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Depression and treatment outcome in anorexia nervosa
Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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Depression and treatment outcome in anorexia nervosa Simona Calugi n, Marwan El Ghoch, Maddalena Conti, Riccardo Dalle Grave Department of Eating and Weight Disorders, Villa Garda Hospital, Via Montebaldo 89, I-37016 Garda, VR, Italy
art ic l e i nf o
a b s t r a c t
Article history: Received 29 December 2013 Received in revised form 8 February 2014 Accepted 6 April 2014
Aim of this study was to compare the immediate and long-term effect of a cognitive-behavior therapy program for anorexia nervosa inpatients with and without concomitant Major Depressive Episodes (MDE). The program has been adapted from the “enhanced” form of Cognitive Behavior Therapy (CBT) for eating disorders. Sixty-three consecutive underweight adult patients with severe eating disorder were treated with inpatient CBT. MDE was assessed with the structured clinical interview for DSM-IV. The Eating Disorder Examination, and the Brief Symptom Inventory were recorded at entry, at the end of treatment, and 6- and 12-month later. MDE was present in 60.3% of participants. No significant differences were observed in the demographic and baseline clinical variables between patients with and without MDE. Significant improvements in weight, and in eating disorder and general psychopathology were showed. There were no differences between participants with and without MDE in terms of treatment outcome, and the severity of depression was not associated with changes in global Eating Disorder Examination score. These findings suggest that a diagnosis of MDE does not influence the outcome of inpatient treatment for anorexia nervosa patients, and that the severity of depression cannot be used to predict the success or failure of such treatment. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Eating disorders Major depressive episode Cognitive behavior therapy Inpatient treatment
1. Introduction Anorexia nervosa has high rates of co-morbidity with other psychiatric disorders, especially major depressive disorder. Indeed, several studies have found that major depressive disorder is the most common co-morbid diagnosis in these patients (Herzog et al., 1992; Kaye, 2008), with lifetime rates ranging between 50% and 75% (American Psychiatric Association, 2006). In the existing literature, clinical depression has been linked with worse anorexia nervosa outcome (Lowe et al., 2001), higher rates of suicide attempt (Bulik et al., 2008; Franko et al., 2004) and suiciderelated mortality (Crow et al., 2009). However, hard data on the role of clinical depression in anorexia nervosa treatment outcome is scarce, and a general consensus still appears remote. For instance, while a few studies have found that pretreatment depression is predictive of poor immediate or long-term outcome of cognitive behavior therapy in patients with bulimia nervosa (Agras et al., 2000; Bossert et al., 1992; Bulik et al., 1998) no such link has been found in anorexia nervosa patients (Collin et al., 2010; Herpertz-Dahlmann et al., 1995). Clinical trials evaluating antidepressant efficacy in the treatment of eating disorders found that antidepressants reduced
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significantly the number of binge eating and self-induced vomiting episodes in bulimia nervosa and in binge eating disorder participants regardless the presence of comorbid depression (Goldstein et al., 1999). However, in another study on binge eating disorder participants, cognitive behavior therapy produced a significant higher reduction of depression and overevaluation of shape and weight than antidepressants (Grilo et al., 2012). Finally, antidepressants have not been associated with major depressive disorder recovery in anorexia nervosa participants (Mischoulon et al., 2010). Despite the paucity of evidence, NICE guidelines, erring on the side of caution, list severe depression as one of the contraindications for eating disorder treatment, and recommend that such treatment be postponed until the depression has been dealt with (National Institute of Clinical Excellence, 2004). Cognitive behavioral theorists are also of the opinion that clinical depression should be treated with full-dose antidepressants prior to launching the psychological treatment (Fairburn et al., 2008). However, some clinicians have suggested that it is, instead, preferable to focus initially on the treatment of eating disorders, the goal being to normalize weight and food intake before assessing and prescribing any treatment for co-existing psychiatric disorders (Garner, 1993; Mattar et al., 2012). The rationale behind this recommendation is based on the observation that many of the symptoms postulated to be a sign of psychiatric co-morbidity, including clinical depression, may actually result from low body
http://dx.doi.org/10.1016/j.psychres.2014.04.024 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Calugi, S., et al., Depression and treatment outcome in anorexia nervosa. Psychiatry Research (2014), http://dx. doi.org/10.1016/j.psychres.2014.04.024i
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weight and calorie restriction (American Psychiatric Association, 2006). In order to shed some light on the issue, we set out to investigate the prevalence and associated features of ongoing clinical depression in a large group of inpatients with eating disorders, and to assess whether it influences treatment outcome.
Assessed for eligibility (N=106)
Not eligible: eating disorder not sufficiently severe (N=27)
2. Methods
Excluded (N=16) 2.1. Design The study was conducted at an inpatient eating disorder unit. Consecutive eligible patients were treated with inpatient Cognitive Behavioral Therapy (CBT). Patients were assessed before treatment, after the end of treatment, and at 6- and 12-month follow-up. The period of hospitalization lasted 20 weeks, in which the treatment was administered in an inpatient setting for the first 13 weeks and in day hospital for the remaining seven. The ethical committee of the Local Health Unit 22-Bussolengo approved the study, and all participants gave informed written consent to their participation and to the anonymous use of their personal data.
Met exclusion criteria (N=3) Declined to participate (N=13)
Entered study (N=63)
2.2. Participants The sample consisted of 63 adult anorexia nervosa patients consecutively admitted to the inpatient eating disorder unit of Villa Garda Hospital (Northern Italy). The patients were referred from all over Italy by general practitioners or outpatient eating disorder specialists. For admission, patients had to be aged between 18 and 65 years, to fulfill the DSM-IV diagnostic criteria for anorexia nervosa (American Psychiatric Association, 2006) bar the amenorrhea criterion, as judged by both the referring clinician and an in-house eating disorder specialist (RDG), and to require inpatient treatment either as a result of failure of outpatient treatment or because the eating disorder could not be managed safely on an outpatient basis. Eighty percent (63/79) of eligible patients agreed to undergo the treatment, and were added to the unit's waiting list. During the waiting period, which lasted up to eight weeks, the patients were managed by their referring clinician. Four percent (3/79) of the eligible patients were excluded from the study for the following reasons (acute psychotic state, N ¼1; significant substance abuse, N ¼ 2), while 16% (13/79) declined to participate. Fig. 1 shows the recruitment and retention figures for the participants. 2.3. Inpatient treatment protocol The treatment adopted as standard in the unit has been adapted from the “enhanced” form of CBT for eating disorders (Fairburn, 2008) to make it suitable for an inpatient setting. The program retains all the main strategies and procedures of enhanced CBT, which were delivered in both individual and group sessions. However, the program differs from outpatient enhanced CBT in that meals are assisted by dietitians in the early weeks of hospitalization. Details of the program are provided elsewhere (Dalle Grave, 2012; Dalle Grave et al., 2008). Psychotropic medications were not prescribed during the treatment, and the psychotropic drugs being taken by patients at admission were gradually phased out during the first 2 weeks of hospitalization, while patients were under the supervision of clinic staff. 2.4. Assessment and measures 2.4.1. Demographic and clinical variables Demographic and clinical variables were obtained in the course of a direct interview. Weight (to the nearest 0.1 kg) was measured on calibrated scales, and height (to the nearest 0.5 cm) using a stadiometer. Patients were weighed and measured in their underwear, without shoes. 2.4.2. Eating disorder features These were assessed using the validated Italian version of the 12th edition of the Eating Disorder Examination interview (Fairburn and Cooper, 1993; Mannucci et al., 1997). The Eating Disorder Examination was administered by assessors who were trained and supervised by RDG, an expert in the use of the tool. The assessors had no involvement in the treatment itself. 2.4.3. General psychopathological features These were measured using the validated Italian version of the Brief Symptom Inventory (De Leo et al., 1993; Derogatis and Melisaratos, 1983) a short version of the Symptom Checklist-90 (Derogatis and Cleary, 1977). The Brief Symptom Inventory includes three scales designed to measure global psychological distress
Completed treatment (N=54) Dropped out (N=9)
Completed follow-up (N=50) Declined follow-up(N=13) Fig. 1. Consort diagram. and nine, more specific, subscales. For the purpose of our study we used the Global Severity Index (GSI) and the Depression subscale. The Structured Clinical Interview for DSM-IV (First et al., 1995) was used at baseline to identify the presence of coexisting axis I psychiatric disorders.
2.5. Statistical analyses Continuous variables were categorized as means (S.D.) or medians (interquartile range), and categorical variables as frequencies and percentages. The significance of differences between the groups at baseline was calculated by means of the T-test or chi-squared test or Fisher's Exact test, as appropriate. To assess the different effects of inpatient enhanced CBT intervention on each outcome (body weight, body mass index, Eating Disorder Examination global and subscale scores, Brief Symptom Inventory global and depression scores) at the end of therapy and at 6- and 12-month follow-up in participants with Major Depressive Episodes (MDE) and without (no-MDE), we used linear mixed model that included all four time-point outcome as dependent variables. Fixed parts of the model included a dummy variable indicating MDE and no-MDE groups, to account for the differences between the two groups, and the two groups (MDE vs. no-MDE) time interaction, to evaluate different changes in the two groups over time. As covariates we included the baseline measure of the outcome. Mixed effect models have been endorsed as a rigorous method of analyzing longitudinal repeated-measures data from therapy studies (Houck et al., 2004). Moreove, when the missing data is ignorable, and the model describing individual growth patterns is correctly specified, the mixed effect model provides valid inferences in the presence of missing data (Laird, 1988). These models can be applied to both normally distributed continuous outcomes as well as categorical outcomes and other nonnormally distributed outcomes, and allow us to analyze data under general assumptions regarding the missing data (i.e., missing at random) (Gibbons et al., 2010). We found evidence to support the missing-at-random assumption in the present data. We assessed a number of baseline variables (age, occupation, length of illness duration) for their ability to predict missingness at each time point measured by a categorical variable (missing data at that time point for that participant Yes/No) using logistic regression. These variables, and their interactions with time, did not predict changes in any of our dependent variables, suggesting that missing data did not influence outcomes. We therefore analyzed the effect of
Please cite this article as: Calugi, S., et al., Depression and treatment outcome in anorexia nervosa. Psychiatry Research (2014), http://dx. doi.org/10.1016/j.psychres.2014.04.024i
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Table 1 Characteristics of the two samples at baseline. Data are shown as mean (S.D.) unless otherwise indicated. Characteristics
All patients (N ¼ 63)
No-MDE (N ¼ 25)
MDE (N ¼38)
Test
P (value)
Age, years Gender, n (%) female Marital status, n (%) Single, never married Married or living as such Separated or divorced Occupation, n (%) Higher Intermediate Lower Unclassifiable Full-time student Current other axis I disorder, n (%) present Panic disorder w/wt agoraphobia Generalized anxiety disorder Obsessive compulsive disorder Post-traumatic stress disorder Social phobia Specific phobia Any anxiety disorder Duration of eating disorder, ys, median (range) Body weight (kg) Body mass index (kg/m2) Eating disorder psychopathology Overall severity (global EDE) Dietary restraint (EDE subscale) Eating concern (EDE subscale) Weight concern (EDE subscale) Shape concern (EDE subscale) Eating disorder behavior (EDE) Objective bulimic episodes, n (%) present If present, episodes/28 days, median (range) Self-induced vomiting, n (%) present If present, episodes/28 days, median (range) Laxative misuse, n (%) present If present, episodes/28 days, median (range) Excessive exercise, n (%) present If present, episodes/28 days, median (range) Brief symptom inventory Depression Global Severity Index
26.4 (5.8) 61 (96.8)
25.8 (6.6) 25 (100)
26.5 (6.0) 36 (94.7)
0.48 1.36
0.633 0.244
55 (87.3) 6 (9.5) 2 (3.2)
21 (84.0) 3 (12.0) 1 (4.0)
34 (89.5) 3 (7.9) 1 (2.6)
0.41
0.816
3.33
0.504
1 17 3 24 17
(1.6) (27.0) (4.8) (38.1) (27.0)
0 9 2 8 6
1 8 1 16 11
(6.3) (3.2) (6.3) (9.5) (4.8) (1.6) (23.8) (0–26.0) (6.6) (2.1)
0 0 1 (4.0) 3 (12.0) 1 (4.0) 0 5 (20.0) 5.0 (0–23.0) 37.6 (7.0) 14.2 (2.3)
(10.5) (5.3) (7.9) (7.9) (5.3) (2.6) (26.3) (1–26.0) (6.3) (2.0)
0.24 1.34 1.15 1.25
0.132 0.372 0.495 0.428 0.669 0.613 0.623 0.181 0.251 0.217
(1.1) (1.1) (1.3) (1.5) (1.4)
3.7 4.2 3.3 3.5 3.7
(1.1) (1.1) (1.5) (1.4) (1.4)
0.75 0.62 1.57 0.77 0.47
0.457 0.539 0.121 0.445 0.636
(36.5) (1–280) (39.7) (3–336) (30.2) (1–112) (63.5) (6–240)
7 (28.0) 10.0 (1–126) 8 (32.0) 30.0 (5–112) 10 (40.0) 28.0 (1–84) 14 (56.0) 18.0 (6–240)
1.29 0.30 1.02 0.13 1.91 0.26 1.00 1.77
0.255 0.762 0.312 0.898 0.167 0.842 0.316 0.077
1.87 1.25
0.067 0.214
4 2 4 6 3 1 15 7.0 38.8 14.6 3.8 4.1 3.6 3.7 3.8 23 10.0 25 40.0 19 28.0 40 28.0
2.4 (1.0) 1.9 (0.8)
(36.0) (8.0) (32.0) (24.0)
(1.0) (1.2) (1.1) (1.5) (1.4)
2.1 (1.1) 1.8 (0.8)
4 2 3 3 2 1 10 8 39.6 14.9 3.9 4.0 3.8 3.8 3.8
(2.6) (21.1) (2.6) (42.1) (28.9)
16 (42.1) 11.5 (1–280) 17 (44.7) 50.0 (3–336) 9 (23.7) 28.0 (2–112) 26 (68.4) 28.0(6–28) 2.6 (0.8 2.0 (0.7)
MDE – Major Depressive Episode. EDE – Eating Disorder Examination (version 12.0D).
the treatment on the two groups by intention to treat that included all study participants. Using only individuals who completed the treatment, a linear regression analysis, adjusting for body mass index and Eating Disorder Examination global score at baseline, was performed to evaluate whether the baseline severity of depression, assessed with the Brief Symptom Inventory depression subscale, was associated with any change in Eating Disorder Examination global score. Finally, using a logistic regression analysis we evaluated the significance of the relationship between the baseline severity of depression and patients reaching an Eating Disorder Examination global score lower than 1S.D. above the community mean (i.e., o 1.74) (Kendall et al., 1999) and a body mass index Z 18.5, at end of therapy and at follow-ups. The statistical analyses were carried out using SPSS (IBM SPSS Statistics, version 20.0).
3. Results 3.1. Participant characteristics The majority of participants were adult patients in their mid20s. Table 1 shows the demographic and clinical features of the whole sample, and of MDE and no-MDE groups. MDE was present in 60.3% (38/63) of participants and no differences were found between MDE and no-MDE groups on all demographics variables, on current other Axis I comorbidity and on clinical variables.
3.2. Depression and treatment outcome We calculated estimated treatment effects on outcomes at end of therapy and 6- and 12-month follow-up (with baseline outcome values held constant) to examine the main effect over time and change over time into the two groups. Over time, a significant increase was found on weight and body mass index and a significant decrease on Eating Disorder Examination global and subscales scores in both groups (Table 2). This result indicated that there was a significant effect of receiving inpatient enhanced CBT on the overall sample, with mean body mass index increasing from baseline to end of therapy by 4.68 (95% CI 4.03–5.34) and to 6- and 12-month follow-up by 3.64 (95% CI 2.76–4.51) and 3.42 (95% CI 2.47–4.36), respectively. There was also an effect of being given treatment on Eating Disorder Examination global score, with mean Eating Disorder Examination global score decreasing from baseline to discharge by 2.28 (95% CI 2.70–1.89) and to 6- and 12-month follow-up by 2.37 (95% CI 2.89– 1.85) and 2.05 (95% CI 2.57–1.53), respectively. Table 3 indicated that no significant effect was found for time×group in terms of each outcome variable, indicating that the two groups had similar changes over time on each outcome variables.
Please cite this article as: Calugi, S., et al., Depression and treatment outcome in anorexia nervosa. Psychiatry Research (2014), http://dx. doi.org/10.1016/j.psychres.2014.04.024i
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Table 2 Estimated treatment effect in the two groups (MDE and no-MDE) over time (main effect of the time). Results from the linear mixed models. Baseline to end of therapy
Body weight (kg) Body mass index (kg/m2) Eating disorder psychopathology Overall severity (global EDE) Dietary restraint (EDE subscale) Eating concern (EDE subscale) Weight concern (EDE subscale) Shape concern (EDE subscale) Brief symptom inventory Depression Global Severity Index
Baseline to 6 month follow-up
Baseline to 12 month follow-up
Estimate
95% CI
P
Estimate
95% CI
P
Estimate
95% CI
P
12.46 4.68
10.67 to 14.24 4.03 to 5.34
o 0.001 o 0.001
10.15 3.64
7.89 to 12.41 2.76 to 4.51
o0.001 o0.001
9.41 3.42
7.05 to 11.76 2.47 to 4.36
o 0.001 o 0.001
2.28 3.32 2.69 1.96 1.16
2.70 to 1.86 3.75 to 2.90 3.17 to 2.21 2.55 to 1.38 1.83 to 0.49
o 0.001 o 0.001 o 0.001 o 0.001 0.001
2.37 2.82 2.16 2.40 2.10
2.89 to 3.38 to 2.84 to 2.98 to 2.74 to
1.85 2.26 1.47 1.82 1.45
o0.001 o0.001 o0.001 o0.001 o0.001
2.05 2.10 2.05 2.27 1.79
2.57 2.71 2.69 2.84 2.43
1.53 1.48 1.42 1.70 1.14
o 0.001 o 0.001 o 0.001 o 0.001 o 0.001
1.47 1.25
1.83 to 1.10 1.53 to 0.96
o 0.001 o 0.001
1.11 0.99
1.59 to 1.10 1.29 to 0.68
o0.001 o0.001
1.0 0.91
1.48 to 0.63 1.20 to 0.62
o 0.001 o 0.001
to to to to to
EDE – Eating Disorder Examination (version 12.0D). Table 3 Estimated treatment effect in the two groups (MDE and no-MDE) over time (time group interaction). Results from the linear mixed models. Baseline to end of therapy
Body weight (kg) Body mass index (kg/m2) Eating disorder psychopathology Overall severity (global EDE) Dietary restraint (EDE subscale) Eating concern (EDE subscale) Weight concern (EDE subscale) Shape concern (EDE subscale) Brief symptom inventory Depression Global severity index
Baseline to 6 month follow-up
Baseline to 12 month follow-up
Estimate
95% CI
P
Estimate
95% CI
P
Estimate
95% CI
P
0.56 0.17
2.18 to 3.30 0.84 to 1.17
0.684 0.740
1.29 0.14
4.84 to 2.26 1.53 to 1.24
0.470 0.834
0.46 0.08
4.16 to 3.24 1.59 to 1.43
0.803 0.917
0.24 0.25 0.36 0.61 0.25
0.42 0.92 0.39 0.31 0.79
to 0.91 to 0.42 to 1.11 to 1.52 to 1.30
0.462 0.461 0.336 0.189 0.628
0.28 0.15 0.09 0.54 0.62
0.53 to 1.09 1021 to 0.73 0.98 to 1.16 0.37 to 1.46 0.39 to 1.63
0.496 0.736 0.867 0.237 0.223
0.01 0.62 0.14 0.41 0.11
0.83 to 0.85 1.62 to 0.38 0.88 to 1.17 0.51 to 1.33 0.93 to 1.15
0.980 0.220 0.777 0.377 0.834
0.47 0.15
0.10 to 1.05 0.30 to 0.60
0.102 0.515
0.08 0.02
0.63 to 0.80 0.49 to 0.46
0.812 0.942
0.19 0.17
0.89 to 0.50 0.64 to 0.30
0.577 0.465
EDE – Eating Disorder Examination (version 12.0D).
21.5
No-MDE
5.0
MDE
4.5
No-MDE
4.0
MDE
20.5 19.5
EDE Global score
3.5
BMI
18.5 17.5 16.5
3.0 2.5 2.0 1.5
15.5
1.0
14.5
0.5
13.5
0.0 Baseline
12.5 Baseline
End of treatment
6-Month Follow-Up
12-Month Follow-Up
Fig. 2. Predicted mean body mass index at each time point in MDE and no-MDE groups.
Figs. 2 and 3 show the estimated treatment effect on body mass index and on Eating Disorder Examination global score in MDE and no-MDE groups at each time point. 3.3. Depression and eating disorder psychopathology in completers Fifty-four participants (85.7%) completed the treatment (completers), whereas 9 (14.3%) left the program before concluding the planned 20 weeks of treatment (dropouts). The dropout rate was
End of treatment
6-Month Follow-Up
12-Month Follow-Up
Fig. 3. Predicted mean Eating Disorder Examination global score at each time point in MDE and no-MDE groups.
not significantly different between MDE and no-MDE groups (15.8% vs. 12.0% respectively; χ2(1, N ¼ 63)¼ 0.18, P ¼0.674). A post-hoc analysis, comparing the demographic and baseline clinical variables of completers and dropouts showed no significant differences between the two groups. 88.9% of completers received outpatient treatment after the discharge, and there were no differences between the two groups in this respect (MDE 90.6% vs. no-MDE 86.4%, χ2(1, N ¼54) ¼0.26, P ¼ 0.624). Among those, 97.9% received psychotherapy and 10.9% pharmacotherapy, and there were no differences between MDE and no-MDE patients
Please cite this article as: Calugi, S., et al., Depression and treatment outcome in anorexia nervosa. Psychiatry Research (2014), http://dx. doi.org/10.1016/j.psychres.2014.04.024i
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regarding the type of psychotherapy received (χ2(1, N ¼ 48) ¼1.56, P ¼0.212; χ2(1, N ¼48) ¼0.002, P ¼0.996, respectively). The severity of baseline depression, assessed with Brief Symptom Inventory depression subscale score, was not associated with any change in Eating Disorder Examination global score from baseline to end of therapy (beta ¼0.18, t¼ 1.38, P ¼0.175) and from baseline to 6- and 12-month follow-up (beta ¼ 0.17, t¼1.29, P ¼.204; beta ¼0.16, t ¼1.07, P ¼0.288; respectively). In addition, no significant relationship was observed between baseline depression scores and participants reaching an Eating Disorder Examination global score of less than 1 S.D. above the community mean at the end of therapy and at follow-up (end of therapy P¼ 0.925; 6month follow-up P¼ 0.791; 12-month follow-up P ¼0.992). Finally, no significant association was found between baseline depression scores and participants with a body mass index Z18.5 at the end of therapy or at 6- and 12-month follow-up (end of therapy P ¼0.230; 6-month follow-up P ¼0.567; 12-month follow-up P ¼0.472).
4. Discussion In this study we compared the effects of an inpatient CBT program in underweight eating disorder participants with or without a co-morbid current mood disorder at baseline. We also set out to investigate whether the severity of depression influenced the treatment outcome. The investigation yielded four main findings. The first was that the prevalence of MDE in our sample (60.3%) was high and similar to those reported by a previous study assessing current depression in an large sample of female inpatients with anorexia nervosa (Blinder et al., 2006). The second finding was that, at baseline, the MDE group displayed similar eating disorder behaviors and psychopathology to the no-MDE group. We did not confirm the direct association between eating disorder behaviors (i.e. binge eating, vomiting) and clinical depression in anorexia nervosa patients. A few of studies indicated a prevalence of mood disorders significantly higher in patients with anorexia nervosa binge eating purging type compared to those with anorexia nervosa restricting type (Godart et al., 2007). Nevertheless, it is possible that these discrepancies arose from the fact that our study assessed ongoing depression, while others have factored in lifetime depression. The third finding was that patients responded well to the inpatient CBT program, regardless of their depression status. This finding, obtained by adjusting the calculations for the baseline measure of the outcome, suggests that baseline MDE diagnosis is not a prognostic indicator of outcome either at the end of treatment or at follow-up, and should therefore not be considered an obstacle to inpatient CBT, as has previously maintained. The intensive support given to inpatients in our treatment program may have helped them overcome the feelings of hopelessness about the possibility of change and the reduction of motivation that characterize individuals with clinical depression (obstacles that the program has been specifically designed to address), thereby countering the negative role of MDE in treatment outcome. In addition, our data are in line to that found in a recent review indicating that main prognostic factors identified across studies of anorexia nervosa outcome are duration of illness and duration of treatment but not psychiatric comorbidity or general psychiatric symptom severity (Keel and Brown, 2010). The fourth and final finding of our study was that depressive symptoms, as measured using Brief Symptom Inventory depression subscale, improved from baseline to end of therapy, and that this change was sustained over follow-up. No link in this improvement in baseline depressive symptoms and improvement in eating psychopathology was found. This data appears to indicate that
5
inpatient CBT, by targeting eating disorder psychopathology alone, nevertheless improved depressive symptoms without any adjunctive psychopharmacological intervention, and that baseline depression does not influence treatment outcome. Unfortunately, the study design does not enable us to provide a definitive explanation for the means by which inpatient CBT improved depression status. Nonetheless, four explanations may tentatively be proposed. First, it may be that inpatient CBT exerts a direct effect on the depression scores by normalizing the weight and eating habits, improving the socialization, and reducing the overevaluation of shape and weight, which are specific targets of the intervention. Second, it may also be that the program has an indirect effect on depressive symptoms by improving eating disorder psychopathology, which in turn may increase the feeling of self-efficacy and hope. Third, it is possible that the procedures and strategies addressing mood intolerance included in the “enhanced” CBT protocol may have a positive effect on depressive symptoms. Finally, the improvement of depressive symptoms without the aid of specific psychotherapy for depression and antidepressant medications may be the direct result of weight restoration, rather than specific CBT procedures and strategies. The strengths of this study lie in the large sample size, the low dropout rates and the statistical procedure adopted, not to mention the fact that the diagnosis of mood disorder was made using the SCID-IV. These factors enable us to consider our findings as robust and generalizable. Other factors in its favor are the study’s assessment of patients at four time points and the long-term follow-up conducted for over a year after hospitalization. It is also crucial to note that no psychopharmacological treatments were administered during the study period, and inpatient CBT was the patients’ sole treatment. This allows us to consider the “pure” effect of inpatient CBT on the eating disorder and general psychopathology. Nevertheless, the study does have five main limitations. First, the data were gathered from a single inpatient unit that treats mainly adult patients with severe eating disorders. The sample may therefore not be representative of patients seeking treatment in other inpatient or outpatient settings. Second, the study did not include a control group treated with other form of treatments, a limit very difficult to overcome in inpatient setting studies. This limitation does not permit to generalize results obtained with the inpatient CBT to other inpatient treatments. Third, the Brief Symptom Inventory depression subscale is not the gold-standard instrument to assess the dimensional component of the depression. This could also explain the absence of significant difference between the two groups at baseline. The fourth drawback is that we did not evaluate the presence of MDE at the end of therapy, or at 6- and 12-month follow-up. The final limitation of our study is rooted in the conceptualization of depressive symptoms in patients with anorexia nervosa. Unfortunately, our study design does not enable clarification of whether such symptoms are ascribable to coexisting clinical depression, or whether they are caused by malnutrition interacting with the eating disorder psychopathology. This is an important area for future research because if depressive symptoms are an integral part of anorexia nervosa, there would be no expected correlation between their presence at baseline, as suggested by our data, and the eating disorder outcome. It is also possible that the current diagnostic criteria for MDE may be too broad when applied to severely underweight patients with anorexia nervosa, failing to distinguish the subgroup of patients with “real” coexisting clinical depression, who might benefit from treatment for such depression. Nonetheless, the findings we can report do suggest that a diagnosis of MDE is not an obstacle to inpatient CBT, and that the severity of depression does not influence the treatment outcome.
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These data, if confirmed by other studies, will have clinical implications, suggesting that (our) inpatient treatment of eating disorder psychopathology with cognitive behavioral procedures and strategies produces a lasting improvement in both eating disorder psychopathology and depressive symptoms without needing to resort to psychopharmacological intervention or to postpone treatment until the mood has been stabilized.
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Depression and treatment outcome in anorexia nervosa Simona Calugi n, Marwan El Ghoch, Maddalena Conti, Riccardo Dalle Grave Department of Eating and Weight Disorders, Villa Garda Hospital, Via Montebaldo 89, I-37016 Garda, VR, Italy
art ic l e i nf o
a b s t r a c t
Article history: Received 29 December 2013 Received in revised form 8 February 2014 Accepted 6 April 2014
Aim of this study was to compare the immediate and long-term effect of a cognitive-behavior therapy program for anorexia nervosa inpatients with and without concomitant Major Depressive Episodes (MDE). The program has been adapted from the “enhanced” form of Cognitive Behavior Therapy (CBT) for eating disorders. Sixty-three consecutive underweight adult patients with severe eating disorder were treated with inpatient CBT. MDE was assessed with the structured clinical interview for DSM-IV. The Eating Disorder Examination, and the Brief Symptom Inventory were recorded at entry, at the end of treatment, and 6- and 12-month later. MDE was present in 60.3% of participants. No significant differences were observed in the demographic and baseline clinical variables between patients with and without MDE. Significant improvements in weight, and in eating disorder and general psychopathology were showed. There were no differences between participants with and without MDE in terms of treatment outcome, and the severity of depression was not associated with changes in global Eating Disorder Examination score. These findings suggest that a diagnosis of MDE does not influence the outcome of inpatient treatment for anorexia nervosa patients, and that the severity of depression cannot be used to predict the success or failure of such treatment. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Eating disorders Major depressive episode Cognitive behavior therapy Inpatient treatment
1. Introduction Anorexia nervosa has high rates of co-morbidity with other psychiatric disorders, especially major depressive disorder. Indeed, several studies have found that major depressive disorder is the most common co-morbid diagnosis in these patients (Herzog et al., 1992; Kaye, 2008), with lifetime rates ranging between 50% and 75% (American Psychiatric Association, 2006). In the existing literature, clinical depression has been linked with worse anorexia nervosa outcome (Lowe et al., 2001), higher rates of suicide attempt (Bulik et al., 2008; Franko et al., 2004) and suiciderelated mortality (Crow et al., 2009). However, hard data on the role of clinical depression in anorexia nervosa treatment outcome is scarce, and a general consensus still appears remote. For instance, while a few studies have found that pretreatment depression is predictive of poor immediate or long-term outcome of cognitive behavior therapy in patients with bulimia nervosa (Agras et al., 2000; Bossert et al., 1992; Bulik et al., 1998) no such link has been found in anorexia nervosa patients (Collin et al., 2010; Herpertz-Dahlmann et al., 1995). Clinical trials evaluating antidepressant efficacy in the treatment of eating disorders found that antidepressants reduced
n
Corresponding author. Tel.: þ 39 045 8103915; fax: þ39 045 8102884. E-mail address: [email protected] (S. Calugi).
significantly the number of binge eating and self-induced vomiting episodes in bulimia nervosa and in binge eating disorder participants regardless the presence of comorbid depression (Goldstein et al., 1999). However, in another study on binge eating disorder participants, cognitive behavior therapy produced a significant higher reduction of depression and overevaluation of shape and weight than antidepressants (Grilo et al., 2012). Finally, antidepressants have not been associated with major depressive disorder recovery in anorexia nervosa participants (Mischoulon et al., 2010). Despite the paucity of evidence, NICE guidelines, erring on the side of caution, list severe depression as one of the contraindications for eating disorder treatment, and recommend that such treatment be postponed until the depression has been dealt with (National Institute of Clinical Excellence, 2004). Cognitive behavioral theorists are also of the opinion that clinical depression should be treated with full-dose antidepressants prior to launching the psychological treatment (Fairburn et al., 2008). However, some clinicians have suggested that it is, instead, preferable to focus initially on the treatment of eating disorders, the goal being to normalize weight and food intake before assessing and prescribing any treatment for co-existing psychiatric disorders (Garner, 1993; Mattar et al., 2012). The rationale behind this recommendation is based on the observation that many of the symptoms postulated to be a sign of psychiatric co-morbidity, including clinical depression, may actually result from low body
http://dx.doi.org/10.1016/j.psychres.2014.04.024 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
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weight and calorie restriction (American Psychiatric Association, 2006). In order to shed some light on the issue, we set out to investigate the prevalence and associated features of ongoing clinical depression in a large group of inpatients with eating disorders, and to assess whether it influences treatment outcome.
Assessed for eligibility (N=106)
Not eligible: eating disorder not sufficiently severe (N=27)
2. Methods
Excluded (N=16) 2.1. Design The study was conducted at an inpatient eating disorder unit. Consecutive eligible patients were treated with inpatient Cognitive Behavioral Therapy (CBT). Patients were assessed before treatment, after the end of treatment, and at 6- and 12-month follow-up. The period of hospitalization lasted 20 weeks, in which the treatment was administered in an inpatient setting for the first 13 weeks and in day hospital for the remaining seven. The ethical committee of the Local Health Unit 22-Bussolengo approved the study, and all participants gave informed written consent to their participation and to the anonymous use of their personal data.
Met exclusion criteria (N=3) Declined to participate (N=13)
Entered study (N=63)
2.2. Participants The sample consisted of 63 adult anorexia nervosa patients consecutively admitted to the inpatient eating disorder unit of Villa Garda Hospital (Northern Italy). The patients were referred from all over Italy by general practitioners or outpatient eating disorder specialists. For admission, patients had to be aged between 18 and 65 years, to fulfill the DSM-IV diagnostic criteria for anorexia nervosa (American Psychiatric Association, 2006) bar the amenorrhea criterion, as judged by both the referring clinician and an in-house eating disorder specialist (RDG), and to require inpatient treatment either as a result of failure of outpatient treatment or because the eating disorder could not be managed safely on an outpatient basis. Eighty percent (63/79) of eligible patients agreed to undergo the treatment, and were added to the unit's waiting list. During the waiting period, which lasted up to eight weeks, the patients were managed by their referring clinician. Four percent (3/79) of the eligible patients were excluded from the study for the following reasons (acute psychotic state, N ¼1; significant substance abuse, N ¼ 2), while 16% (13/79) declined to participate. Fig. 1 shows the recruitment and retention figures for the participants. 2.3. Inpatient treatment protocol The treatment adopted as standard in the unit has been adapted from the “enhanced” form of CBT for eating disorders (Fairburn, 2008) to make it suitable for an inpatient setting. The program retains all the main strategies and procedures of enhanced CBT, which were delivered in both individual and group sessions. However, the program differs from outpatient enhanced CBT in that meals are assisted by dietitians in the early weeks of hospitalization. Details of the program are provided elsewhere (Dalle Grave, 2012; Dalle Grave et al., 2008). Psychotropic medications were not prescribed during the treatment, and the psychotropic drugs being taken by patients at admission were gradually phased out during the first 2 weeks of hospitalization, while patients were under the supervision of clinic staff. 2.4. Assessment and measures 2.4.1. Demographic and clinical variables Demographic and clinical variables were obtained in the course of a direct interview. Weight (to the nearest 0.1 kg) was measured on calibrated scales, and height (to the nearest 0.5 cm) using a stadiometer. Patients were weighed and measured in their underwear, without shoes. 2.4.2. Eating disorder features These were assessed using the validated Italian version of the 12th edition of the Eating Disorder Examination interview (Fairburn and Cooper, 1993; Mannucci et al., 1997). The Eating Disorder Examination was administered by assessors who were trained and supervised by RDG, an expert in the use of the tool. The assessors had no involvement in the treatment itself. 2.4.3. General psychopathological features These were measured using the validated Italian version of the Brief Symptom Inventory (De Leo et al., 1993; Derogatis and Melisaratos, 1983) a short version of the Symptom Checklist-90 (Derogatis and Cleary, 1977). The Brief Symptom Inventory includes three scales designed to measure global psychological distress
Completed treatment (N=54) Dropped out (N=9)
Completed follow-up (N=50) Declined follow-up(N=13) Fig. 1. Consort diagram. and nine, more specific, subscales. For the purpose of our study we used the Global Severity Index (GSI) and the Depression subscale. The Structured Clinical Interview for DSM-IV (First et al., 1995) was used at baseline to identify the presence of coexisting axis I psychiatric disorders.
2.5. Statistical analyses Continuous variables were categorized as means (S.D.) or medians (interquartile range), and categorical variables as frequencies and percentages. The significance of differences between the groups at baseline was calculated by means of the T-test or chi-squared test or Fisher's Exact test, as appropriate. To assess the different effects of inpatient enhanced CBT intervention on each outcome (body weight, body mass index, Eating Disorder Examination global and subscale scores, Brief Symptom Inventory global and depression scores) at the end of therapy and at 6- and 12-month follow-up in participants with Major Depressive Episodes (MDE) and without (no-MDE), we used linear mixed model that included all four time-point outcome as dependent variables. Fixed parts of the model included a dummy variable indicating MDE and no-MDE groups, to account for the differences between the two groups, and the two groups (MDE vs. no-MDE) time interaction, to evaluate different changes in the two groups over time. As covariates we included the baseline measure of the outcome. Mixed effect models have been endorsed as a rigorous method of analyzing longitudinal repeated-measures data from therapy studies (Houck et al., 2004). Moreove, when the missing data is ignorable, and the model describing individual growth patterns is correctly specified, the mixed effect model provides valid inferences in the presence of missing data (Laird, 1988). These models can be applied to both normally distributed continuous outcomes as well as categorical outcomes and other nonnormally distributed outcomes, and allow us to analyze data under general assumptions regarding the missing data (i.e., missing at random) (Gibbons et al., 2010). We found evidence to support the missing-at-random assumption in the present data. We assessed a number of baseline variables (age, occupation, length of illness duration) for their ability to predict missingness at each time point measured by a categorical variable (missing data at that time point for that participant Yes/No) using logistic regression. These variables, and their interactions with time, did not predict changes in any of our dependent variables, suggesting that missing data did not influence outcomes. We therefore analyzed the effect of
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Table 1 Characteristics of the two samples at baseline. Data are shown as mean (S.D.) unless otherwise indicated. Characteristics
All patients (N ¼ 63)
No-MDE (N ¼ 25)
MDE (N ¼38)
Test
P (value)
Age, years Gender, n (%) female Marital status, n (%) Single, never married Married or living as such Separated or divorced Occupation, n (%) Higher Intermediate Lower Unclassifiable Full-time student Current other axis I disorder, n (%) present Panic disorder w/wt agoraphobia Generalized anxiety disorder Obsessive compulsive disorder Post-traumatic stress disorder Social phobia Specific phobia Any anxiety disorder Duration of eating disorder, ys, median (range) Body weight (kg) Body mass index (kg/m2) Eating disorder psychopathology Overall severity (global EDE) Dietary restraint (EDE subscale) Eating concern (EDE subscale) Weight concern (EDE subscale) Shape concern (EDE subscale) Eating disorder behavior (EDE) Objective bulimic episodes, n (%) present If present, episodes/28 days, median (range) Self-induced vomiting, n (%) present If present, episodes/28 days, median (range) Laxative misuse, n (%) present If present, episodes/28 days, median (range) Excessive exercise, n (%) present If present, episodes/28 days, median (range) Brief symptom inventory Depression Global Severity Index
26.4 (5.8) 61 (96.8)
25.8 (6.6) 25 (100)
26.5 (6.0) 36 (94.7)
0.48 1.36
0.633 0.244
55 (87.3) 6 (9.5) 2 (3.2)
21 (84.0) 3 (12.0) 1 (4.0)
34 (89.5) 3 (7.9) 1 (2.6)
0.41
0.816
3.33
0.504
1 17 3 24 17
(1.6) (27.0) (4.8) (38.1) (27.0)
0 9 2 8 6
1 8 1 16 11
(6.3) (3.2) (6.3) (9.5) (4.8) (1.6) (23.8) (0–26.0) (6.6) (2.1)
0 0 1 (4.0) 3 (12.0) 1 (4.0) 0 5 (20.0) 5.0 (0–23.0) 37.6 (7.0) 14.2 (2.3)
(10.5) (5.3) (7.9) (7.9) (5.3) (2.6) (26.3) (1–26.0) (6.3) (2.0)
0.24 1.34 1.15 1.25
0.132 0.372 0.495 0.428 0.669 0.613 0.623 0.181 0.251 0.217
(1.1) (1.1) (1.3) (1.5) (1.4)
3.7 4.2 3.3 3.5 3.7
(1.1) (1.1) (1.5) (1.4) (1.4)
0.75 0.62 1.57 0.77 0.47
0.457 0.539 0.121 0.445 0.636
(36.5) (1–280) (39.7) (3–336) (30.2) (1–112) (63.5) (6–240)
7 (28.0) 10.0 (1–126) 8 (32.0) 30.0 (5–112) 10 (40.0) 28.0 (1–84) 14 (56.0) 18.0 (6–240)
1.29 0.30 1.02 0.13 1.91 0.26 1.00 1.77
0.255 0.762 0.312 0.898 0.167 0.842 0.316 0.077
1.87 1.25
0.067 0.214
4 2 4 6 3 1 15 7.0 38.8 14.6 3.8 4.1 3.6 3.7 3.8 23 10.0 25 40.0 19 28.0 40 28.0
2.4 (1.0) 1.9 (0.8)
(36.0) (8.0) (32.0) (24.0)
(1.0) (1.2) (1.1) (1.5) (1.4)
2.1 (1.1) 1.8 (0.8)
4 2 3 3 2 1 10 8 39.6 14.9 3.9 4.0 3.8 3.8 3.8
(2.6) (21.1) (2.6) (42.1) (28.9)
16 (42.1) 11.5 (1–280) 17 (44.7) 50.0 (3–336) 9 (23.7) 28.0 (2–112) 26 (68.4) 28.0(6–28) 2.6 (0.8 2.0 (0.7)
MDE – Major Depressive Episode. EDE – Eating Disorder Examination (version 12.0D).
the treatment on the two groups by intention to treat that included all study participants. Using only individuals who completed the treatment, a linear regression analysis, adjusting for body mass index and Eating Disorder Examination global score at baseline, was performed to evaluate whether the baseline severity of depression, assessed with the Brief Symptom Inventory depression subscale, was associated with any change in Eating Disorder Examination global score. Finally, using a logistic regression analysis we evaluated the significance of the relationship between the baseline severity of depression and patients reaching an Eating Disorder Examination global score lower than 1S.D. above the community mean (i.e., o 1.74) (Kendall et al., 1999) and a body mass index Z 18.5, at end of therapy and at follow-ups. The statistical analyses were carried out using SPSS (IBM SPSS Statistics, version 20.0).
3. Results 3.1. Participant characteristics The majority of participants were adult patients in their mid20s. Table 1 shows the demographic and clinical features of the whole sample, and of MDE and no-MDE groups. MDE was present in 60.3% (38/63) of participants and no differences were found between MDE and no-MDE groups on all demographics variables, on current other Axis I comorbidity and on clinical variables.
3.2. Depression and treatment outcome We calculated estimated treatment effects on outcomes at end of therapy and 6- and 12-month follow-up (with baseline outcome values held constant) to examine the main effect over time and change over time into the two groups. Over time, a significant increase was found on weight and body mass index and a significant decrease on Eating Disorder Examination global and subscales scores in both groups (Table 2). This result indicated that there was a significant effect of receiving inpatient enhanced CBT on the overall sample, with mean body mass index increasing from baseline to end of therapy by 4.68 (95% CI 4.03–5.34) and to 6- and 12-month follow-up by 3.64 (95% CI 2.76–4.51) and 3.42 (95% CI 2.47–4.36), respectively. There was also an effect of being given treatment on Eating Disorder Examination global score, with mean Eating Disorder Examination global score decreasing from baseline to discharge by 2.28 (95% CI 2.70–1.89) and to 6- and 12-month follow-up by 2.37 (95% CI 2.89– 1.85) and 2.05 (95% CI 2.57–1.53), respectively. Table 3 indicated that no significant effect was found for time×group in terms of each outcome variable, indicating that the two groups had similar changes over time on each outcome variables.
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Table 2 Estimated treatment effect in the two groups (MDE and no-MDE) over time (main effect of the time). Results from the linear mixed models. Baseline to end of therapy
Body weight (kg) Body mass index (kg/m2) Eating disorder psychopathology Overall severity (global EDE) Dietary restraint (EDE subscale) Eating concern (EDE subscale) Weight concern (EDE subscale) Shape concern (EDE subscale) Brief symptom inventory Depression Global Severity Index
Baseline to 6 month follow-up
Baseline to 12 month follow-up
Estimate
95% CI
P
Estimate
95% CI
P
Estimate
95% CI
P
12.46 4.68
10.67 to 14.24 4.03 to 5.34
o 0.001 o 0.001
10.15 3.64
7.89 to 12.41 2.76 to 4.51
o0.001 o0.001
9.41 3.42
7.05 to 11.76 2.47 to 4.36
o 0.001 o 0.001
2.28 3.32 2.69 1.96 1.16
2.70 to 1.86 3.75 to 2.90 3.17 to 2.21 2.55 to 1.38 1.83 to 0.49
o 0.001 o 0.001 o 0.001 o 0.001 0.001
2.37 2.82 2.16 2.40 2.10
2.89 to 3.38 to 2.84 to 2.98 to 2.74 to
1.85 2.26 1.47 1.82 1.45
o0.001 o0.001 o0.001 o0.001 o0.001
2.05 2.10 2.05 2.27 1.79
2.57 2.71 2.69 2.84 2.43
1.53 1.48 1.42 1.70 1.14
o 0.001 o 0.001 o 0.001 o 0.001 o 0.001
1.47 1.25
1.83 to 1.10 1.53 to 0.96
o 0.001 o 0.001
1.11 0.99
1.59 to 1.10 1.29 to 0.68
o0.001 o0.001
1.0 0.91
1.48 to 0.63 1.20 to 0.62
o 0.001 o 0.001
to to to to to
EDE – Eating Disorder Examination (version 12.0D). Table 3 Estimated treatment effect in the two groups (MDE and no-MDE) over time (time group interaction). Results from the linear mixed models. Baseline to end of therapy
Body weight (kg) Body mass index (kg/m2) Eating disorder psychopathology Overall severity (global EDE) Dietary restraint (EDE subscale) Eating concern (EDE subscale) Weight concern (EDE subscale) Shape concern (EDE subscale) Brief symptom inventory Depression Global severity index
Baseline to 6 month follow-up
Baseline to 12 month follow-up
Estimate
95% CI
P
Estimate
95% CI
P
Estimate
95% CI
P
0.56 0.17
2.18 to 3.30 0.84 to 1.17
0.684 0.740
1.29 0.14
4.84 to 2.26 1.53 to 1.24
0.470 0.834
0.46 0.08
4.16 to 3.24 1.59 to 1.43
0.803 0.917
0.24 0.25 0.36 0.61 0.25
0.42 0.92 0.39 0.31 0.79
to 0.91 to 0.42 to 1.11 to 1.52 to 1.30
0.462 0.461 0.336 0.189 0.628
0.28 0.15 0.09 0.54 0.62
0.53 to 1.09 1021 to 0.73 0.98 to 1.16 0.37 to 1.46 0.39 to 1.63
0.496 0.736 0.867 0.237 0.223
0.01 0.62 0.14 0.41 0.11
0.83 to 0.85 1.62 to 0.38 0.88 to 1.17 0.51 to 1.33 0.93 to 1.15
0.980 0.220 0.777 0.377 0.834
0.47 0.15
0.10 to 1.05 0.30 to 0.60
0.102 0.515
0.08 0.02
0.63 to 0.80 0.49 to 0.46
0.812 0.942
0.19 0.17
0.89 to 0.50 0.64 to 0.30
0.577 0.465
EDE – Eating Disorder Examination (version 12.0D).
21.5
No-MDE
5.0
MDE
4.5
No-MDE
4.0
MDE
20.5 19.5
EDE Global score
3.5
BMI
18.5 17.5 16.5
3.0 2.5 2.0 1.5
15.5
1.0
14.5
0.5
13.5
0.0 Baseline
12.5 Baseline
End of treatment
6-Month Follow-Up
12-Month Follow-Up
Fig. 2. Predicted mean body mass index at each time point in MDE and no-MDE groups.
Figs. 2 and 3 show the estimated treatment effect on body mass index and on Eating Disorder Examination global score in MDE and no-MDE groups at each time point. 3.3. Depression and eating disorder psychopathology in completers Fifty-four participants (85.7%) completed the treatment (completers), whereas 9 (14.3%) left the program before concluding the planned 20 weeks of treatment (dropouts). The dropout rate was
End of treatment
6-Month Follow-Up
12-Month Follow-Up
Fig. 3. Predicted mean Eating Disorder Examination global score at each time point in MDE and no-MDE groups.
not significantly different between MDE and no-MDE groups (15.8% vs. 12.0% respectively; χ2(1, N ¼ 63)¼ 0.18, P ¼0.674). A post-hoc analysis, comparing the demographic and baseline clinical variables of completers and dropouts showed no significant differences between the two groups. 88.9% of completers received outpatient treatment after the discharge, and there were no differences between the two groups in this respect (MDE 90.6% vs. no-MDE 86.4%, χ2(1, N ¼54) ¼0.26, P ¼ 0.624). Among those, 97.9% received psychotherapy and 10.9% pharmacotherapy, and there were no differences between MDE and no-MDE patients
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regarding the type of psychotherapy received (χ2(1, N ¼ 48) ¼1.56, P ¼0.212; χ2(1, N ¼48) ¼0.002, P ¼0.996, respectively). The severity of baseline depression, assessed with Brief Symptom Inventory depression subscale score, was not associated with any change in Eating Disorder Examination global score from baseline to end of therapy (beta ¼0.18, t¼ 1.38, P ¼0.175) and from baseline to 6- and 12-month follow-up (beta ¼ 0.17, t¼1.29, P ¼.204; beta ¼0.16, t ¼1.07, P ¼0.288; respectively). In addition, no significant relationship was observed between baseline depression scores and participants reaching an Eating Disorder Examination global score of less than 1 S.D. above the community mean at the end of therapy and at follow-up (end of therapy P¼ 0.925; 6month follow-up P¼ 0.791; 12-month follow-up P ¼0.992). Finally, no significant association was found between baseline depression scores and participants with a body mass index Z18.5 at the end of therapy or at 6- and 12-month follow-up (end of therapy P ¼0.230; 6-month follow-up P ¼0.567; 12-month follow-up P ¼0.472).
4. Discussion In this study we compared the effects of an inpatient CBT program in underweight eating disorder participants with or without a co-morbid current mood disorder at baseline. We also set out to investigate whether the severity of depression influenced the treatment outcome. The investigation yielded four main findings. The first was that the prevalence of MDE in our sample (60.3%) was high and similar to those reported by a previous study assessing current depression in an large sample of female inpatients with anorexia nervosa (Blinder et al., 2006). The second finding was that, at baseline, the MDE group displayed similar eating disorder behaviors and psychopathology to the no-MDE group. We did not confirm the direct association between eating disorder behaviors (i.e. binge eating, vomiting) and clinical depression in anorexia nervosa patients. A few of studies indicated a prevalence of mood disorders significantly higher in patients with anorexia nervosa binge eating purging type compared to those with anorexia nervosa restricting type (Godart et al., 2007). Nevertheless, it is possible that these discrepancies arose from the fact that our study assessed ongoing depression, while others have factored in lifetime depression. The third finding was that patients responded well to the inpatient CBT program, regardless of their depression status. This finding, obtained by adjusting the calculations for the baseline measure of the outcome, suggests that baseline MDE diagnosis is not a prognostic indicator of outcome either at the end of treatment or at follow-up, and should therefore not be considered an obstacle to inpatient CBT, as has previously maintained. The intensive support given to inpatients in our treatment program may have helped them overcome the feelings of hopelessness about the possibility of change and the reduction of motivation that characterize individuals with clinical depression (obstacles that the program has been specifically designed to address), thereby countering the negative role of MDE in treatment outcome. In addition, our data are in line to that found in a recent review indicating that main prognostic factors identified across studies of anorexia nervosa outcome are duration of illness and duration of treatment but not psychiatric comorbidity or general psychiatric symptom severity (Keel and Brown, 2010). The fourth and final finding of our study was that depressive symptoms, as measured using Brief Symptom Inventory depression subscale, improved from baseline to end of therapy, and that this change was sustained over follow-up. No link in this improvement in baseline depressive symptoms and improvement in eating psychopathology was found. This data appears to indicate that
5
inpatient CBT, by targeting eating disorder psychopathology alone, nevertheless improved depressive symptoms without any adjunctive psychopharmacological intervention, and that baseline depression does not influence treatment outcome. Unfortunately, the study design does not enable us to provide a definitive explanation for the means by which inpatient CBT improved depression status. Nonetheless, four explanations may tentatively be proposed. First, it may be that inpatient CBT exerts a direct effect on the depression scores by normalizing the weight and eating habits, improving the socialization, and reducing the overevaluation of shape and weight, which are specific targets of the intervention. Second, it may also be that the program has an indirect effect on depressive symptoms by improving eating disorder psychopathology, which in turn may increase the feeling of self-efficacy and hope. Third, it is possible that the procedures and strategies addressing mood intolerance included in the “enhanced” CBT protocol may have a positive effect on depressive symptoms. Finally, the improvement of depressive symptoms without the aid of specific psychotherapy for depression and antidepressant medications may be the direct result of weight restoration, rather than specific CBT procedures and strategies. The strengths of this study lie in the large sample size, the low dropout rates and the statistical procedure adopted, not to mention the fact that the diagnosis of mood disorder was made using the SCID-IV. These factors enable us to consider our findings as robust and generalizable. Other factors in its favor are the study’s assessment of patients at four time points and the long-term follow-up conducted for over a year after hospitalization. It is also crucial to note that no psychopharmacological treatments were administered during the study period, and inpatient CBT was the patients’ sole treatment. This allows us to consider the “pure” effect of inpatient CBT on the eating disorder and general psychopathology. Nevertheless, the study does have five main limitations. First, the data were gathered from a single inpatient unit that treats mainly adult patients with severe eating disorders. The sample may therefore not be representative of patients seeking treatment in other inpatient or outpatient settings. Second, the study did not include a control group treated with other form of treatments, a limit very difficult to overcome in inpatient setting studies. This limitation does not permit to generalize results obtained with the inpatient CBT to other inpatient treatments. Third, the Brief Symptom Inventory depression subscale is not the gold-standard instrument to assess the dimensional component of the depression. This could also explain the absence of significant difference between the two groups at baseline. The fourth drawback is that we did not evaluate the presence of MDE at the end of therapy, or at 6- and 12-month follow-up. The final limitation of our study is rooted in the conceptualization of depressive symptoms in patients with anorexia nervosa. Unfortunately, our study design does not enable clarification of whether such symptoms are ascribable to coexisting clinical depression, or whether they are caused by malnutrition interacting with the eating disorder psychopathology. This is an important area for future research because if depressive symptoms are an integral part of anorexia nervosa, there would be no expected correlation between their presence at baseline, as suggested by our data, and the eating disorder outcome. It is also possible that the current diagnostic criteria for MDE may be too broad when applied to severely underweight patients with anorexia nervosa, failing to distinguish the subgroup of patients with “real” coexisting clinical depression, who might benefit from treatment for such depression. Nonetheless, the findings we can report do suggest that a diagnosis of MDE is not an obstacle to inpatient CBT, and that the severity of depression does not influence the treatment outcome.
Please cite this article as: Calugi, S., et al., Depression and treatment outcome in anorexia nervosa. Psychiatry Research (2014), http://dx. doi.org/10.1016/j.psychres.2014.04.024i
S. Calugi et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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These data, if confirmed by other studies, will have clinical implications, suggesting that (our) inpatient treatment of eating disorder psychopathology with cognitive behavioral procedures and strategies produces a lasting improvement in both eating disorder psychopathology and depressive symptoms without needing to resort to psychopharmacological intervention or to postpone treatment until the mood has been stabilized.
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