An AK-47
Despite the stellar success of the drug in the treatment of depression, from early on there was a dark undercurrent to the fluoxetine story. Martin Teicher and Jonathan Cole, a pair of Harvard psychiatrists, along with a registered nurse named Carol Glod, noted in 1990 that a group of six patients, all of whom had been free of any suicidal ideation when they commenced the drug, became acutely suicidal while on it, experiencing ‘intense, violent suicidal preoccupation’. One patient said she ‘felt like jumping out of her skin’ and that ‘death would be a welcome result’. Another escaped from the hospital, was caught by security guards and, upon her return, banged her head repeatedly against the floor while trying to mutilate herself, until physical restraint was the only option. It appeared to the treating psychiatrists that fluoxetine, far from making their patients well, had unleashed monstrous and deeply dangerous urges. Suddenly stories began cropping up in other medical journals as well. Some depressed patients, it appeared, had a paradoxical response to fluoxetine: the drug agitated them to the point of extreme violence. There were reports of patients pacing backwards and forwards, pounding walls and becoming paranoid.
Shortly after the deadly shootings at Columbine High School in April 1999, it was reported that one of the young gunmen had been taking an SSRI. In the widely read and highly acclaimed novel We Need to Talk about Kevin, which was later made into a film, author Lionel Shriver creates an adolescent male character who is put on fluoxetine and who then, using a bow and arrow, shoots a group of students, along with a canteen worker and a teacher, in the high school gym, which he barricades so no one can get in, killing his victims slowly, first an arrow in the foot, pinning the victim in place, then a half hour later another arrow to the chest and so on, all eleven of his victims dying excruciatingly, bleeding out on the burnished gymnasium floor while the killer, spiked on serotonin, coldly watches their lives ebb away in a tide of total red.
The fluoxetine-linked shooting that perhaps most caught the public’s attention involved a 47-year-old man named Joseph Wesbecker, who had worked at the Standard Gravure printing press in Louisville in Kentucky for seventeen years until August 1988, when he left the company, after having filed a complaint the previous year regarding discrimination against him for his manic depression. Subsequently he reached a settlement with the company and was put on disability leave in 1989, with the understanding that he could return to work once he was better.
But Wesbecker, who had a significant history of psychological problems and had been on an array of different psychiatric drugs, was not destined to improve. Soon after his psychiatrist started him on fluoxetine in August 1989, a year after he’d left his job, Wesbecker took a sharp turn for the worse. He became irritable, restless and paranoid. The following month, when his psychiatrist saw how psychologically unbalanced his patient had become, he told Wesbecker to stop taking the drug. Wesbecker, however, insisted he did not want to because he believed the drug was helping him to remember. ‘Remember what?’ his psychiatrist wanted to know. On fluoxetine, Wesbecker falsely believed he was recalling how his foreman at Standard Gravure had forced him into fellatio in front of all the other workers, a ‘memory’ that only served to fuel the rage boiling within him. Again his psychiatrist told him to stop taking the drug, but Wesbecker did not heed his advice.
Three days later, on the morning of 14 September, Wesbecker loaded an AK-47 semiautomatic rifle and a German-made pistol, and packed into a duffel bag two other semiautomatic pistols and a revolver, along with back-up rounds of ammunition. He went to work and took the lift to the second floor, where the Standard Gravure executive offices were located. When the lift door opened, Wesbecker walked out into the reception area with the rifle pointed straight ahead and opened fire, in what became, according to journalist Mark Ames, ‘the first modern private workplace massacre in American history.’ Wesbecker moved through the Standard Gravure offices and plant ‘like a zombie, an automaton’, ultimately killing eight co-workers and wounding another twelve before turning the loaded gun on himself, as his final act.
It took five more years, in the autumn of 1994, before the survivors and the families of the slain victims were able to bring Eli Lilly to court. Some of them came to the trial leaning on canes or in wheelchairs. Their claim: Lilly had mutilated their bodies and traumatised their minds by making fluoxetine – which to them was a deadly drug – available to a man they had once counted as a friend, whom they had nicknamed ‘Rocky’. Lilly’s defence: given Wesbecker’s long history of psychiatric problems, fluoxetine could not be blamed for the horror that had occurred. This had become Lilly’s standard defence to accusations that fluoxetine caused violence or suicidality. (The Wesbecker case was not the first fluoxetine-related legal action brought against the drug manufacturer. Within two years of fluoxetine’s release, there were already fifty-four suits pending, and in the mid-1990s, 160 suits would be consolidated into one large class action against Lilly.) The company maintained that the drug was entirely safe – why else would the FDA have approved it? – and that when bad things happened, it was because the people taking the drug had pre-existing proclivities towards self-destruction or murder. In the case of Wesbecker, getting to the truth was complicated because he had in fact tried to commit suicide five years before his rampage, and had purchased a number of the firearms before going on fluoxetine.
Thus, in the courtroom, Lilly’s lawyers claimed that Wesbecker had been a train wreck long before fluoxetine entered his life. Attorneys for the survivors and the families of the victims, for their part, brought in experts, such as Wesbecker’s psychiatrists, who claimed that although Wesbecker had a history of psychiatric problems, he had never displayed any violent tendencies towards others until being started on fluoxetine. A turning point in the trial came when the judge ruled that lawyers for the survivors could introduce evidence of a painkiller called benoxaprofen that Lilly had manufactured, marketed as Oraflex in the United States and Opren in Europe. The drug had been responsible for at least 150 deaths in the UK and the United States, and Lilly had been forced not only to withdraw the drug from the market but also to pay penalties and settlements in the millions of dollars related to 1,500 lawsuits. But then a strange thing happened. Just a day after plaintiffs won the right to include the benoxaprofen evidence, and with arguments ongoing, attorneys for the survivors abruptly informed the judge that in order to get the case to the jury as soon as possible, they had elected not to introduce any new evidence and instead would wait until the second phase of the trial, which covered punitive damages.
Unbeknownst to the judge, Lilly, panicked at the thought of how the benoxaprofen evidence could turn the trial, had reached a secret settlement with the plaintiffs. Under a ‘high/low’ arrangement, Lilly agreed to pay to the survivors and the family members of victims what an attorney for one of the claimants later referred to as ‘a tremendous amount of money’, a sum so huge ‘it boggles the mind’. (Because the amount of the settlement is sealed, it remains unknown, though pretrial estimates for a Lilly loss had been in the range of $150 million to $500 million.) According to the agreement, which came to light only years afterwards when the judge in the case himself sued to have it disclosed, if the survivors won their case, Lilly would pay on the high side of its offer; if the jury found in favour of the defendants, Lilly would pay out the lower, though still enormous, figure. Payment was contingent, however, on the jury reaching a verdict. Because of that stipulation, there was a huge disincentive for the survivors’ attorneys to really press their case, since if they fell short and wound up with a hung jury, their clients would get nothing. ‘The incentives,’ wrote Joseph Glenmullen, ‘shifted in favor of “losing” to be sure the victims and their attorneys went home well compensated.’ In addition, as part of the agreement the plaintiffs had also conceded that, regardless of the outcome, they would not appeal. What followed was an utter charade. The two sides went back into the courtroom, and as the lawyers acted out their parts, a t
rial that had been tense from the beginning was suddenly placid. Objections were desultory or entirely overlooked.
The entire deal raised profound concerns about the justice system and underscores the questions that have been part and parcel of the development of fluoxetine from its inception – a drug that appears to be one thing (site-specific) but that is really something else (far-reaching in its neural effects over the entire sprawl of the serotonin system, a system that is furthermore intimately tied to other neurotransmitters); a drug that was marketed as basically safe, despite the fact that, at the very least, it depresses the dopamine system and thus causes all sorts of troubling side effects; a drug Americans accepted as their darling, unable or unwilling to ask the difficult questions that ought to have been asked: where are the studies on long-term side effects? Why has Eli Lilly not pursued them? Is it justifiable to start patients on a path to taking a drug for years, for decades, when we know so little about its long-term effects? What does it mean that drugs with similar profiles, such as dexfenfluramine, show disturbing brain damage in animal studies? If you depress your dopamine neurons, does that make you more vulnerable to developing dopamine-related disorders such as Parkinson’s disease, either now or later in life?
But for a whole host of reasons, these are questions that very few people are asking. In both its clinical trials and this legal trial, Lilly managed to come out looking clean despite challenges to its due diligence. In the end, the company ‘won’ the Wesbecker case, by a margin of 9–3 on the jury, the minimum number of votes it could receive and prevail, though the company’s CEO presented it as nothing less than a complete vindication, claiming, in a New York Times article under the headline ‘Jury Rules Out Drug as Factor in Killings’, that Eli Lilly had ‘proven in a court of law . . . that Prozac is safe and effective’. And how did it achieve this victory? By effectively placating the survivors with what may be the world’s best, albeit short-term, antidepressant – cash.
The Myth of Low Serotonin
But the question of why depression is on the rise when we putatively have a chemical cure has not yet been answered. Psychopharmacology celebrated the serotonin boosters as clean, safe and highly effective drugs to treat depression. Then the field went one step beyond that by claiming that at last it had the science and the knowledge to treat human despair, a belief exemplified by Jeffrey A. Lieberman, chair of the psychiatry department at Columbia University in New York and former president of the American Psychiatric Association, who wrote, ‘My profession now practices an enlightened and effective medicine of mental health, giving rise to the most gratifying moments in a psychiatrist’s career: bearing witness to clinical triumphs.’
One of these triumphs is certainly fluoxetine. But how do psychiatrists square their enlightened and effective medicine with the fact that the number of people with mental illness just keeps going up? Earlier in this chapter we considered a couple of possible sociological explanations for the rise of depression and other affective disorders: first, that the increase in diagnoses is due to the lowering of stigma associated with depression, meaning that people suffering from the disease these days are more willing to admit their struggles and seek treatment, and secondly, that the rise in depression is the result of our becoming a more individualistic and less communal society.
Robert Whitaker, a finalist for the Pulitzer Prize for public service journalism and a Polk Award winner for his writing on medicine and science, proposes another scenario, which is that serotonin boosters, rather than treating a chemical imbalance, may instead be causing one. For starters, despite drug company advertisements and the prevailing ‘neuro-speak’, there is, as we’ve seen, little evidence that mental illness is the result of a chemical imbalance. Scientists have searched and searched for evidence of this imbalance and have not been able to find it. Perhaps more to the point, when researchers have compared serotonin levels in depressed versus non-depressed subjects, they have found that the happy subjects do not necessarily have more serotonin than their depressed counterparts. In fact, sometimes the happy subjects have less serotonin than the depressed research subjects. Because of the hypothesis about schizophrenia being the result of excess dopamine in the brain, scientists have also compared dopamine levels in schizophrenic versus non-schizophrenic subjects. But in a similar result to the serotonin studies, the schizophrenic subjects did not have any more dopamine than their non-schizophrenic counterparts. In some instances they even had less.
The results of these studies and others like them have turned psychiatry’s dominant narrative of mental illness on its head. After all, if there is no proof that a depressed person has a chemical imbalance, and you choose nevertheless to put that person on a medication that will alter neurotransmitter levels in his or her brain, then in effect you are causing a chemical imbalance rather than curing one. According to Steven Hyman, a neuroscientist and former director of the US National Institute of Mental Health, all psychotropic drugs cause ‘perturbations in neurotransmitter functions’. And this is Whitaker’s main point. We are subjecting millions of brains to drugs that change natural neurotransmission, sometimes radically, disturbing and upsetting the complex interplay inside our heads, clogging neural pathways with excess chemicals and sometimes causing the entire brain, which is intricately interlinked, to malfunction in ways we do not yet understand. An unmedicated depressed patient does not have a known chemical imbalance in his brain, but once he ingests fluoxetine, he will. The drug crosses the blood-brain barrier and gets to work, jamming serotonin into the synaptic cleft. Whitaker explains the result this way: ‘Several weeks later the serotonergic pathway is operating in a decidedly abnormal manner. The presynaptic neuron is putting out more serotonin than usual. Its serotonin reuptake channels are blocked by the drug. The system’s feedback loop is partially disabled. The postsynaptic neurons are “desensitised” to serotonin. Mechanically speaking, the serotonergic system is now rather mucked up.’
As far as Whitaker, Glenmullen, and other critics are concerned, the bewildering rise in mental illness is due not to social pressures but to the fact that so many people are drugged on serotonin boosters among other psychiatric medications and are therefore walking around with abnormal brain functioning that, in the long term, exacerbates the very symptoms the drugs are trying to treat. In other words, our antidepressants are making us increasingly depressed; thus we turn to them still more keenly, upping the dose, which causes still more neural perturbations and abnormal functioning, and so we go round and round, down and down. While, as we’ve seen, we have very little in the way of studies on long-term side effects for antidepressants or other psychotropics, we do have studies comparing the fates of medicated versus unmedicated patients. These have found that 23 per cent of adults, if they have never been psychiatrically medicated, will experience remission of a depressive episode without treatment in one month, 67 per cent in six months and 85 per cent in a year, while medicated patients tend only to get sicker, with the intervals between their depressive episodes shortening as time goes on.
The picture looks especially glum for depressed patients who ‘recovered’ on an antidepressant and then went off it. A whole range of studies has demonstrated that when patients begin taking an antidepressant and then go off it, they are likely to have a relapse of their depression within eighteen months at a rate of anywhere from 50 to 70 per cent. ‘Everywhere, the message was the same,’ Whitaker wrote. ‘Depressed people who were treated with an antidepressant and then stopped taking it regularly got sick again.’ And to make matters worse, a person who is on an antidepressant for a long period of time can expect to relapse faster, more furiously, than he would if treated for a shorter period. In a sense the drug becomes, over time, so intertwined with the user’s physiology that he or she simply cannot do without it as the years tick on. This conclusion is buttressed by another study in which large doses of fluoxetine were fed to rats, whose brains were then examined post-mortem, whereupon the scientists conducting the st
udy found that the rats’ neurons were ‘swollen’ and ‘twisted like corkscrews’.
Examination of these studies is disturbing, and one can well understand why the field of psychiatry might want to marginalise Whitaker’s reportage and the arguments he has culled. But because psychiatry highly values, or is supposed to value, honest self-assessment, all who work within the field are called upon to address the issues that this research has raised, and to do so with a steady and serious concern that has thus far not been evident. Instead, mainstream psychiatry has largely ignored the studies Whitaker cites, clumping him with the ‘antipsychiatry establishment’ as a kind of modern-day Thomas Szasz, a radical incapable of thinking beyond his own bias. This is a shame, because the hypotheses put forward by thinkers like Whitaker and Glenmullen are entirely plausible. In attempting to exile such critics, the field has lost a chance to examine itself and learn something important in the process. If the studies that Whitaker cites are correct and we are in fact causing brain damage with our antidepressants, then, at the very least, we ought to know. Were this the case, patients would deserve to be told. Many might opt for the medication anyway, the same as many in the middle of the last century, in pursuit of mental serenity, opted for lobotomies despite the danger of neural destruction involved, so pervasive and severe was their suffering.
The Drugs That Changed Our Minds Page 20
