The essence of the experience of taking Prozac was for me a freeing-up of my mind, a loosening of the rigid bonds that kept my thoughts and actions tightly tied, though that change was mediated by extreme tiredness, weakness, and a sense of profound disconnection from myself. I’ll outline in the second half of this post reasons to suspect that the placebo effect may have played a large role in my experience of taking the drug, and I do think that the simple fact of having started taking medication, in acknowledgement of my illness and the need to do something about it (even if not eat more, yet), was a critical factor in making the foundations of my anorexia begin to shift. Another factor that may have played a significant role in the changes that occurred was setting off on a family holiday to a Greek island three days after I took the first pills, though I’d been there often before and remained as ill as ever, unlike this time.
Part of that shift away from the depths of illness was the simple, crucial fact of just eating more. On the first evening in Greece, I ate more unplanned, unfamiliar foods than I had for years, and I felt the fear of wanting to eat more, along with exhilaration at the potential for fundamental change and conviction of the inevitable dead-end waiting for me otherwise:
‘Slept briefly but deliciously, got up to lie by pool then drink tawny port, walked to sunset restaurant with S. [my mother], tried the salmon mousse & the sea bream, & ordered expensive wine of which I also drank lots – & a fragment of bread – & felt a moment of terrifying longing just to be eating S.’s whole fish, & coming home & going to bed. But then told her some of the week’s events […]; how things are converging. I feel I’m failing for not doing more – but fish x 2, + alcohol, + bread, is something. […] So much in that book [Overcoming Anorexia Nervosa, by Christopher Freeman] rang – rings – true. In both the reasons for changing & the reasons I feel I can’t. […] If I don’t [seize this constellation of circumstances] I probably never will change anything. It’ll probably always be like this. Only narrower & narrower. I feel that everywhere, in everything, now. Even the agonies of getting here – the terror as my bag failed to appear on the carousel, beginning to contemplate doing without all my food. My eyes are dizzy now. […] I went out to the pool & thought how terribly lucky I am to have a family that will let me come here, will tolerate me. […] I wonder what the hell my poor body really makes of all this.’
Those small additions to my daily diet – little bits of bread and fish and wine – were momentous to me, and they made a difference to my family too: ‘[I was] frightened at delighting in all that, & craving more, even while hating the uncertainty of accepting as opposed to denial’s pure simplicity. But S.’s sadness as she told the [restaurant] owner that I “live on air”, & her shrug of the shoulders, made me persist; she said yesterday how it does feel very different, even just bread, as opposed to only wine – there being something on a plate, getting smaller.’
Another interesting thing that happened very quickly was that my ecstatic night-time eating became distinctly less ecstatic. That could have been the heat and the change in ingredients, but I’d been on holiday many times before without it happening, and it was as frightening to me as anything else: ‘3:57 a.m. It was nice, but not all-encompassingly, mind-weakeningly so as at home. Maybe it’s just everything messed up in time & temperature – or is the magic really waning?’ ‘2:55 a.m. I don’t know how much it’s the food itself, how much the temperature, how much myself, my mood or attitudes or what – but it just isn’t nice in the way it is at home – not nice at all, mostly. Let alone fabulous. Rather a dull chore, it feels, working through lettuce & salted cucumber.’ ‘3:56 a.m. [The ice cream] was lovely – creamy, cool, crunchy. But nothing quite delights as it did.’
The physical side-effects were quite frightening at first: the day after ingesting those first coloured capsules, I wrote of how ‘Today has been really terrifying. Dizziness, weakness, mental distance & confusion. I really didn’t know whether I could – or should try to – manage my ride; all the way I felt nervous about the next little hill. Just walking has been hard. Decision-making has been terrifying.’ I wanted to stop taking them, and I blamed them for physical clumsiness I’d never had before: ‘Oh, my body rebels against three more of those pills. 4:19 a.m. I feel a bit better, but not as wholly as food usually makes me – & much of it tasted oddly bitter. […] I realize how wrong something is with me, everything: just upturned my whole bowl of All Bran. Thank God it was dry, thank God it wasn’t yesterday’s muesli with yoghurt; & I think I’ve retrieved most of it. But all is not well. I’ve never done anything like it before – just turned, moved my arm, absolutely without looking. Anyway, ten minutes’ sleep lost. But little more than that, I hope. Except confidence.’ When everything’s as fragile as anorexia makes it, even upturning a bowl of cereal could be the cause of feverish anger and misery, so this was just one way in which the drugs, or the placebo effect, forced me to acknowledge that things couldn’t remain as they were.
The general mental loosening-up manifested itself as a softening almost to jelly of both my rigid mind and my wasted muscles: ‘A frightening day in so many conflicting directions. Fear at the mental flaccidness […]. And then eating a bit, again, of [S’s] chocolate & biscuit sandwich – both bits today, not just biscuit. Frightened at feeling so weak, lying on my verandah sofa at 3 p.m., that I couldn’t walk at all, couldn’t drag myself up to put on my shoes & work out a picnic, couldn’t even read more than a page of Vile Bodies, before sinking back into torpor – yet then, after two hours’ walking, feeling I could still carry on indefinitely.’ The old illusion of invincibility crept back in the end, but while it was gone, it was utterly gone, and this brief absence constituted just one more little reason to take illness and hence the idea of recovery (through eating more) seriously: ‘If you decide on the treatment it’ll be more than this. Every day till I start getting fatter. Don’t think. Eyes swimming.’ More immediately, it was also just a reason to dare to eat a little more, a little earlier: ‘I’ve felt really dreadful today. So weak & vacant that I dared eat some oats & a nibble of chocolate before setting off [on the long walk with my mother in the afternoon heat].’ Perhaps the most striking, though far from the most significant, effect was the awareness of my own heartbeat, which stayed with me for a few days, and made me a little more aware of my body in general, and its fragility in particular.
With the deep weariness that I felt the drugs brought to the surface in me came the feeling of being powerfully disconnected from my own mind and body, from myself altogether. Back in England, I described how ‘I’ve been so unbelievably tired all day; terrifyingly incapable of waking up, or feeling connected to myself. I stared at myself for minutes in the mirror after getting up; my eyes looked insane. Not mine.’ This self-disconnect was bound up with feeling hungrier and eating more, even if not the 500 calories extra I knew I’d have to eat every day if I embarked on recovery: ‘And I’ve been so hungry, & eaten so many tiny things; more oats & chocolate for “breakfast”, a fragment of biscuit to keep R. company when I made him a walker’s biscuit sandwich; some crumbs of the chocolate & biscuits from the bags from which I created them for him. But not 500, is it? […] I just wish I could feel myself, or feel alive, or awake. […] How much is it the drugs doing all this, how much just my eternal weakness, my tired readjustment to England?’
The weakness and disconnection seemed to get worse and worse, so that two weeks after starting to take the Prozac, trying to do some testing for a reading experiment, I was describing how ‘I’m terrified. All day I’ve wanted to do nothing but sleep. Battling against lethargy, or succumbing to it; lying listening to the Archers & Front Row not knowing how I’d ever get up again. Getting up at 2 pm having slept so long yet feeling so awful. Eating more oats & chocolate; but walking to the department & doing all I had to there with a terrifying sense of distance, & fragility, & dazed inability to be present & have any confidence in any single act or decision. It’s awful. And though I have done some transcriptions now, after the third I felt so completely dreadful I could only wander stiltedly around the garden, breathing in the cold air, & then sink into the armchair with a book […]. I just long to wake up feeling better, different, tomorrow. […] Slight nausea, too, to make it all worse. Shaking with weakness.’
Above all, the Prozac, or my response to it as placebo, as part of a growing conviction of the need for change, or whatever it was that made it effective, took away my ability to deceive myself into believing everything was all right: ‘It’s just so much harder to pretend with these pills. Everything’s more violent, more obvious, more irrefutable. […] 3:30 a.m. Funny how the magic of the plate of food was suddenly lost in Corfu, for a few meals, & now is as intensely powerful as ever. Of course, setting, temperature, the variations on the ingredients, matter a good deal – but it’s weird to think how hollow all this felt, briefly, when the magic didn’t work.’ The magic of food had come back, but the fact that it had been absent, if only for a week or so, meant it could never quite be the same again. So, what’s the clinical logic behind prescribing Prozac to a not-yet recovering (or a still recovering) anorexic? There isn’t a straightforward answer, because the connections and distinctions between anorexia and depression are unclear. The symptoms of being severely underweight are similar in some respects to those of clinical depression: low mood, impaired concentration, lack of energy, irritability, poor sleep, loss of interest in sex, and obsessive thoughts and actions. Other aspects of eating disorders (including anorexia) which may not be attributable directly to the underweight state are the same as those observed in depression, notably low self-esteem and self-critical thinking (see Fairburn 2008, Cognitive Behavior Therapy and Eating Disorders, p. 246). It can therefore be difficult to assess whether clinical depression is present comorbidly (simultaneously) with anorexia, or whether the anorexia is manifesting traits highly similar to those of depression. There are, however, some symptoms more likely to indicate ‘semi-independent’ depression, such as extreme negative thinking beyond food- and body-related matters, impaired decision-making, neglect of personal appearance, hygiene, or everyday activities, or other impairments in sociability or cognitive functioning beyond what would be expected or had previously been manifested as part of the eating disorder.
If clinical depression is diagnosed, there may be significant benefits to be gained from treating it with antidepressants, because this can make the eating disorder easier to overcome. The cognitive-behavioural treatment programme outlined by Christopher Fairburn (2008) recommends a moderate to high dose (40-60 mg as standard) of fluoxetine for around 4-6 weeks in most cases, followed by treatment of the eating disorder using CBT-E (‘enhanced’ cognitive behavioural therapy, developed specifically for eating disorders). Fairburn also notes that antidepressants can reduce the frequency of binge eating, which can in turn have positive secondary effects like reduction of the fear of losing control over eating. However, he acknowledges too that recovery from depression, although it can motivate the patient to engage more fully in recovery, can in some cases have the effect of heightening restrictive eating habits because of increased drive and determination. In other words, even if the treatment of a comorbid depression is successful in anorexic patients, it can be risky.
Although Fairburn makes it clear that antidepressants should be used only if the depression is diagnosed as at least ‘semi-independent’ from the eating disorder, the distinction between depression-like symptoms resulting from the underweight state and ‘semi-independent’ clinical depression may not be meaningful. Depressive symptoms may or may not be identified as predating the onset of the eating disorder, or as extending significantly beyond the scope of the eating disorder’s symptoms, but treatment of anorexia-as-depression could still be warranted and beneficial. There are several grounds for drawing connections between the two, including their neurobiological basis, their frequent comorbidity, their shared genetic risk and associated personality traits, and their experiential similarities, like low mood, loss of interest and motivation, social isolation, and obsessive-compulsive behaviours.
On the question of whether antidepressants may have a role to play in recovery from anorexia regardless of whether depression is diagnosed as an independent or semi-independent condition, one perspective comes from the neurobiology of anorexia in relation to that of depression. (Here I base my discussion on Claudino et al. 2009: 3-4) Abnormalities have been identified in anorexic patients during the acute phase of illness in specific neurotransmitters like serotonin, dopamine, and norepinephrine/noradrenaline (involved, broadly speaking, in pleasure, reward-motivated behaviour, and concentration/anxiety respectively) as well as in neuropeptides (neuronal signalling molecules) and neuroendocrine hormones and the hormone leptin (key to regulating energy intake and expenditure). Most have been attributed to the starved state and disturbed eating behaviours, although some seem to persist after recovery: for instance, Kaye et al. (1999) found persistent differences in dopamine metabolism in former anorexics who had maintained at least 90% of average body weight for at least a year. The functional activity of central serotonin systems seems to be diminished in the underweight state but then abnormally increased in long-term weight-restored patients, which suggests that those who develop anorexia may have high levels of serotonin activity before the onset of illness. However, an alternative hypothesis is that decreased levels of cerebrospinal fluid (CSF) 5-HIAA, the main product of serotonin metabolism, in underweight anorexia patients is related to their low dietary intake of tryptophan, an essential amino acid found in eggs, dairy, red meat, and some nuts and seeds, which is (amongst other things) the precursor of serotonin, and that elevated levels of CSF 5-HIAA are a long-term consequence of chronic malnutrition. Some of the same neurobiological abnormalities found in anorexia are also manifested in depression, especially in dysfunction related to serotonin activity and the activity of the neurotransmitters adrenaline, noradrenaline, and dopamine. We might therefore expect antidepressants to act on anorexia as they do on depression.
Different classes of antidepressants can be expected to act in different ways when treating anorexia. Serotonergic drugs (including fluoxetine/Prozac) are expected to re-establish homeostasis between the neurotransmitters dopamine, noradrenaline, and GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter), all of which are involved in bodyweight control and food intake. The reduction of noradrenergic activity has been considered potentially treatable by tricyclic antidepressants that stimulate alpha-noradrenergic receptors in the hypothalamus. Clinical researchers have also been interested in using antidepressants to treat anorexia because of the capacity of some of them, particularly the tricyclics, to induce weight gain.
The question is: do any antidepressants actually work in the treatment of anorexia?
The review study ‘Antidepressants for anorexia nervosa’ by A.M. Claudino and colleagues (2009) is a Cochrane Collaboration meta-analysis of randomised controlled trials of antidepressants as part of the treatment of acute anorexia. The authors found only seven trials – from an original total of 1303 citations – that fulfilled their stringent quality criteria relating to type of intervention, outcome measures, and the potential for bias in the results. There is clearly a serious lack of high-quality research in this area, with very few studies testing antidepressants against a placebo, sample sizes typically being very small, total intervention duration being very short without follow-up, and completion rates – an important factor when it comes to medication with potentially serious side-effects – not always being given. There’s also significant variability between trials in factors like reporting of weight gain and secondary outcome measures, the treatment packages provided alongside the medication, and the age and acuteness of illness in the patients treated. In addition, the trials were all were carried out in inpatient settings, which doesn’t accurately reflect the treatment structure for many anorexic patients. With those shortcomings in mind, however, the randomised controlled trials included in the review study were unable to demonstrate any effect of antidepressants compared with placebo in the majority of outcomes considered. The two positive findings concerned comparisons between types of antidepressant, but the authors stress that these shouldn’t be taken as evidence of efficacy of a specific drug or class of drugs. Correspondingly, the regulatory agencies in the UK and US, for example, haven’t approved any medication for the treatment of anorexia. There have been more promising results using fluoxetine to help prevent relapse in weight-restored patients, to help reduce residual symptoms and prevent weight loss at follow-up (e.g. Kaye et al. 1991), so this may be a better point at which to consider incorporating antidepressants into recovery from anorexia. But proper replications need doing.
There are various possible reasons why the drugs might not work in the context of severe anorexia. The malnourished state of anorexia may reduce the efficacy of the antidepressants: for example, low oestrogen levels and low intake of nutrients (including essential fatty acids and zinc) that seem to influence serotonin pathway function may impair the release of serotonin in the brain, which would lead to a down-regulation of its receptor and a reduction in antidepressant function. Inadequate nutrition has been challenged as a reason for lack of response to selective serotonin reuptake inhibitor (SSRI) medications like fluoxetine by a trial (Barbarich et al. 2004) that added nutritional supplements (tryptophan, vitamins, minerals, and essential fatty acids) or placebo to fluoxetine, finding no effect, but this was a small trial (26 participants) with a high drop-out rate (only nine participants completed the 26-week study).
As with any drug, there’s also a risk of side-effects. The tricyclic class of antidepressants are associated with more discomfort than newer, safer classes of drugs with better side-effect profiles such as SSRIs, and also with increased cardiac risks due to their ability to alter the heart rhythm (QT interval), which can be a problem for anorexic patients in any case. A possible heightened suicide risk is also associated with the use of antidepressants, and only fluoxetine has been found to have on balance a positive effect – fluoxetine is therefore the only approved drug in the UK and US for treating depression in under-18s (Claudino et al. 2009: 16). All antidepressants carry the risk of withdrawal symptoms including dizziness, nausea, lethargy, and headaches, and more serious symptoms such as mania or hypomania (see a blog post by Gwyneth Olwyn). I never experienced any withdrawal symptoms at all, though, as it happens; when I came off the Prozac it wasn’t even a significant enough event to record in my diary.
Much more good-quality research needs to be done, but for now there’s little basis for confidence in the efficacy of antidepressants in treating anorexia. I was surprised to find this out when researching this post, because for me, starting to take Prozac really felt like the beginning of the end of my illness. I may in fact have responded well to the drug neurochemically, or its effects may all have been those of a placebo, in that I was ready at last to face up to my physical and cognitive dysfunction and the drug was what I needed to give me a feeling of change. There was also, of course, that powerful confounding factor, the holiday in Corfu beginning at almost the same time. But whatever the causal factors, it really felt like it did things to me.
It was a long road from there to living without anorexia, taking in the milestones of a second visit to the clinic, the decision to start eating those 500 calories more in order to make the minimum weight for admittance to the clinical trial, the start of therapy, the coping with everything that weight gain brought with it, and the reconstruction of a life that wasn’t all about eating and not eating, but I’ve always felt that those green and yellow torpedoes of the unknown were a necessary stage on that journey. Embracing the unknown is, after all, what abandoning anorexia is all about, and putting those pills into my mouth, that first night five years ago, felt like embracing it in the bravest way I knew how: by eating.