room. After the patient has been hooked up to monitors, medical attendants put gel on his temples and then apply electrodes for either unilateral ECT to the nondominant side of the brain only—which is the preferred starting strategy, usually to right brain—or bilateral ECT. Unilateral ECT has fewer side effects, and recent research shows that high-dose unilateral ECT is as effective as bihemispheric treatment. The administering doctor also chooses between sine-wave stimulus, which gives more sustained stimulation, and brief-pulse square-wave stimulus, which induces seizures with fewer side effects. A short-acting IV general anesthetic is given, which will put the patient out completely for about ten minutes, and a muscle relaxant is also given to prevent physical spasms (the only movement during the treatment is a slight wiggling of the toes—unlike ECT of the 1950s, in which people thrashed around and injured themselves). The patient is connected to an EEG machine and an electrocardiogram (EKG) machine, so that a brain scan and a heart scan are running at all times. Then a one-second shock causes a temporal and vertex seizure in the brain that usually goes on for some thirty seconds—long enough to change brain chemistry, not long enough to fry up the grey matter. The shock is usually about two hundred joules, which is equivalent to the output of a hundred-watt bulb; most of this is absorbed by the soft tissue and skull, and only a tiny fraction of it reaches the brain. Within ten or fifteen minutes, the patient wakes up in the recovery room. Most people who receive ECT have ten or twelve treatments over about six weeks. ECT is being administered increasingly on an outpatient basis.
The writer Martha Manning has described her depression and ECT in a beautiful and surprisingly hilarious book called Undercurrents. She is now stabilized on Wellbutrin, a little lithium, some Depakote, Klonopin, and Zoloft—“It’s like having the rainbow coalition in my hands when I look at ’em all,” she jokes. “I’m a science project with no due date.” She had intense and protracted experience with ECT when her depression was at its most severe. She took herself in for treatment the day she found the address for a gun shop to kill herself. “I didn’t want to die because I hated myself; I wanted to die because I loved myself enough to want this pain to end. I had leaned against my daughter’s bathroom door every day and listened to her singing—she was eleven, and always sang in the shower—and that was an invitation not to try for one more day. I just couldn’t care enough, but suddenly I knew that if I did get and use a gun, I would stop that child’s song. I would silence her. And that day, I checked myself in for ECT. It was like I finally said ‘Uncle’ to the one who’d wrestled me to the ground. I had treatment for weeks—waking up after each round feeling hungover, asking for a Diet Coke, knowing it’s going to be a sort of Tylenol day.”
ECT does result in disruption of short-term memory and can affect long-term memory. The disruptions are usually temporary, but some patients have had permanent memory deficits. One woman I met, who had been a practicing lawyer, came out of ECT minus any recollection of law school. She could not remember anything she’d studied, nor where she had studied, nor whom she had known during her studies. This is extreme and rare, but it does happen. ECT has also been associated with the death of about one in ten thousand patients, according to one study, usually because of cardiac problems after the treatment. Whether those deaths are coincident with ECT or caused by it is not entirely clear. Blood pressure does increase significantly during ECT. ECT does not appear to cause physiological damage; indeed, Richard Abrams, author of a seminal book on ECT, describes a patient who had received more than 1,250 bilateral ECT treatments and whose brain, when she died at the age of eighty-nine, was in perfectly good shape. “There is simply no evidence—and virtually no chance—that ECT as presently administered is capable of producing brain damage,” he writes. Many of the short-term side effects—including grogginess and nausea—come from the anesthesia that is used with ECT, rather than from the ECT itself.
ECT is still the most stigma-loaded treatment. “You do feel like Frankenstein on the table there,” says Manning. “And people don’t want to hear about it; nobody brings you casseroles when you’re in for ECT. It’s very isolating for the family.” It can be traumatizing conceptually for the patient as well. “I know it works,” says one mental health worker. “I’ve seen it work. But the thought of losing precious memories of my kids and my family—you know, I don’t have parents and I don’t have a husband. Who finds those memories for you? Who tells you about them? Who’ll remember the special recipe for pie that we made fifteen years ago? It would add to my depression to feel more dreamless. Memories are what helps me through the day, thoughts of love in the past.”
On the other hand, ECT can be miraculously effective. “Before, I was aware of every swallow of water, that it was just too much work,” Manning says. “Afterwards, I thought, do regular people feel this way all the time? It’s like you’ve been not in on a great joke for the whole of your life.” And the effects are usually rapid. “Vegetative symptoms went; then my body felt lighter; then I really wanted a Big Mac,” says Manning. “I felt like I’d been hit by a truck for a while, but that was, comparatively speaking, not so bad.” Manning is unusual. Many people who have electro-convulsive therapy are resistant to the idea that it is useful, especially if transient memory deficits have afflicted them, or if the reconstruction of their life has been gradual. Two people I know had ECT in early 2000. Both had been at rock bottom
—unable to get out of bed or get dressed, eternally exhausted, direly negative about life, uninterested in food, incapable of work, and often suicidal. They had electroshock within a few months of each other. The first suffered severe manifest memory loss after the treatments—he had been an engineer and now couldn’t remember how a circuit worked. The second came out as morose as she had gone in because she was still confronted with authentic life problems. The engineer’s memory began to resurface about three months later, and by the end of the year, he was getting up, going out, had returned to a job, and was functioning well. He said it was “probably a coincidence.” The second one went in for a second round of treatments despite her insistence that the first round had done her no good. After the second round, her personality began to return, and by the autumn she had not only a job but also a new apartment and a boyfriend. She continued to say that the ECT had been more upsetting than it was worth, until I finally suggested to her that what the ECT had wiped out was her memory of how she had been before it. When Manning’s book was published, picket lines of people objecting to “electronic mind control” marched when she read. There have been laws against ECT in many states in the United States; the treatment methodology is subject to abuse and it’s not for everyone and it should certainly not be used indiscriminately or without full patient consent—but it can be a wondrous thing.
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