Why Is Anorexia Nervosa Neglected for Drug Development?

Atypical Antipsychotic Olanzapine

Eating disorders have been a neglected area for high-quality psychopharmacologic research.  There are probably several reasons for this.  The classic eating disorder anorexia nervosa is relatively rare and identifying 500 to 1000 subjects for a clinical trial would likely be a significant (but not impossible) research challenge.   There are currently no FDA approved drugs indicated for the treatment of anorexia nervosa.

One drug in the U.S. has FDA approval for bulimia nervosa, the antidepressant fluoxetine.  But this approval occurred in the late 1980’s meaning we are approaching twenty-five years without a new drug approval for bulimia nervosa.  Pharmaceutical company interest in bulimia may be tempered somewhat by the experience of a trial using the drug bupropion.  Bupropion appeared effective in reducing binge eating in bulimia nervosa but a the clinical trial participants on bupropion had an increased risk of seizures during the trial.  The electrolyte disruption seen in bulimia (from bingeing and purging behaviors) may contribute to an increased risk of seizure—particularly for drugs with a known risk of reducing seizure thresholds.

So is anorexia nervosa neglected because there just are no potential candidates?  There is some evidence of the potential for the atypical antipsychotic medications in anorexia nervosa.  This evidence comes from outside the FDA approval process and typically involves small numbers of subjects.  McKnight and Park from the Department of Psychiatry at the University of Oxford recently summarized the research knowledge base in this area.

Why should atypical antipsychotics be considered for an eating disorder?  McKnight and Park propose three reasons:

• Atypicals reduce agitation and anxiety—common hindrances in refeeding underweight patients with anorexia nervosa
• Atypical often cause weight gain
• Some features of anorexia nervosa resemble psychosis—persistent belief of being overweight despite starvation and weight loss

Only three double-blind trials have been published according to this review.  All involve olanzapine versus placebo.  Two of these studies found and increase in BMI (weight) with the drug.  All of the these studies found some favorable effect on anxiety, depression or eating disorder psychological symptoms.

One single blind study compared the atypical antipsychotic drug amisulpride to fluoxetine and placebo.  Amisulpride produced a significant weight gain compared to the other two treatment arms. 

Four open label non-blinded studies suggest the potential for quetiapine to have a favorable effect on weight gain and/or reduction in eating disorders psychological variables.

Evidence for the use of other atypical agents (i.e. risperidone, aripiprazole) is limited to a few case reports, but these have generally been favorable.  One case report noted development of hyperglycemia in adult with anorexia receiving 15 mg of olanzapine daily.

I searched the ClinicalTrials.gov website for anorexia nervosa and found only two active clinical trials recruiting subjects:

• Olanzapine versus placebo for outpatients with anorexia nervosa (an NIMH-sponsored study) conducted by Cornell, University of Pittsburgh, Johns Hopkins and the University of Toronto with a targeted enrollment of 160
• Aripiprazole versus placebo—a phase III study being conducted at the University of Barcelona in Spain with a targeted enrollment of 60

So the history of neglecting anorexia nervosa for drug development seems to be continuing.  What will it take for more research attention to this important disorder so that clinicians will have more to offer the patients and their families?

Image of Chemical Structure of Olanzapine provided in the public domain by author Ben Mills.

McKnight RF, & Park RJ (2010). Atypical antipsychotics and anorexia nervosa: a review. European eating disorders review : the journal of the Eating Disorders Association, 18 (1), 10-21 PMID: 20054875