Resurgence of Eating Disorders with Olanzapine

Introduction

Olanzapine is an atypical antipsychotic with potent antiemetic activity. There is currently good evidence for its utility in the treatment of chemotherapy-induced nausea,^1–6 and palliative care subspecialists have used it to treat complex intractable nausea for more than a decade.^7,8 Olanzapine's unique receptor targets potentially increase its off-label uses in a variety of palliative care settings, given its potential to reduce nausea, decrease anxiety, improve sleep, and stimulate appetite. ⁷ Olanzapine antagonizes many receptors including muscarinic receptors, H1, D2, and 5HT2, leading to antiemetic effects on the vestibular system, chemoreceptor trigger zone, and the vomiting center.^9,10 Weight gain is a common side effect of olanzapine, due both to increased appetite and to metabolic changes that accompany its administration. However, there is a paucity of data regarding the potential use of olanzapine as an appetite stimulant in chronically ill patients with disease-related anorexia. In addition, olanzapine has been shown to induce a reappearance of eating disorders (EDs) in otherwise medically healthy individuals.^11–16 We present a case from outpatient palliative care clinic in which relapse of bulimia nervosa (BN) was observed in a patient receiving olanzapine for nausea. These symptoms resolved with reduction in dose of olanzapine.

Case Description

A 70-year-old woman with a diagnosis of recurrent ovarian cancer was referred to the palliative care clinic for assistance in managing nausea, abdominal pain, and dysgeusia in the setting of disease progression. Her nausea persisted despite scheduled ondansetron supplemented by prochlorperazine utilized on an as needed basis for breakthrough nausea. Owing to her persistent nausea and her history of anxiety, we initiated scheduled olanzapine 2.5 mg twice daily and changed the ondansetron and prochlorperazine to intermittent as needed dosing. Within a matter of days, she reported a complete resolution of her nausea.

In the following weeks, she noted improvements in her appetite and dysgeusia, and she began to notice weight gain. She returned to clinic four weeks later in distress, noting a “ravenous” appetite, and describing the re-emergence of binging and purging behaviors that she had not experienced in over a decade. She acknowledged a prior diagnosis of BN, previously unknown to her providers. Olanzapine was decreased to 2.5 mg daily at bedtime. Within one week her binging and purging had resolved. Because her nausea had also resolved, olanzapine was discontinued at that time. Two years later the patient was started on a clinical trial and experienced nausea as a side effect of the medication she received as part of the study. She was once again started on olanzapine and experienced re-emergence of binging and purging. The dose was reduced and her binging and purging behaviors resolved.

Discussion

This case highlights the resurgence of BN related to the use of olanzapine for cancer-associated nausea. To our knowledge, this is the first described case of olanzapine-related resurgence of ED in a severely medically ill patient.

Atypical neuroleptics have been implicated in cases of compulsive behavioral disorders such as binge eating disorder (BED) and BN. The exact mechanism is unknown, although it is thought that serotonin receptors may have a role. ¹¹ According to a systematic review by Dahlgren et al., ¹⁷ the lifetime prevalence of BN is between 0.6% and 2.6% in females and the lifetime prevalence of BED was around 3% in females and 2% in males. BED is characterized by recurrent episodes of eating a larger portion of food within a two-hour time period than what is considered normal and is associated with a sense of lack of control and concern about binge eating. ¹⁸ Binge eating occurs at least once weekly for a minimum of three months. ¹⁸ It is also associated with at least three of the following: eating rapidly, eating until uncomfortably full, eating large amounts when not hungry, eating alone out of embarrassment, or feeling disgusted, depressed, or guilty after eating. ¹⁸ In addition to recurrent episodes of binge eating and lack of control occurring once per week for three months, BN also includes recurrent inappropriate compensatory behaviors to prevent weight gain. ¹⁸ BED is associated with increased anxiety and depression scores and a lower health-related quality of life. ¹⁹

In our case, BN behaviors were described within five weeks of initiating olanzapine at a dose of 2.5 mg twice daily and resolved within one week of decreasing the dose to olanzapine 2.5 mg daily at bedtime. This is consistent with other reports in which ED developed within one to six weeks of olanzapine initiation at doses as low as 5 mg per day.^12,13 Unfortunately, the current data looking at olanzapine-induced ED does not report on patients' experiences after discontinuation or dose reduction of olanzapine.^12,13,15,16 The likelihood of developing an ED from olanzapine is much greater in patients with a history of an ED, although ED still occurred even among patients with no history. ¹²

The association between olanzapine use and ED is important for the palliative care physician to recognize, as weight gain in the palliative care setting may be viewed as a beneficial side effect. When used in the treatment of psychiatric illness, olanzapine is associated with weight gain, with studies showing a median weight gain of 2.6 kg for six weeks. ²⁰ Weight gain in patients receiving olanzapine for symptom relief after a diagnosis of a serious illness is not well defined, although, if present, may be viewed as beneficial. Similar to our case, patients who developed ED tended to have increased weight gain, although not always significant.^13,15 Palliative care providers may miss signs of ED and assume that increased appetite and weight gain are positive effects of olanzapine. Given the significant negative impact ED has on health-related quality of life, it is important to recognize and screen for ED behaviors. Appropriate screening questions during patient encounters for any history of psychiatric illness or mental health diagnoses that have impacted quality of life should be asked before prescribing olanzapine or other psychotropics. For patients in whom a history of EDs is suspected or elicited, Herman et al. developed a 7-item BED screener that can be used by palliative care providers to help screen for BED in patients receiving olanzapine. ²¹ The questionnaire addresses episodes of excessive overeating in the last three months, distress about overeating, lack of control, eating when not hungry, embarrassment regarding eating, feelings of disgust or guilt, and self-induced vomiting. ²¹ The questionnaire has a sensitivity of 100% and a specificity of 38.7% and can be easily used in the clinical setting to identify patients who may have BED.^21,22

Providers caring for seriously ill patients should recognize that a resurgence of ED can occur in patients taking olanzapine just as it can in otherwise healthy patients. Certainly this case represents a single example and it is not yet known how commonly ED occurs in severely ill patients taking olanzapine. Fortunately, effective screening tools for ED exist, and ED can be treated with dose reduction/discontinuation of olanzapine, or referral to a health care provider specialized in ED.