Journal of Adolescent Health 57 (2015) 66e72
www.jahonline.org Original article
Use of Psychopharmacologic Medications in Adolescents With Restrictive Eating Disorders: Analysis of Data From the National Eating Disorder Quality Improvement Collaborative Maria C. Monge, M.D., M.A.T. a, *, Sara F. Forman, M.D. a, Nicole M. McKenzie a, David S. Rosen, M.D., M.P.H. b, c, d, Kathleen A. Mammel, M.D. e, S. Todd Callahan, M.D., M.P.H. f, Rebecca Hehn, M.A. g, Ellen S. Rome, M.D., M.P.H. h, Cynthia J. Kapphahn, M.D., M.P.H. i, Jennifer L. Carlson, M.D. i, Mary E. Romano, M.D., M.P.H. f, Joan B. Malizio, M.S.N. j, Terrill D. Bravender, M.D., M.P.H. k, l, Eric J. Sigel, M.D. m, Mary R. Rouse, M.D. n, Dionne A. Graham, Ph.D. o, M. Susan Jay, M.D. p, Albert C. Hergenroeder, M.D. q, Martin M. Fisher, M.D. j, r, Neville H. Golden, M.D. i, and Elizabeth R. Woods, M.D., M.P.H. a a
Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital, Boston, Massachusetts Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan c Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan d Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan e Division of Adolescent Pediatrics, Beaumont Children’s Hospital, Royal Oak, Michigan f Division of Adolescent Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee g Program for Patient Safety and Quality, Boston Children’s Hospital, Boston, Massachusetts h Section of Adolescent Medicine, Department of General Pediatrics, Cleveland Clinic Children’s Hospital, Cleveland, Ohio i Division of Adolescent Medicine, Stanford University School of Medicine, Stanford, California j Division of Adolescent Medicine, Steven and Alexandra Cohen Children’s Medical Center, North Shore-Long Island Jewish Health System, New Hyde Park, New York k Department of Pediatrics, The Ohio State University, Columbus, Ohio l Nationwide Children’s Hospital, Columbus, Ohio m Children’s Hospital of Colorado, Section of Adolescent Medicine, University of Colorado, Aurora, Colorado n Department of Pediatrics, Indiana University School of Medicine, Indiana University Health, Indianapolis, Indiana o Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts p Division of Adolescent Medicine, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin q Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas r Department of Pediatrics, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, New York b
Article history: Received December 19, 2014; Accepted March 25, 2015 Keywords: Restrictive eating disorders; Psychopharmacology; Adolescents; Anorexia nervosa; Medications; Psychiatric comorbidity
A B S T R A C T
Purpose: Psychopharmacologic medications are often prescribed to patients with restrictive eating disorders (EDs), and little is known about the frequency of use in adolescents. We examined the use of psychopharmacologic medications in adolescents referred for treatment of restrictive ED, potential factors associated with their use, and reported psychiatric comorbidities. Methods: Retrospective data from the initial and 1-year visits were collected for patients referred for evaluation of restrictive ED at 12 adolescent-based ED programs during 2010 (Group 1), including diagnosis, demographic information, body mass index, prior treatment modalities, and psychopharmacologic medications. Additional data regarding patients’ comorbid psychiatric conditions * Address correspondence to: Maria C. Monge, M.D., M.A.T., Director of Adolescent Medicine, Dell Children’s Medical Center of Central Texas, Texas Child Study Center, 1600 W. 38th St, Jefferson Building, Ste 212, Austin, TX 78731. E-mail address: [email protected] (M.C. Monge). 1054-139X/Ó 2015 Society for Adolescent Health and Medicine. All rights reserved. http://dx.doi.org/10.1016/j.jadohealth.2015.03.021
IMPLICATIONS AND CONTRIBUTION
Psychopharmacologic medications are prescribed at high rates to adolescents with restrictive eating disorders both at intake and 1-year follow-up. Reported psychiatric comorbidity
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72
and classes of psychopharmacologic medications were obtained from six sites (Group 2). Results: Overall, 635 patients met inclusion criteria and 359 had 1-year follow-up (Group 1). At intake, 20.4% of Group 1 was taking psychopharmacologic medication and 58.7% at 1 year (p .0001). White, non-Hispanic race (p ¼ .020), and prior higher level of care (p < .0001) were positively associated with medication use at 1 year. Among Group 2 (n ¼ 256), serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors use was most common, and 62.6% had a reported psychiatric comorbidity. Presence of any psychiatric comorbidity was highly associated with medication use; odds ratio, 10.0 (5.6, 18.0). Conclusions: Adolescents with restrictive ED treated at referral centers have high rates of reported psychopharmacologic medication use and psychiatric comorbidity. As more than half of this referral population were reported to be taking medication, continued investigation is warranted to ensure the desired outcomes of the medications are being met. Ó 2015 Society for Adolescent Health and Medicine. All rights reserved.
Restrictive eating disorders (EDs) are a well-recognized problem in the adolescent population and impact multiple aspects of adolescent wellbeing. Treatment of an adolescent with a restrictive ED often includes multidisciplinary care with input from medical, mental health, and nutrition professionals [1,2]. The cornerstone of treatment is weight restoration and behavior modification [3]. Psychiatric comorbidity is common among patients with restrictive ED; more than half of adolescents diagnosed with anorexia nervosa and more than three quarters of adolescents with subthreshold anorexia nervosa also meet criteria for another psychiatric condition [4,5]. Often, it is difficult to determine if symptoms of the comorbid psychiatric condition preceded the onset of the restrictive eating behaviors or if these symptoms developed during the course of the ED. Anxiety and depressive symptoms can be the result of malnutrition and may improve with nutritional rehabilitation [6]. The presence of comorbid psychiatric conditions has been associated with worse outcomes, including increased rates of suicide attempts and increased suicide-related mortality [7]. Psychopharmacologic medications are often prescribed as adjunctive therapy, targeting both the restrictive ED and psychiatric comorbid symptoms [6,8]. Fazeli et al. (2012) reported that more than half of adult women with anorexia nervosa referred to their program were treated with these medications and 30% were taking more medications at follow-up than intake. Antipsychotics and selective serotonin reuptake inhibitors/ serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) were the most commonly prescribed classes of medications. In their study, the rate of atypical antipsychotics use doubled over the 12 years from 1997 to 2009 increasing from 8.9% to 18.5%, whereas rates of SSRI/SNRI use were stable but higher over the same interval with approximately 50% of patients reporting use. Despite the increased use of psychopharmacologic medications, multiple studies in adults have not found them to be effective in the treatment or recovery/relapse prevention phase for patients with anorexia nervosa [9e15]. Less is known about rates of medication use and efficacy in adolescents with restrictive ED. One small study reported that 40% of adolescents, with restrictive ED, enrolled in a risperidone study were taking an antidepressant medication at time of enrollment [16]. A recent cross-sectional community population study estimated that overall psychopharmacologic medication use in adolescents diagnosed with any ED (19.3%) is approximately equivalent to that in the treatment of mood disorders
67
was also high and highly associated with medication use.
(19.7%) [17]. To date, there have been few medication trials in adolescent patients with restrictive ED, and these trials have not demonstrated benefit in sustaining weight recovery [16,18e20], but they are limited by small size, problems with recruitment, high drop-out rates, and short duration [12,20]. The goal of the present study was to investigate rates of reported psychopharmacologic medication use in a sample of U.S. adolescents and a few young adults referred to adolescent medicine-based ED programs for treatment of restrictive ED and to explore if the presence of psychiatric comorbidities and other factors were associated with reported psychopharmacologic medication use in this population. Methods Data source and collection procedures The National Eating Disorder Quality Improvement Collaborative (NEDQIC), initially a group of 11 Adolescent Medicinebased ED programs, was formed in 2006 to address knowledge gaps in treatment outcomes in adolescents with restrictive ED [21]. The first phase of the NEDQIC reviewed data from 2006, and the second phase of the collaborative commenced in 2011 with the review of data from 2010. For Phase 2 of the collaborative, 12 adolescent medicine sites throughout the United States provided data for patients who met the following inclusion criteria: diagnosis of restrictive ED based on the proposed DSM-5 criteria for anorexia nervosa (AN), atypical anorexia nervosa (AAN), or avoidant/restrictive food intake disorder (ARFID); aged 9e21 years; initial program visit between January 1, 2010 and December 31, 2010; and a total of at least three program visits [22]. Data were collected through retrospective chart review as part of the second phase of the NEDQIC. A 90-question extraction tool designed by members of the collaborative was used to collect information including demographics (age, sex, race/ ethnicity), growth, and weight parameters (height, weight, body mass index), percent median body mass index [% MBMI]), restrictive eating diagnosis, duration of illness, treatment modalities including “higher level of care” (inpatient medical or psychiatric hospitalization, residential ED program, day treatment program or intensive outpatient program), outpatient therapy, psychopharmacologic medication use, and follow-up status. Data were extracted from the patient’s initial program visit and the visit closest to 1 year after intake (between 9 and
68
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72
Patients meeting inclusion criteria (n=635) 1. 2. 3. 4.
Diagnosis of restrictive eating disorder (DSM-5) Age 9-21 years Initial program visit January 1-December 31, 2010 Minimum 3 program visits
GROUP 1
Patients without 1-year follow-up data (n=276)
Patients with 1-year follow-up data (n=359)
GROUP 2 Patients with additional psychopharmacologic medication and psychiatric comorbidity data (n=256)
Patients without additional psychopharmacologic medication and psychiatric comorbidity data (n=103)
Figure 1. Flow diagram of patients with restrictive EDs included in analysis.
15 months). For purposes of analysis, patients with 1-year follow-up data comprised Group 1 (Figure 1). Six sites used a supplemental data extraction tool, also designed by members of the NEDQIC, to collect additional information on psychiatric comorbidities (depression, anxiety, obsessive-compulsive disorder, attention deficit hyperactivity disorder, bipolar disorder, autism spectrum disorder, and other) and psychopharmacologic medication classes (SSRI/SNRI, other antidepressant, antipsychotic, mood stabilizer, anxiolytic, stimulant, atomoxetine, and other). Psychiatric comorbid diagnosis information was obtained from the medical chart, and if a formal diagnosis was made by a mental health professional, this was noted. Data were collected for the initial visit and 1-year follow-up visit (between 9 and 15 months). Patients with this additional data, who had a 1-year follow-up visit, comprised Group 2 (Figure 1). Each participating site was provided with data shells in SPSS (SPSS Inc. 2009. PASW Statistics for Windows, version 18.0; Chicago, IL) or Excel (Microsoft Excel, 2010, Redmond, WA). De-identified data from each site were pooled at the lead site (Boston Children’s Hospital). A Health Insurance Portability and Accountability Act data sharing agreement was obtained from each site, and each site received approval from their institutional review board for a quality improvement chart review with de-identified data. At the six sites collecting additional psychopharmacologic data, an institutional review board amendment was submitted. Data analysis was performed at the Boston Children’s Hospital site using SPSS (SPSS Inc. 2009) and SAS version 9.3 (Cary, NC). Statistical analyses Chi-square tests, independent sample t-tests, and Wilcoxon rank sum test (illness duration) were used to assess differences between individuals with and without 1-year follow-up. Chi-square test was used to compare the percentage of psychopharmacologic medication use at intake among the three diagnostic groups (AN, AAN, and ARFID). Logistic regression modeling
was used to examine potential predictors of psychopharmacologic medication use at 1 year. Significant or borderline predictors of medication use in the univariate logistic regression model (inclusion criteria: p value < .20) were included in a multivariate logistic regression model, and a risk-adjusted model was constructed to assess differences between the sites for medication use. McNemar’s test was used to assess the association between psychopharmacologic use at baseline and follow-up. Fisher’s exact test was used to examine the association between weight recovery (1-year % MBMI 90%) and medication use for patients who were underweight at intake (intake % MBMI 18 months, and diagnosis of anorexia nervosa were all borderline significant at the univariate level. In subsequent multivariate analysis, only white, non-Hispanic, race and intensive therapy before intake were associated with reported medication use at 1 year when controlling for indicators of disease severity (underweight at intake [18 months). Older age was borderline significant (p ¼ .055; Table 2). When Group 1 was restricted to patients 18 months, intensive therapy before intake). Two sites did not have sufficient data for inclusion in the model. There was no statistically significant difference between sites with respect to reported medication use at 1-year follow-up (Figure 2). Group 2 included 256 patients who had been followed for 1 year and had additional data on pharmacologic medication classes and comorbid psychiatric conditions. Race/ethnicity was the only significant difference between those patients in Group 2 and those without additional information, as patients in Group 2 were less likely to be white, non-Hispanic (Table 1). At intake, 20.7% of Group 2 had reported psychopharmacologic medication use, and this increased significantly to 55.9% at 1-year follow-up (p < .0005). There was no difference in medication use between restrictive eating diagnoses (p ¼ .52, baseline; p ¼ .18, 1-year follow-up; Figure 3). Of patients with reported medication use at 1 year, SSRI/SNRI was the most often reported class (82.5%) followed by anxiolytic (17.5%),
Table 2 Predictors of reported psychopharmacologic medication use at 1-year follow-up (Group 1)
Older age (5-year increments) Female gender White, non-Hispanic race 18 months Diagnosis of anorexia nervosa Intensive treatment before intake
Univariate analysis (odds ratio)
p value
Multivariate analysis (odds ratio)
p value
1.7 1.9 2.6 1.3 1.7 1.5 2.5
.029 .053 .0092 .22 .062 .081 .0077
1.7 1.3 2.8 1.1 1.4 1.6 2.5
.055 .54 .012 .72 .37 .10 .018
(1.05, 2.71) (1.0, 3.7) (1.3, 5.3) (.85, 2.0) (.97, 3.0) (.97, 2.2) (1.3, 4.8)
Bold denotes the significant results. % MBMI ¼ % median body weight (patient’s BMI/50% BMI for age 100).
(.99, 2.9) (.58, 2.8) (1.3, 6.5) (.62, 2.0) (.69, 2.7) (.91, 2.9) (1.2, 5.5)
70
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72 2.5
Observed/Expected
2
1.5
1
0.5
0 A
B
C
D
E
F
G
H
I
J
Site Figure 2. Comparison of adolescent medicine sites* reported medication use at 1 year, controlled for restrictive ED severity. *Two sites without sufficient data for inclusion in model.
antipsychotic (16.8%), other antidepressant (14.7%), mood stabilizer (7.7%), other psychopharmacologic medication not listed elsewhere (cyproheptadine, gabapentin and guanfacine; 6.3%), stimulant (5.6%), and atomoxetine (1.4%); 30.1% of patients on psychopharmacologic medications were taking two or more medications at 1-year follow-up. At 1-year follow-up, 62.6% of patients had a listed psychiatric comorbidity: anxiety in 43.7%, depression in 25.7%, attention deficit hyperactivity disorder in 2.1%, bipolar disorder in .5%, other diagnosis in 1.6% (including post-traumatic stress disorder, personality disorder, drug abuse, conversion disorder, trichotillomania, oppositional defiant disorder, body dysmorphic disorder). Anxiety was reported significantly more often in patients with AN and ARFID than that in patients with AAN (AN 47.7%, ARFID 44.4%, AAN 24.7%; p ¼ .002), whereas reported depression was not statistically different between diagnostic groups (AN 25.8%, AAN 26.8%, ARFID 22.2%; p ¼ .89).
Of patients with a listed psychiatric comorbid condition, 41.4% were known to have received a formal diagnosis by a mental health professional. In addition, 90.9% of patients receiving a formal diagnosis had a listed psychopharmacologic medication, whereas 74.2% of patients without a formal diagnosis were listed as taking medication, which was not significantly different (p ¼ .17). Reported medication use increased as the number of reported psychiatric conditions increased. Among Group 2, 25.0% of patients who had no reported psychiatric comorbidities had been prescribed a psychopharmacologic medication(s), compared with 68.8% of patients with one reported comorbidity and 91.1% of patients with two or more comorbidities. Having any psychiatric comorbid condition listed had an odds ratio of 10.0 (5.6, 18.0) for reported medication use. Anxiety had an odds ratio of 5.3 (2.9, 9.4) and depression 7.7 (3.5, 16.4) for medication use. At 1-year follow-up, 84.9% of patients with a listed diagnosis
100
Percent paƟents with reported medicaƟon use
90 80
p=0.18 70 61.4 60
55.9 49.5
50
51.9
Overall AN AAN
40
p=0.52
ARFID
30 20.7
23.5 17.5
20
18.5
10 0 Intake Program Visit
1-year f/u 1-year follow-up
Figure 3. Group 2 reported psychopharmacologic medication use overall and by diagnosis at intake and 1-year follow-up (n ¼ 256). AN ¼ anorexia nervosa; AAN ¼ atypical anorexia nervosa; ARFID ¼ avoidant/restrictive food intake disorder.
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72
of depression, 76.6% with anxiety, and 76.0% with any psychiatric comorbidity had reported medication use. When Group 2 was restricted to patients
www.jahonline.org Original article
Use of Psychopharmacologic Medications in Adolescents With Restrictive Eating Disorders: Analysis of Data From the National Eating Disorder Quality Improvement Collaborative Maria C. Monge, M.D., M.A.T. a, *, Sara F. Forman, M.D. a, Nicole M. McKenzie a, David S. Rosen, M.D., M.P.H. b, c, d, Kathleen A. Mammel, M.D. e, S. Todd Callahan, M.D., M.P.H. f, Rebecca Hehn, M.A. g, Ellen S. Rome, M.D., M.P.H. h, Cynthia J. Kapphahn, M.D., M.P.H. i, Jennifer L. Carlson, M.D. i, Mary E. Romano, M.D., M.P.H. f, Joan B. Malizio, M.S.N. j, Terrill D. Bravender, M.D., M.P.H. k, l, Eric J. Sigel, M.D. m, Mary R. Rouse, M.D. n, Dionne A. Graham, Ph.D. o, M. Susan Jay, M.D. p, Albert C. Hergenroeder, M.D. q, Martin M. Fisher, M.D. j, r, Neville H. Golden, M.D. i, and Elizabeth R. Woods, M.D., M.P.H. a a
Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital, Boston, Massachusetts Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan c Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan d Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan e Division of Adolescent Pediatrics, Beaumont Children’s Hospital, Royal Oak, Michigan f Division of Adolescent Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee g Program for Patient Safety and Quality, Boston Children’s Hospital, Boston, Massachusetts h Section of Adolescent Medicine, Department of General Pediatrics, Cleveland Clinic Children’s Hospital, Cleveland, Ohio i Division of Adolescent Medicine, Stanford University School of Medicine, Stanford, California j Division of Adolescent Medicine, Steven and Alexandra Cohen Children’s Medical Center, North Shore-Long Island Jewish Health System, New Hyde Park, New York k Department of Pediatrics, The Ohio State University, Columbus, Ohio l Nationwide Children’s Hospital, Columbus, Ohio m Children’s Hospital of Colorado, Section of Adolescent Medicine, University of Colorado, Aurora, Colorado n Department of Pediatrics, Indiana University School of Medicine, Indiana University Health, Indianapolis, Indiana o Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts p Division of Adolescent Medicine, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin q Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas r Department of Pediatrics, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, New York b
Article history: Received December 19, 2014; Accepted March 25, 2015 Keywords: Restrictive eating disorders; Psychopharmacology; Adolescents; Anorexia nervosa; Medications; Psychiatric comorbidity
A B S T R A C T
Purpose: Psychopharmacologic medications are often prescribed to patients with restrictive eating disorders (EDs), and little is known about the frequency of use in adolescents. We examined the use of psychopharmacologic medications in adolescents referred for treatment of restrictive ED, potential factors associated with their use, and reported psychiatric comorbidities. Methods: Retrospective data from the initial and 1-year visits were collected for patients referred for evaluation of restrictive ED at 12 adolescent-based ED programs during 2010 (Group 1), including diagnosis, demographic information, body mass index, prior treatment modalities, and psychopharmacologic medications. Additional data regarding patients’ comorbid psychiatric conditions * Address correspondence to: Maria C. Monge, M.D., M.A.T., Director of Adolescent Medicine, Dell Children’s Medical Center of Central Texas, Texas Child Study Center, 1600 W. 38th St, Jefferson Building, Ste 212, Austin, TX 78731. E-mail address: [email protected] (M.C. Monge). 1054-139X/Ó 2015 Society for Adolescent Health and Medicine. All rights reserved. http://dx.doi.org/10.1016/j.jadohealth.2015.03.021
IMPLICATIONS AND CONTRIBUTION
Psychopharmacologic medications are prescribed at high rates to adolescents with restrictive eating disorders both at intake and 1-year follow-up. Reported psychiatric comorbidity
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72
and classes of psychopharmacologic medications were obtained from six sites (Group 2). Results: Overall, 635 patients met inclusion criteria and 359 had 1-year follow-up (Group 1). At intake, 20.4% of Group 1 was taking psychopharmacologic medication and 58.7% at 1 year (p .0001). White, non-Hispanic race (p ¼ .020), and prior higher level of care (p < .0001) were positively associated with medication use at 1 year. Among Group 2 (n ¼ 256), serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors use was most common, and 62.6% had a reported psychiatric comorbidity. Presence of any psychiatric comorbidity was highly associated with medication use; odds ratio, 10.0 (5.6, 18.0). Conclusions: Adolescents with restrictive ED treated at referral centers have high rates of reported psychopharmacologic medication use and psychiatric comorbidity. As more than half of this referral population were reported to be taking medication, continued investigation is warranted to ensure the desired outcomes of the medications are being met. Ó 2015 Society for Adolescent Health and Medicine. All rights reserved.
Restrictive eating disorders (EDs) are a well-recognized problem in the adolescent population and impact multiple aspects of adolescent wellbeing. Treatment of an adolescent with a restrictive ED often includes multidisciplinary care with input from medical, mental health, and nutrition professionals [1,2]. The cornerstone of treatment is weight restoration and behavior modification [3]. Psychiatric comorbidity is common among patients with restrictive ED; more than half of adolescents diagnosed with anorexia nervosa and more than three quarters of adolescents with subthreshold anorexia nervosa also meet criteria for another psychiatric condition [4,5]. Often, it is difficult to determine if symptoms of the comorbid psychiatric condition preceded the onset of the restrictive eating behaviors or if these symptoms developed during the course of the ED. Anxiety and depressive symptoms can be the result of malnutrition and may improve with nutritional rehabilitation [6]. The presence of comorbid psychiatric conditions has been associated with worse outcomes, including increased rates of suicide attempts and increased suicide-related mortality [7]. Psychopharmacologic medications are often prescribed as adjunctive therapy, targeting both the restrictive ED and psychiatric comorbid symptoms [6,8]. Fazeli et al. (2012) reported that more than half of adult women with anorexia nervosa referred to their program were treated with these medications and 30% were taking more medications at follow-up than intake. Antipsychotics and selective serotonin reuptake inhibitors/ serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) were the most commonly prescribed classes of medications. In their study, the rate of atypical antipsychotics use doubled over the 12 years from 1997 to 2009 increasing from 8.9% to 18.5%, whereas rates of SSRI/SNRI use were stable but higher over the same interval with approximately 50% of patients reporting use. Despite the increased use of psychopharmacologic medications, multiple studies in adults have not found them to be effective in the treatment or recovery/relapse prevention phase for patients with anorexia nervosa [9e15]. Less is known about rates of medication use and efficacy in adolescents with restrictive ED. One small study reported that 40% of adolescents, with restrictive ED, enrolled in a risperidone study were taking an antidepressant medication at time of enrollment [16]. A recent cross-sectional community population study estimated that overall psychopharmacologic medication use in adolescents diagnosed with any ED (19.3%) is approximately equivalent to that in the treatment of mood disorders
67
was also high and highly associated with medication use.
(19.7%) [17]. To date, there have been few medication trials in adolescent patients with restrictive ED, and these trials have not demonstrated benefit in sustaining weight recovery [16,18e20], but they are limited by small size, problems with recruitment, high drop-out rates, and short duration [12,20]. The goal of the present study was to investigate rates of reported psychopharmacologic medication use in a sample of U.S. adolescents and a few young adults referred to adolescent medicine-based ED programs for treatment of restrictive ED and to explore if the presence of psychiatric comorbidities and other factors were associated with reported psychopharmacologic medication use in this population. Methods Data source and collection procedures The National Eating Disorder Quality Improvement Collaborative (NEDQIC), initially a group of 11 Adolescent Medicinebased ED programs, was formed in 2006 to address knowledge gaps in treatment outcomes in adolescents with restrictive ED [21]. The first phase of the NEDQIC reviewed data from 2006, and the second phase of the collaborative commenced in 2011 with the review of data from 2010. For Phase 2 of the collaborative, 12 adolescent medicine sites throughout the United States provided data for patients who met the following inclusion criteria: diagnosis of restrictive ED based on the proposed DSM-5 criteria for anorexia nervosa (AN), atypical anorexia nervosa (AAN), or avoidant/restrictive food intake disorder (ARFID); aged 9e21 years; initial program visit between January 1, 2010 and December 31, 2010; and a total of at least three program visits [22]. Data were collected through retrospective chart review as part of the second phase of the NEDQIC. A 90-question extraction tool designed by members of the collaborative was used to collect information including demographics (age, sex, race/ ethnicity), growth, and weight parameters (height, weight, body mass index), percent median body mass index [% MBMI]), restrictive eating diagnosis, duration of illness, treatment modalities including “higher level of care” (inpatient medical or psychiatric hospitalization, residential ED program, day treatment program or intensive outpatient program), outpatient therapy, psychopharmacologic medication use, and follow-up status. Data were extracted from the patient’s initial program visit and the visit closest to 1 year after intake (between 9 and
68
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72
Patients meeting inclusion criteria (n=635) 1. 2. 3. 4.
Diagnosis of restrictive eating disorder (DSM-5) Age 9-21 years Initial program visit January 1-December 31, 2010 Minimum 3 program visits
GROUP 1
Patients without 1-year follow-up data (n=276)
Patients with 1-year follow-up data (n=359)
GROUP 2 Patients with additional psychopharmacologic medication and psychiatric comorbidity data (n=256)
Patients without additional psychopharmacologic medication and psychiatric comorbidity data (n=103)
Figure 1. Flow diagram of patients with restrictive EDs included in analysis.
15 months). For purposes of analysis, patients with 1-year follow-up data comprised Group 1 (Figure 1). Six sites used a supplemental data extraction tool, also designed by members of the NEDQIC, to collect additional information on psychiatric comorbidities (depression, anxiety, obsessive-compulsive disorder, attention deficit hyperactivity disorder, bipolar disorder, autism spectrum disorder, and other) and psychopharmacologic medication classes (SSRI/SNRI, other antidepressant, antipsychotic, mood stabilizer, anxiolytic, stimulant, atomoxetine, and other). Psychiatric comorbid diagnosis information was obtained from the medical chart, and if a formal diagnosis was made by a mental health professional, this was noted. Data were collected for the initial visit and 1-year follow-up visit (between 9 and 15 months). Patients with this additional data, who had a 1-year follow-up visit, comprised Group 2 (Figure 1). Each participating site was provided with data shells in SPSS (SPSS Inc. 2009. PASW Statistics for Windows, version 18.0; Chicago, IL) or Excel (Microsoft Excel, 2010, Redmond, WA). De-identified data from each site were pooled at the lead site (Boston Children’s Hospital). A Health Insurance Portability and Accountability Act data sharing agreement was obtained from each site, and each site received approval from their institutional review board for a quality improvement chart review with de-identified data. At the six sites collecting additional psychopharmacologic data, an institutional review board amendment was submitted. Data analysis was performed at the Boston Children’s Hospital site using SPSS (SPSS Inc. 2009) and SAS version 9.3 (Cary, NC). Statistical analyses Chi-square tests, independent sample t-tests, and Wilcoxon rank sum test (illness duration) were used to assess differences between individuals with and without 1-year follow-up. Chi-square test was used to compare the percentage of psychopharmacologic medication use at intake among the three diagnostic groups (AN, AAN, and ARFID). Logistic regression modeling
was used to examine potential predictors of psychopharmacologic medication use at 1 year. Significant or borderline predictors of medication use in the univariate logistic regression model (inclusion criteria: p value < .20) were included in a multivariate logistic regression model, and a risk-adjusted model was constructed to assess differences between the sites for medication use. McNemar’s test was used to assess the association between psychopharmacologic use at baseline and follow-up. Fisher’s exact test was used to examine the association between weight recovery (1-year % MBMI 90%) and medication use for patients who were underweight at intake (intake % MBMI 18 months, and diagnosis of anorexia nervosa were all borderline significant at the univariate level. In subsequent multivariate analysis, only white, non-Hispanic, race and intensive therapy before intake were associated with reported medication use at 1 year when controlling for indicators of disease severity (underweight at intake [18 months). Older age was borderline significant (p ¼ .055; Table 2). When Group 1 was restricted to patients 18 months, intensive therapy before intake). Two sites did not have sufficient data for inclusion in the model. There was no statistically significant difference between sites with respect to reported medication use at 1-year follow-up (Figure 2). Group 2 included 256 patients who had been followed for 1 year and had additional data on pharmacologic medication classes and comorbid psychiatric conditions. Race/ethnicity was the only significant difference between those patients in Group 2 and those without additional information, as patients in Group 2 were less likely to be white, non-Hispanic (Table 1). At intake, 20.7% of Group 2 had reported psychopharmacologic medication use, and this increased significantly to 55.9% at 1-year follow-up (p < .0005). There was no difference in medication use between restrictive eating diagnoses (p ¼ .52, baseline; p ¼ .18, 1-year follow-up; Figure 3). Of patients with reported medication use at 1 year, SSRI/SNRI was the most often reported class (82.5%) followed by anxiolytic (17.5%),
Table 2 Predictors of reported psychopharmacologic medication use at 1-year follow-up (Group 1)
Older age (5-year increments) Female gender White, non-Hispanic race 18 months Diagnosis of anorexia nervosa Intensive treatment before intake
Univariate analysis (odds ratio)
p value
Multivariate analysis (odds ratio)
p value
1.7 1.9 2.6 1.3 1.7 1.5 2.5
.029 .053 .0092 .22 .062 .081 .0077
1.7 1.3 2.8 1.1 1.4 1.6 2.5
.055 .54 .012 .72 .37 .10 .018
(1.05, 2.71) (1.0, 3.7) (1.3, 5.3) (.85, 2.0) (.97, 3.0) (.97, 2.2) (1.3, 4.8)
Bold denotes the significant results. % MBMI ¼ % median body weight (patient’s BMI/50% BMI for age 100).
(.99, 2.9) (.58, 2.8) (1.3, 6.5) (.62, 2.0) (.69, 2.7) (.91, 2.9) (1.2, 5.5)
70
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72 2.5
Observed/Expected
2
1.5
1
0.5
0 A
B
C
D
E
F
G
H
I
J
Site Figure 2. Comparison of adolescent medicine sites* reported medication use at 1 year, controlled for restrictive ED severity. *Two sites without sufficient data for inclusion in model.
antipsychotic (16.8%), other antidepressant (14.7%), mood stabilizer (7.7%), other psychopharmacologic medication not listed elsewhere (cyproheptadine, gabapentin and guanfacine; 6.3%), stimulant (5.6%), and atomoxetine (1.4%); 30.1% of patients on psychopharmacologic medications were taking two or more medications at 1-year follow-up. At 1-year follow-up, 62.6% of patients had a listed psychiatric comorbidity: anxiety in 43.7%, depression in 25.7%, attention deficit hyperactivity disorder in 2.1%, bipolar disorder in .5%, other diagnosis in 1.6% (including post-traumatic stress disorder, personality disorder, drug abuse, conversion disorder, trichotillomania, oppositional defiant disorder, body dysmorphic disorder). Anxiety was reported significantly more often in patients with AN and ARFID than that in patients with AAN (AN 47.7%, ARFID 44.4%, AAN 24.7%; p ¼ .002), whereas reported depression was not statistically different between diagnostic groups (AN 25.8%, AAN 26.8%, ARFID 22.2%; p ¼ .89).
Of patients with a listed psychiatric comorbid condition, 41.4% were known to have received a formal diagnosis by a mental health professional. In addition, 90.9% of patients receiving a formal diagnosis had a listed psychopharmacologic medication, whereas 74.2% of patients without a formal diagnosis were listed as taking medication, which was not significantly different (p ¼ .17). Reported medication use increased as the number of reported psychiatric conditions increased. Among Group 2, 25.0% of patients who had no reported psychiatric comorbidities had been prescribed a psychopharmacologic medication(s), compared with 68.8% of patients with one reported comorbidity and 91.1% of patients with two or more comorbidities. Having any psychiatric comorbid condition listed had an odds ratio of 10.0 (5.6, 18.0) for reported medication use. Anxiety had an odds ratio of 5.3 (2.9, 9.4) and depression 7.7 (3.5, 16.4) for medication use. At 1-year follow-up, 84.9% of patients with a listed diagnosis
100
Percent paƟents with reported medicaƟon use
90 80
p=0.18 70 61.4 60
55.9 49.5
50
51.9
Overall AN AAN
40
p=0.52
ARFID
30 20.7
23.5 17.5
20
18.5
10 0 Intake Program Visit
1-year f/u 1-year follow-up
Figure 3. Group 2 reported psychopharmacologic medication use overall and by diagnosis at intake and 1-year follow-up (n ¼ 256). AN ¼ anorexia nervosa; AAN ¼ atypical anorexia nervosa; ARFID ¼ avoidant/restrictive food intake disorder.
M.C. Monge et al. / Journal of Adolescent Health 57 (2015) 66e72
of depression, 76.6% with anxiety, and 76.0% with any psychiatric comorbidity had reported medication use. When Group 2 was restricted to patients
