We have shown that the use of atypical antipsychotic medications and antidepressants in anorexia nervosa is common. The use of atypical antipsychotics has doubled over a span of 13 years and the number of women with this disorder taking psychotropic medications has increased significantly over this same time period. Despite more recent data reporting that antidepressant medications are not effective in the treatment of anorexia nervosa or in individuals with co-morbid psychopathology (10
), we have also shown that the use of antidepressants has remained stable over this 13-year period.
Anorexia nervosa affects 0.5–1% of college-aged women in the US and its incidence has been increasing (1
). Anorexia nervosa is a chronic illness with long-term relapse rates approaching 50% (3
) and has the highest mortality rate of any psychiatric disorder (5
). Individuals with this disorder typically display symptoms of depression, obsessive-compulsive behavior and their distorted body image may be considered a symptom of psychosis. Therefore, medications that treat these symptoms in other populations have been prescribed for individuals with anorexia nervosa.
Few randomized, placebo-controlled studies investigating the use of psychopharmacologic agents in anorexia nervosa have been completed. Anorexia nervosa treatment studies are difficult to perform and complete due to high drop-out rates. While early case reports, open-label studies, and non-randomized studies suggested a potential benefit of the use of SSRIs in the treatment of anorexia nervosa (30
), a randomized, placebo-controlled study of the use of fluoxetine for 7-weeks during inpatient treatment failed to show benefit as compared with placebo (16
Similarly, randomized, placebo-controlled trials investigating the use of atypical antipsychotics for the treatment of anorexia nervosa (25
) have not demonstrated definitive benefit. Whereas two shorter-term studies demonstrated a benefit in weight gain with olanzapine after 8–10-weeks (26
), a longer-term trial did not demonstrate any difference in weight gain between the olanzapine and placebo groups after three months of treatment (25
). Although benefits with respect to psychological symptoms in the group receiving olanzapine were found, these results are in a small group of participants and larger, long-term studies will be needed to determine if there is truly any benefit to these medications and whether these effects persist over time. Therefore, at the present time there is no conclusive evidence that atypical antipsychotics have any benefit in the treatment of anorexia nervosa.
Our data demonstrate that despite published data, these medications continue to be commonly used in anorexia nervosa and the use of atypical antipsychotics has doubled. These data are concerning because of the potential adverse effects of these medications. Side-effects of atypical antipsychotics include hyperglycemia, hyperlipidemia, cardiovascular effects, hyperprolactinemia and neuroleptic malignant syndrome. Side-effects of SSRIs include headache, nausea and importantly both SSRIs and atypical antipsychotics may negatively impact bone health and increase fracture risk. Use of SSRIs has been shown to be associated with bone loss (18
) and a two-fold increased risk of fracture in older adults (20
). The mechanism of bone loss is thought to be due to the antagonistic effects of SSRIs on the serotonin (5– hydroxytryptamine) transporter, as mouse models demonstrate decreased bone mineral accrual in mice lacking this transporter and in mice treated with SSRIs (22
). Similarly, atypical antipsychotic agents may also affect bone mineral density. Hyperprolactinemia, a side-effect commonly associated with typical antipsychotic agents and the atypical antipsychotic, risperidone, causes suppression of the hypothalamic-pituitary-ovarian axis which results in hypoestrogenemia and subsequent bone loss. While risperidone is the atypical antipsychotic most commonly associated with hyperprolactinemia, a number of other atypical antipsychotics, including quetiapine (39
) and ziprasidone (40
) have also been associated with increased prolactin levels and atypical antipsychotic agents have been associated with decreased bone mineral density in both postmenopausal women (24
) and in premenopausal women with schizophrenia (23
Women with anorexia nervosa are at risk for severe bone loss. Nearly ninety percent of women with anorexia nervosa have some degree of bone loss (41
) with 30% meeting WHO criteria for osteoporosis (41
). Thirty percent of women with anorexia nervosa also have a history of fracture (41
) and the fracture rate in women with anorexia nervosa is seven-times greater than that of age-matched controls (42
). Therefore, medications which may have a negative impact on bone health should be avoided in this population.
Rapid weight-gain is also a known side-effect of atypical antipsychotics (43
) and is thought to be a potentially beneficial effect in anorexia nervosa. Studies suggest that the weight-gain associated with atypical antipsychotic medication use is due to increases in both visceral and subcutaneous fat (44
). Visceral fat has recently been associated with decreased bone mineral density (46
) and therefore may be a potential mediator of the decreased bone density seen in individuals on atypical antipsychotics. Furthermore, whether this rapid weight-gain would in fact be beneficial to women with anorexia nervosa, or whether it may be detrimental to the psychological state of these women and potentially lead to relapse, is currently unknown.
The limitations of our study include the fact that our participants were women presenting to a clinical research center for a research study and therefore may not be representative of all women with anorexia nervosa. However, our group of patients is drawn from a large number of community-based practitioners and is representative of participants receiving treatment for anorexia nervosa. Another limitation of our study is the fact that medication use was self-reported by participants. We believe that this likely underestimates the number of medications prescribed for this group of women, as participants may not report medications they have been prescribed. Therefore, it is likely that more psychotropic medications are being prescribed for the treatment of anorexia nervosa than our data reflect.
We have demonstrated that 48.4% of women with anorexia nervosa report the use of antidepressants and 13% report the use of antipsychotics between 1997 and 2009. While the use of antidepressants has remained stable over the 13 year period, the rate of atypical antipsychotic use has doubled over this time period despite the fact that these medications have not been shown to be efficacious in anorexia nervosa and may have significant negative consequences on the bone health of this population. Longer-term studies investigating the use of these medications are needed to evaluate the efficacy and benefit of these medications prior to their continued wide-spread use.