Adjunctive Use of Olanzapine in the Treatment of Avoidant Restrictive Food Intake Disorder in Children and Adolescents in an Eating Disorders Program

Abstract

Objective:

There is little information about the pharmacological treatment of avoidant and restrictive food intake disorder (ARFID), a challenging feeding disorder associated with marked impairment and developmental arrest. This brief clinical report seeks to fill this gap.

Methods:

A retrospective chart review of nine patients with ARFID treated in an eating disorder (ED) program (residential, partial hospital, and intensive outpatient levels of care) with adjunctive olanzapine was undertaken.

Results:

The mean initial and final olanzapine doses were 0.9 + 0.63 mg/day and 2.8 + 1.47 mg/day, respectively. There was a statistically significant difference in weight gain pre- versus post-olanzapine treatment (3.3 ± 7.3 lbs vs. 13.1 ± 7.9 lbs [2.99 ± 6.62 lb SI vs. 11.88 ± 7.17 lb SI], paired t-test (p < 0.04, t = −2.48). Clinically, adjunctive olanzapine was helpful for not only weight gain but also reduction of associated anxious, depressive, and cognitive symptoms. Clinical Global Impressions scale scores indicated marked improvement in patients receiving adjunctive olanzapine.

Conclusion:

These cases illustrate that judicious use of low-dose olanzapine, when used as an adjunct to other treatment modalities, may facilitate eating, weight gain, and the reduction of anxious, depressive, and cognitive symptoms in ARFID patients. Future randomized, placebo-controlled studies in ARFID are warranted.

Avoidant and restrictive food intake disorder, ARFID, is a newly defined and challenging DSM-5 feeding disorder that is of major interest to feeding and eating disorder (ED) clinicians across disciplines (American Psychiatric Association 2013). Unlike EDs, such as anorexia nervosa (AN), restricted food intake and weight loss or failure to “thrive” or gain is not driven by body image distortion or fear of weight gain. Instead, food avoidance, restriction and the subsequent nutritional deprivation, and growth retardation that usually follows tend to be based on (1) extreme sensitivity to the sensory characteristics of food, such as taste, texture, smell, color, appearance, or temperature, and/or (2) a conditioned negative response involving the expectancy that a previous aversive experience will be repeated, such as difficulty swallowing and choking (pseudodysphagia) or repeated vomiting (emetophobia). Hence, ARFID is a serious, clinically challenging childhood onset feeding disorder that causes significant morbidity and higher mortality risk in those afflicted (Kreipe and Palomaki 2012; Bryant-Waugh 2013a, 2013b; Fisher et al. 2014).

The treatment of ARFID usually requires a team approach that may include pediatricians, child psychiatrists, therapists, nurses, dieticians, and occupational therapists. ARFID is often treated in ED programs that employ a variety of approaches borrowed from the treatment of AN and other EDs (Bryant-Waugh 2013a, 2013b; Ornstein et al. 2013; Nicely et al. 2014). Basic treatment principles, including behavior therapy, cognitive therapy, family therapy, and psychopharmacological interventions, are often essential ingredients. Notably, no specific pharmacological treatments have been reported that successfully treat ARFID (Kreipe and Palomaki 2012; Norris et al. 2014; Norris and Katzman 2015). However, clinicians have borrowed approaches for other related conditions, such as AN, especially olanzapine in doses much lower than those typically used in schizophrenia and bipolar disorder (Brewerton 2012).

The specific aim of this study is to document the clinical progress made in a series of children and adolescents (age range 9–19 years old) with chronic ARFID using low doses of adjunctive olanzapine.

Methods

Subjects

The participants included eight girls and three boys who were diagnosed with ARFID using DSM-5 criteria after admission by two board-certified psychiatrists and treatment team consensus. All patients with ARFID had been undiagnosed before admission but were symptomatic for many years. Of these 11 patients, 9 of them (8 females and 1 male) received adjunctive olanzapine. The two patients who did not receive olanzapine were not as ill as the others were and responded to the structured program immediately with adequate weight gain of at least 1 lb/week (.91 lb SI/week), so these patients were not included in this report. The mean age of the nine patients who received adjunctive olanzapine was 14.4 ± 4.1 years with a range of 9–19 years. Mean admission weight was 77.7 ± 17.9 lbs (70.40 ± 16.24 lb SI), and mean height was 58.8 ± 6.5 inches (149.35 ± 16.51 cm). Mean admission BMI was 15.6 ± 1.8 kg/m², and the mean admission BMI index-for-age percentile was 11.0 ± 14.7. Six of the nine patients were admitted with a BMI index-for-age percentile of <5 and five of the nine were <3.

Procedure

All participants and their parents gave written informed consent for evaluation and treatment upon admission to the Hearth Center for Eating Disorders. As part of this consent to treatment, parents also gave consent for the use of nonidentifiable clinical data in clinical research reports. This study involves a retrospective chart review of the clinical data for nine patients with ARFID who were admitted and treated with adjunctive olanzapine at the Hearth Center for Eating Disorders, a residential and partial hospital ED program, in Columbia, SC, during 2013–2015. Upon admission to the program, patients were treated in a structured behavioral program, including meal behavior therapy six times a day (three meals and three snacks) modified for patients with ARFID. In addition, patients received all other treatment modalities offered to ED patients, including individual, group and family therapies, nutrition counseling, and pharmacotherapy. If patients did not respond to the structured program by demonstrating improved eating and weight gain during the initial phase of treatment (a mean weight gain of ≥1 lb/week), they were offered low-dose olanzapine therapy, which was started at a dose of 0.625 mg at bedtime in seven of nine cases (ages 9–18), 1.25 mg at bedtime in one case (age 17), and 2.5 mg at bedtime in one case (age 18 and only because pill cutting instructions were not followed by the patient). Dosage was then titrated slowly based on clinical response and side effects. Daily eating behavior, weights, and psychological responses were monitored on an ongoing basis. The Clinical Global Impressions scale (CGIS) Severity scores were determined upon admission and at discharge by the authors, and Clinical Global Impressions (CGI) Global Improvement and Efficacy scale scores were administered by the authors upon discharge (Guy 1976). This research was approved by the Institutional Review Board of the Medical University of South Carolina.

Statistics

Descriptive statistics (mean ± standard deviation [SD]) were determined for demographic and baseline and/or discharge clinical characteristics, including age, weight, height, BMI, olanzapine dose, duration of treatment, and days on olanzapine. A paired t-test was performed to compare weight gain during the preolanzapine period versus the postolanzapine period. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), version 24.

Results

For the nine patients who received adjunctive olanzapine, the mean number of days in the program, including residential, partial hospital, and intensive outpatient levels of care, was 68.1 ± 20.6 days, and the mean number of days on olanzapine was 53.4 ± 22.4 days. The mean initial olanzapine dose was 0.9 ± 0.63 mg/day, and the mean discharge dose was 2.8 ± 1.47 mg/day. The mean change in weight and BMI from admission to discharge, respectively, was 16.4 ± 9.6 lbs (14.88 ± 8.71 lb SI) and 3.1 ± 1.34 kg/m². The mean change in BMI index-for-age percentile from admission to discharge was from 11.0 ± 14.7 to 35.9 ± 27.5 (paired t-test, p ≤ 0.002 (t = −4.64). The mean rate of weight gain during the entire treatment time in the program was 0.25 ± 0.12 lbs/day (.23 ± .11 lb SI/day) or 1.75 lbs/week (1.59 lb SI/week). When weight gain pretreatment versus posttreatment with olanzapine was compared, there were statistically significant differences in terms of weight (3.3 ± 7.3 lbs vs. 13.1 ± 7.9 lbs [2.99 ± 6.62 lb SI vs. 11.88 ± 7.17 lb SI], paired t-test, p < 0.04, t = −2.48) and BMI-for-weight percentiles (2.4 + 2.6 vs. 22.4 ± 16.5, paired t-test, p < 0.009, t = −3.46). This amounted to an average weight gain of 0.1 ± 0.25 lbs/day (.09 ± .23 lb SI/day) before initiating olanzapine (0.7 lb/week [.64 lb SI/week]) as compared with 0.27 ± 0.13 lbs/day (.24 ± .12 lb SI/day) (1.9 lbs/week [1.72 lb SI/week]) while on olanzapine.

All nine of the patients treated with olanzapine were diagnosed with current comorbid psychiatric disorders by clinical interview during initial psychiatric evaluation performed by experienced child–adolescent psychiatrists, including one or more of the following: separation anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social anxiety disorder. Six of the nine patients also had significant major depressive symptoms at the time of admission. By the time of discharge, all patients and their families reported significant improvement in anxiety and depressive symptoms. In addition, the cognitive functioning of all patients improved as noted by parents, therapists, and teachers in terms of school attendance, participation, and performance.

The mean CGI Severity scale scores at the time of admission were 5.3 ± 0.87 [5 = “markedly ill”] at the time of admission and 3.2 ± 1.1 [3 = “mildly ill”] at discharge (paired t-test, p ≤ 0.001, t = 8.1). Other mean CGI scale scores at the time of discharge were as follows: (1) CGI–Improvement scores: 1.9 ± 0.78 [1 = “very much improved,” 2 = “much improved”], (2) CGI–Efficacy scores: 3.3 ± 2.0 [marked therapeutic effect with no side effects (01): n = 3; marked therapeutic effect with side effects that do not significantly interfere with functioning (02): n = 1; moderate therapeutic effect with no side effects (05): n = 5; minimal therapeutic effect with no side effects (09): n = 1 (see Follow-up notes section)].

Follow-up notes

One patient (9 years old, male) with the atypical presentation of intermittent involuntary vomiting was subsequently diagnosed as having a mid-brain tumor and was lost to follow-up in another state.

Discussion

In this case series of nine patients with ARFID treated in an ED program for children and adolescents, we found that adjunctive olanzapine facilitated recovery, in terms of not only promoting eating and weight gain but also relieving related symptoms of anxiety, depression, and cognitive impairment. This report contributes to the paucity of information regarding the psychopharmacological treatment of ARFID as well as a rationale for the use of low doses of olanzapine in ARFID. Olanzapine is arguably the most efficacious psychopharmacological agent for AN (Brewerton 2012), which shares similarities with ARFID. In addition to enhancing reduced appetite, which is a common clinical feature of ARFID, olanzapine also promotes mood stabilization, reduction of obsessional anxiety, and enhanced cognitions (Brewerton 2012). Its safety profile in children and adolescents has been well established (Norris et al. 2011; Swenne and Rosling 2011). In this case series, we strived to use the least effective dose possible to produce a clinical effect while simultaneously limiting potential side effects. The mean starting dose was <1 mg/day and the mean discharge dose was <3 mg/day. The rationale for this cautious strategy has been discussed in detail previously with regard to the use of olanzapine in AN (Brewerton 2012).

Limitations of this study include its open nature and lack of a control treatment. In addition, other active treatments were being administered in addition to drug treatment. Moreover, the profound positive effects on the brain, body, and psyche of normalizing eating and achieving weight restoration, as well as reversing previously arrested development, cannot be underestimated, nor can it be separated from the possible therapeutic effects of olanzapine. Nevertheless, given our encouraging results, future randomized, placebo-controlled studies in ARFID are warranted. Until such time, the adjunctive use of olanzapine in the treatment of ARFID in children and adolescents may be a rational strategy, particularly in patients who do not respond to nonpharmacological interventions.

Conclusions

In this brief report of nine cases of ARFID treated in a structured ED program, it was shown that the prudent use of low-dose olanzapine, when used as an adjunct to other treatment modalities, may facilitate eating, weight gain, and the reduction of anxious, depressive, and cognitive symptoms. Although this study lacked a control, the patients gained significantly more weight after the initiation of olanzapine compared to before olanzapine, and their CGI scale scores indicated marked improvement with minimal side effects. Given this favorable benefit-risk profile, the adjunctive use of low-dose olanzapine in ARFID appears justified, and future randomized, placebo-controlled studies of olanzapine in ARFID would be a rational extension of this study.

Clinical Significance

These findings help to fill a gap in the literature regarding the psychopharmacologic treatment of ARFID, a highly debilitating condition that is quite challenging to clinicians of all disciplines. There are currently no randomized, controlled trials demonstrating the efficacy of any psychotropic agents for ARFID, so this study offers a basis and some guidance for the use of olanzapine in treating this serious condition. Although these nine young patients were being treated in a structured ED program setting, olanzapine appeared to significantly facilitate normalized eating behavior and weight restoration, as well as improvements in mood, anxiety and cognition. Such clinical improvements are likely due to a combination of the effects of olanzapine, the behavioral components of structured treatment, and the subsequent normalization of body weight. The authors emphasize the importance of starting with very low doses (requiring pill cutting) and titrating doses slowly upwards as tolerated in order to avoid adverse effects and to assuage parental and patient concerns.

Footnotes

Disclosures

The authors have no conflicts of interest to declare.

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