Original article 209

Armodafinil in binge eating disorder: a randomized, placebo-controlled trial Susan L. McElroya,b, Anna I. Guerdjikovaa,b, Nicole Moria, Thomas J. Blomb, Stephanie Williamsa, Leah S. Casutoa,b and Paul E. Keck Jra,b This study evaluated the efficacy, tolerability, and safety of armodafinil in the treatment of binge eating disorder (BED). Sixty participants with BED were randomized to receive armodafinil (150–250 mg/day) (N = 30) or placebo (N = 30) in a 10-week, prospective, parallel-group, double-blind, flexible-dose, single-center trial. In the primary longitudinal analysis, armodafinil and placebo produced similar rates of improvement in binge eating day frequency (the primary outcome measure); however, armodafinil was associated with a statistically significantly higher rate of decrease in binge eating episode frequency. In the secondary baselineto-endpoint analyses, armodafinil was associated with statistically significant reductions in obsessive–compulsive features of binge eating and BMI. The mean (SD) armodafinil daily dose at endpoint evaluation was 216.7 (43.9) mg. There were no serious adverse events, although one armodafinil recipient developed markedly increased

blood pressure that resolved upon drug discontinuation. The small sample size may have limited the detection of important drug–placebo differences. As some of the observed effect sizes appeared clinically meaningful, larger studies of armodafinil in the treatment of BED are warranted. Int Clin Psychopharmacol 30:209–215 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Introduction

carried out a prospective, randomized, parallel-group, double-blind, placebo-controlled study of armodafinil in BED. Here, we report the results of that study.

Binge eating disorder (BED) is characterized by recurrent, distressing binge eating episodes without the inappropriate compensatory weight loss behaviors of bulimia nervosa (Wonderlich et al., 2009; American Psychiatric Association, 2013). It is the most common eating disorder, with an estimated lifetime prevalence of 2–3% (Hudson et al., 2007; Kessler et al., 2013). BED is associated with psychiatric comorbidity, general medical comorbidity, including obesity and metabolic dysfunction, reduced quality of life, and disability (Masheb and Grilo, 2004; Striegel-Moore et al., 2004; Hudson et al., 2007, 2010; Kessler et al., 2013). Psychotherapy and pharmacotherapy reduce binge eating pathology in BED, but not all patients respond (Reas and Grilo, 2008; Wilson et al., 2010; Reas and Grilo, 2014). Novel treatments are therefore needed for BED. Armodafinil, an active isomer of modafinil, is a wakefulness-promoting agent approved for the treatment of excessive sleepiness in patients with obstructive sleep apnea, narcolepsy, or shift work disorder (Bogan, 2010). Because BED may involve dopamine (DA) dysfunction (i.e. enhanced striatal DA release during food stimulation) (Mathes et al., 2009; Wang et al., 2011) and armodafinil binds to the DA transporter and inhibits DA uptake (Spencer et al., 2010; Loland et al., 2012), we http://www.clinicaltrials.gov Identifier: NCT01010789.

International Clinical Psychopharmacology 2015, 30:209–215 Keywords: armodafinil, binge eating disorder, dopamine a Lindner Center of HOPE, Mason and bDepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Correspondence to Susan L. McElroy, MD, Lindner Center of HOPE, Research Institute, 4075 Old Western Row Road, Mason, Ohio 45040, USA Tel: + 1 513 536 0700; fax: + 1 513 536 0709; e-mail: [email protected] Received 12 February 2015 Accepted 16 April 2015

Methods Patient population

Participants were recruited by radio and newspaper advertisements and were enrolled if they fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th ed. – text revision (DSM-IV-TR) (American Psychiatric Association, 2000) criteria for BED, had at least three binge eating days per week for the 2 weeks before receiving study medication confirmed with prospective diaries, had a BMI of at least 25 mg/kg2, and were male or female 18 through 65 years of age. Individuals were excluded from study participation if they had current anorexia nervosa or bulimia nervosa, clinically significant suicidality, a substance use disorder (except nicotine dependence) within 6 months of study entry, or a lifetime history of psychosis, mania or hypomania, or dementia. Participants were also excluded if they had a clinically unstable medical illness, clinically significant laboratory or ECG abnormalities, or had received any psychotropic medications (other than hypnotics) within 4 weeks before randomization. Women were excluded if they were pregnant, lactating, or, if of childbearing age, not practicing a medically accepted form of contraception.

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DOI: 10.1097/YIC.0000000000000079

210 International Clinical Psychopharmacology 2015, Vol 30 No 4

The Institutional Review Board at the University of Cincinnati Medical Center approved the study protocol and the study was carried out in compliance with the Declaration of Helsinki. All participants signed approved written informed consent forms after the study procedures had been fully explained and before any study procedures were performed. Participants were enrolled from 18 November 2009 to 15 August 2014. Study design

This was a prospective, randomized, parallel-group, double-blind, placebo-controlled, flexible-dose study carried out at the Lindner Center of HOPE, Mason, Ohio. The trial consisted of a 2-week screening period; a 10-week double-blind treatment period; and a 1-week treatment discontinuation period. Participants were evaluated at least twice during the screening period; after 1, 2, 3, 4, 6, 8, and 10 weeks during the treatment period; and 1 week after study medication discontinuation. Screening evaluation included the Structured Clinical Interview for DSM-IV-TR (First et al., 2007) to establish BED and comorbid axis I diagnoses; the Eating Disorder Examination-Questionnaire (Fairburn and Beglin, 1994) to confirm the diagnosis of BED; a medical history and physical examination; vital signs; height and weight; an ECG; routine blood chemical and hematological tests; and urine drug screen. At this evaluation and at each subsequent visit, participants received take-home diaries in which to record any binge eating episodes (see outcome measures). At the last visit of the screening period (the baseline assessment), participants continuing to fulfill entry criteria were assigned randomly to therapy with armodafinil or placebo. At each visit following the baseline visit, participants were assessed for the number of binge eating episodes and binge eating days experienced since the last visit; other outcome measures; medication compliance ascertained by capsule count; treatment-emergent adverse events; use of nonstudy medications; vital signs; and weight. All study medication was in identically appearing capsules (50 mg of armodafinil or matching placebo) supplied in numbered containers and dispensed to participants according to a predetermined randomization schedule. Study medication was started at 150 mg/day, taken as three capsules in the morning. If the patient had not stopped binge eating after 4 weeks of treatment, study medication was increased to 250 mg/day, taken as five capsules in the morning. Study medication could be reduced back to a minimum of 150 mg/day because of side effects during the subsequent 6 weeks of treatment. Participants were randomized to receive armodafinil or placebo in a 1 : 1 ratio according to computer-generated coding. Randomization was balanced using permuted blocks. Allocation concealment was achieved by having research pharmacy personnel perform the randomization,

package the study medication, and maintain the integrity of the blinded information throughout the trial. Outcome measures

The primary efficacy outcome was the weekly frequency of binge eating days (binge eating days/week), defined as the mean number of binge eating days per week in the interval between visits (total number of binge eating days in the interval divided by number of days in the interval, and then multiplied by 7). A binge eating day was defined as a day during which the participant had at least one binge eating episode. Binge eating episodes were defined using the DSM-IV-TR criteria, and assessed by clinical interview and review of participant take-home diaries, on which participants recorded binge eating episodes, duration of binge eating episodes, and food consumed during binge eating episodes. Secondary efficacy measures were weekly frequency of binge eating episodes (binge eating episodes/week); scores on the Clinical Global Impression-Severity (CGI-S) and Improvement Scales (CGI-I) (Guy, 1976), Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (YBOCS-BE) (Goodman et al., 1989), Eating Inventory (EI) (Stunkard and Messick, 1985), Brief Fatigue Inventory (BFI) (Mendoza et al., 1999), Inventory of Depressive Symptomatology (IDS) (Rush et al., 1996), and Beck Anxiety Inventory (BAI) (Beck et al., 1988); weight (kg); and BMI (calculated by dividing body weight in kg by height in m2). All scales were administered at all postbaseline visits, except for the EI, IDS, and BAI, which were administered at baseline and at weeks 4, 8, and 10. Weight was obtained at every visit, assessed with the participant in light clothing without shoes on the same scale zeroed at each measurement. Finally, global improvement and 4-week cessation of binge eating were assessed; these were defined, respectively, as having a CGI-I of 1 or 2 (very much or much improved) at endpoint and as having no binge eating episodes in the last 4 weeks that the participant received study medication. Safety measures assessed were treatment-emergent adverse events, clinical laboratory and ECG data, and vital signs. Suicidality was monitored using the ColumbiaSuicide Severity Rating Scale (Posner et al., 2011). Adherence was ascertained with returned capsule count. Statistical methods

The baseline characteristics of each group were compared using χ2 or Fisher’s exact test for categorical variables and independent-samples t-tests or Wilcoxon rank sum tests for continuous variables. SAS software (version 9.2; SAS Institute Inc., Cary, North Carolina, USA) was used to carry out all analyses. Statistical assessments of outcome variables were performed with the full analysis set (all randomized participants taking ≥ 1 study drug dose and having ≥ 1 postbaseline efficacy assessment).

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Armodafinil in binge eating disorder McElroy et al. 211

Safety and tolerability assessments were performed in the safety analysis set (all randomized patients taking ≥ 1 study drug dose and having ≥ 1 postbaseline safety assessment). All statistical tests and confidence intervals were two-sided, with a significance level of 0.05. The statistical methods used were similar to those used in other pharmacotherapy trials in BED (Hudson et al., 1998; McElroy et al., 2000, 2003a, 2003b, 2006, 2007a, 2007b; Arnold et al., 2002; Appolinario et al., 2003; Guerdjikova et al., 2008, 2009, 2012; Wilfley et al., 2008). The primary efficacy analysis was a longitudinal analysis comparing the rate of change of binge eating days/week during the treatment period between groups. The same analysis was applied to the secondary outcomes. The difference in the rate of change was estimated by random regression methods, as described in the study by Gibbons et al. (1993) and Fitzmaurice et al. (2004). We used a model for the mean of the outcome variable that included terms for treatment, time, and treatment-by-time interaction. Time was modeled as a continuous variable, expressed as the square root of days since randomization (baseline). For the analyses of binge eating day frequency and binge eating episode frequency, we used the logarithmic transformations log [(binge days/week) + 1] and log [(binges/week + 1)], respectively, to normalize the data and stabilize the variance. In addition, log transformations were used on other outcome measures when appropriate. To simultaneously account for individual differences in the initial level of the outcome, rate of change over time, and serial autocorrelation, we used the SAS procedure MIXED. These mixed models included random coefficients for the intercept and time variables. The best-fitting correlation structure for the error terms, as determined by the lowest AIC value, was chosen for each model from compound symmetric, firstorder antedependence, and first-order autoregressive forms. The longitudinal analyses included all available observations from all participants in the full analysis set. Several secondary analyses were carried out. Using the last observation carried forward, baseline-to-endpoint change scores were computed for each measure and independent-sample t-tests or Wilcoxon rank sum tests were used to compare these changes between the treatment groups. Fisher’s exact tests or χ2 tests were used to analyze categorical response to treatment and adverse events. For laboratory measures, the mean difference between endpoint and baseline measures was computed for each treatment group and then compared using independent-sample t-tests or Wilcoxon rank sum tests.

Results Of 139 individuals assessed for eligibility, 60 fulfilled the entry criteria and were randomized to armodafinil (N = 30) or placebo (N = 30) (Fig. 1). Of these 60 participants, 51 (85%) were women, 46 (77%) were White, and

the mean (SD) baseline weekly binge eating day frequency was 4.4 (1.2) (Table 1). Lifetime depressive disorders were the most common comorbid psychiatric disorders, occurring in 12 (20%) of participants. The two treatment groups were well matched in demographic and clinical variables at baseline (Table 1). Thirty-one participants (16 receiving armodafinil and 15 receiving placebo, P = 0.80) completed the 10-week treatment period (Fig. 1). The mean (SD) daily dose of armodafinil at endpoint evaluation was 216.7 (43.9) mg; for placebo, it was 208.9 (62.4) mg. The mean binge eating day frequency decreased over the study period in both treatment groups, but the rate of reduction was similar for armodafinil recipients and placebo recipients (Table 2 and Fig. 2). However, compared with placebo, armodafinil was associated with a statistically significantly higher rate of reduction in binge eating episode frequency (Table 2 and Fig. 3). There were no statistically significant differences between groups on change in CGI-S, YBOCS-BE, EI, BFI, IDS, or BAI scores; weight; or BMI. In the secondary analyses of baseline-to-endpoint change scores, armodafinil was associated with statistically significant decreases in YBOCS-BE total scores and in BMI compared with placebo (Table 2). The associated standardized effect sizes were moderate in range (Cohen’s D = 0.60 and 0.60, respectively). For categorical response, numerically more patients in the armodafinil group showed at least a moderate improvement on the CGI-I at endpoint [21 (78%)] compared with placebo recipients [15 (54%)], but this difference was not statistically significant (P = 0.06). Armodafinil was not associated with a statistically significantly higher 4-week binge eating cessation rate (26 vs. 21% for placebo, P = 0.69). Feeling jittery and dry mouthed were significantly more common with armodafinil than placebo (Table 3). Two participants discontinued armodafinil and two discontinued placebo because of adverse events. For armodafinil, these were excessive fatigue and anxiety in one patient and elevated blood pressure (from 128/64 mmHg at baseline to 210/100 mmHg after 2 days of treatment) in another. The patient’s elevated blood pressure was treated successfully with intravenous labetalol in an emergency room and by discontinuation of armodafinil. Adverse events leading to placebo discontinuation were abdominal cramping and worsening of depressive symptoms. Armodafinil was associated with a statistically significant increase in pulse at the last visit compared with change in the placebo group (5.5 vs. − 2.6 beats/min, respectively, P = 0.02). Two patients developed tachycardia (each 105 bpm). In both cases, the tachycardia was asymptomatic and transient. There were no significant differences

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212 International Clinical Psychopharmacology 2015, Vol 30 No 4

Fig. 1

139 individuals assessed for eligibility

60 individuals randomized

79 individuals not randomized (a) 54 did not meet entry criteria (b) 25 chose not to participate

30 assigned to armodafinil (a) 27 full analysis seta (b) 28 safety analysis setb

30 assigned to placebo (a) 28 full analysis seta (b) 29 safety analysis setb

14 discontinued (a) Adverse event (2) (b) Personal reasons (1) (c) Lost to follow-up (8) (d) Lack of efficacy (1) (e) Study nonadherence (2)

15 discontinued (a) Adverse event (2) (b) Personal reasons (3) (c) Lost to follow-up (3) (d) Lack of efficacy (2) (e) Study nonadherence (3) (f) Onset of new medical condition (2)

16 completed double-blind treatment

15 completed double-blind treatment

Participants who entered a 10-week, randomized, placebo-controlled trial of armodafinil in binge eating disorder. aFull analysis set defined as all randomized participants who received at least study medication dose and had at least postbaseline efficacy assessment. bSafety population defined as all randomized participants who received at least one dose of study medication and for whom at least one postbaseline safety measure was available.

Table 1

Demographic and clinical characteristics at baselinea

Sex (female) [n (%)] Age (years) Race [n (%)] White African-American Binge days per week Binge episodes per week CGI-severity BED age onset Lifetime depressive disorder [n (%)] Lifetime anxiety disorder [n (%)] Lifetime substance use disorder [n (%)] YBOCS-BE total EI-restraint EI-disinhibition EI-hunger BFI IDS BAI Weight (kg) BMI (kg/m2) Obesity (BMI ≥ 30) [n (%)]

Total (n = 60)

Armodafinil (n = 30)

Placebo (n = 30)

P-valueb

51 (85) 41.3 (12.0)

28 (93) 40.8 (12.7)

23 (77) 41.9 (11.4)

0.15 0.73 0.76

46 14 4.4 5.4 4.8 24.0 12 4 0 20.8 6.8 13.4 11.4 36.4 16.9 6.6 110.0 40.1 55

(77) (23) (1.2) (2.5) (0.8) (12.9) (20) (7) (0) (4.1) (4.1) (2.0) (2.8) (20.0) (9.5) (5.9) (25.2) (8.0) (92)

22 8 4.5 5.9 4.8 22.8 6 1 0 21.2 7.0 13.7 11.4 34.0 15.4 5.7 108.3 39.7 27

(73) (27) (1.5) (4.8) (0.9) (12.1) (20) (3) (0) (3.7) (4.4) (1.5) (3.1) (21.4) (9.5) (6.4) (25.0) (9.1) (90)

24 6 4.4 5.0 4.9 25.1 6 3 0 20.4 6.5 13.1 11.4 38.7 18.5 7.5 113.6 40.4 28

(80) (20) (1.0) (1.6) (0.7) (13.7) (20) (10) (0) (4.5) (3.8) (2.4) (2.5) (18.6) (9.4) (5.3) (25.6) (7.0) (93)

0.63 0.14 0.87 0.49 1.00 0.61 NA 0.45 0.62 0.25 1.00 0.38 0.21 0.04 0.42 0.74 1.00

BAI, Beck Anxiety Inventory; BED, binge eating disorder; BFI, Brief Fatigue Inventory; CGI, Clinical Global Impression; EI, Eating Inventory; IDS, Inventory of Depressive Symptomatology; NA, not applicable; YBOCS-BE, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating. a Mean (SD) or n (%) shown. b Fisher’s exact tests, t-tests, or Wilcoxon rank sum tests.

between armodafinil-treated patients and those administered placebo in mean change from baseline to final visit for blood pressure and laboratory values (laboratory data,

n = 35), except that armodafinil was associated with decreased glucose (− 2.5 vs. 13.5 mg/dl, P = 0.02) and increased sodium (0.88 vs. − 0.35 mmol/l, P = 0.02)

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Armodafinil in binge eating disorder McElroy et al. 213

Primary (longitudinal) and secondary (endpoint) analyses of each outcome measure

Table 2

Estimated difference between groups at 10 weeks (n = 55) Armodafinil change from BL − placebo change from BL [95% CI]

Change (endpoint − baseline) Armodafinil (n = 27) − 3.1 − 4.2 − 2.3 − 12.5 2.7 − 2.9 − 3.7 − 16.7 − 5.4 − 1.1 − 1.6 − 0.6

Binge days per week Binge episodes per week CGI-severity YBOCS-BE total EI-restraint EI-disinhibition EI-hunger BFI IDS BAI Weight (kg) BMI (kg/m2)

Placebo (n = 28) − 2.4 − 2.8 − 1.5 − 8.5 2.4 − 1.8 − 2.7 − 15.9 − 5.5 − 1.1 0.0 0.1

(2.1) (3.1) (1.7) (6.9) (5.2) (4.6) (3.4) (24.3) (6.9) (6.0) (2.4) (0.8)

Longitudinal analysis

(1.6) (1.8) (1.5) (6.4) (4.6) (3.9) (3.8) (17.2) (7.9) (5.9) (3.6) (1.2)

0.78 0.71 − 0.7 − 3.1 0.5 − 1.3 − 1.4 0.66 0.99 1.18 0.98 0.98

P-value

[0.55–1.10]b [0.51–1.00]b [ − 1.6 to 0.2] [ − 6.6 to 0.5] [ − 2.5 to 3.5] [ − 4.0 to 1.5] [ − 3.6 to 0.9] [0.34–1.30]b [0.64–1.52]b [0.63–2.2]b [0.97–1.0]b [0.97–1.0]b

Endpoint analysis − 0.7 − 1.3 − 0.8 − 4.0 0.3 − 1.1 − 1.0 − 0.8 0.1 − 0.1 − 1.6 − 0.6

0.15 0.05 0.14 0.09 0.76 0.36 0.23 0.35 0.95 0.60 0.08 0.07

[ − 1.7 to 0.3] [ − 2.7 to 0.0] [ − 1.7 to 0.1] [ − 7.6 to − 0.4] [ − 2.6 to 3.2] [ − 3.6 to 1.4] [ − 3.1 to 1.1] [ − 12.1 to 10.6] [ − 4.2 to 4.4] [ − 3.5 to 3.4] [ − 3.3 to 0.0] [ − 1.2 to − 0.1]

P-value

da

0.16 0.06 0.07 0.03 0.84 0.37 0.35 0.89 0.96 0.97 0.06 0.03

0.38 0.52 0.51 0.60 − 0.06 0.26 0.28 0.04 − 0.01 0.02 0.52 0.58

BAI, Beck Anxiety Inventory; BFI, Brief Fatigue Inventory; BL, baseline; CGI, Clinical Global Impression; CI, confidence interval; EI, Eating Inventory; IDS, Inventory of Depressive Symptomatology; YBOCS-BE, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating. a Cohen’s effect size; positive values indicate a greater reduction in the armodafinil group. b Log transformation used; estimate equals ratio of (Armweek 10/Armbaseline) to (Placeboweek10/Placebobaseline).

Fig. 2

Fig. 3

5

7

4.5

6

4

Placebo

5

Binge eating days

Binge eating episodes

Armodaf inil

Armodafinil

4 3 2

Placebo

3.5 3 2.5 2 1.5 1

1 0.5 0 0

1

2

3

4 5 6 Study week

7

8

9

10

Weekly mean binge eating episodes by treatment group.

compared with the change in the placebo group. There were no instances of hypernatremia (serum sodium ≥146 mmol/l). There were no serious adverse events, no instances of ECG abnormalities or suicidality, no indications of misuse, and no discontinuation symptoms.

Discussion In the primary longitudinal analysis of this 10-week, randomized trial in 60 individuals with BED, armodafinil was not significantly superior to placebo in reducing binge eating day frequency. However, compared with placebo, armodafinil was associated with a significantly greater reduction in binge eating episode frequency. In secondary baseline-to-endpoint analyses, armodafinil was

0 0

1

2

3

4 6 5 Study week

7

8

9

10

Weekly mean binge eating days by treatment group.

associated with statistically significant decreases in obsessive–compulsive features of binge eating and BMI. These findings provide preliminary evidence that armodafinil may have some clinical utility in BED, at least for the short-term reduction of binge eating episode frequency, obsessive–compulsive features of binge eating, and BMI. Taken together, these clinical findings are in agreement with research findings of central DA dysregulation in BED (Mathes et al., 2009; Wang et al., 2011) and with clinical trial results suggesting that enhancement of DA function may exert therapeutic effects in BED (McElroy et al., 2015). That one participant developed severely elevated blood pressure with armodafinil and that pulse was significantly increased in armodafinil recipients compared with placebo recipients,

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214 International Clinical Psychopharmacology 2015, Vol 30 No 4

Treatment-emergent adverse events occurring in at least three participants

Table 3

n (%)

Adverse event Headache Insomnia Nausea Feeling jittery Dry mouth Anxiety Fatigue Diarrhea/abnormal stool Disturbance in attention Hot flashes Irritability Abnormal/vivid dreams Dizziness Somnolence

Total (n = 60) 25 22 11 9 8 5 5 5

(42) (37) (18) (15) (13) (8) (8) (8)

Armodafinil (n = 30) 15 13 7 9 7 3 1 2

(50) (43) (23) (30) (23) (10) (3) (7)

Placebo (n = 30) 10 9 4 0 1 2 4 3

(33) (30) (13) (0) (3) (7) (13) (10)

P-valuea 0.29 0.42 0.51 < 0.01 0.05 1.00 0.35 1.00

4 (7)

2 (7)

2 (7)

1.00

4 (7) 4 (7) 3 (5)

3 (10) 0 (0) 2 (7)

1 (3) 4 (13) 1 (3)

0.61 0.11 1.00

3 (5) 3 (5)

1 (3) 2 (7)

2 (7) 1 (3)

1.00 1.00

a

Fisher’s exact test.

however, indicates that further studies of armodafinil in this patient population will need to carefully monitor cardiovascular parameters. Indeed, armodafinil may cause modest increases in pulse and blood pressure in patients with excessive sleepiness (Black et al., 2010; Bogan, 2010). Several limitations of this study should be considered. First, the small sample size may have compromised the ability of the study to detect clinically important therapeutic or adverse effects. Second, the attrition rate was high (48% of patients withdrew before study completion) and the results may not be consistent with armodafinil’s effects after 10 weeks of treatment. However, dropouts did not vary by treatment group, demographics, or baseline binge eating severity (data not shown), suggesting that missing data from dropouts were random. Third, the results may not generalize to treatment periods longer than 10 weeks, or to BED when it co-occurs with psychotic, bipolar, or substance use disorders, or with clinically unstable medical conditions. In addition, it cannot be concluded that armodafinil is safe or effective for individuals with bulimia nervosa or anorexia nervosa. In conclusion, in a 10-week trial in outpatients with BED, armodafinil was not superior to placebo in reducing binge day frequency in the primary longitudinal analysis, but was associated with a significantly greater reduction in binge eating episode frequency. In secondary analyses, armodafinil was associated with significant improvements in obsessive–compulsive features of binge eating and BMI. As some of the observed effect sizes appeared clinically meaningful, further controlled trials of armodafinil in larger groups of patients with BED appear warranted.

Acknowledgements The authors acknowledge Genie Groff for manuscript preparation. The study was supported by a grant from Teva Pharmaceuticals. Conflicts of interest

Dr Susan McElroy is a consultant to or member of the scientific advisory boards of Bracket, F. Hoffmann-La Roche Ltd, MedAvante, Myriad, Naurex, Novo Nordisk, Shire, and Sunovion. She is a principal or coinvestigator on studies sponsored by the Agency for Healthcare Research & Quality (AHRQ), Alkermes, Cephalon, Forest, Marriott Foundation, National Institute of Mental Health, Naurex, Orexigen Therapeutics Inc., Shire, and Takeda Pharmaceutical Company Ltd. She is also an inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent’s assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr Paul Keck is a consultant to, or member of the scientific advisory boards, and/or a principal or coinvestigator on research studies sponsored by Alkermes, Forest, Cephalon, Marriott Foundation, National Institute of Mental Health (NIMH), Shire, and Sunovion. He is also inventor on United States Patent No. 6,387,956: Shapira NA, Goldsmith TD, Keck, PE Jr. (University of Cincinnati) Methods of treating obsessive–compulsive spectrum disorder comprises the step of administering an effective amount of tramadol to an individual. Filed 25 March 1999; approved 14 May 2002. For the remaining authors there are no conflicts of interest.

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Armodafinil in binge eating disorder McElroy et al. 215

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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Armodafinil in binge eating disorder: a randomized, placebo-controlled trial.

This study evaluated the efficacy, tolerability, and safety of armodafinil in the treatment of binge eating disorder (BED). Sixty participants with BE...
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