The Drugs That Changed Our Minds

by Lauren Slater

  This is a rare admission. For the most part, researchers insist deep brain stimulation has nothing to do with mind control or social shaping. They are simply psychiatrists targeting symptoms, they say. These doctors have seen severe psychiatric anguish and know that its remission is always a blessing. But of course any time a psychiatrist tries to tweak a patient’s mind, he or she does so in accordance with social expectations.

  Tap, tap. Mario felt a surge inside him. Later, outside, he peered at the world turned on, turned up, and indeed it did look different, the grass a cheerful green, the daffodils a bright yellow. When he went home, Mario wanted to talk. He had things to do. Who needed sleep?

  ‘You’re like the Energizer bunny,’ his wife said to him.

  ‘I feel revved,’ Mario agreed.

  Mario is not the only person to have become a little too happy on the wire. ‘That’s one of the dangers,’ Greenberg said. Don Malone concurred: ‘We don’t want hypomania. Some patients like that state. It can be pleasurable. But this is just like having a drug prescription. We decide how much, when and how.’

  But it’s not the same as a drug prescription. A patient can decide to take no drugs, or five drugs. A patient can split his drugs with his spouse, feed them to the dog or switch to a different psychopharmacologist. Despite prescription regulations, there is tremendous freedom in being a ‘pill popper’. Not so for those with implants. True, no longer is anyone dragged to the operating table in terror. No one is cut without exquisite and careful consideration both beforehand and during the procedure. Instruments have been honed, imaging devices advanced. And yet patients do not, cannot fully understand or appreciate the degree to which they will be under their doctor’s control after the surgery. Once a month deep brain stimulation patients must visit their psychiatrist for what are called adjustments. (For depression patients, however, Mayberg said the rule is ‘set it and forget it’.) Adjustment decisions – altering what are commonly called the ‘stimulation parameters’ – reflect how the patient scores on a subjective paper-and-pencil test of symptom intensity, but ultimately control lies with the treatment provider.

  At a 2004 meeting of the President’s Council on Bioethics, when Massachusetts General Hospital neurosurgeon and Harvard University professor G. Rees Cosgrove concluded his presentation on the issues surrounding deep brain stimulation, another Harvard professor asked him, ‘Who holds the clicker?’

  Cosgrove’s answer: ‘The doctor.’

  Long-Term Prospects and Conundrums

  Mario’s good mood continued. He had obsessions and compulsions, but they were smaller, and were dominated by the grand energy that saturated his existence. For two weeks he saw Greenberg every day. Greenberg adjusted the settings, turning the frequency, current and pulse up or down. Sometimes, as a setting was changed, Mario felt that peculiar wash of sadness. Then he evened out.

  Six weeks went by. Mario’s daughter Kaleigh was born. She was a textbook-perfect case of a baby; she screamed, she pooed, she drooled, her entire unregulated being was a little vortex of chaos. When Mario changed her nappy and saw the golden smear, in his heart he backed up – way up. He had cleaning compulsions after all. Over the next few months, his mood started to dip. He had a terrible time feeding the baby. Sometimes it seemed it took him so long to give her breakfast that it would be time for lunch already, and he’d have to start all over again. Perfect. It had to be perfect. The baby, strapped in the high chair, screamed, with squash all over her mouth. Wipe that up, he thought. Right away. He was better, yes, but not enough.

  Mario went back to see Greenberg. Over a span of a few months, with Mario reporting the waxing and waning of his symptoms, Greenberg eventually got the setting right. Mario began to pick up dirty things. It was, at last, okay.

  When Mario spoke about that time in his early days of recovery, tears came to his eyes. ‘It was like a miracle,’ he said. ‘I still have some OCD symptoms but way, way less. Drs Greenberg and Rasmussen saved my life. Sometimes they travel to conferences together on the same plane. I tell them not to do it. It makes me very nervous. Who would adjust me if the plane went down? No one else in this country knows how to do it. It’s like the president and the vice president travelling together.’

  The hopes of implant makers, like Minneapolis-based Medtronic, the first developer of the neural electrodes, are as big as the market they imagine. They forecast a day when neural implants will treat a wide variety of psychiatric problems, from eating disorders to substance abuse to schizophrenia. Yet as these devices proliferate, so too will the ethical twisters that swirl around them. Can a severely mentally ill patient provide informed consent? Whose head is it, after all? By directly manipulating the brain, might we turn ourselves into white appliance technicians, programming speed cycles and rinses? Could it be possible to actually control the content of another person’s thinking, as opposed to merely his or her affective states? And setting aside these sci-fi concerns, should doctors wade into apparently healthy brain tissue when they have yet to precisely locate mental pathology?

  It isn’t just critics of the procedure who worry. Even advocates of brain implants concede that the ethical issues can be thorny. At that same 2004 meeting, Cosgrove, who believes the procedure holds great promise, acknowledged the dilemmas, such as there being no possibility of large-scale, placebo-blind trials. ‘We don’t understand how deep brain stimulation works,’ he admitted. ‘We are not clear what the optimal targets are. We don’t even know what the optimal stimulation parameters are, and we don’t know what the long-term effects are . . . It’s not as simple as we make it out to be.’

  And beyond all of these questions, some critics worry that rather than curing problems antidepressants have been unable to address, the implant industry could simply duplicate the problems that have scandalised the pharmaceutical world. Despite the extremely cautious way neurosurgeons and psychiatrists are going about using the implants in the treatment of anxiety and depression, and despite their impressive results, fears continue to hover that deep brain stimulation could fall into the hands of the state, or overworked prison systems, and be used as a management device. After all, both of these things nearly did happen in the last century. ‘It’s easy for any good neurosurgeon to do this now,’ Cosgrove himself pointed out. ‘That’s the dangerous part – it’s easy.’ And if it’s easy, what will stop neurosurgeons both mercenary and curious from performing these operations on people clamouring for relief? How long until implants are used to treat milder forms of mental illness? To take this one inevitable step further, what will stop people from pursuing implants for augmentation purposes? Cosgrove described one patient, for instance, who became more creative after implantation. We’ve heard much of this before, in the great ‘Prozac: better than well’ debate, but twenty-five years after Peter Kramer’s influential book, people do not seem better than well. The promise of fluoxetine has faded. Chances are that neural implants may prove to be every bit as disappointing.

  For Mario Della Grotta, however, it was simple. ‘I’ve had a hard life,’ he said. ‘My parents got divorced. My father died. I broke my foot. I have OCD.’ He paused. ‘But’, he said, ‘I have been helped.’

  Back in 1958, Swedish surgeon Åke Senning installed the world’s first implantable cardiac pacemaker, which made some people nervous. The first patient, then forty-three, went on to live a further forty years, and now, pacemakers, like open-heart surgery and organ transplants, are, if not common, at least not unusual. Perhaps there will come a time when neural prosthetics will seem just as banal, when we will view the brain and its surgical manipulations without awe and hand-wringing. And yet the scary potential exists for a surgeon to acutely and immediately make memories evaporate, dreams rise, fingers freeze, hope sputter. For while it’s true that we are not entirely our kidneys, we do live entirely within the circle of our skull.

  For Mario, this was all armchair philosophising, irrelevant to his situation. ‘I don’t care what it means,’ he said
. ‘I care that I’m better. I’m not all better, but I’m better.’ So much better that eventually he would let the batteries to his implants run down on occasion, though whether this indicated a deep brain stimulation cure or just an obsessive-compulsive disorder remission, Greenberg said, it was far too soon to tell.

  Either way, Mario was proud of his progress after the procedure. His wife had given birth to their second child in the intervening years. He carried with him pictures of his young daughter, a beautiful girl. She and Mario used to play ‘tent’ in the morning, climbing under the quilts, where he showed her shadow puppets. A flying bird. A crawling spider. This is the chapel, this is the steeple, open it up and here are the people. While his wife showered and water hit the walls with a sound like static and cars roared outside on the roads, under the quilted tent, so close to his daughter, Mario could hear her breathe. He was not afraid to hold her hand. Some might say that Mario, with his implants, agreed to a strange sort of bondage, but he didn’t think so. He would say he had been freed enough to love.

  Epilogue

  Where We’re Headed

  It all depends on whom you ask. Jeffrey A. Lieberman touts a psychiatry that has finally become truly scientific, a psychiatry that has unfettered itself from the shackles of Freud, whose theories were rooted in pure conjecture, and is embracing high-tech tools that put the profession on par with other medical subspecialties. We’re seeing a psychiatry hitched to PET scans and fMRIs, machines that allow doctors to peer beyond the bony casement of the skull, catching glimpses into memory, into speech, into fear, into love. The psychiatry of the future will use these tools, and others, to become ever more intimate with our minds, and will be practised by doctors with the ability to saw open the scalp and place tiny electrodes powered by battery packs into regions of the brain that may be responsible for our mental distress.

  The brain is cunningly complex, with more neuronal connections, some say, than there are stars in the Milky Way, making it one of the most intricate pieces of architecture in the known universe. How, then, will we ever truly master it? Can the brain understand the brain, or do we need a higher intelligence to interpret our grey matter? And what would that higher intelligence be? Some sort of supercomputer with enough bandwidth and RAM and processing speed to outwit us as it interprets us, explaining, finally, the aetiology of the disorders that cause chaos in our lives, disorders about which current-day psychiatry still knows so little?

  What, for instance, causes schizophrenia? How durable is the dopamine hypothesis, and what does it mean that when it comes to schizophrenics, drugs which dampen dopamine seem to diminish hallucinations and drugs that increase dopamine appear to make schizophrenic symptoms worse, even though, when researchers compare dopamine levels in so-called normal subjects with those in schizophrenic subjects, they find no correlation between high dopamine levels and psychiatric problems in the general population? Perhaps more compellingly, the low-serotonin story suffers the same fate. We have been told that depression and obsessive-compulsive disorder are the result of too little serotonin in the brain, and that this is the reason why serotonin-boosting drugs such as fluoxetine work. But some depressed people have a lot of serotonin while some well-adjusted people have less.

  The psychiatry of the future would be able to address these phenomena. The psychiatry of the future, an ideal psychiatry that exists perhaps only in my mind, would finally be able to point to some lesion, some spurt, some crooked molecule or cracked neural pathway amenable to repair by tonic or surgery or even just by exercise. The cure itself matters less to me than the knowledge of the aetiology, a psychiatry in which disorders can finally become diseases attached to tissue samples, blood in a test tube, the delicate cells that live in the lining of our cheeks. Perhaps the psychiatry of the future would have a good enough handle on genes to predict with satisfying accuracy who was in for what sort of trouble on the basis of his or her DNA.

  Almost a century ago, in the early 1930s, neurosurgeon Wilder Penfield opened up the skull of his epileptic patient and touched the patient’s brain with a probe. Despite the fact that the patient’s skull was sawed open like a pumpkin, the top cut off in a circle, the patient was awake and alert. Penfield moved the probe around to different parts of the brain. When he touched the motor cortex, his patient’s toes curled up, and when he tickled the speech centre, the patient began to babble. He was able to stimulate memories of sights, sounds and smells. Imagine, under Penfield’s ministrations, a patient weeping while recalling a low stone wall, or, as he moved his probe to the left, aching with anger. This was one of the first demonstrations of brain specificity, proof that this roughly 1.4-kilogram (3-pound) organ is a series of regions, each one responsible for different things, all of them linked together in a stunningly elaborate network. Laughter lives in some spot in our brain. Memory is tricky and notoriously unreliable, but it has its physical place too. Memories hide in the hippocampus and then get uploaded for long-term storage as if to a friable file cabinet corroded by rust and holes. The psychiatry of the future should fully understand these places, and know how a short-term recollection graduates to a memory so meaningful and solid that it can survive the ravages of Alzheimer’s.

  But right now this is all a dream. While some, like Lieberman, feel they are part of a rejuvenated profession that has sloughed off Freud and solidly stepped into science, other psychiatrists, such as Daniel Carlat, who discusses how psychiatrists can be paid to push certain psychotropics, question why psychiatrists should even go to medical school, seeing as most of what they actually do is prescribe drugs they don’t understand in fifteen-minute sessions. Indeed, in the future, psychiatry might become diffuse, giving up its status consciousness, as we might be getting our drugs not only from psychopharmacologists but also from psychologists, some of whom already have prescribing privileges in several states in the United States. Besides, any honest psychopharmacologist will tell you that when he or she prescribes, it’s largely a guessing game – could be escitalopram or could be citalopram; there are fluoxetine doctors and then there are those who prefer paroxetine as their first response to fear or despair. And since there are plenty of patients to go around, if prescribing drugs remains a guessing game, it seems there is no good reason not to let others in on it.

  I’m a psychologist by training, but I’d rather not have prescribing privileges in the future, even though that might be good for my bank account. The fact is, if I were to get prescribing privileges, psychiatry would have failed its mission as a science and, more importantly, as a medical science. I’d rather see psychiatry come up with a few theories that finally pan out, theories that illuminate the pathophysiology or aetiology of depression, the structure of schizophrenia, the reason for the retreat that autism so often is. The field has a history of practitioners who have developed theories, some of them quite compelling, but they have all proved to be wrong, or misguided, or not quite enough.

  There was, for instance, the monoamine theory of depression which I discussed earlier – the idea that depression is the result of a deficit of monoamines, which are neurotransmitters such as dopamine, epinephrine, noradrenaline, and serotonin. But the monoamine hypothesis did not survive as a theory for at least three reasons. First of all, drugs that raise levels of monoamines in the human brain do so immediately, and yet their effects can take six to eight weeks before becoming apparent in a patient, a discrepancy for which the hypothesis has never been able to adequately account. Beyond that, the monoamine hypothesis fails to explain why some antidepressants, such as the tricyclic iprindole, have had success despite the fact that they do not raise the levels of any of the brain’s monoamines. Finally, once fluoxetine and its chemical cousins were released, the monoamine hypothesis was replaced with the somewhat simpler serotonin hypothesis, which posits that depression and obsessive-compulsive disorder are the result of low levels of this single neurotransmitter. And yet the serotonin hypothesis suffers from the same weaknesses as the monoamine hypothesis,
namely, that it too cannot adequately explain why the drug raises serotonin immediately and yet it can take the patient sometimes as long as eight weeks to feel better. Nor can it explain why not all depressed people have low serotonin when the neurotransmitter is measured in cerebrospinal fluid.

  Lacking blood, tissue, or cells, psychiatry has had no choice but to retreat into pure description. Because the field cannot hold up a test tube of blood and find within it, say, the virus or low levels of a neurotransmitter that cause despair or delusions, it has instead relied solely on symptoms, absent any known cause. Groups of psychiatrists are constantly working to delineate the symptoms of various mental illnesses, and their work is recorded in the Diagnostic and Statistical Manual of Mental Disorders. The first DSM, published in 1952, was full of psychoanalytic language, neurotic nail-biting patients labelled as, say, reactive depressives, in concert with the dominant view of the day. Since 1952 there have been multiple iterations of the DSM, about once a decade, give or take, with diagnoses appearing, disappearing and transforming. The result is a slippery sort of manual. Theodore Millon, the founding editor of the Journal of Personality Disorders and one of the members of the committee charged with assembling the third DSM, published in 1980, admitted that ‘the amount of good, solid science upon which we were making our decisions was pretty modest’. It wasn’t that there was no research whatsoever, but rather that it was, in Millon’s words, ‘a hodgepodge – scattered, inconsistent and ambiguous.’