Trigger warning: This article contains discussion of suicide
It is 2024 and there are still no highly-effective treatment options for anorexia nervosa, and our understanding of the biological factors involved in eating disorders is far behind other fields within psychiatry. We are hoping that this is soon to change.
My name is Johanna, and I am a postdoctoral researcher working in the field of eating disorders. I’ve written multiple papers on the topic, and the first sentence of any publication I write about anorexia nervosa always starts with the shocking reality that anorexia is one of the most fatal illnesses across the spectrum of psychiatric disorders. The sentence might as well be copied and pasted. However, what is less known is that one of the driving factors of its high mortality rates is the high rate of suicide. Depression and hopelessness are extremely common experiences for people that experience an eating disorder.
These miserable statistics, commonly used to introduce this topic, can be counteracted by the promising news that we are beginning to understand a bit more about the biological reasons that may be behind the “stuckness” that so many people experience.
Stereotyped depictions of anorexia nervosa involve mainly white, middle-class, Western women from privileged upbringings. New research counteracts this stereotype, with the finding of a role for metabolic genes (which regulate chemical reactions that convert food to energy) leading to a reconceptualization of anorexia as a “metabo-psychiatric disorder”.
The brain is the hungriest organ in the body, using around 20% of our daily energy intake, and certain parts of our diet (e.g., healthy fats) are very important for brain health. When people lose large amounts of weight in their body, perhaps unsurprisingly, this culminates in weight loss in the brain too. In anorexia nervosa, this loss is around 6%, which is the greatest amount of loss across all of the psychiatric disorders. Other aspects of the biology change too, likely as an adaptation to weight loss. For example, one molecule that is particularly important for the growth and adaptation of brain cells, called “brain-derived neurotrophic factor” reduces. Luckily, evidence suggests that these changes are largely reversible with weight gain and nutritional reinstatement. However, it is clear that more approaches to promote brain recovery are needed.
The onset of depression is a common experience for people with anorexia, which may come from multiple places. For example, in the famous 1944 “Minnesota Starvation Experiment”, young men were starved for six months in order to learn about how best to refeed malnourished populations across Europe at the time. These previously healthy men not only developed obsessions around food, but also became extremely anxious and depressed.
Depression could also be a side effect of living with anorexia nervosa, for example the toll it takes on one’s psychosocial functioning and one’s ability to engage in everyday life (e.g., work, school, social relationships) as a result of obsessive thoughts, poor cognitive functioning and having life interrupted by frequent visits to services or hospitalisation.
The problem is that standard antidepressants are usually ineffective in people with anorexia. It has been speculated that starvation leads to a shortage of the amino acid tryptophan, which is present in most protein-based foods and cannot be created by the body by itself. Such nutrients are necessary for the production, storage and release of serotonin, the molecule which is believed to be decreased in depression. Therefore, there are no evidence-based methods of helping alleviate depression in this population.
Ketamine is a drug that is traditionally used in medical settings as an anaesthetic. In much lower doses, ketamine has shown rapid antidepressant properties and research looking at its use for treating depression has rapidly expanded in the last decade. One form of it has been licensed for use in treatment-resistant depression.
Ketamine can be given by vein, as an injection, through the nostrils, or swallowed as a capsule or liquid. Many studies have shown that ketamine has fast, but temporary, anti-depressant and anti-suicide effects. However, there are significant side effects that depend on the type of administration and the amount that is given. Dissociation, or feeling “detached from one’s surroundings” is a common side effect, as is feeling nauseous. Therefore, it is important that patients given ketamine for depression are closely monitored and are in a safe and medically-supervised environment.
Several studies have also found that ketamine may increase the brain-boosting molecule mentioned before, brain-derived neurotrophic factor. It also works via a different biological pathway than do usual anti-depressants.
Therefore, for several reasons we believe that it may have the potential to help reduce depression and help promote recovery in people with anorexia nervosa, and several case studies have shown promising initial evidence.
The first important step in the scientific process is to demonstrate the safety of this medication, as well as the likelihood that people want to take part in such a study. Excitingly, we will be running a small-scale study beginning in 2025 in order to gain data on this and to pave the way towards more research.
It is likely that there is no one-sized-fits-all approach to the treatment of anorexia nervosa, and other research teams are looking at using compounds such as psilocybin (a molecule derived from magic mushrooms) and metreleptin (a synthetic form of the hormone leptin). I am not sure if I believe in a “wonder-drug” per se, but if shown to be effective, new evidence-based approaches to help people with this hard-to-treat and extremely distressing condition would be a huge step forward.