Death Is Not a Side Effect: Antidepressants and the Suicide Problem
| Matthew Pianalto |
| A Cause for Suicide? When the FDA called for the manufacturers of ten of the most commonly prescribed antidepressants to publish stronger label warnings about possible suicide risks, they publicly reopened the case of antidepressants, their usefulness, and their drawbacks or dangers. The major point is that physicians and psychiatrists need to monitor patients, especially when an antidepressant is first prescribed, for any indications of increased suicidal thought, behavior, or other agitation. Although the link remains speculative, the seriousness of the issue makes for disturbing irony: for some, antidepressants may make matters worse. In fact, the debate over whether antidepressants can ‘cause’ suicide has been ongoing for well over a decade. In Listening to Prozac (1993), Peter D. Kramer pointed out that between 1%-5% of all depressed patients “experience a paradoxical worsening of suicidal thoughts on any antidepressant.” [1] Clinical studies of the ‘new generation’ antidepressants (selective serotonin reuptake inhibitors, or SSRIs—Celexa, Effexor, Lexapro, Luvox, Paxil, Prozac, and Zoloft) report an average “dropout rate” of 5%. Dropouts are those taken off the medication (and generally excluded from the final data) due to an experience of increased agitation, anxiety, or akathisia (characterized by extreme physical restlessness). These side effects fall under the category ‘increased activation’ and have some researchers worried that antidepressants may give rise to the “roll back phenomenon” in depressed patients—the medication may give certain people the boost needed to act upon suicidal thoughts which required too much energy of them while in a depressive state. Studies of antidepressant efficacy tend to screen out subjects who pose a high risk for suicide because there are ethical worries attached to including high risk subjects in preliminary studies. In practice, however, physicians often prescribe antidepressants off-label (for conditions other than those for which the medication is explicitly approved). Furthermore, if those with a history of suicidal risk were to commit suicide during a study, these cases would not show that the drug itself was to blame, since the person was already suicidal before beginning medication. These drugs are intended to treat depression, not suicide. Since there is a strong clinical link between depression and suicide, it is believed that an effective treatment of the prior ought to decrease the risk of the latter. The concept of suicide has undergone marked change since the word was first coined in the 17th century and made popular by Voltaire. Before this time, there was no single word for suicide, but only phrases such as “self-murder” or “self-homicide.” In the beginning, “suicide” referred to a willed act of self-destruction resulting in death. The morality of suicide could be discussed only on the condition that suicide represented a choice. English laws in the 18th century held that such a choice was punishable by confiscation of property, burial at a crossroads, and ironically, death for those who were unsuccessful in their suicide attempts. This is stage upon which the conceptual shift began. Local officials, sympathetic with the surviving family of suicides, sought to evade the law so that widows and children would not be forced out of their homes. Thus, it was determined that if a person was “not of sound mind,” then that person could not be held morally (or legally) responsible for having committed suicide. In this strategy we have both the origins of the insanity plea and the germ of our contemporary medical view of suicide and mental disorders. We now see suicide as the result of depression or other psychological disorders: suicide has become the side effect of mental disease. We seek to sympathize with the victim of suicide while at the same time condemning the act, by claiming that it wasn’t really an act at all, but a disease—some psycho-neurological force beyond the control of the individual. What is worrisome about such a view is that suicide loses its status as “suicide” in the stronger sense; it ceases to be a chosen act, but rather a fatal force which takes humans and drags them to their deaths. Thus, we equally fear depression, anxiety, and any other ills which might precipitate the “disease” of suicide. Our view of ourselves as psychological agents in the world has become increasingly medicalized. Our mental lives are subject to the categorization and scrutiny of a class of professionals and companies, and it often seems as if the synthetic manufacture of our happiness is up for grabs. The March warning issued by the FDA regarding antidepressants and the potential suicide risk in minors again raises the question as to how much progress science has made in combating suicide and depression; the theories remain incomplete, and antidepressants are far from sure-fire “cures”—as it turns out, it is still unclear just how effective antidepressants are. Somewhere in the confusion raised by suicide and its supposed psychological causes, there is a tension: on one end of the conceptual spectrum, we regard suicide as a self-willed act, resultant of despair over one’s life situation, and on the other end, suicide is not a moral or existential problem but only the name for the terminus of a condition we have entitled “depression.” Favoring the interpretation of suicide as a choice overlooks the seeming truth that there is a process which leads to suicide—certain psychological factors, behavioral indicators, environmental factors, which influence the self-destructive ways in which humans sometimes act. Leaning too hard on the psychological explanation, though, seems to neglect our conception of ourselves as free moral agents who make choices and are held responsible for them on the very presumption that they really are our choices. Although there is much to be gained in psychology, science, and medicine, these ways of looking at and treating the problem of suicide are likely to be only a part of the larger picture. We need both to get clear on the climate of antidepressant research and to take into consideration a more phenomenological account of suicide and despair which presents these problems in the everyday, human ways in which they are encountered. The Trial (and Error?) of Antidepressants The FDA’s new warning comes in the wake of recent concerns raised about Paxil. The combined results of three studies of subjects under 18 taking Paxil demonstrated that 1%-2% of those given a placebo and 2%-3.5% of those given Paxil exhibited suicidal behavior. [2] The FDA recommended in June 2003 that Paxil not be prescribed in pediatric settings and called for other antidepressant manufacturers to look for similar red flags in their own data. In the mean time, there have been enough anecdotal reports of antidepressants acting as an impetus toward suicide and other violent acts in order to raise and sustain the worry. At the meeting between the Psychopharmacologic Drugs Advisory Committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee (February 2, 2004), which led to the FDA’s warning, the majority of speakers in the open hearing had come to speak against the effects of antidepressants on their children or patients, to relate, in their allotted two minutes, unmistakably horrific events—children who took their own lives and in some cases the lives of others while on antidepressants. [3] Tom Woodward, for example, speaking of his daughter’s self-inflicted death only seven days after beginning a Zoloft prescription, summed up the general consensus of the morning testimony when he claimed, “We are 100 percent convinced that Zoloft killed our daughter.” [4] The split between the two sides of the debate as to whether antidepressants cause suicide reveals two different concerns, which are not necessarily mutually exclusive. First, antidepressant supporters point out that, globally, antidepressants are successful in treating depression and that the new generation drugs such as Prozac and other SSRIs do so with less side effects and a lower overall dropout rate than older drugs. Furthermore, it has been difficult so far to discover a direct link between SSRIs and suicidality. The second concern, emphasized by antidepressant detractors, is that just because the medications are effective for many, this does not preclude the possibility of their having devastating effects on others. Add to this a general acceptance, prescription, and use of these drugs (a $17.1-billion industry globally, which produced drugs for 15 million American patients in 2001)—the kind of acceptance which suggests to many professionals that these drugs are being sloppily prescribed—and there exists for some persons a potentially deadly cocktail, the chemistry of which remains too little understood. Even if a risk-benefit analysis of antidepressants justifies their use, the justification and support is far from one hundred percent, and those who have experienced what they believe to be the worst of antidepressants urge that we should not lose sight of ourselves in the fog of statistics. When narrowed to the case of children and whether they should be taking antidepressants, the issue becomes far more complicated. Adults may to an extent do as they please. Stock arguments against antidepressants fail to consider the obvious truth that humans have always been self-medicating animals, whether the medicine is aspirin, booze, candy bars, or St. John’s Wort. But everyone also knows that we don’t give these same things to our children, either not at the same dosage or not at all. Children metabolize antidepressants differently than adults, and the FDA is pursuing indications that SSRIs “have an effect on growth” in children. [5] Furthermore, there is an ethical dilemma; children cannot consent. They have no say on what is given to them, and so it is entirely up to parents, clinicians, researchers, and regulatory agencies to ensure that the drugs given to children not only have a positive effect, but are also safe. Regarding antidepressants, the current worry is that there is systematic failure on both counts—first, the efficacy of antidepressants over placebo has not been conclusively established, and second, as has already been suggested, the potential risks involved with these drugs might outweigh any positive effect they could have, especially in minors. The British Medicines and Healthcare Products Regulatory Agency (the UK equivalent of the FDA) has already banned all but Prozac for the treatment of depression in minors, based upon the same data received by the FDA from clinical trials. On this side of the Atlantic, the FDA is concerned that the existing data will be insufficient since the correlation between medication and suicidal thoughts or behavior was not directly studied in clinical trials. New studies aimed at this specific issue, although they would take time, would be far better than trying to re-analyze the existing studies. But new studies also cost money, and the FDA may not have the authority to require companies themselves to conduct new studies on already approved drugs. Robert Nelson, of the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee, suggested that if companies won’t provide new data, the FDA should simply go along with the British decision and issue a full warning. But when one looks at the efficacy data, one might still wonder how things reached this point of entanglement—no one, neither the FDA nor the majority of researchers, or even the drug companies themselves can claim that the placebo-controlled clinical trials provide sweeping proof of antidepressant effectiveness. No one doubts that the drugs are doing something—targeting serotonin levels in the brain, in order to normalize secretions of this neurotransmitter. What remains unclear is how much of this normalization is due to the drug and how much is due to other factors, such as the placebo effect and the treatment settings under which these trials are performed. A recent analysis of the FDA data suggests that as much as 82% of the improvement on antidepressants is replicated by administering a placebo. [6] The expectation that one will get better, combined with the attentive environment of these clinical trials, seems to have as much to do with effective treatment of depression as the antidepressants. Of course, several researchers have pointed out that you can’t simply do away with the drug, give the patient a sugar pill, and tell her that things will improve—doctors can’t lie to their patients, even though it appears as if this is an effective treatment method. But to argue in the other direction, as some researchers have, to claim that because antidepressants and the expectation that they will eradicate depression seem to combine for a robust placebo effect, that antidepressants should therefore be prescribed, sounds a bit like voodoo medicine. Professor Jonathan Lear of the University of Chicago recently commented in conversation that voodoo curses are highly effective because the cultures in which voodoo is practiced place a great amount of faith in their effectiveness. For all our convictions that science corresponds with an objective truth and reality, have we let antidepressants become the hocus pocus of the Western world? This analogy shouldn’t be pushed too far. For one thing, it appears difficult to give a qualitative analysis of what exactly the 18% benefit of antidepressants is, but in some cases, this benefit may be quite valuable, if not indispensable. Also, many have pointed out that the placebo-controlled trials are highly selective of test patients, ending with a class of subjects which represents only about 15% of the total population of antidepressant users. Dropouts are often excluded from the final data, as well as subjects who display too thorough a response to placebo (called “placebo-washouts,” those who really would benefit just as well from a sugar pill as an active drug). Test patients are generally those who display only a single mental disorder; whereas, in practice, patients prescribed antidepressants are often taking other medications or can be classified as having more than one mental disorder. As mentioned, patients with suicidal history are excluded as well. Thus, the range of people in the general population is much more heterogeneous than the class of subjects in clinical studies. The result is that there isn’t much clinical data on how antidepressants actually work in the “real world.” Presumably, they are more effective in real practice; if they are any less effective than in trials, then the question as to why they are being prescribed only grows more pressing. The ‘real world concern’ raises a further set of issues. By and far the largest question is why primary care physicians prescribe 80% of the antidepressants in the United States. Studies show that primary care physicians correctly diagnose depressed patients less than 50% of the time, and that only 25% of depressed people are effectively treated within the primary care setting. [7] One answer: marketing. In 2000, the Pharmaceutical Research and Manufacturers of America, a 35 company trade group, spent $2.5 billion in direct to consumer advertising and $13.2 billion dollars marketing to physicians (which averages out to $22,000 per physician in the U.S.). [8] Brand-name-recognition prompts 88% of patients to ask their physicians for an antidepressant by brand name, and 25% of those patients seek another physician if their request is not met. [9] Physicians are under the gun to assign a cure, and patients are insistently demanding these drugs, even though “the majority of the English-speaking population cannot read at a level that will make [the information aimed at prescribers on labels and pharmaceutical company websites] accessible.” [10] That is, most of the information made public about these drugs is over the head of the average citizen, and the remaining public information is generally shaped by marketing strategy. (For example, company websites rarely publish the efficacy data or detailed accounts of side effect risks.) Despite all these questions and unfavorable data, antidepressants have carved out a place in society and are here to stay, at least in the foreseeable future. Thus, more studies need to be done—more diverse, “real” patient populations need to be identified, risk factors need to be continually assessed and monitored by physicians and psychiatrists. There is still much ignorance in this field, which is why the FDA called for the stronger warning. The mid-90’s craze over Prozac as a wonder-drug may be dead, but the risk now would be to simply fall into antidepressant-complacency, when there are still many reasons to approach these drugs with care. The Suicidal Problem Conceptual vagueness regarding suicide comprises another difficulty, sometimes overlooked. What are we talking about when we claim that a medication can “cause” suicide? This seems to mean that the medication has adversely affected the individual in a manner which has compelled the individual to end his or her life. How much of an influence on decision-making must a medication exert for the drug itself to be culpable? And when medication exerts this force on how we choose, can we even say that we are choosing? First of all, if medications can cause suicide, then that isn’t exactly suicide. If anything, it’s murder, or the pill-induced equivalent, since pills themselves can’t form murderous intentions. (Recall Mr. Woodward’s conviction that Zoloft “killed” his daughter.) People who aren’t able to control their choices (because of some form of mental impairment) can’t properly be said to have committed suicide. “Crazy” people can’t commit suicide just as they cannot commit murder, if by definition a “crazy” person is not of sound mind and unable to form true intent. In short, it is very odd to conceive of death as a side effect; it’s death, the end of all effects and the termination of all affect. Dry mouth seems more like a side effect. There is no shortage of literature which parades suicide as the outspoken epidemic of our time. In 2001, it was the 11th leading cause of death in the U.S.; over 30,000 people ended their own lives. One recent article on teen suicide in U.S. News & World Report editorializes, “Young suicide inspires no March of Dimes, Race for the Cure, or colored lapel ribbons. Let’s face it, it’s a disease that hits too raw a nerve.” [11] Suicide does indeed strike a raw nerve, but to call it a “disease” seems a quick attempt to categorize a fatal action, one which many of us disapprove of, in a manner which will alleviate some of our own responsibility for addressing the problem of suicide. One strategy we might try at this point is to attempt to conceive of suicide, as much as it may disturb us, as more than simply a disease, but rather as a complex response to a not-so-medicalized conception of mental anguish and despair. But what is the problem of suicide? Is it the fact that people do commit suicide? Is that the problem? What we’re discussing here is something more than a mere sociological issue, but a problem experienced by individual human beings. The problem of suicide is the suicidal project itself. The psychological community has sought to cast this project in its own terms, and to connect suicide with the categories of mental disorder. In a sense, it is absolutely unsurprising that as many as 90% of suicides are classified with depression or some other mental disorder upon psychological autopsy. If suicide is regarded as a response to an unbearable life-situation, then the notion that the person who commits suicide was ‘depressed’ follows almost by definition—who could despair over life and yet fail to exhibit some of the ‘warning signs’ of depression? The topic itself hovers beneath a depressive gloom. The problem with the psychological picture of depression and suicide is that it often seems to focus too much on individual symptoms and coping deficiencies, leaving out the fact that individuals exist within a world and exist through a series of responses to the world—life is, on this ‘worldly’ account, a continual process of coping with oneself and the world. Rather than speaking of depression, it might be more fruitful to speak of suicide as a response to despair. This, too, appears an obvious connection, but in working out the concept of despair—a concept which extends back to the writings of Kiekegaard and was appropriated by the existentialist philosophers and psychologists—we may find ourselves looking at a richer picture of the problem of suicide, a picture which hesitates to accept the thin account of suicide as a disease (or a side effect) and views it instead in terms of the total life-situation of the individual. This life-situation is certainly not exclusive from psychological explanations, but it seeks to go further than the scientific picture and to expose life as it is fundamentally experienced by human beings. To despair is essentially to desire to be rid of oneself. The reasons for this desire might stem from the individual herself, from a distorted conception of her own situation which depicts the world of possibilities or her own self as small, inconsequential, inauthentic, or something to be rid of. Such perceptions may be the illusions of the individual, but it is also conceivable that despair can be a response to a real and awful situations—an oppressive, abusive home life, a professional failing, or other environmental provocation which is ‘too much’ for the individual to cope with. This is observed in teen suicides, in which the youth perceives himself or his situation as unbearable and inescapable. In such a situation, suicide poses not a solution, but a way out of the pain of despair and entrapment. At the same time, it might be fine to claim that the individual is depressed, but this explanation seems to presume, perhaps too much, that the majority of the problem resides in the individual. The case of teens, who are not autonomous citizens, illustrates the difficulty with this picture. The teen in large part is responding to her environment and what strikes her as the impossibility of coping with some situation: breakup, abuse, loss, and so on. Whereas an adult can take leave of an oppressive situation, the teen often cannot. Adding to this the high emotional energy and sensitivity of teenagers, there is some truth to the idea that the teen might not be fairly assessing his situation—things are generally not as bad as they feel to us as teenagers—but subjective emotions are rather resistant to old saws, adages, and advice of the form, “Get over it.” The solution, briefly put, to such despairing responses as suicide depends heavily on what could be regarded as creativity—the individual must be able to widen her perspective so that it extends past and incorporates other possibilities, projects which would pull her out of despair, and motivate her into seeing future possibilities, and drive toward the pursuit of life-affirming goals. This is where the antidepressant solution, in isolation from other interpersonal forms of interaction and therapy, might be lacking: can you sell creativity in a pill? Can a person learn from a drug how to see the world in new ways which will inspire an urge toward life instead of death? Maybe the idea is not completely far-fetched. (Those who remember the psychedelic 1960’s might agree.) But to rely on the medications alone might be to forget how much we can learn from others, both professionals and friends, through talk and attentiveness. Furthermore, recent brain-imaging research has suggested that certain forms of psychotherapy (such as cognitive therapy) generate similar neurochemical changes as SSRIs. What this means is that there’s more than one way to work on the brain and to elicit the chemical changes which are believed to be tied in with treatment of depression. The relapse rate in one comparative study was significantly lower in the cognitive therapy group (25%) than in the drug group (40%). It may be that the interpersonal therapies provide precisely what drugs alone might not, by equipping the individual not only with a neurochemical lift, but also with coping mechanisms and strategies which the recovered person can actively apply to his or her life, even after the professional therapy ends. In a time when pharmaceutical treatments are so prevalent, in part because they appear to be the most cost- and time-efficient method, it is important for the public not to forget that there are other tenable treatments and approaches to these problems. In general, it is quite difficult to inspire people to change, but in the case of despair, some kind of change seems necessary in order to get the person out of the cramped ways of seeing oneself and the world, which if unattended may lead one to regard suicide as the only release. The Human Picture In the weeks and months to come, it seems doubtful that the independent researchers at Columbia University appointed to sift once again through the FDA databases will find a causal link between antidepressant use and suicide. In part, this is because it is a contradiction of terms to say that a drug can “cause” someone to commit suicide. What they are really looking for is a variety of behavioral indicators which might be classed as ‘suicidal’—changes ranging from suicidal thoughts to self-damaging behavior. Also, since suicide is identified as a risk factor in depressed persons, it is very difficult, if not impossible, to sort out all the confounding factors in the data. Solomon Iyasu, of the Division of Pediatric Drug Development, said at the February 2 meeting, quite bluntly, that “it is very difficult from these reports to sort out what is going on.” [12] That meeting serves as a reminder that antidepressants remain in some ways ‘experimental drugs,’ insofar as there is still much research to be done (especially regarding long-term effects). On the other hand, the FDA doesn’t want to scare people away from antidepressants; the target population of the current concerns about suicidal risk is a very small sub-group of the total number of patients who take antidepressants (around 1% of the 1%-5% of patients who go off medication due to adverse side effects). Even before this meeting, warnings existed in the drug labels indicating that patients ought to be monitored for behavioral changes, especially increased ‘activation’ or manic behavior. The FDA advisory notice primarily re-emphasizes those warnings, and directs physicians’ and parents’ attention toward their patients and children—the point: don’t assume that a prescription is the end of the matter. That assumption, it seems, is the potentially deadly fallacy. Medicines are only tools, and are not a replacement for human care and interaction. In any case, we feel that something has gone wrong when a youth commits suicide, and can hardly believe that a young person, with so much life left to live and so many possibilities, could ever look at his or her life, believe that there was nothing left but to die, and want to die. If we consider suicidal thoughts as a function of despair, what we see for a young person whose choices are in some ways limited by home life and legal considerations regarding minors is that the “desire” to die is in some sense a metaphor for the deep need for a radical change in one’s life. The desire to die is a desire to get rid of oneself—to be someone other than oneself, because one’s current self-image is painful and unbearable. No one knows what death itself is like, and so it is unclear what it would be to desire death. But we are all familiar with change, and we know that sometimes a change, whether in diet, social settings, or habits, can often provide the means through which the quality of life is improved. Teens are perhaps more given to dichotomous thinking than adults—to regard their lives as filled with ultimatums and either/or decisions which make each moment seem like life or death. Twenty-four hours for a sixteen-year-old feels like a vastly longer amount of time than it does to a mature adult. As adults, perhaps we lose some of our nerve and the stomach needed to endure life as an emotional roller coaster—we deaden ourselves a bit to the wildness of emotional, sensory, and social experience, and save ourselves from anxiety by erecting stoic facades. It is worth asking ourselves, in regard to the youth of the country and our responsibility to care for and educate them, what kinds of messages we want to send to them about coping with their own mental and social lives. At the present time, the psychological picture of human beings and the consumer culture’s commitment to medication-based treatments of psychological problems, seems to send only a partial and incomplete message—we learn to treat our minds and bodies as externally malleable objects. Given the unanswered questions about drug treatments, we shouldn’t forget that we experience life internally and subjectively, and that for all the tools provided by science and technology, if we neglect the vastness of our inner experience and the ability to share these experiences through language and its artistic corollaries, and if we forget the value of caring and need-directed human interaction, then we reduce ourselves to biological machines. It is easy to look at a small blue pill in our hand and to recognize its material currency, to expect that ingesting it will have material effects. Probably, we should not forget that there is a currency to ideas, words, and images, too, and that no matter how we regard the interaction between the mental and the physical, scientific reductions of human life to the functions of the body often fail to capture the ways in which we experience our lives in the world—as filled with cares, concerns, worries, and hopes; projections into the future and recollections into the past. The problem of suicide is a human problem; the complexity of our experience and our human make-up make this action a possibility. As such, it is a hard pill to swallow to suppose that antidepressants themselves could pose a total solution on the one hand, or a total scapegoat on the other. The FDA’s questions and the inconclusiveness of the scientific data will perhaps remind us that a one-dimensional characterization of human beings fails to capture the richness and the difficulty of human existence, and will motivate people to seek broader and more encompassing ways of characterizing and dealing with ourselves. E-Mail Author Post Comments NOTES: [1] New York: Penguin Books (1993) 306. [2] Harvard Mental Health Letter (December 2003) 5. Source further notes that no suicides occurred in either group. [3] A full transcript is available at http://www.fda.gov. [4] FDA transcript (2/2/04) 85-86. [5] FDA transcript (2/2/04) 37. [6] Kirsch, et al., “The Emperor’s New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration,” Prevention & Treatment, Vol. 5, Article 23 (July 15, 2002). [7] Supplement to the Journal of Family Practice (December 2003) S4. [8] Jay Palmer, “After the Boom, No Reason to Smile,” Barron’s (May 20, 2002) 26. [9] Mark A. Graber and Michelle Wreckmann, “Pharmaceutical Company Internet Sites As Sources of Information About Antidepressant Medications,” CNS Drugs, 16:6 (2002) 422. [10] Graber and Wreckmann, 421. [11] Bernadine Healy, “Dying of Depression,” U.S. News & World Report, 135:6 (November 11, 2003) 67. [12] FDA transcript (2/2/04) 209. FURTHER READING ON SUICIDE: Améry, Jean. On Suicide: A Discourse on Voluntary Death. Trans. John D. Barlow. Bloomington: Indiana UP, 1999. Cholbi, Michael. “Suicide.” Stanford Encyclopedia of Philosophy, 2004. Colt, George Howe. The Enigma of Suicide. New York: Touchstone, 1991. Donnelly, John, ed. Suicide: Right or Wrong? Second Edition. Buffalo: Prometheus, 1998. Shneidman, Edwin. The Suicidal Mind. New York: Oxford UP, 1996. Szasz, Thomas S. Fatal Freedom: The Ethics and Politics of Suicide. Westport: Praeger, 1999. |
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