Misuse of Atypical Antipsychotics in Youths With Anorexia

Treatment of anorexia nervosa in adolescents is often difficult due to the ego-syntonic nature of some of its expressions, such as strict dieting, excessive exercising, and low weight. Indeed, adolescents with anorexia nervosa not only struggle to see these features as a problem but, on the contrary, often experience an intense sense of realization when they are able to follow their extreme and rigid dietary rules and lose weight.

According to the biological-disease model, anorexia nervosa is a mental disorder determined by biological alterations that lead the person to develop some characteristic symptoms such as:

1. Restriction of energy intake relative to requirement, leading to significantly low weight.
2. Intense fear of gaining weight or becoming fat, or persistent behavior that interferes with weight gain, even in the presence of significantly low weight.
3. Alteration in the way the subject experiences his own weight or shape of his body, excessive influence of weight or body shape on self-esteem levels, or persistent refusal to admit the severity of the current underweight condition.

The biological-disease model, even though not dismissing the importance of environmental risk factors, focuses mainly on genetics, neurotransmitters, neurophysiology, neuroanatomy, and so on. According to this model anorexia nervosa has primarily an organic cause related to the structure and functioning of the brain.

The biological-disease model, which is used more frequently by psychiatrists than psychologists, traditionally makes large use of psychopharmacological substances to modify the chemistry of brain functioning to treat the eating disorder. However, despite the extensive research carried out, specific biomarkers explaining the development and maintenance of anorexia nervosa that can be targeted by drugs have not yet been found. In addition, although practically all available psychopharmacological substances have been tested, none have been shown to be effective in improving the specific psychopathology of anorexia nervosa.

In recent years, a class of drugs called "atypical antipsychotics" has increasingly been used in patients with anorexia nervosa. These, also known as second-generation antipsychotics and serotonin–dopamine antagonists, are a class of drugs used for the treatment of psychiatric diseases such as schizophrenia, bipolar disorder, autism, and as an adjunct in major depressive disorder.

Atypical antipsychotics, in comparison to first-generation antipsychotics, have a lower affinity for dopaminergic receptors and an action on some serotonin receptor subtypes (such as antagonism at 5HT2A and 5HT2C). This mechanism of action allows them not to cause extrapyramidal motor control disabilities in patients such as unsteady Parkinson's disease-type movements, body rigidity, and involuntary tremors. However, as well as first-generation drugs, atypical antipsychotics also have sometimes severe side effects, including tardive dyskinesia (a serious movement disorder), neuroleptic malignant syndrome, and increased risk of stroke, sudden cardiac death, blood clots, and diabetes. Significant weight gain may also occur.

Atypical antipsychotics are also increasingly used in the treatment of adolescents with anorexia nervosa, because of their potential positive effects on weight regain, reduction of excessive exercising, eating-related anxiety, and overall functioning, although available studies have not yielded promising results.

Indeed, a double-blind placebo-controlled study, which evaluated the addition of olanzapine to a standard program for the treatment of 20 adolescents with anorexia nervosa, found that the change in % median body weight did not differ between the treatment groups at midpoint or end of the study. Both groups gained weight at a similar rate and had similar improvements in eating attitudes and behaviors, psychological functioning and resting energy expenditure.

Similar conclusions have been reached in a placebo-controlled double-blind study that evaluated the safety and efficacy of risperidone in 40 young females with anorexia nervosa. The study did not show a benefit for the addition of risperidone during the weight-restoration phase of care.

These disappointing results and the presence of potentially serious side effects associated with the use of atypical antipsychotics indicate that their prescription in adolescents with anorexia nervosa has an unfavorable risk-benefit ratio. Therefore, in the absence of psychiatric comorbidities such as schizophrenia, psychosis, bipolar disorder, and major depression, their use to treat adolescents with anorexia nervosa appears not to be appropriate.