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Hi! David Rosenberg here for the Psychopharmacology Institute. In this CAP—or Child and Adolescent Psychiatry—Smart Take, we will examine the tolerability, safety, and effectiveness of low-dose olanzapine in adolescents with anorexia nervosa (AN). Olanzapine, of course, is an intriguing choice for study in patients with AN, as it is one of the medications most associated with weight gain and increased appetite.
So, this side effect may have some appeal for patients with AN. However, due to its association with diabetes, carbohydrate metabolic problems, and lipid alterations, when using this medicine, close monitoring is essential, particularly in patients with AN who can be exquisitely sensitive to medication side effects—although, the increased appetite side effect has some appeal in patients with AN. Surprisingly, only 1 small study of 13 girls with AN has evaluated the use of olanzapine. This retrospective study enrolled 118 patients, comparing 37 patients treated with low-dose olanzapine—5 mg or less per day—to 29 patients treated with full-dose olanzapine—doses greater than 5 mg per day—and 52 patients treated without antipsychotic medications. All the patients had been in an inpatient or partial hospitalization setting with multidisciplinary interventions. I like that this study has a control group comparator of patients not treated with antipsychotic medication and compared low-and high-dose olanzapine. This is relevant because AN patients have many medical complications and may be exquisitely sensitive to medication side effects. Unlike bulimia nervosa, where fluoxetine is FDA approved for its treatment, there is no FDA-approved medication for AN. SSRIs are also contraindicated in the weight-depleted state in patients with AN, although they can help prevent relapse in the weight-recovered state. Some interesting data suggests that when you use SSRIs for patients with AN in the weight-depleted state—which can adversely impact the brain’s chemistry—subsequent use of SSRIs in the weight-recovered state is not quite as effective. That merits further study; however, avoiding using SSRIs in the weight-depleted state is best.
So, there is great clinical relevance to identifying medications that can augment a multidisciplinary approach to medical, behavioral, and environmental interventions. I also like that this study looked not only at female adolescents with AN, as is often the case in the studies published, but included male adolescents, albeit at a much lower rate—94% of the sample was comprised of female patients. We know that eating disorders are increasing significantly in males, so including males in this type of studies is essential. So, what did they find?
First, low-dose olanzapine was found to be safe and well tolerated for an average of 132 days, about 18 weeks. Patients treated with olanzapine gained more weight than those not treated with antipsychotic medication, which is not surprising. Unfortunately, there were no differences in eating disorder psychopathology or eating attitudes in patients treated with either low-or high-dose olanzapine vs patients not treated with antipsychotic medication. However, patients had an increase in weight, which is expected with antipsychotic medication.
However, whether they were treated with low-or high-dose olanzapine or not, there was no difference in attitude regarding the psychopathology of the eating disorder. Something exciting was that adolescents with AN treated with low-dose olanzapine and patients without any antipsychotic medications showed a greater improvement in depressive symptom severity than patients treated with higher dose olanzapine. This is highly relevant because comorbid depression is frequent in patients with AN. Moreover, it is consistent with augmentation with second-generation antipsychotic medications in other disorders, such as OCD, where a low dose is a rule and often has better efficacy and more favorable tolerability than higher doses. Similar to OCD patients, AN patients appear to do better on lower dose antipsychotic augmentation. Higher doses expose the patients to more potentially toxic side effects. So, the bottom line here is that this is an up-and-coming line of study.
It merits future controlled studies of olanzapine and other medications in the weight-depleted and-recovered states as well as which medications may help decrease the risk for relapse, underscoring that medication alone will never be sufficient in this population. A multidisciplinary approach is critical, which gives clinicians working with patients with anorexia—a very challenging population, particularly when looking for pharmacologic interventions— another tool to assist in the treatment. In conclusion, this is auspicious support for low-dose olanzapine in adolescent patients with AN.
Abstract
Low-Dose Olanzapine in the Treatment of Adolescents with Anorexia Nervosa: An Observational Naturalistic Case-Control Study
Jacopo Pruccoli, Ilaria Pettenuzzo, Antonia Parmeggiani
Background: Although recent articles have investigated the use of low-dose olanzapine in different psychiatric conditions, only one study so far has assessed this treatment in 13 girls with anorexia nervosa (AN).
Methods: Observational naturalistic case-control study aimed at reporting the use and tolerability of low-dose olanzapine in the context of a multidisciplinary hospital intervention for adolescents with AN. Three groups with AN were compared: group 1 was treated with low-dose olanzapine (≤5 mg/day), group 2 with full-dose olanzapine (>5 mg/day), and group 3 (control group) was treated without antipsychotics. Psychopathology was assessed at admission (T0) and discharge (T1) with Eating Disorders Inventory-3 Eating Disorders Risk, Body Uneasiness Test Global Severity Index (BUT-GSI), Beck’s Depression Inventory-II (BDI-II), and Self-administered Psychiatric Scales for Children and Adolescents, Depression subtest (SAFA-D). Possible differences among the three groups, concerning clinical and treatment variables, were screened. Then, potential differences of T0-T1 modifications in psychopathological variables among the three treatment groups were assessed with analyses of covariance, corrected for baseline psychopathology and potential confounders, including possible concurrent antidepressants.
Results: A total of 118 patients were enrolled (F= 94.1%; mean age = 15.4 ± 1.7 years), including 52 controls, 37 treated with low-dose olanzapine, and 29 with full-dose olanzapine. Low-dose olanzapine was well tolerated and used for a mean of 132.1 (±98.6) days, starting with a dosage of 3.4 (±1.2) mg/day and increasing to a maximum dose of 4.4 (±1.1) mg/day. The multidisciplinary intervention resulted in an improvement of BUT-GSI (p< 0.001), BDI-II (p< 0.001), and SAFA-D (p< 0.001) for the entire sample. Individuals treated with full-dose olanzapine experienced a significantly lower improvement in depressive measures: BDI-II (F[2,61] = 12.653, p< 0.001, η2= 0.269) and SAFA-D (F[2,57] = 7.413, p= 0.001, η2= 0.170), than the other groups.
Discussion: This naturalistic controlled study expands the existing evidence on the use and tolerability of low-dose olanzapine in adolescents with AN. These results should be assessed in wider and prospective samples.
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Reference
Pruccoli, J., Pettenuzzo, I., & Parmeggiani, A. (2022). Low-dose olanzapine in the treatment of adolescents with anorexia nervosa: An observational naturalistic case–control study. Journal of Child and Adolescent Psychopharmacology, 32(5), 304-310.
