FT. LAUDERDALE, FLA. — What do atypical antipsychotics, an analeptic, and targeted magnets have in common? They all might play a role in the treatment of anorexia nervosa.
“When you have a disorder that is so treatment resistant, it's like metastatic breast cancer; you have to think outside the box for new interventions,” Dr. Allan S. Kaplan said at a workshop on eating disorders at the annual meeting of the American College of Psychiatrists.
Current statistics indicate that 20% of patients diagnosed with anorexia are resistant to any intervention. The needs of these patients have been largely neglected even though their numbers continue to grow as a result of the mortality decreasing from 22% in older studies to about 8%–10% today, said Dr. Kaplan, professor of psychiatry at the University of Toronto.
In his experience, many of these patients are now in their 40s and 50s and have been ill for 20-30 years. Most have significant medical complications: renal failure, cardiac arrhythmias, and osteoporosis with resulting hip fractures that have left them wheelchair-bound.
“They are unbelievably disabled,” he said. “They are more disabled on quality-of-life scales than a comparative group of schizophrenics in the hospital.”
One novel approach that might be useful is use of repetitive transcranial magnetic stimulation (rTMS), which has been shown to be effective in some patients with depression, schizophrenia, and obsessive-compulsive disorder. Current magnets stimulate superficial cortical areas of the brain, but Dr. Kaplan suggests that a better target might be the insula—a cerebral cortex structure that plays a role in interoceptive awareness and motor control. His group recently completed an unpublished meta-analysis of neuroimaging studies in anorexia that provides evidence for overactivity in the insula.
The team members have subsequently contracted with an Israeli biotechnology firm to construct a patented magnet for rTMS that will specifically target the insula.
The approach is not without controversy, Dr. Kaplan acknowledged. Although the seizure rate with rTMS is very low in patients with depression, patients with anorexia are at an increased risk for seizures at a rate of about 10% in general.
Atypical antipsychotics have come under increased scrutiny for anorexia, but with limited success in the few small studies and case reports to date. A recent meta-analysis of 43 publications concluded that there is not enough evidence in anorexia to confirm that these medications increase weight (Eur. Eat. Disord. Rev. 2010;18:10-21).
Olanzapine is the atypical antipsychotic that has been the most reported drug in the literature for treating anorexia and has been the subject of three small randomized controlled trials. Researchers in Ottawa showed that 10 weeks of olanzapine plus intensive day treatment resulted in faster weight gain and a greater decrease in obsessive symptoms than placebo in 34 patients with anorexia, but overall the same amount of weight gain (Am. J. Psychiatry 2008;165:1281-8).
Dr. Kaplan and Dr. Evelyn Attia of Columbia University reported in a separate unpublished trial in 2005 that patients gained a mean of almost 2 kgrafter 8 weeks of up to 10 mg olanzapine. Patients credited this not to an increase in hunger, but to being less anxious and consumed by thoughts of weight and shape. Importantly, there was no change in lipids, glucose, or insulin sensitivity, suggesting something might be different about the way the anorexic brain handles these drugs, he said.
Positive results on both weight gain and cognition have been seen with ziprasidone and quetiapine, but their use has been limited by concerns about QT interval prolongation, which is already an issue in anorexia. Because of this concern, olanzapine was selected instead of ziprasidone as the study drug for a large multicenter anorexia trial that is planned, he said.
Finally, workshop attendee Dr. Charles Price reported an acute response in a single patient with anorexia given modafinil and followed for 6 months. In a counterintuitive finding, the drug did not have the weight loss aspects observed with other stimulants.
“Basically, it cured her anorexia; now it is an 'N' of one,” said Dr. Price, who is in private practice in Reno, Nev.
Dr. Kaplan reported having no conflicts of interest. Dr. Attia reported having received research support from Pfizer and Eli Lilly.