Olanzapine for Anorexia Nervosa

With the arguable exception of clozapine, olanzapine confers the highest risk of weight gain, obesity, and metabolic adverse effects among the second-generation, atypical neuroleptics. Yet, might that adverse effect become a therapeutic one in persons with anorexia nervosa? So wondered clinical researchers Evelyn Attia and colleagues, of Columbia University (American Journal of Psychiatry 176:6:449-456, 2019), who randomly and double-blindedly added olanzapine (up to 10 mg/day) or placebo to the regimens of 152 patients with DSM-IV-TR anorexia nervosa, and then assessed their progress for up to 16 weeks. Studying their patients’ responses with weekly weighings, objective psychiatric ratings (including the Yale-Brown Obsessive-Compulsive Scale and customized ratings of obsessionality themed by shape, body fat, and food,) and biochemical markers of metabolic adversity, the authors then subjected the differences between olanzapine- and placebo-cotreated patients (via their primary outcome criterion, rate of weight change) to a statistical analysis with greater than a 90-percent power of detecting a weekly weight change of a little over a half-pound.

The authors’ principal result (the one that rigorous research protocol required them to commit to in advance–rate of weight gain) favored olanzapine, albeit with modest effect size and a small, but statistically significant, mean rate of weight gain (tantamount in the U.S. to one pound per month in an adult female of average height).

The rate of weight gain in their olanzapine-treated patients with anorexia nervosa was, in fact, lower than that reported in patients receiving olanzapine for other diagnoses (reported to be as much as a pound per week during the first year of treatment!)

Obsessive-compulsive thoughts and behaviors, associated or not with weight gain, excessive concern about body shape, food, or appearing fat, improved no more in olanzapine- than in placecbo-treated patients. Obsessive-compulsive symptoms of all kinds likewise appeared no more improved in the olanzapine-treated patients, who withal showed no improvements of anxiety or depression over the entire 16 weeks of study. No significant difference between groups were reported with respect to any adverse effect.

The authors believe that patients with anorexia nervosa may experience modest weight gain unaccompanied by improvements of obsessionality about body image or food during up to 16 weeks of exposure to relatively low dosages of olanzapine. (Obiter: The generalizability of findings in the authors’ patient sample, uncertain amid exiguous documentation of a sparse literature,  

is withal informed by criteria for study exclusion (acute medical illness, biochemical abnormalities associated with tissue damage or dysfunction, current substance use disorder); typology of comorbid psychiatric diagnosis (including mood disorders in 32.9 percent and anxiety spectrum disorders in 40.1 percent); mean number of comorbid psychiatric disorders per patient (2.1); percentage of patients receiving pharmacotherapy for them (41.4, including antidepressants in 29.6 percent, neuroleptics in 12.9 percent, and sedative/hypnotics in 15.1 percent); and percentage of patients noncompliant with pharmacotherapy by midterm of study (35.2). )

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