The Drugs That Changed Our Minds

by Lauren Slater

  ‘I’m sorry,’ the woman said at last, ‘but I can’t fill this for you.’

  ‘What’s wrong?’ I said. ‘It’s from my doctor.’

  ‘Your doctor’s handwriting is exceedingly difficult to read.’

  ‘It’s for lithium,’ I said, aware that everyone behind me could hear the conversation, but now I didn’t care. By this point I’d been off the olanzapine for several days. My body felt as if it had hollows that were filled with shrill chirps and sharp shards. A desperation came over me, quickly and completely, a belief that lithium alone could fill the hollows with its soothing salts. ‘Lithium,’ I said again, a little louder this time, although my voice sounded tiny, as if it were coming from some smothered place far away.

  ‘I can’t fill a prescription I cannot read,’ the pharmacist said, her lips a slender seam I wanted to reach over and rip.

  A tiny stream of sweat was trickling from the nape of my neck down my back. The line of people behind me sighed and shifted once more, as if they were a single organism moving as one. ‘I can read the prescription just fine,’ I said. ‘It says “Eskalith XR”. The “XR” stands for extended release.’

  ‘Can you read that?’ she said to me, her finger pointing to a bit of scrawl, her voice triumphant.

  ‘I can,’ I said, throwing back my shoulders. But when I looked down at the words, I saw how worthless they were, the typical script of a rushed doctor, and I sagged inside.

  ‘I’m sorry,’ the pharmacist said, ‘but I can’t make heads or tails of what’s on here, and my licence forbids me to fill a script I can’t read.’

  I left the pharmacy, stepping out into the yellow day. The people moved as if they had battery packs in their backs, everyone powered by something suspicious and inhuman. My mood was wobbly, a wall of compressed tears aching in my throat. I wanted to cry but was afraid to. After all, what else are eyes but holes in the head and who knows what might emerge? I pictured a girl with marbles sliding down her face.

  On the walk home I stopped in a woody grove and pulled a slinky pink worm from the chocolate earth, watching as he coiled in the cup of my hand, his slender body as cool as the soil he’d come from. I would take my comforts wherever I could find them: a worm, the sun-warmed wood, or the trefoil feet of a sparrow on my window ledge. When I got home, I called my psychiatrist and left a message with his answering service.

  Several hours later I was back, this time at a different pharmacy, after my doctor phoned in the prescription. I waited half an hour in an orange plastic chair and, when my name was called, paid, grabbed the bag and left. In my kitchen I took out the bottle, inside of which were jammed thirty lithium tablets, each one an orb with no score marks, just smooth and cool and fat against my cheek. I filled a glass with water, planning to wash one down, but instead, at the last minute, I dropped the tablet into my glass and watched as it dissolved, thinking, as my medicine turned from solid to bubbles, of long ago, of the lithia waters given for every ailment under the sun. It took time for the tablet to completely dissolve, but once it did, I drank it all down, cool and tangy on my tongue.

  The next morning, when I woke up, my room seemed oddly peaceful. This, I knew, was a placebo response, but I take my cures in whatever form they come to me. Downstairs the laughter of my children sounded lovely. The shadows of the trees made lace on my walls and I watched as the lace lifted and swayed, a continuous dance of dapples. I got up and then stood on my bed, the better to see out my wide windows, which looked down on to my tiered garden growing at the base of a wetland. The soil there is so packed with nutrients and so continually drenched that everything thrives, the roses in profusion, the chocolate mint spilling from level to level, sporting tall purple spires that tangle with the masses of yellow asters and the spiky pink bee balm and the butterfly bushes’ long branches topped with mounds of tiny pink flowers that attract the monarchs and the moths I could see right now. Huge orange butterflies were landing on the plants, their wings flexing as they drank, butterflies as big as books, it seemed, the pages of their wings opened to black dots and zigzags of gold. The moths were much plainer but beautiful in their alabaster flights. I had seeded this land and tilled it and cultivated it and coaxed from its willing soil every bush and flower below me.

  Lithium takes at least a week to build up in the blood. One swig from a glass won’t buy you your prophylaxis; the drug needs to accrue in the body. So the day after that first dose I could confidently claim my sudden spurt of joy as my own. For the next seven days I walked around tentatively, almost on tiptoes, with one ear cocked to my innards, as if listening for some click to tell me my medication would work. I was happy when I noticed a fine slight tremor in my hand, a sign that the drug was present and that it might provide me with a portal out of olanzapine. I worried not at all about lithium poisoning; I knew to get my blood levels checked once a month. More days passed. Two weeks became three. July had rounded the bend into August, which then became September. The evenings took on cooler currents and the stars seemed defined against the black backdrop of sky, each one a speck of precious salt. The kids and I took the telescope out on to the deck and peered through its lens. I had traded one of the most popular mood stabilisers psychiatry has to offer – the highly profitable olanzapine – for an old standby whose workings were mysterious. John Cade’s earliest hypothesis is still as good as any – that lithium works because those with manic depression have a dearth of lithium ions in the body.

  Sure enough, as the weeks passed, my mood evened out, the ground glass in my hollows went away and was replaced by a certain silky softness. Not much bothered me, but neither was I numb. There is nothing as precious as the recession of mental illness, which leaves in its wake a gorgeous clarity. The dividends of darkness, I call it. Every day when I am even is a blessed day, a banquet day, the long table set with an array of colours, the white cloth as bright as a sail walking on water. With lithium, my bones returned. My hands, no longer wrapped in fat, displayed a certain elegance, and so I wore a ring with a simple white moonstone on it. The sugar left my bloodstream, and after four weeks off olanzapine, my GP told me I was on my way to becoming non-diabetic. But it was still too early to know for sure whether lithium would work for me in the long term, whether it would do for me what it had done for Schou’s brother and for many of his patients, too – which is to prevent recurrent depressions from returning while also keeping me from mania.

  No Profit to Be Made

  Mogens Schou died in 2005. Aside from Cade, he was probably lithium’s fiercest champion. In fact, when the drug began to receive approval for psychiatric use around the world, Cade himself credited Schou as ‘the person who had done the most to achieve this recognition’ for lithium. Schou saw it cure countless patients and save his brother. Unlike drug researchers of today, at least some of whom are motivated by profit, Schou, and Cade before him, had a purity about their pursuits. Despite Shepherd’s accusation, these men knew that lithium would never make them rich. It existed as a natural element first found on the rocky island of Utö, and was thus available for free. Yet they dedicated their lives to it anyway. What they saw in the drug was a powerful treatment for a devastating disorder, a capsule that raised some of psychiatry’s most fascinating questions. Unlike chlorpromazine, lithium appears to act with unusual specificity, eradicating manic excitement while leaving other symptoms untouched. Schizophrenics who take it calm down, but their hallucinations and delusions continue unabated. According to Erik Strömgren, the Danish psychiatrist who had first suggested the compound to Schou, lithium, because it is chemically so simple, provides a potential lens into the neurocircuitry of mood much more effectively than the ‘therapeutic effects of complicated compounds which had no clear preference with regard to the different disorders they were used for’.

  Given lithium’s specificity, one would think it would be a highly studied drug, that researchers would be probing the patients who take it in an attempt to understand what regions of the brain it affe
cts, how it dampens or excites neurotransmission signalling, all in an attempt to better understand the extremes of human emotion – mania and despair – which, once grasped, once marked and mapped, might also shed light on their more common cousins: sadness and happiness, grief and joy. But, oddly, few scientists have spent much time looking through lithium to the brain beneath, trying to grasp the hows and whys of the drug’s machinery and the delicate dance it does in the human head. ‘It’s done a lot for psychiatry, without question,’ said Alexander Vuckovic. ‘But it has never really excited neuroscientists, because there’s no profit in it, no money to be made.’

  Perhaps better than any other drug, lithium reveals the extent to which psychiatry is tightly tied to capitalistic corporate interests, how closely allied the field is with the major pharmaceutical houses, where millions, even billions of dollars are made in mere months. This is why, although lithium had worked so well for so many people, drug developers set about discovering new mood stabilisers that had patent and profit possibilities, whipping up in their high-tech cauldrons scores of new pharmaceuticals to treat bipolar disorder or, better yet, converting already existing medications – drugs, say, for epilepsy – into treatments.

  The pharmaceutical company Abbott Laboratories, in 1983, obtained a licence for a drug called valproate, which was an anticonvulsant. Abbott then twice successfully applied for a patent to make valproate semisodium, a more stable sodium. This new compound differed from its predecessor, valproate, by just one sodium ion, and so, according to David Healy, it was ‘as good a symbol of the vacuity of current patent law as any’. The next step occurred when psychiatrist Harrison Pope and his colleagues completed a study which showed that valproate semisodium was an effective treatment for mania, an outcome that guaranteed Abbott financial success.

  The Abbott example is but one of many. Numerous anticonvulsants – drugs used to treat epilepsy – were repurposed in the 1980s and ’90s as drugs to treat manic depression, now known as bipolar disorder. This came about when doctors became aware that a drug called carbamazepine could suppress seizures kindled by the amygdala, a part of the brain’s limbic system that detects fear. Psychiatrists then went on to study carbamazepine in mania and found it effective. Perhaps, psychiatrists thought, mood disorders could be seen as a kind of psychological convulsant, as if the bipolar brain was flipping from despair to euphoria in a kind of seizure-esque way.

  Once bipolar disorder was refashioned as a convulsive equivalent, all sorts of drugs previously used only for epilepsy became not just possible but relevant, and pharmaceutical houses, smelling potential profit in this new paradigm, began offering up their antiepileptics with new labels hastily applied to the bottle. The term ‘mood stabiliser’ came into wide use around this time, and drugs that before had been confined only to treating epilepsy now saw a broader and more profitable purpose. One of these, gabapentin, grossed $1.3 billion a year once it became a mood stabiliser. This new class of drugs seized the field and went some way towards eradicating the use of lithium, to the point where, in the 1990s, newly minted psychiatrists going through or just emerging from their residencies usually had far less experience with lithium than they did with anticonvulsants – this despite the fact that there existed no evidence that the ‘new’ mood stabilisers worked any better than lithium did. More significantly, there was virtually no evidence that bipolar disorder actually was the moody equivalent of epilepsy. It was simply one possibility, one model, but it created the paradigm that justified the newfound ‘mania’ for anticonvulsants, especially in the United States.

  The Magic Fades

  On lithium, I no longer dreamt of depression returning. I was, literally, lighter than before, when I had been weighed down by olanzapine’s side effects. I would not go so far as to say I was cured of my cycling moods; there were days here and there when I could sense a slippage, a sudden slit in the air and a sense of dropping down. I tried not to flail as I fell, because experience has shown me that only makes it worse. I have learned how to still myself as I tumble through that rent and go down, down, to an empty beach below, with black rocks jutting up, seagulls screaming, bloated boats overturned and the carcasses of crabs on the sand. I don’t want to land there, and after starting lithium I didn’t, although there were days I came so close I could feel the sand skim the soles of my feet, could smell the salt in the rotten air and the matted tangles of seaweed decomposing in the dampness, could hear the scuttle of some bug as it made its way towards the waves, with a lone lighthouse off in the fog, its single beam too anaemic to pierce the muffled mist.

  In the long run, however, despite my expectations, the drug did not work as well as I had hoped. Sometime that winter, to my dismay, when the skies were darkening in the afternoon, when light leaked out and disappeared, when the wind bit into the back of my neck, my depression returned and, frightened, I reached for my olanzapine, trading my body for my mind. For many people, though, lithium, that salt from a stone, is enough, is in fact all they need. I envy them. And when Alexander Vuckovic said, ‘I use lithium with many of my depressed patients and I’ve found it to be as effective as an antidepressant as it is for bipolar disorder’, I wish I were one of the ones he is talking about.

  I don’t think there exists any drug that can totally seal the ruptures I so often sense around me. But sometimes I wonder: do I even want a drug that could set me solid on some shelf, where I could pose, all pretty? Perhaps there is a part of me that likes my madness, in measured drips, the dreams of rocks and black hats and girls of swirling sugar. Perhaps I like my drugs too. Perhaps I like the act of taking them, which I did each evening, always dropping the fat lithium tablet into a tall glass of cool water, watching as it bubbled white and frothy, like some kind of magical concoction. In the moments after I’d swallowed it, a syrupy lethargy came over me, a lethargy not unlike the one Cade observed in his guinea pigs, a lethargy that was almost enough to induce bromide dreams of springs and spas, of bottled waters we once believed in, of vast salt plains dazzling in the strong sunlight.

  3

  Early Antidepressants

  The Three-Ringed Molecule and the Psychic Energiser

  The Beginning

  No, I don’t know when it started. I could have been ten, or two. I could have been unborn, a fleck and then a foetus with the haze of my new heart visible beneath translucent skin. When does the brain first form? It could have started then, whenever that is, or it could have been that God, if you believe in him, accidentally nicked my corrugated cortex with his silver chisel, and from that dent darkness poured and poured until I was covered in it, complete. I don’t know how I was held in my earliest days, or even if I was held, although my mother has told me that, as an infant, I cried so wretchedly, so continuously, that she put me in a wind-up swing and let me scream as I careened back and forth. Unable to be comforted, I was not, as they say, an easy baby. So perhaps it started when I started, and has been with me ever since. I’m speaking of depression – the night without a moon.

  I remember a stifling day, when I was six or seven, in a dead-quiet July, the roses on their stalks brown balls of burn, the street almost fluorescent with light from a white-hot sun in a white sky, the gardens gone limp and the trees shifting with the barest hint of a breeze. My older sister and I were sitting outside on the steps, two little girls in pinafores and Mary Janes, our white ankle socks edged with frills. We were going somewhere special, although now, at the age of fifty-four, I cannot recall where. What I recall is the heat, heat, heat and the black tarmac on the road turning taffy-soft and my skin beginning to crisp. I recall seeing, from the steps, far down the road, a figure coming towards us, his outline resolving as the distance diminished, a man dressed in a dark suit with his jacket buttoned up and fastened by two golden pins glaring in the summer day. His face perspired heavily as he knelt by my sister and me and asked if we would like to see his monkey dance. He was so close I could smell his cinder breath and then I saw his hand, or rather his la
ck of a hand, how one empty cuff just hung down, the skin at the knob of his bony wrist marbled and seamed. A monkey, a little creature with fur the colour of driftwood and a tiny triangular hat on his tiny head, leapt from I know not where and began to jig on the smoking pavement. Then the man sang and the monkey danced to the sound of the song and my sister laughed and laughed. But I felt horrified – by this man, this monkey, this absent hand, this heat everywhere over me and in me as the creature shimmied and spun. I can’t recall the song the man sang or how it ended, only that he and his monkey were there one moment and gone the next, seemingly sucked up into the sky by the enormous force of the golden heat, or the crooked magic of midsummer itself.

  That night I dreamt I was trying to call someone but despite looking everywhere could not find my hand and thus could not complete the call. I woke up, drank from a paper cup by my bedside, the water warm, the cup damp and close to collapsing. I fell back asleep and when I awoke again the night was gone and my room was filled with a blinding whiteness that obliterated everything. It was the whiteness of a blizzard except the air was heavy with heat and when I tried to call for help my voice got lost in the particles, fine as flour, that had dusted everything out of existence. I lay awake, alarmed, surrounded by a terrible dazzle and unable to speak or move. How or why it ended I do not know, but somehow, eventually, the regular world resumed its rightful place and my bedroom furniture came back into being and my body came back into being and I held up my hands – two of them, ten fingers, each one working and complete. Something, however, was wrong. There was a weight in my limbs, a stone in my stomach. I looked out my window, afraid the monkey man might return. But very early in the morning the streets were empty and quiet except for Mr Slotnick in his back garden, cleaning his pool with a large net filled with green and gleaming leaves.