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An open-label efficacy trial of escitalopram for night eating syndrome
Eating Behaviors 14 (2013) 199–203
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Eating Behaviors
An open-label efficacy trial of escitalopram for night eating syndrome☆ Kelly C. Allison a,⁎, Stacia K. Studt b, Robert I. Berkowitz a, c, Louise A. Hesson a, Reneé H. Moore a, d, Jacob G. Dubroff e, Andrew Newberg f, Albert J. Stunkard a a
Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA The Food Trust, Philadelpia, PA 19103, USA c Department of Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA d Department of Statistics, North Carolina State University, Raleigh, NC, USA e Division of Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA f Center for Integrative Medicine, Thomas Jefferson University Hospital and Medical College, Philadelphia, PA 19107, USA b
a r t i c l e
i n f o
Article history: Received 1 November 2012 Received in revised form 7 January 2013 Accepted 14 February 2013 Available online 5 March 2013 Keywords: Night eating syndrome Eating disorders SSRIs Binge eating disorder Insomnia
a b s t r a c t Objective: Night eating syndrome (NES) has become increasingly recognized as a disorder in need of effective treatments. Selective serotonin reuptake inhibitors have shown efficacy in previous trials, so we sought to expand our understanding of the efficacy of escitalopram in the current trial. Method: Thirty-one adults with NES participated in a 12-week open-label trial of escitalopram. Outcome measures included the Night Eating Symptom Scale (NESS), percent of daily intake after the evening meal (% intake) and number of nocturnal ingestions/week (NI), weight, total awakenings/week, mood, and quality of life. Mixed-effects models were used to assess change over time. Results: Significant reductions were observed from week 0 to week 12 for the NESS (30.2 to 15.2), % intake (46% to 17%), NI (5.8 to 1.2), weight (90.2 to 88.6 kg), awakenings (8.1 to 2.7), and BDI-II (12.1 to 7.7). Outcomes did not differ significantly by gender, age, race, or psychiatric co-morbidity status. Eighteen of 31 completed 12 weeks of treatment. Discussion: This open-label trial of escitalopram showed significant reductions in symptoms associated with NES. Randomized controlled trials are warranted to test these findings. Trial Registration: clinicaltrials.gov identifier: NCT01401595. © 2013 Elsevier Ltd. All rights reserved.
1. Introduction Night eating syndrome (NES) affects about 1.5% of the general population (Rand, Macgregor, & Stunkard, 1997; Striegel-Moore, Franko, Thompson, Affenito, & Kraemer, 2006). The core features include a delayed circadian pattern of eating manifested by evening hyperphagia (consumption of at least 25% of daily food intake after the evening meal) and/or nocturnal ingestions (waking to eat) at least twice a week (Allison et al., 2010). Three of five additional modifiers are also required: morning anorexia, insomnia, strong cravings to eat in the evening or night, depressed mood, and the belief that one must eat to fall (back) asleep, along with distress or impairment in functioning. It is not currently included in the Diagnostic and Statistical Manual, Fourth Edition (DSM) (American Psychiatric Association, 2000), but it will likely appear in DSM 5 (American Psychiatric Association, 2012) under the category
☆ All authors completed this work in the Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. ⁎ Corresponding author at: Center for Weight and Eating Disorders, 3535 Market St., Suite 3027, Philadelphia, PA 19104-3309, USA. E-mail address: [email protected] (K.C. Allison). 1471-0153/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.eatbeh.2013.02.001
Feeding and Eating Conditions Not Elsewhere Classified. As such, more data regarding treatment efficacy are needed. NES occurs in persons of all weights, but the prevalence seems to grow with increasing body mass. Tholin et al. (2009) showed an increased risk for obesity (2.5 times for men and 2.8 times for women) among participants in the Swedish Twin Register STAGE cohort who screened positive for night eating. In a clinical sample, psychiatric patients with NES were five times more likely to be obese than patients without NES (Lundgren et al., 2006). Night eating is also predictive of weight gain in prospective studies (Andersen, Stunkard, Sorensen, Pedersen, & Heitman, 2004; Gluck, Venti, Salbe, & Krakoff, 2008). However, some epidemiological studies have not shown a positive relationship between weight and night eating symptoms (Striegel-Moore et al., 2006). While research on the treatment of NES is still sparse, the disorder has been successfully treated with selective serotonin reuptake inhibitors (SSRIs) in a limited number of trials. Open label trials have shown efficacy with sertraline (O'Reardon, Stunkard, & Allison, 2004; Stunkard et al., 2006), and one randomized controlled trial has illustrated the superiority of sertraline over placebo (O'Reardon et al., 2006). In this 8-week controlled trial, 71% of participants on sertraline (n = 17) were considered “responders” on the Clinical Global Impression of Improvement Scale
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(CGII) (Guy, 1976) as compared to 18% of those on placebo (n = 17); 41% of participants in the sertraline condition were considered remitters. More recently, Vander Wal, Gang, Griffing, and Gadde (2012) reported large improvements in night eating symptoms in their randomized controlled trial of escitalopram, with 60% vs. 35% much improved or very much improved on the CGII in the drug vs placebo group. However, these reductions were not significant between groups, likely due to sample size limitations (n = 20 in each group). While fairly typical of placebo-controlled trials, the 35% placebo response rate was double that of the 18% response rate found in the RCT of sertraline (O'Reardon et al., 2006). Escitalopram is an enantiomer of citalopram and is currently approved by the Food and Drug Administration for the treatment of depression and generalized anxiety disorder. With consistent symptom reductions found across these studies (O'Reardon et al., 2004, 2006; Stunkard et al., 2006; Vander Wal et al., 2012), we sought to extend the treatment literature with another trial of escitalopram, wanting to confirm the results reported by Vander Wal et al. (2012), and expecting that it would reduce the core features of NES significantly in this sample. 2. Material and methods 2.1. Participants Potential participants were recruited through television and Internet advertisements, along with flyers posted at the University Hospital and around campus targeting persons who experienced overeating at night and/or waking during the night to eat. Men and women between the ages of 18–70 of all races and ethnicities were included. Exclusion criteria were: pregnancy; insulin-dependent diabetes; thyroid or other metabolic disorders; use in the past month of any psychotropic medication, oral steroids, diuretics or hypnotics; the presence of anorexia nervosa or bulimia nervosa; current participation in an organized weight reduction program or the use of weight loss medication, current participation in psychotherapy treatment for NES or another eating disorder, an occupation requiring night-shifts or other unusual nighttime requirements; severe major depressive disorder; suicidal risk; bipolar disorder; current or past psychosis; or substance use or abuse within the past 6 months. Weight greater than 400 lb and an allergy to shellfish or iodine were also exclusions, as participants were also completing a brain imaging study. This study's protocol was reviewed and approved by the University of Pennsylvania's Institutional Review Board, with all participants providing informed consent. 2.2. Procedures Participants were screened by phone for inclusion and exclusion criteria before being scheduled for their baseline assessment. At the baseline visit, participants completed a psychological assessment during which the diagnosis of NES was confirmed through questionnaires, clinical interviews, and, subsequently, a 10-day food and sleep log. Study personnel analyzed data from the logs with the Food Processor® program (ESHA research, Salem, OR). All participants included in the study met the full research criteria for NES (Allison et al., 2010). Using the available data, the authors confirmed that participants consumed at least 25% of their caloric intake after their evening meal and/or after waking up during the night to eat at least twice per week. Participants were also required to meet at least three of the five modifiers, have awareness of their nighttime eating, and show distress or impairment in functioning due to their night eating. The NES symptoms had to be present for at least three months. The baseline assessment also included a history and physical examination; drug screen, measurement of height, weight, and blood pressure; metabolic panel; and an electrocardiogram to establish that the participants were healthy enough to participate in a medication
trial. After completing the assessment, participants with confirmed NES were eligible for a brain imaging study (to be described elsewhere) and treatment. Participants were paid for completing the comprehensive assessment and brain imaging portion of the study. Treatment was subsequently provided at no charge. A total of 342 individuals responded to ads to participate in the current study. Of the 342 whom we contacted, 75 individuals provided consent to enroll in the study as night eating participants. Of the 75 who provided consent, 21 were found to be ineligible during their baseline screening appointment for the following reasons (some participants met more than one exclusion): 3 had uncontrolled or undiagnosed diabetes, 3 used illicit drugs, 4 met criteria for severe depression or suicidal ideation, 2 had anemia, 2 had abnormally high blood pressure, 2 had abnormal ECG, 4 had other medical issues deemed unstable or needing further medical care, 1 met criteria for bipolar disorder and 1 for purging disorder, 2 used other psychotropic/sleep medications, and 1 weighed greater than 400 lb. Additionally, 22 did not continue after the baseline assessment: 9 were found to be eligible, but never returned their screening materials (i.e., food/sleep log and survey packet), 3 had scheduling difficulties, 3 did not meet full NES criteria after assessment, 3 declined the study/lost to follow-up after baseline, and 4 did not keep their baseline (week 0) treatment appointments. The remaining 32 entered treatment. Of the 32 who entered treatment, 1 did not return after the initial treatment week and was not included in analysis (as she did not have more than one datapoint). 2.2.1. Treatment Treatment visits occurred at week 0 (start of treatment) and weeks 1, 2, 4, 6, 8, 10, and 12. Dosing of escitalopram began at 10 mg. If participants experienced significant side effects, dose was cut to 5 mg. At week 4, if participants' symptoms were still present, the dose was increased to 20 mg. Likewise, if significant side effects were experienced at 20 mg, dose was cut to 15 mg. 2.3. Measures 2.3.1. Baseline In addition to collecting demographic information, several measures were used at baseline to characterize the sample and to assess for exclusion criteria. The Night Eating Questionnaire (NEQ) (Allison et al., 2008) was completed at baseline. This is a 14-item questionnaire that assesses behavioral and psychological symptoms of NES. Total scores range from 0 to 52. The Beck Depression Inventory-II (BDI-II; Beck, 1996) was also administered; it is a widely used 21-item questionnaire that measures symptoms of depression present during the past week. Total scores range from 0 to 63; the BDI-II has high internal consistency, test–retest reliability and convergent and discriminant validity. The Night Eating Syndrome History and Inventory (NESHI) (Lundgren, Allison, Vinai P, Gluck) was used to confirm a diagnosis of NES. The NEQ is embedded in the NESHI, and additional items describe typical meal and snack patterns, level of distress, and severity and course of NES symptoms. The diagnostic criteria for NES are assessed with the NESHI. Eating disorder psychopathology was assessed with the Eating Disorder Examination, 16th edition (Fairburn, Cooper, & O'Connor, 2008). This measure has been found reliable and valid for assessment of eating pathology (Fairburn, Cooper, & O'Connor, 2001; Grilo, Masheb, LozanoBlanco, & Barry, 2004). The EDE includes assessment of binge eating and overeating episodes, four subscales (Restraint, Eating Concern, Shape Concern, and Weight Concern), and a global disordered eating score. The Eating Inventory was used to characterize common psychological factors related to eating, including cognitive restraint, disinhibition, and hunger (Stunkard & Messick, 1985). Axis I psychopathology was broadly assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P) (First, Spitzer, Gibbon, Williams, & Benjamin, 1996).
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2.3.2. Self-monitoring Participants kept food and sleep records at baseline screening and again during week 12 of treatment. The evening meal was defined as the first meal initiated between 17:00 h and 20:00 h. All energy intake after this meal or after 20:00 h, whichever came first, was included in the % of intake after the evening meal. During treatment, food and sleep logs were not kept so as not to influence participants' eating and sleep by self-monitoring. At treatment week 0, participants were oriented to their baseline percentage of intake consumed after dinner that was computed from their logs. Thereafter they provided their estimates of the percentage of intake after dinner and number of awakenings and nocturnal ingestions by self-report at each treatment visit.
having a high school diploma or GED, 19% had some college, 36% were college graduates, and 16% attended graduate school. Additional baseline demographic and psychosocial information is included in Table 1. There was high lifetime psychiatric comorbidity, with 65% meeting criteria for a history of any axis I disorder (Table 1). Of the 31 who were subsequently included in the analyses, 18 completed the 12-week treatment and 13 were non-completers: 6 dropped before week 4, an additional 2 dropped after week 4, 1 after week 6, 1 after week 8, and three after week 10. The average number of weeks in treatment was 8.9 (SD = 4.3) weeks. Non-completers reported more nocturnal ingestions at baseline compared to completers (8.0 vs. 4.0 per week, p = 0.03), but no other demographic or eating criteria differed.
2.4. Assessment during treatment
3.2. Primary and secondary outcomes
Three questionnaires were administered prior to each treatment session. The Night Eating Symptom Scale-II (NESS-II) (Lundgren, Allison, Vinai, & Gluck, 2012) is a 14-item questionnaire (possible range of 0–56) that contains items similar to the NEQ (Allison et al., 2008), but it assesses the presence of NES features over the course of the previous week. Participants also completed the BDI-II and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q)(Endicott, Nee, Harrison, & Blumenthal, 1993). The QLES-Q contains 14 face-valid items that assess global satisfaction in psychosocial and physical areas of functioning with a possible range of 14–70. Finally, weight was measured before each session in light clothing and without shoes. Body mass index (BMI, weight/height2 in kg/m2) was calculated at baseline and treatment end.
Significant decreases were noted in the three primary outcomes (Fig. 1a–c). The mean estimate of the NESS fell from 30.2 (SE = 1.3) at treatment week 0 to 15.2 (SE = 1.5) at week 12, a 49% decrease. Mean estimate of the percent of daily caloric intake consumed after dinner fell from 46.1% (SE = 3.0) to 17.4% (SE = 3.5), a 62% decrease. Eighteen (58%) reported consuming b 15% of daily caloric intake after dinner at their last study visit, and an additional five (16%) reported consuming between 15 and 25%. Nocturnal ingestions fell from 5.8 (SE = 0.5) to 1.2 (SE = 0.6) per week, an 80% decrease. Twenty (65%) participants reported no nocturnal ingestions and 18 (58%) no longer met core criteria for both features at their last study visit. In pairwise comparisons, all three outcomes significantly decreased after one week of treatment: NESS mean score dropped from 30.2 to 21.2 points, % of calories after dinner dropped from 46% to 28%, and nocturnal ingestions dropped from 5.8 to 2.4 per week, all ps b 0.0001. We added dose, sex, age, race, history of axis I disorder, and BED status as modifiers for each primary outcome variable; none were significant predictors of change over time. The only difference noted at treatment week 0 was a significantly greater percentage of calories consumed after dinner by those with BED (n = 7, 55%) as compared to those without (n = 24, 44%); no differences were noted at treatment end.
2.5. Statistical analysis Primary outcome measures were the change on the NESS total score, percentage of caloric intake consumed after the evening meal, and the number of nocturnal ingestions per week. Secondary outcome measures consisted of number of awakenings and change in weight. Finally, BDI and QLES-Q total scores were examined as global indicators of mood and functioning. Descriptive statistics were used to report means and frequencies of patient demographic and psychosocial characteristics. To assess changes over time in the outcomes, mixed-effects models were fit in which time (weeks 0, 1, 2, 4, 6, 8, 10, 12) was modeled as a categorical within subjects factor to obtain mean (SE) at each time point. These models were fit for each of the outcomes of interest: NESS score, percent of intake consumed after dinner, number of nocturnal ingestions and awakenings, weight, BDI score and QLES-Q score. An advantage of using mixed model analyses over traditional methodology (e.g. analysis of variance) is that all available data can be utilized; therefore, all participants with a baseline measurement and at least one of the seven subsequent measurements are included in these mixed model analyses. In exploratory analyses, moderators were included in the models described above, including age, gender, race, axis I pathology, and BED status. Finally, independent sample t-tests were used to compare baseline characteristics for treatment completers versus drop-outs. 3. Results 3.1. Participant characteristics The 31 participants were 68% (n = 21) female; 35.5% were single, 35.5% were married, and 29% were divorced/separated. Ethnicities included: 14 (45%) Non-Hispanic white, 12 (39%) African Americans, 1 (3%) Hispanic/Latino white, 1 (3%) Asian American, 2 mixed race (7%), and 1 (3%) did not disclose race. Three (9.7%) were of normal BMI (19–24.9 kg/m2), 11 (35.5%) were overweight (25–29.9 kg/m 2), and 17 (54.8%) were obese (≥30 kg/m 2). Education level varied, with 29%
Table 1 Baseline characteristics and psychosocial co-morbidities of participants. Baseline characteristics
Mean (SD)
Age (years) BMI (kg/m2) % calories after dinner until morning awakening % calories evening meal to bedtime % calories after bedtime to morning awakening No. awakenings/week No. nocturnal ingestions/week Baseline total caloric intake NEQ BDI EDE — restraint EDE — eating concern EDE — shape concern EDE — weight concern EDE global score Eating inventory — cognitive restraint Eating inventory — disinhibition Eating inventory — hunger
45.4 31.8 34.9 21.8 13.1 8.7 5.7 2743.3 31.7 14.3 1.9 2.4 3.8 3.4 2.9 8.6 10.5 8.1
Co-morbid psychopathology
N (percentage)
Any lifetime Axis I SCID diagnosis Binge eating disorder (all current) Any lifetime mood disorder Any lifetime anxiety disorder Any lifetime substance/alcohol abuse or dependence
20 7 7 7 5
(11.6) (6.4) (12.3) (14.8) (10.7) (6.2) (5.0) (1051.6) (6.9) (11.0) (1.2) (1.7) (1.6) (1.4) (1.2) (5.6) (3.4) (3.3)
(65%) (23%) (23%) (23%) (16%)
BMI is body mass index; NEQ is the Night Eating Questionnaire; BDI is the Beck Depression Inventory II; EDE is Eating Disorder Examination; SCID is the Structured Clinical Interview for DSM-IV Disorders.
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a
K.C. Allison et al. / Eating Behaviors 14 (2013) 199–203 35
p = 0.004). This result was similar upon excluding the three normal weight participants. Eight participants lost more than 2 lb (0.9 kg), eight maintained their weight (within 2 lb (0.9 kg)), and 13 gained more than 2 lb (0.9 kg). The BDI-II decreased from 12.1 (SE = 1.5) to 7.7 (SE = 1.6) (F (7,159) = 5.25, p b 0.001), but the QLES-Q did not increase significantly.
NESS total score
30
25
20
3.3. Change in binge-eating and overeating episodes 15
10
5
0 0
1
2
4
6
8
10
12
Treatment week
% daily intake consumed after dinner
b
60
3.4. Dosing and adverse events Mean dose of escitalopram at the last study visit was 13.2 (SD = 4.9) mg, with n = 1 participant at 5 mg, n = 19 at 10 mg, n = 1 at 15 mg, and n = 10 at 20 mg. Adverse events experienced by more than one participant included nausea (n = 5), drowsiness (n = 4), dry mouth (n = 3), increased sweating (n = 2), headache (n = 2), diarrhea (n = 2), low libido/impotence (n = 2), and mental cloudiness (n = 2). Drop-outs (n = 13) occurred for the following reasons: 6 were lost to follow-up, 1 discontinued due to epistaxis, 1 due to drowsiness, 1 due to panic attacks, 3 experienced life events/too busy, and 1 forgot to take her medication on a trip and discontinued thereafter.
50
40
30
20
10
4. Discussion
0 0
1
2
4
6
8
10
12
Treatment week
c
10 Nocturnal ingestions/week
9
Awakenings/week
8 7
Events per week
At baseline, participants (n = 30, one participant did not complete the EDE) reported an average of 4.1 (SD = 6.0) objective binge episodes, 5.9 (SD = 11.8) subjective binge episodes, and 1.1 (SD = 2.5) objective overeating episodes in the previous 28 days. At treatment end, 16 participants provided estimates of these behaviors; objective binge episodes decreased by 4, to 0.6 (SD = 0.03) episodes in the previous month, t(15) = 2.7, p = 0.02; subjective binge episodes and objective overeating episodes did not decrease significantly.
6 5 4 3 2 1 0 0
1
2
4
6
8
10
12
Treatment week Fig. 1. a. NESS total score decreased over time (F (7,159) = 26.8, p b 0.001). Mean estimates with standard error bars are shown. b. Percent of total daily intake decreased significantly from baseline to week 12 (F (7,160) = 23.2, p b 0.001). Mean estimates with standard error bars are shown. c. Nocturnal ingestions (F (7,161) = 18.5, p b 0.001) and awakenings (F (7,161) = 7.9, p b 0.001) per week both decreased significantly from baseline to week 12. Mean estimates with standard error bars are shown.
Of the secondary outcome measures, total number of awakenings per week decreased significantly, from 8.1 (SE = 0.8) to 2.7 (SE = 0.9) per week, a drop of 67% (F (7, 161) = 7.90, p b 0.001). Weight was also reduced significantly, but was not clinically significant, with a decrease from 90.2 (SE = 3.5) kg to 88.6 (SE = 3.5) kg, (F (7, 159) = 26.8,
Escitalopram significantly decreased all primary measures of night eating syndrome, including the NESS-II, percent of caloric intake consumed after dinner, and number of nocturnal ingestions per week in this 12-week, open-label trial. Additionally, 58% of participants were in remission at treatment end. In tracking the temporal response to treatment, significant improvements were noted at week 1 across all primary outcome measures, with continued gradual improvement across the 12 weeks. The reductions found in this trial for the percentage of intake after dinner and number of nocturnal ingestions were similar to those reported by O'Reardon et al. (2006) in their RCT of sertraline. Different metrics were reported in Vander Wal et al. (2012), so it is more difficult to compare. Weight decreased by 2.6 kg across the 12 weeks in the current trial. This loss seems similar to the 2.9 kg loss across 8 weeks in the randomized controlled trial of sertraline for NES (O'Reardon et al., 2006). However, there was a wide range of responses with weight, with some participants quite pleased with their weight loss and others showing displeasure at weight gain. Awakenings also improved across the 12 weeks. Depressive symptoms on the BDI-II were not clinically elevated at baseline, and they decreased from the mild to minimal range. Quality of life was not affected by treatment, as measured by the QLES-Q. Vander Wal et al. (2012) partly attributed a lack of significant findings between the placebo and escitalopram groups to a differential response by race; black participants did not reduce symptoms to the same extent as white participants. In the current study, we had similar representation between these groups, and no significant influence of race was noted on outcomes. Likewise, age and gender played no role in outcomes. Co-morbid psychopathology in this sample was high with 65% of the sample reporting a lifetime history of an axis I psychiatric disorder. This factor also had no significant influence on NES symptom response to escitalopram. All co-morbid diagnoses of BED were current,
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so we also examined the impact of this diagnosis on outcome separately. As could be expected, the BED group consumed more calories after dinner at baseline as compared to those without BED, but this difference disappeared by week 4 and was not a significant source of variance in NES outcomes. Binge episodes for the sample as a whole also decreased significantly, as would be expected from previous trials of SSRIs for BED (Appolinario & McElroy, 2004), although one trial of escitalopram specifically showed null results as compared to placebo for reduction of binge episodes (Guerdjikova et al., 2008). While this study builds on the nascent treatment literature for NES, this study has limitations. It is an open-label trial, so the significance of reductions should be viewed with caution. It is possible that the improvements were due to a placebo effect. Further trials are needed to confirm these findings. Additionally, the drop-out rate was larger than expected (42%), some due to medication effects, but the majority due to loss to follow-up, despite persistent efforts at retention by study staff. In conclusion, this open-label trial of escitalopram for NES yielded significant reductions in night eating symptoms, mood, and body weight. A larger controlled trial is warranted to test the efficacy of escitalopram for NES further, given that the evidence for effective treatment options for NES is still quite limited. Role of funding sources This research was supported by an investigator-initiated grant by Forest Laboratories, Incorporated, Jersey City, New Jersey, 07311, USA. Forest Labs had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. Contributors Authors must declare their individual contributions to the manuscript. All authors must have materially participated in the research and/or the manuscript preparation. Roles for each author should be described. The disclosure must also clearly state and verify that all authors have approved the final manuscript. Author Allison supervised the overall study conduct, including recruitment, treatment, and data collection and entry, and she drafted the manuscript. Studt carried out recruitment and was involved with screening, treatment visits, and data processing. Berkowitz and Hesson were involved with participant screenings and provided treatment. Moore planned and conducted the statistical analysis and helped in manuscript preparation. Dubroff was involved in assessing participants, and Newberg assisted in study design, regulatory issues, and participant assessment. Stunkard designed, obtained funding, and helped oversee the study. All authors contributed to and have approved the final manuscript. Conflict of interest This work was funded by Forest Pharmaceuticals, including some salary support for all authors except Moore and Stunkard. Acknowledgments This research was supported by an investigator-initiated grant by Forest Laboratories, Incorporated, Jersey City, New Jersey, 07311, USA. Portions of this manuscript were presented at the International Conference on Eating Disorders in Austin, Texas on May 3, 2012. We would like to thank Jeffery Lavenberg, M.S. for his help with the data preparation and Nitika Jain, M.D., for her efforts as research assistant with this study. We would also like to thank John P. O'Reardon, M.D. for helpful feedback on an earlier draft of this manuscript.
References Allison, K. C., Lundgren, J. D., O'Reardon, J. P., Martino, N. S., Sarwer, D. B., Wadden, T. A., et al. (2008). The Night Eating Questionnaire (NEQ): Predictive properties of a measure of severity of the night eating syndrome. Eating Behaviors, 9, 62–72.
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Allison, K. C., Lundgren, J. D., O'Reardon, J. P., Geliebter, A., Gluck, M., Vanai, P., et al. (2010). Proposed diagnostic criteria for night eating syndrome. International Journal of Eating Disorders, 43, 241–247. American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author (text rev). American Psychiatric Association (2012). http://www.dsm5.org/ProposedRevision/ Pages/proposedrevision.aspx?rid=26 (Last accessed on August 29, 2012) Andersen, G. S., Stunkard, A. J., Sorensen, T. I. A., Pedersen, L., & Heitman, B. L. (2004). Night eating and weight change in middle-aged men and women. International Journal of Obesity, 8, 1138–1143. Appolinario, J. C., & McElroy, S. L. (2004). Pharmacological approaches in the treatment of binge eating disorder. Current Drug Targets, 5, 301–307. Beck, A. T. (1996). Manual for the beck depression inventory II. San Antonio: Harcort Brace. Endicott, J., Nee, J., Harrison, W., & Blumenthal, R. (1993). Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q): A new measure. Psychopharmacology Bulletin, 29, 321–326. Fairburn, C. G., Cooper, Z., & O'Connor, G. T. (2001). A comparison of different methods for assessing the features of eating disorders in patients with binge eating disorder. Journal of Consulting and Clinical Psychology, 69, 317–322. Fairburn, C. G., Cooper, Z., & O'Connor, M. E. (2008). The eating disorder examination. In C. G. Fairburn (Ed.), Cognitive behavior therapy and eating disorders (pp. 265–308). New York: The Guilford Press. First, M. B., Spitzer, R. L., Gibbon, M., Williams, J. B. W., & Benjamin, L. (1996). Structured clinical interview for DSM-IV disorders — Patient edition (with psychotic screen, version 2.0). New York: Biometrics Research Department, New York State Psychiatric Institute. Gluck, M. E., Venti, C. A., Salbe, A. D., & Krakoff, J. (2008). Nighttime eating: Commonly observed and related to weight gain in an inpatient food intake study. American Journal of Clinical Nutrition, 88, 900–905. Grilo, C. M., Masheb, R. M., Lozano-Blanco, C., & Barry, D. T. (2004). Reliability of the eating disorder examination in patients with binge eating disorder. International Journal of Eating Disorders, 35, 80–85. Guerdjikova, A. I., McElroy, S. L., Kotwal, R., Welge, J. A., Nelson, E., Lake, K., et al. (2008). High-dose escitalopram in the treatment of binge-eating disorder with obesity: A placebo-controlled monotherapy trial. Human Psychopharmacology, 23, 1–11. Guy, W. (1976). ECDEU assessment manual for psychopharmacology. Washington DC: US Department of Health, Education and Welfare Publication (ADM). Lundgren, J. D., Allison, K. C., Crow, S., O'Reardon, J. P., Berg, K. C., Galbraith, J., et al. (2006). Prevalence of the night eating syndrome in a psychiatric population. The American Journal of Psychiatry, 163, 156–158. Lundgren, J. D., Allison, K. C., Vinai, P., & Gluck, M. E. (2012). Assessment instruments for night eating syndrome. In J. D. Lundgren, K. C. Allison, & A. J. Stunkard (Eds.), Night eating syndrome: Research, assessment, and treatment (pp. 197–217). New York: The Guilford Press. O'Reardon, J. P., Allison, K. C., Martino, N. S., Lundgren, J. D., Heo, M., & Stunkard, A. J. (2006). A randomized placebo-controlled trial of sertraline in the treatment of the night eating syndrome. The American Journal of Psychiatry, 164, 893–898. O'Reardon, J. P., Stunkard, A. J., & Allison, K. C. (2004). A clinical trial of sertraline in the treatment of night eating syndrome. International Journal of Eating Disorders, 35, 16–26. Rand, C. S. W., Macgregor, M. D., & Stunkard, A. J. (1997). The night eating syndrome in the general population and among post-operative obesity surgery patients. International Journal of Eating Disorders, 22, 65–69. Striegel-Moore, R. H., Franko, D. L., Thompson, D., Affenito, S., & Kraemer, H. C. (2006). Night eating: Prevalence and demographic correlates. Obesity, 14, 139–147. Stunkard, A. J., Allison, K. C., Lundgren, J. D., Martino, N. S., Heo, M., Etemad, B., et al. (2006). A paradigm for facilitating pharmacotherapy at a distance: Sertraline treatment of the night eating syndrome. The Journal of Clinical Psychiatry, 67, 1558–1572. Stunkard, A. J., & Messick, S. (1985). The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. Journal of Psychosomatic Research, 29, 71–83. Tholin, S., Lindroos, A., Tynelius, P., Akerstedt, T., Stunkard, A. J., Bulik, C. M., et al. (2009). Prevalence of night eating in obese and nonobese twins. Obesity, 17, 1050–1055. Vander Wal, J. S., Gang, C. H., Griffing, G. T., & Gadde, K. M. (2012). Escitalopram for treatment of night eating syndrome: A 12-week, randomized, placebo-controlled trial. Journal of Clinical Psychopharmacology, 32, 341–345.
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Eating Behaviors
An open-label efficacy trial of escitalopram for night eating syndrome☆ Kelly C. Allison a,⁎, Stacia K. Studt b, Robert I. Berkowitz a, c, Louise A. Hesson a, Reneé H. Moore a, d, Jacob G. Dubroff e, Andrew Newberg f, Albert J. Stunkard a a
Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA The Food Trust, Philadelpia, PA 19103, USA c Department of Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA d Department of Statistics, North Carolina State University, Raleigh, NC, USA e Division of Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA f Center for Integrative Medicine, Thomas Jefferson University Hospital and Medical College, Philadelphia, PA 19107, USA b
a r t i c l e
i n f o
Article history: Received 1 November 2012 Received in revised form 7 January 2013 Accepted 14 February 2013 Available online 5 March 2013 Keywords: Night eating syndrome Eating disorders SSRIs Binge eating disorder Insomnia
a b s t r a c t Objective: Night eating syndrome (NES) has become increasingly recognized as a disorder in need of effective treatments. Selective serotonin reuptake inhibitors have shown efficacy in previous trials, so we sought to expand our understanding of the efficacy of escitalopram in the current trial. Method: Thirty-one adults with NES participated in a 12-week open-label trial of escitalopram. Outcome measures included the Night Eating Symptom Scale (NESS), percent of daily intake after the evening meal (% intake) and number of nocturnal ingestions/week (NI), weight, total awakenings/week, mood, and quality of life. Mixed-effects models were used to assess change over time. Results: Significant reductions were observed from week 0 to week 12 for the NESS (30.2 to 15.2), % intake (46% to 17%), NI (5.8 to 1.2), weight (90.2 to 88.6 kg), awakenings (8.1 to 2.7), and BDI-II (12.1 to 7.7). Outcomes did not differ significantly by gender, age, race, or psychiatric co-morbidity status. Eighteen of 31 completed 12 weeks of treatment. Discussion: This open-label trial of escitalopram showed significant reductions in symptoms associated with NES. Randomized controlled trials are warranted to test these findings. Trial Registration: clinicaltrials.gov identifier: NCT01401595. © 2013 Elsevier Ltd. All rights reserved.
1. Introduction Night eating syndrome (NES) affects about 1.5% of the general population (Rand, Macgregor, & Stunkard, 1997; Striegel-Moore, Franko, Thompson, Affenito, & Kraemer, 2006). The core features include a delayed circadian pattern of eating manifested by evening hyperphagia (consumption of at least 25% of daily food intake after the evening meal) and/or nocturnal ingestions (waking to eat) at least twice a week (Allison et al., 2010). Three of five additional modifiers are also required: morning anorexia, insomnia, strong cravings to eat in the evening or night, depressed mood, and the belief that one must eat to fall (back) asleep, along with distress or impairment in functioning. It is not currently included in the Diagnostic and Statistical Manual, Fourth Edition (DSM) (American Psychiatric Association, 2000), but it will likely appear in DSM 5 (American Psychiatric Association, 2012) under the category
☆ All authors completed this work in the Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. ⁎ Corresponding author at: Center for Weight and Eating Disorders, 3535 Market St., Suite 3027, Philadelphia, PA 19104-3309, USA. E-mail address: [email protected] (K.C. Allison). 1471-0153/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.eatbeh.2013.02.001
Feeding and Eating Conditions Not Elsewhere Classified. As such, more data regarding treatment efficacy are needed. NES occurs in persons of all weights, but the prevalence seems to grow with increasing body mass. Tholin et al. (2009) showed an increased risk for obesity (2.5 times for men and 2.8 times for women) among participants in the Swedish Twin Register STAGE cohort who screened positive for night eating. In a clinical sample, psychiatric patients with NES were five times more likely to be obese than patients without NES (Lundgren et al., 2006). Night eating is also predictive of weight gain in prospective studies (Andersen, Stunkard, Sorensen, Pedersen, & Heitman, 2004; Gluck, Venti, Salbe, & Krakoff, 2008). However, some epidemiological studies have not shown a positive relationship between weight and night eating symptoms (Striegel-Moore et al., 2006). While research on the treatment of NES is still sparse, the disorder has been successfully treated with selective serotonin reuptake inhibitors (SSRIs) in a limited number of trials. Open label trials have shown efficacy with sertraline (O'Reardon, Stunkard, & Allison, 2004; Stunkard et al., 2006), and one randomized controlled trial has illustrated the superiority of sertraline over placebo (O'Reardon et al., 2006). In this 8-week controlled trial, 71% of participants on sertraline (n = 17) were considered “responders” on the Clinical Global Impression of Improvement Scale
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(CGII) (Guy, 1976) as compared to 18% of those on placebo (n = 17); 41% of participants in the sertraline condition were considered remitters. More recently, Vander Wal, Gang, Griffing, and Gadde (2012) reported large improvements in night eating symptoms in their randomized controlled trial of escitalopram, with 60% vs. 35% much improved or very much improved on the CGII in the drug vs placebo group. However, these reductions were not significant between groups, likely due to sample size limitations (n = 20 in each group). While fairly typical of placebo-controlled trials, the 35% placebo response rate was double that of the 18% response rate found in the RCT of sertraline (O'Reardon et al., 2006). Escitalopram is an enantiomer of citalopram and is currently approved by the Food and Drug Administration for the treatment of depression and generalized anxiety disorder. With consistent symptom reductions found across these studies (O'Reardon et al., 2004, 2006; Stunkard et al., 2006; Vander Wal et al., 2012), we sought to extend the treatment literature with another trial of escitalopram, wanting to confirm the results reported by Vander Wal et al. (2012), and expecting that it would reduce the core features of NES significantly in this sample. 2. Material and methods 2.1. Participants Potential participants were recruited through television and Internet advertisements, along with flyers posted at the University Hospital and around campus targeting persons who experienced overeating at night and/or waking during the night to eat. Men and women between the ages of 18–70 of all races and ethnicities were included. Exclusion criteria were: pregnancy; insulin-dependent diabetes; thyroid or other metabolic disorders; use in the past month of any psychotropic medication, oral steroids, diuretics or hypnotics; the presence of anorexia nervosa or bulimia nervosa; current participation in an organized weight reduction program or the use of weight loss medication, current participation in psychotherapy treatment for NES or another eating disorder, an occupation requiring night-shifts or other unusual nighttime requirements; severe major depressive disorder; suicidal risk; bipolar disorder; current or past psychosis; or substance use or abuse within the past 6 months. Weight greater than 400 lb and an allergy to shellfish or iodine were also exclusions, as participants were also completing a brain imaging study. This study's protocol was reviewed and approved by the University of Pennsylvania's Institutional Review Board, with all participants providing informed consent. 2.2. Procedures Participants were screened by phone for inclusion and exclusion criteria before being scheduled for their baseline assessment. At the baseline visit, participants completed a psychological assessment during which the diagnosis of NES was confirmed through questionnaires, clinical interviews, and, subsequently, a 10-day food and sleep log. Study personnel analyzed data from the logs with the Food Processor® program (ESHA research, Salem, OR). All participants included in the study met the full research criteria for NES (Allison et al., 2010). Using the available data, the authors confirmed that participants consumed at least 25% of their caloric intake after their evening meal and/or after waking up during the night to eat at least twice per week. Participants were also required to meet at least three of the five modifiers, have awareness of their nighttime eating, and show distress or impairment in functioning due to their night eating. The NES symptoms had to be present for at least three months. The baseline assessment also included a history and physical examination; drug screen, measurement of height, weight, and blood pressure; metabolic panel; and an electrocardiogram to establish that the participants were healthy enough to participate in a medication
trial. After completing the assessment, participants with confirmed NES were eligible for a brain imaging study (to be described elsewhere) and treatment. Participants were paid for completing the comprehensive assessment and brain imaging portion of the study. Treatment was subsequently provided at no charge. A total of 342 individuals responded to ads to participate in the current study. Of the 342 whom we contacted, 75 individuals provided consent to enroll in the study as night eating participants. Of the 75 who provided consent, 21 were found to be ineligible during their baseline screening appointment for the following reasons (some participants met more than one exclusion): 3 had uncontrolled or undiagnosed diabetes, 3 used illicit drugs, 4 met criteria for severe depression or suicidal ideation, 2 had anemia, 2 had abnormally high blood pressure, 2 had abnormal ECG, 4 had other medical issues deemed unstable or needing further medical care, 1 met criteria for bipolar disorder and 1 for purging disorder, 2 used other psychotropic/sleep medications, and 1 weighed greater than 400 lb. Additionally, 22 did not continue after the baseline assessment: 9 were found to be eligible, but never returned their screening materials (i.e., food/sleep log and survey packet), 3 had scheduling difficulties, 3 did not meet full NES criteria after assessment, 3 declined the study/lost to follow-up after baseline, and 4 did not keep their baseline (week 0) treatment appointments. The remaining 32 entered treatment. Of the 32 who entered treatment, 1 did not return after the initial treatment week and was not included in analysis (as she did not have more than one datapoint). 2.2.1. Treatment Treatment visits occurred at week 0 (start of treatment) and weeks 1, 2, 4, 6, 8, 10, and 12. Dosing of escitalopram began at 10 mg. If participants experienced significant side effects, dose was cut to 5 mg. At week 4, if participants' symptoms were still present, the dose was increased to 20 mg. Likewise, if significant side effects were experienced at 20 mg, dose was cut to 15 mg. 2.3. Measures 2.3.1. Baseline In addition to collecting demographic information, several measures were used at baseline to characterize the sample and to assess for exclusion criteria. The Night Eating Questionnaire (NEQ) (Allison et al., 2008) was completed at baseline. This is a 14-item questionnaire that assesses behavioral and psychological symptoms of NES. Total scores range from 0 to 52. The Beck Depression Inventory-II (BDI-II; Beck, 1996) was also administered; it is a widely used 21-item questionnaire that measures symptoms of depression present during the past week. Total scores range from 0 to 63; the BDI-II has high internal consistency, test–retest reliability and convergent and discriminant validity. The Night Eating Syndrome History and Inventory (NESHI) (Lundgren, Allison, Vinai P, Gluck) was used to confirm a diagnosis of NES. The NEQ is embedded in the NESHI, and additional items describe typical meal and snack patterns, level of distress, and severity and course of NES symptoms. The diagnostic criteria for NES are assessed with the NESHI. Eating disorder psychopathology was assessed with the Eating Disorder Examination, 16th edition (Fairburn, Cooper, & O'Connor, 2008). This measure has been found reliable and valid for assessment of eating pathology (Fairburn, Cooper, & O'Connor, 2001; Grilo, Masheb, LozanoBlanco, & Barry, 2004). The EDE includes assessment of binge eating and overeating episodes, four subscales (Restraint, Eating Concern, Shape Concern, and Weight Concern), and a global disordered eating score. The Eating Inventory was used to characterize common psychological factors related to eating, including cognitive restraint, disinhibition, and hunger (Stunkard & Messick, 1985). Axis I psychopathology was broadly assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P) (First, Spitzer, Gibbon, Williams, & Benjamin, 1996).
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2.3.2. Self-monitoring Participants kept food and sleep records at baseline screening and again during week 12 of treatment. The evening meal was defined as the first meal initiated between 17:00 h and 20:00 h. All energy intake after this meal or after 20:00 h, whichever came first, was included in the % of intake after the evening meal. During treatment, food and sleep logs were not kept so as not to influence participants' eating and sleep by self-monitoring. At treatment week 0, participants were oriented to their baseline percentage of intake consumed after dinner that was computed from their logs. Thereafter they provided their estimates of the percentage of intake after dinner and number of awakenings and nocturnal ingestions by self-report at each treatment visit.
having a high school diploma or GED, 19% had some college, 36% were college graduates, and 16% attended graduate school. Additional baseline demographic and psychosocial information is included in Table 1. There was high lifetime psychiatric comorbidity, with 65% meeting criteria for a history of any axis I disorder (Table 1). Of the 31 who were subsequently included in the analyses, 18 completed the 12-week treatment and 13 were non-completers: 6 dropped before week 4, an additional 2 dropped after week 4, 1 after week 6, 1 after week 8, and three after week 10. The average number of weeks in treatment was 8.9 (SD = 4.3) weeks. Non-completers reported more nocturnal ingestions at baseline compared to completers (8.0 vs. 4.0 per week, p = 0.03), but no other demographic or eating criteria differed.
2.4. Assessment during treatment
3.2. Primary and secondary outcomes
Three questionnaires were administered prior to each treatment session. The Night Eating Symptom Scale-II (NESS-II) (Lundgren, Allison, Vinai, & Gluck, 2012) is a 14-item questionnaire (possible range of 0–56) that contains items similar to the NEQ (Allison et al., 2008), but it assesses the presence of NES features over the course of the previous week. Participants also completed the BDI-II and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q)(Endicott, Nee, Harrison, & Blumenthal, 1993). The QLES-Q contains 14 face-valid items that assess global satisfaction in psychosocial and physical areas of functioning with a possible range of 14–70. Finally, weight was measured before each session in light clothing and without shoes. Body mass index (BMI, weight/height2 in kg/m2) was calculated at baseline and treatment end.
Significant decreases were noted in the three primary outcomes (Fig. 1a–c). The mean estimate of the NESS fell from 30.2 (SE = 1.3) at treatment week 0 to 15.2 (SE = 1.5) at week 12, a 49% decrease. Mean estimate of the percent of daily caloric intake consumed after dinner fell from 46.1% (SE = 3.0) to 17.4% (SE = 3.5), a 62% decrease. Eighteen (58%) reported consuming b 15% of daily caloric intake after dinner at their last study visit, and an additional five (16%) reported consuming between 15 and 25%. Nocturnal ingestions fell from 5.8 (SE = 0.5) to 1.2 (SE = 0.6) per week, an 80% decrease. Twenty (65%) participants reported no nocturnal ingestions and 18 (58%) no longer met core criteria for both features at their last study visit. In pairwise comparisons, all three outcomes significantly decreased after one week of treatment: NESS mean score dropped from 30.2 to 21.2 points, % of calories after dinner dropped from 46% to 28%, and nocturnal ingestions dropped from 5.8 to 2.4 per week, all ps b 0.0001. We added dose, sex, age, race, history of axis I disorder, and BED status as modifiers for each primary outcome variable; none were significant predictors of change over time. The only difference noted at treatment week 0 was a significantly greater percentage of calories consumed after dinner by those with BED (n = 7, 55%) as compared to those without (n = 24, 44%); no differences were noted at treatment end.
2.5. Statistical analysis Primary outcome measures were the change on the NESS total score, percentage of caloric intake consumed after the evening meal, and the number of nocturnal ingestions per week. Secondary outcome measures consisted of number of awakenings and change in weight. Finally, BDI and QLES-Q total scores were examined as global indicators of mood and functioning. Descriptive statistics were used to report means and frequencies of patient demographic and psychosocial characteristics. To assess changes over time in the outcomes, mixed-effects models were fit in which time (weeks 0, 1, 2, 4, 6, 8, 10, 12) was modeled as a categorical within subjects factor to obtain mean (SE) at each time point. These models were fit for each of the outcomes of interest: NESS score, percent of intake consumed after dinner, number of nocturnal ingestions and awakenings, weight, BDI score and QLES-Q score. An advantage of using mixed model analyses over traditional methodology (e.g. analysis of variance) is that all available data can be utilized; therefore, all participants with a baseline measurement and at least one of the seven subsequent measurements are included in these mixed model analyses. In exploratory analyses, moderators were included in the models described above, including age, gender, race, axis I pathology, and BED status. Finally, independent sample t-tests were used to compare baseline characteristics for treatment completers versus drop-outs. 3. Results 3.1. Participant characteristics The 31 participants were 68% (n = 21) female; 35.5% were single, 35.5% were married, and 29% were divorced/separated. Ethnicities included: 14 (45%) Non-Hispanic white, 12 (39%) African Americans, 1 (3%) Hispanic/Latino white, 1 (3%) Asian American, 2 mixed race (7%), and 1 (3%) did not disclose race. Three (9.7%) were of normal BMI (19–24.9 kg/m2), 11 (35.5%) were overweight (25–29.9 kg/m 2), and 17 (54.8%) were obese (≥30 kg/m 2). Education level varied, with 29%
Table 1 Baseline characteristics and psychosocial co-morbidities of participants. Baseline characteristics
Mean (SD)
Age (years) BMI (kg/m2) % calories after dinner until morning awakening % calories evening meal to bedtime % calories after bedtime to morning awakening No. awakenings/week No. nocturnal ingestions/week Baseline total caloric intake NEQ BDI EDE — restraint EDE — eating concern EDE — shape concern EDE — weight concern EDE global score Eating inventory — cognitive restraint Eating inventory — disinhibition Eating inventory — hunger
45.4 31.8 34.9 21.8 13.1 8.7 5.7 2743.3 31.7 14.3 1.9 2.4 3.8 3.4 2.9 8.6 10.5 8.1
Co-morbid psychopathology
N (percentage)
Any lifetime Axis I SCID diagnosis Binge eating disorder (all current) Any lifetime mood disorder Any lifetime anxiety disorder Any lifetime substance/alcohol abuse or dependence
20 7 7 7 5
(11.6) (6.4) (12.3) (14.8) (10.7) (6.2) (5.0) (1051.6) (6.9) (11.0) (1.2) (1.7) (1.6) (1.4) (1.2) (5.6) (3.4) (3.3)
(65%) (23%) (23%) (23%) (16%)
BMI is body mass index; NEQ is the Night Eating Questionnaire; BDI is the Beck Depression Inventory II; EDE is Eating Disorder Examination; SCID is the Structured Clinical Interview for DSM-IV Disorders.
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a
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p = 0.004). This result was similar upon excluding the three normal weight participants. Eight participants lost more than 2 lb (0.9 kg), eight maintained their weight (within 2 lb (0.9 kg)), and 13 gained more than 2 lb (0.9 kg). The BDI-II decreased from 12.1 (SE = 1.5) to 7.7 (SE = 1.6) (F (7,159) = 5.25, p b 0.001), but the QLES-Q did not increase significantly.
NESS total score
30
25
20
3.3. Change in binge-eating and overeating episodes 15
10
5
0 0
1
2
4
6
8
10
12
Treatment week
% daily intake consumed after dinner
b
60
3.4. Dosing and adverse events Mean dose of escitalopram at the last study visit was 13.2 (SD = 4.9) mg, with n = 1 participant at 5 mg, n = 19 at 10 mg, n = 1 at 15 mg, and n = 10 at 20 mg. Adverse events experienced by more than one participant included nausea (n = 5), drowsiness (n = 4), dry mouth (n = 3), increased sweating (n = 2), headache (n = 2), diarrhea (n = 2), low libido/impotence (n = 2), and mental cloudiness (n = 2). Drop-outs (n = 13) occurred for the following reasons: 6 were lost to follow-up, 1 discontinued due to epistaxis, 1 due to drowsiness, 1 due to panic attacks, 3 experienced life events/too busy, and 1 forgot to take her medication on a trip and discontinued thereafter.
50
40
30
20
10
4. Discussion
0 0
1
2
4
6
8
10
12
Treatment week
c
10 Nocturnal ingestions/week
9
Awakenings/week
8 7
Events per week
At baseline, participants (n = 30, one participant did not complete the EDE) reported an average of 4.1 (SD = 6.0) objective binge episodes, 5.9 (SD = 11.8) subjective binge episodes, and 1.1 (SD = 2.5) objective overeating episodes in the previous 28 days. At treatment end, 16 participants provided estimates of these behaviors; objective binge episodes decreased by 4, to 0.6 (SD = 0.03) episodes in the previous month, t(15) = 2.7, p = 0.02; subjective binge episodes and objective overeating episodes did not decrease significantly.
6 5 4 3 2 1 0 0
1
2
4
6
8
10
12
Treatment week Fig. 1. a. NESS total score decreased over time (F (7,159) = 26.8, p b 0.001). Mean estimates with standard error bars are shown. b. Percent of total daily intake decreased significantly from baseline to week 12 (F (7,160) = 23.2, p b 0.001). Mean estimates with standard error bars are shown. c. Nocturnal ingestions (F (7,161) = 18.5, p b 0.001) and awakenings (F (7,161) = 7.9, p b 0.001) per week both decreased significantly from baseline to week 12. Mean estimates with standard error bars are shown.
Of the secondary outcome measures, total number of awakenings per week decreased significantly, from 8.1 (SE = 0.8) to 2.7 (SE = 0.9) per week, a drop of 67% (F (7, 161) = 7.90, p b 0.001). Weight was also reduced significantly, but was not clinically significant, with a decrease from 90.2 (SE = 3.5) kg to 88.6 (SE = 3.5) kg, (F (7, 159) = 26.8,
Escitalopram significantly decreased all primary measures of night eating syndrome, including the NESS-II, percent of caloric intake consumed after dinner, and number of nocturnal ingestions per week in this 12-week, open-label trial. Additionally, 58% of participants were in remission at treatment end. In tracking the temporal response to treatment, significant improvements were noted at week 1 across all primary outcome measures, with continued gradual improvement across the 12 weeks. The reductions found in this trial for the percentage of intake after dinner and number of nocturnal ingestions were similar to those reported by O'Reardon et al. (2006) in their RCT of sertraline. Different metrics were reported in Vander Wal et al. (2012), so it is more difficult to compare. Weight decreased by 2.6 kg across the 12 weeks in the current trial. This loss seems similar to the 2.9 kg loss across 8 weeks in the randomized controlled trial of sertraline for NES (O'Reardon et al., 2006). However, there was a wide range of responses with weight, with some participants quite pleased with their weight loss and others showing displeasure at weight gain. Awakenings also improved across the 12 weeks. Depressive symptoms on the BDI-II were not clinically elevated at baseline, and they decreased from the mild to minimal range. Quality of life was not affected by treatment, as measured by the QLES-Q. Vander Wal et al. (2012) partly attributed a lack of significant findings between the placebo and escitalopram groups to a differential response by race; black participants did not reduce symptoms to the same extent as white participants. In the current study, we had similar representation between these groups, and no significant influence of race was noted on outcomes. Likewise, age and gender played no role in outcomes. Co-morbid psychopathology in this sample was high with 65% of the sample reporting a lifetime history of an axis I psychiatric disorder. This factor also had no significant influence on NES symptom response to escitalopram. All co-morbid diagnoses of BED were current,
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so we also examined the impact of this diagnosis on outcome separately. As could be expected, the BED group consumed more calories after dinner at baseline as compared to those without BED, but this difference disappeared by week 4 and was not a significant source of variance in NES outcomes. Binge episodes for the sample as a whole also decreased significantly, as would be expected from previous trials of SSRIs for BED (Appolinario & McElroy, 2004), although one trial of escitalopram specifically showed null results as compared to placebo for reduction of binge episodes (Guerdjikova et al., 2008). While this study builds on the nascent treatment literature for NES, this study has limitations. It is an open-label trial, so the significance of reductions should be viewed with caution. It is possible that the improvements were due to a placebo effect. Further trials are needed to confirm these findings. Additionally, the drop-out rate was larger than expected (42%), some due to medication effects, but the majority due to loss to follow-up, despite persistent efforts at retention by study staff. In conclusion, this open-label trial of escitalopram for NES yielded significant reductions in night eating symptoms, mood, and body weight. A larger controlled trial is warranted to test the efficacy of escitalopram for NES further, given that the evidence for effective treatment options for NES is still quite limited. Role of funding sources This research was supported by an investigator-initiated grant by Forest Laboratories, Incorporated, Jersey City, New Jersey, 07311, USA. Forest Labs had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. Contributors Authors must declare their individual contributions to the manuscript. All authors must have materially participated in the research and/or the manuscript preparation. Roles for each author should be described. The disclosure must also clearly state and verify that all authors have approved the final manuscript. Author Allison supervised the overall study conduct, including recruitment, treatment, and data collection and entry, and she drafted the manuscript. Studt carried out recruitment and was involved with screening, treatment visits, and data processing. Berkowitz and Hesson were involved with participant screenings and provided treatment. Moore planned and conducted the statistical analysis and helped in manuscript preparation. Dubroff was involved in assessing participants, and Newberg assisted in study design, regulatory issues, and participant assessment. Stunkard designed, obtained funding, and helped oversee the study. All authors contributed to and have approved the final manuscript. Conflict of interest This work was funded by Forest Pharmaceuticals, including some salary support for all authors except Moore and Stunkard. Acknowledgments This research was supported by an investigator-initiated grant by Forest Laboratories, Incorporated, Jersey City, New Jersey, 07311, USA. Portions of this manuscript were presented at the International Conference on Eating Disorders in Austin, Texas on May 3, 2012. We would like to thank Jeffery Lavenberg, M.S. for his help with the data preparation and Nitika Jain, M.D., for her efforts as research assistant with this study. We would also like to thank John P. O'Reardon, M.D. for helpful feedback on an earlier draft of this manuscript.
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