On the evening of 20th June 2008, I started taking Prozac. Halfway through the day’s single, extended meal, I described in my diary my fears about taking the drug. What frightened me most was the thought that doing so, just like beginning to eat more (which I hadn’t yet begun to do), might take my anorexic identity away from me. I admitted to my diary that I was scared
of turning into a different person even by this means, let alone by eating. […] They even look frightening, like green & yellow torpedoes of the unknown. But, well, I feel fine, & restored by all that starch & fat & salt (& veg); & now time for the ever-incredible luxuries of muesli & two sorts of milk […]
...and so on into a long discussion of calories and grams and the incomparable ecstasy of eating chocolate at dawn, which almost made me forget my fear.
I had recently visited an eating-disorders treatment centre and responded to a series of questions about my mood, and as a result had been prescribed 60 mg a day of fluoxetine, prior to the possible start of weight gain supported by cognitive-behavioural therapy. The hope was that the Prozac would improve my mood and motivation such that I’d be more likely to embark on treatment.
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 tied in tight knots. But 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. I’d been there often before and remained as ill as ever, but this time was a little different.
Part of that shift away from the depths of illness was the simple, crucial fact of feeling newly able to just eat more - not systematically, according to plan, or enough more to gain any significant weight; mainly just fragments of other people's dinners. But, still, 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 makes for confusion and feverish self-recrimination. And even though I blamed the drugs for it, there being things like this to blame on them was just one way in which the drugs, or the placebo effect, or mere coincidence, forced me to acknowledge that things couldn’t remain as they were. No trivial accident should make one feel like that.
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 daily long walk with my mother in the afternoon heat, because I didn't wake until lunchtime].
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 of participants 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, or as something that might support my growing conviction of the need for change, or whatever else 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, the question persists: how much of all this was the drug's direct chemical action? What is the clinical logic behind prescribing Prozac to someone not-yet recovering (or still recovering) from anorexia? There isn’t a straightforward answer, because the connections and distinctions between anorexia and depression are not entirely clear. 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. And 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, 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 - or whether this is a sustainable distinction. 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, and 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 Chris 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 reducing the fear of losing control over eating. However, he also acknowledges 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 people with anorexia, 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 comparable 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., 2006, pp. 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 and interpretive 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 of these abnormalities have been attributed to the starved state and disturbed eating behaviours. Some researchers have claimed that the differences may persist after recovery: for instance, Walter Kaye and colleagues (1999) found persistent differences in dopamine metabolism in people who had maintained at least 90% of a population average body weight for at least a year after their anorexia. But I've written elsewhere about the widespread problem in anorexia research of setting this kind of implausibly low threshold for 'recovery'. The authors of this study even admit that because of 'the difficulty of finding recovered AN subjects' (p. 504), they included four who hadn't reached even this obvious underestimate of what a post-anorexic healthy weight is. Meanwhile, another of Kaye and colleagues' studies (1991) found that functional activity of central serotonin systems seems to be diminished in the underweight state but then abnormally increased in long-term weight-restored patients, from which they concluded that those who develop anorexia may have high levels of serotonin activity before the onset of illness.
Decreased levels of cerebrospinal fluid (CSF) 5-HIAA, the main product of serotonin metabolism, in underweight anorexia patients may be related to their low dietary intake of tryptophan. (Tryptophan is an essential amino acid found in eggs, dairy, red meat, and some nuts and seeds, and is (amongst other things) the precursor of serotonin.) So the unusually elevated levels of (CSF) 5-HIAA found in the weight-restored participants relative to healthy controls may also be a result of the nutritional normalisation process, and/or hormonal changes accompanying recovery (ovarian steroids are thought to increase serotonin neuronal activity). Throughout, the same caveats apply to their definition of 'weight-restored': here, participants had to have maintained only 85% of population average bodyweight for six months (where their prior anorexia involved having been at less than 75% - an oddly narrow gap), and in interviews reported 'mild to moderate concerns with body image' (p. 557); that is, they were categorically not recovered, and any findings about their physiological state should be interpreted as reflecting the phase of partial not full recovery.
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 similarly to how they do on depression. But different classes of antidepressants can be expected to act in different ways when treating anorexia (or depression). Serotonergic drugs (including fluoxetine, aka 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 also 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 (Pope and Hudson, 2013, pp. 78-79, give a brief overview; see also Corwin et al., 1995, who found no difference in weight gain between tricyclics and fluoxetine). But tricyclics also have side-effects which seem to be particularly pronounced in anorexic patients - and of course, experiencing chemically induced weight gain not mediated also by increased nutrition might induce more panic than progress in someone with anorexia.
So now we've made our way round to the central question: do any antidepressants actually work in the treatment of anorexia?
The review study ‘Antidepressants for anorexia nervosa’ by A.M. Claudino and colleagues (2006) is a Cochrane Collaboration meta-analysis of randomised controlled trials of antidepressants prescribed 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 people with anorexia.
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 should not 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, have not approved any medication for the treatment of anorexia. There have been more promising results using fluoxetine to contribute to preventing relapse in weight-restored patients, by helping 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 are needed. Meanwhile medical practice takes its own course: given the absence of evidence for efficacy, there has been a worryingly rapid increase in the prescription of psychotropic medications (including antidepressants and antipsychotics) to people with anorexia over the past twenty years: double the number were reported as having been used between 2003 and 2009 compared to 1997-2002 (Fazeli et al., 2012).
There are various possible reasons why, in the context of severe anorexia, the drugs might not work. 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, however, been challenged as a reason for lack of response to selective serotonin reuptake inhibitor (SSRI) medications like fluoxetine, in 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 is 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., 2006, p. 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 high-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 discover this 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 unusually well to the drug neurochemically, or its effects may all have been those of a placebo (whose power shouldn't be underestimated), 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 something new.
Barbarich, N.C., McConaha, C.W., Halmi, K.A., Gendall, K., Sunday, S.R., Gaskill, J.,... and Kaye, W.H. (2004). Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa. International Journal of Eating Disorders, 35(1), 10-15. Direct PDF download here.
Claudino, A.M., de Lima, M.S., Hay, P.P.J., Bacaltchuk, J., Schmidt, U.U.S., and Treasure, J. (2006). Cochrane Database of Systematic Reviews. Abstract here.
Corwin, J., Connelly, S., Paz, S., Schwartz, M., and Wirth, J.A. (1995). Chart review of rate of weight gain in eating disorder patients treated with tricyclic antidepressants or fluoxetine. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 19(2), 223-228. Abstract here.
Fairburn, C. G. (2008). Cognitive behavior therapy and eating disorders. New York: Guilford. Google Books preview here.
Fazeli, P.K. Calder, G.L., Miller, K.K., Misra, M. Lawson, E.A., Meenaghan, E.,... and Klibanski, A. (2012). Psychotropic medication use in anorexia nervosa between 1997 and 2009. International Journal of Eating Disorders, 45(8), 970-976. Full text here.
Freeman, C. (2001/2012). Overcoming anorexia nervosa. London: Constable & Robinson. Google Books preview here.
Kaye, W., Frank, G.K.W., M.D., and McConaha, C. (1999). Altered dopamine activity after recovery from restricting-type anorexia nervosa. Neuropsychopharmacology, 21(4), 503-506. Full text here.
Kaye, W.H., Gwirtsman, H.E., George, D.T., and Ebert, M.H. (1991). Altered serotonin activity in anorexia nervosa after long-term weight restoration: Does elevated cerebrospinal fluid 5-hydroxyindoleacetic acid level correlate with rigid and obsessive behavior? Archives of General Psychiatry, 48(6), 556-562. Abstract here.
Olwyn, G. (2013). Depression in recovery: Assessment, treatment and options. The Eating Disorder Institute, 4 April. Full text here.
Pope, H., and Hudson, J. (2013). Biological treatments of eating disorders. In S.W. Emmett (Ed.), Theory and treatment of anorexia nervosa and bulimia: Biomedical, sociocultural, and psychological perspectives (pp. 73-92). New York: Brunner/Mazel. Google Books preview here.