The Drugs That Changed Our Minds

by Lauren Slater

  Can Lithium Cure Depression?

  Over the next several years Schou continued to experiment with lithium, and by 1959 he was able to report that he had treated in total 167 manic-depressive patients with the drug and that 77 per cent of them had significantly improved. Meanwhile, scientists in other countries were beginning to take note, as Cade’s paper combined with Schou’s research finally began having an effect. In France there were two reports of thirty-five patients treated with lithium, with an 86 per cent improvement rate. In England researchers treated thirty-seven patients and got a 92 per cent improvement rate. Ten years after Cade’s paper was originally published, there were records on 718 manic patients treated with lithium, and 64 per cent of them, according to their doctors, had shown ‘discernable improvement’.

  One day, in reviewing his records, Schou noted that one man had responded to lithium with a reduction not only in his manic episodes but in his depressive episodes as well. (Cade had found that lithium did not help lift depressions once they were started, while Schou hypothesised that lithium might work prophylactically, preventing a depression from occurring in the first place.) This set Schou to thinking. Might lithium be an effective prophylaxis against the depressive cycle in bipolar disorder? Mania and depression, after all, in true bipolar disorder, are hitched at the hip, one following the other with real regularity and, in doing so, suggesting that, although depression and mania might be ‘symptomatically different’, they also might share a common source or substrate. And if this in fact was the case, then was it not also reasonable to hypothesise that lithium would be an effective agent in treating each of the polarised mood states that constitute manic depression?

  Here is where Poul Christian Baastrup, a fellow Dane who had read Schou’s studies, enters the picture. In 1957 Baastrup carried out his own clinical trial at the state hospital in Vordingborg and found the same thing all the other researchers had found, namely, that lithium dampened, if not destroyed, manic excitation. As part of his trial he conducted follow-up examinations on discharged patients, all of whom had been ordered to cease taking lithium because Baastrup wanted to determine whether lithium might cause late and undesired side effects. ‘The result’, wrote Baastrup, ‘was hair-raising’. A number of study participants had not listened to him. Instead, ‘eight patients, all with a bipolar course, had continued to take lithium and two of them had even bestowed these “miracle pills” upon manic-depressive relatives. None of these people had had any kind of check-up, of course. Their reason for continuing the treatment in spite of our agreement was consistent: all of them said that continuous lithium treatment prevented psychotic relapse.’

  Baastrup went on to do a retrospective study of patients on lithium in order to examine more closely whether the drug really did have a prophylactic effect on manic and depressive psychoses. He looked back over the three years during which his patients had been on lithium and compared their rates of relapse during this time to their rates of relapse when they had not been on lithium. When he published his results several years later, in 1964, the evidence was compelling. Lithium, according to Baastrup’s findings, did indeed prevent recurrences of depressive episodes in patients suffering from bipolar disorder.

  Meanwhile, Geoffrey P. Hartigan, a psychiatrist working around the same time at St Augustine’s Hospital in Canterbury, England, gave lithium to twenty of his patients, most of them with chronic or intermittent manic episodes, except for a group of seven who suffered from recurrent depression only. Five of these seven, once started on lithium treatment, did not merely recover from their current depression but ceased having recurrences altogether. Hartigan did not publish his results, but he spoke about them at a meeting in 1959. While admitting there wasn’t much in the published studies that was encouraging about lithium’s chances of improving depressive syndromes, and cautioning against its use during an acute depressive episode, he nevertheless gave vivid accounts of five patients’ struggles and successes.

  The first, a man of forty-seven, had always been ineffectual and unassertive, a pale-as-plaster type with a timid and banal disposition, ‘subject to spells of depression’. He occasionally attended therapy, drifting in and out of treatment, and, when his condition really worsened, submitted to courses of electroconvulsive shock. The current and concomitant seizure would relieve his mood for short periods of time, after which the dark dogs returned, again and again, and the patient found himself plodding along in an anaemic and desultory manner, his spirits sinking lower and lower each time a new bout took hold. At one point during this dreary existence, his mother and father both died within a month of each other and his symptoms became still more serious. He was admitted to the hospital, where Hartigan and the nursing staff persuaded him to try the lithium and to take it on a regular basis. ‘He is now on a maintenance dose’, Hartigan noted, ‘and has remained symptom-free for the last eighteen months. His wife reports that during this period he has shown more self-confidence than ever before.’

  Hartigan also reported on the graver case of a forty-eight-year-old man whose father had committed suicide and whose mother suffered from a ‘nervous illness’ of an unknown nature. In 1929 this man had tried to kill himself by slitting open his own throat with a pair of scissors. He was hospitalised and recovered from that depression, stayed well for many years, and then, in 1949, relapsed into a severe depressive episode which led to his rehospitalisation, whereupon he received thirteen electroshock treatments. These seemed to straighten him out, and he was discharged, only to fall back into blackness five months later, when he was once again readmitted as an inpatient. This time around he underwent twelve more electroshock treatments, without success, until, in the summer of 1950, he submitted to the scalpel that severed the fibres of his brain: a prefrontal leucotomy. Even this extreme measure, however, did not bring this man peace of mind; he continued to fall back into states of dread and despair, necessitating many psychiatric hospital admissions.

  It was during one of these admissions, in 1958, that Hartigan introduced him to lithium carbonate. The man developed, as a result of the drug, a tremor in his hands and a facial tic, but both patient and doctor stayed the course, lowering the dose and waiting to see what would happen. Over time, the tremors faded and the tic went away. Eventually the man was discharged from the hospital and he returned to work. Despite the severity of both his depressions and the types of treatment he had sought, Hartigan wrote that he stabilised and ‘has kept very well since and says that he feels better now than he has for a long time. His present cheerful appearance at out-patients contrasts markedly with his former apprehensive and crestfallen demeanour.’

  Schou heard about Hartigan’s work from Hartigan himself, who wrote to Schou and subsequently sent him a copy of the talk he had given. Schou urged Hartigan to convert the speech into a publishable paper, but Hartigan, by nature a shy and self-effacing man, was hesitant. In 1961 Schou wrote to Hartigan to ask if he had any further clinical data. ‘I am asking about this not only out of interest in the use of lithium in psychiatry’, Schou confessed, ‘but also because one of my brothers has been suffering from depressions that recur with great regularity.’ Hartigan was sympathetic, but the revelation would later be used by others against Schou in a malicious way.

  In fact what Schou had written to Hartigan was something of an understatement. Schou’s younger brother was more or less decimated by the regular recurrence of his black moods. Schou eventually medicated his brother with lithium, and the results were dramatic, giving the man a whole new way to live a life that had previously been stunted by melancholy. Suddenly, the periodic depressions that had so plagued Schou’s brother vanished. He was able to be reliable in ways that before had been impossible for him. In 1981, when Schou received an honorary degree from Aix-Marseille University, he described what his brother’s depression and its disappearance had been like:

  From the age of twenty he suffered from repeated attacks of depression, which periodically made him unable,
in spite of high intelligence, to carry out his chosen profession. The attacks usually lasted some months, and then disappeared, but they reappeared again and again, year after year, inevitably. Then, about fourteen years ago, he was started on a maintenance treatment with lithium, and since then he has not had a single depressive relapse. He still needs to take the medication to keep the disease under control, but functionally he is a cured man. You will understand what such a change meant to himself and to his wife and children, and how much of a miracle it appeared to us in the family. Fear of the future has been replaced by confidence and new hope.

  A Promising Prescription

  I have a recurrent nightmare, very simple, very stark. I dream of depression. I dream of a black hat rolling across a dark road, of a girl turning to sugar and swirling away. I dream I am hunched in a rocket roaring across space. Sometimes the images jumble. Ants are everywhere. Fish fly. Things snap. A whip. A wand. A whisper.

  Once every night I dream these dreams. My sheets are wet with sweat. I dream my dreams summer, autumn, winter and spring. And always when I awaken it is with a sense of a great and grateful relief tinged with dread because I know what lies in store for me, somewhere down the line. Ever since the age of ten I have been regularly felled and then regularly resurrected, but the resurrection does not dilute the dread. Depression is so many things, but for me, primarily, it is the loss of love – my people falling away – and the loss of language, my words dwindling so low that my thought seems to move without rhythm or reason.

  I had been on lithium before and hadn’t found it helpful. The drug had never relieved my depressions or stabilised my mood. Furthermore, the white salt caused a tremor in my hands – just as with Hartigan’s patient – a very slight, almost imperceptible tremble that became apparent only in my handwriting, which got shaky under the influence of the drug. The tablets are huge, fat white oblongs that leave in the throat the feeling of having swallowed a stone. Prescribed to me not as an anti-manic agent but rather as an adjunct to my antidepressant – a little step stool, so to speak, allowing fluoxetine to more easily influence my neurotransmitters, specifically serotonin – lithium turned out to be a dud. The effects of my SSRI were exactly the same whether ‘lifted’ by lithium or not. I must confess, however, that I never stayed on lithium long enough for it to really work. I disliked the tremble in my hand, the way words slipped sideways on the page, my sentences resembling ones composed by a nursery school child, tipping downwards and skating off the paper.

  My doctor’s surgery is in the cellar of one of the buildings at McLean, the large mental hospital in genteel Belmont, Massachusetts. Once a month, for the past thirty years, I have been coming to this old private asylum known for the famous people it has housed – Sylvia Plath, Anne Sexton, Robert Lowell, to name a few. The buildings, mostly red brick, are bearded with ivy, the paths between them pebbled, with fountains burbling and birds’ nests spilling from the rafters of gracious entryways where ancient corbels hold up cresting roofs. It feels less like an asylum than a university campus, and the only sign it is the former is the occasional patient in a stained shirt walking aimlessly and mumbling to the voices in his head.

  A rickety lift takes me down to the bowels of the building holding my doctor’s surgery, and I step out into a long hall painted a dirty beige, with a complex mesh of leaking pipes overhead, their corroded copper gone green, the water pooling in small puddles on the concrete floor or dripping into plastic buckets the caretakers have set out. The closed blank doors lining either side of the hall, with no names or numbers or anything else to identify them, can appear a little magical. Often I imagine they open on to rooms filled with old copper baths, or skulls with trepanned holes, or a science lab from another century, with dusty test tubes stored in rusty racks.

  At the end of the hall, my doctor’s door was wedged open, which meant he was expecting me. He is a funny, frumpy man with curls framing his face and a bald scalp, like a clown’s, except he is not scary. He wears baggy trousers and carries a rucksack bursting with books and papers and who knows what else. His office is a world I never tire of: a massive mahogany desk, papers stacked erratically in all corners of the room, a bubbling aquarium, the small half windows at ground level, so all you ever see is speckled dirt or the feet of the occasional passerby, the room dimly lit despite the long fluorescent tubing that runs the length of the water-stained ceiling.

  In his spare time, my doctor collects gems and crystals from all over the world; displayed on his shelves are huge geodes halved by blades, so you can see their swirling centres, their galaxy of specks that look like embedded stars. Gems from South America, sea-blue, deep turquoise, royal purple. A scatter of crimson pebbles that might be from Mars or the moon, strange bumpy rocks that have a haunted history – you can tell just by looking at them – rocks that were once part of meteors hurtling through the heavens, broken-off bits that fell to Earth. Because of my former manic rock obsession, I take an interest in his collection, and before we start each session we talk about his newest acquisitions, from Belize or Chile or even Antarctica, with their seemingly endless and mesmerising depths of purple or teal interiors.

  Today, however, was different. Today I was a woman on a mission. I walked into his office, breezed past his sizeable display cases, took my seat in front of his desk and crossed one leg purposefully over the other. Usually my doctor starts the session with the rote ‘How are you?’ but not this time. This time I began, catching his bright blue gaze and holding it in my own. ‘I think I should be on lithium,’ I said.

  ‘Lithium?’ he said. ‘I love lithium. Lithium is a wonderful drug.’

  ‘Why’s that?’ I asked.

  ‘Studies show’, my doctor said, ‘that lithium can stop suicidal ideation. Isn’t that something? If you have a patient in danger of killing himself, pop him on to lithium and chances are that idea will just waste away.’

  ‘I’m not in danger of killing myself,’ I said, and then related the reading I’d been doing about lithium acting as a prophylactic against recurring or periodic depressions of the sort I have.

  ‘Your Zyprexa does the same thing,’ my doctor said, referring to olanzapine as he lifted both hands to his chin, smoothing the skin there as if he were stroking an invisible beard.

  ‘It might,’ I said, but countered that with the weight gain, diabetes and dangerously high triglycerides, all serious side effects. ‘Why not lithium?’ I asked.

  ‘You’ve been on lithium before,’ he reminded me. ‘And you didn’t like it.’

  ‘I wasn’t on it for long enough. I’m willing now to really give it a go.’

  My doctor, I could tell, did not much like this idea. I asked him if he was familiar with the work of Mogens Schou, and how research from the 1950s and ’60s shows that lithium can prevent depressive recurrences, especially in those with a bipolar diagnosis, and to my surprise my doctor said no, he hadn’t heard of any such thing. Zyprexa, meanwhile, was a newer (and, the thinking goes, better) medication, and a blockbuster at that, earning for its maker, Eli Lilly, billions of dollars a year as one of the most prescribed psychotropics in an ever more obese America. Weighing in at just over 72.5 kilograms (11 stone 6 lb) at only 152 centimetres (5 ft) tall, I was another example.

  Behind me, the aquarium bubbled patiently and persistently, and I turned to look. The blue water was filled with fish floating like ghosts in and around the exotic rocks made to resemble ancient castles. The fish flickered. I reached over and sprinkled some of their food on the surface, and they all shot upwards, their mouths forming tiny o’s. The biggest and fastest fish reached the surface first. He puffed himself up and ate with gusto.

  Taking inspiration, I puffed myself up as well. ‘I think if you read the studies of Mogens Schou and Poul Christian Baastrup,’ I told my doctor, ‘you’d be convinced, as am I.’

  ‘Going off Zyprexa,’ my doctor said, ‘is no easy thing.’

  But I insisted I was willing to try. And I was. I knew ps
ychotropics could be hell to get off, but the thought of finding a drug that would reliably prevent my periodic depressions from recurring and that, unlike olanzapine, would not cause me to swell like a puffer fish, until my blood was thick with sugar and grease – that was something I was willing to fight for.

  In the end, I won. My doctor took out his pen and wrote me a prescription for Eskalith, the brand name for an extended-release form of lithium. ‘You have to go down slowly on the Zyprexa’, he advised. ‘You won’t feel well. After one week of being completely off the Zyprexa, you can start in on the lithium.’

  That night I shook a single olanzapine tablet out of its brown bottle and held it in my palm. Tiny writing embossed on the surface announced the name of its maker: Lilly. My doctor had instructed me to go down in increments of an eighth, but keen as I was to start the lithium, I ignored that injunction. I snapped the tablet smartly in half and popped it into the chute of my throat. Olanzapine is intensely sedating, and that night, with only half a dose, I had some trouble sleeping. When slumber did finally come, I dreamt of monkeys perched on balconies in a strange hot city. I woke up parched with my head full of fizz and felt unbalanced all day. The second night I broke off just a quarter of a tablet and wound up awake until dawn, the daylight a fevered pink line, like an infection, at the seam of the sky. The fact that I knew why I felt the way I did was helpful. My good mood, my balance, was all but gone and I wobbled through the world as my body tried to figure out how to function without its daily dose.

  Psychiatrists hate to admit that their drugs are no different in many senses from whatever you might buy on the street. Heroin addicts need to detox from heroin the same as olanzapine users need to detox from olanzapine. Detox is difficult – it’s a burden on the body – but I knew, if I could just get through, that waiting on the other side was another kind of medication that might be even better. On a Sunday, while the kids were out with my husband, I lay in bed and looked at the prescription my doctor had given me, and decided that I would fill it when I was down to a sixteenth of a tablet, essentially just some dust and crumbles that I’d bite off and swill down with water.