Anxiety Disorders, Somatoform Disorders
Conditions
Keywords
Body Dysmorphic Disorder, Escitalopram, Lexapro, BDD, Body Image
Brief summary
This study's primary aim is to compare time to relapse and relapse rates in responders to acute escitalopram who are then randomized to placebo versus continuation treatment with escitalopram.
Detailed description
We propose to conduct the first pharmacotherapy relapse prevention study in body dysmorphic disorder (BDD). BDD, an often-delusional preoccupation with a nonexistent or slight defect in appearance, is a distressing, impairing, and common body image disorder. It is associated with high rates of functional impairment and markedly poor quality of life. It appears that serotonin reuptake inhibitors (SRIs) are often--and selectively--efficacious for BDD and that many BDD patients receive SRIs. It also appears that most patients discontinue an efficacious SRI at some point, as the alternative is life-long treatment. However, no relapse prevention studies have been done. Such a study is important from a clinical and public health perspective, because BDD appears to often be chronic and require long-term treatment. It is therefore critically important to investigate the risk of relapse with SRI discontinuation, and whether continuation SRI treatment decreases relapse risk. Subjects will be enrolled and first treated openly for 14 weeks with escitalopram; 58 escitalopram responders will then be randomized to double-blind continuation treatment with escitalopram or placebo for 6 additional months. Our primary aim is to compare time to relapse and relapse rates in responders to acute escitalopram who are then randomized to placebo versus continuation treatment with escitalopram. Secondary/exploratory aims will explore 1) Whether subjects who receive continuation escitalopram perform better on secondary outcome measures (e.g., quality of life) than those on placebo; 2) Change in symptoms with continuation of escitalopram during the continuation phase; and 3) Acute treatment response. In summary, this study will be the first relapse prevention study in BDD and the first study of continuation pharmacotherapy in BDD. It will provide critically important information on relapse with continuation versus discontinuation of an SRI, whether continuation treatment protects against relapse, and change in symptoms with continuation treatment. This study will yield unique and clinically important data, and will fill gaps in knowledge about this common, severe, and understudied illness.
Interventions
DRUGEscitalopram
At the end of the initial 14-week phase (open-label escitalopram), participants who responded to open-label escitalopram were randomly assigned to receive escitalopram (same dose as received in Phase I) for an additional 6 months.
DRUGPlacebo
At the end of the initial 14-week phase (open-label escitalopram), participants who responded to open-label escitalopram were randomly assigned to receive placebo for an additional 6 months.
Sponsors
National Institute of Mental Health (NIMH)
Rhode Island Hospital
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatient men and women age 18 and older * Diagnosis of BDD within 6 months of study start date based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) * Score of 24 or higher on the BDD-Yale-Brown Obsessive Compulsive Scale * Lives within driving distance of Boston, MA or Providence, RI
Exclusion criteria
* Suicidal or homicidal tendencies * Alcohol/drug abuse or dependence within 3 months of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase II Relapse of Body Dysmorphic Disorder (BDD) Symptoms (as Measured by the BDD-YBOCS) | Phase II: Biweekly for six months after randomization | We compared the rate of relapse (accounting for time from randomization to relapse and censoring) by treatment arm in Phase II. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Response to Escitalopram (as Measured by the BDD-YBOCS) | Phase I: Weekly for weeks 1-4, biweekly from weeks 6-14 | We calculated the proportion of patients who achieved response in Phase I, defined as a \>=30% reduction in BDD-YBOCS total score from baseline through the last phase 1 visit. |
| Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Measured bi-weekly in phase 2 from week 14 (start of randomization for relapse prevention) to week 40 | Depressive symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D), a widely used 21-item depression scale. Of the 21 items on the scale, only the first 17 are used to calculate the total score. Eight of these items are scored on a 5-point scale, ranging from 0 (not present) to 4 (severe symptom), and nine are scored from 0-2. The total score ranges from 0 to 50, where higher scores indicate a greater severity of depression and scores greater than 19 are generally considered indicative of severe depression. |
| Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Measured three times throughout phase 2 of study (Weeks 14, 28 and 40) | Subjects switched to placebo were compared to those remaining on escitalopram (double-blind randomization) to assess functional impairment as measured by the Longitudinal Interval Followup Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT). The tool assesses psychosocial functioning in multiple domains, consisting of 5- to 7-point clinician administered scales that obtain information about work, household duties, student work, relationships with family and friends, recreation, life satisfaction, and global social adjustment. Scores can range from 3-22 with higher scores indicating poorer functioning. |
| Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Measured three times throughout phase 2 of study (Weeks 14, 28 and 40) | Subjects switched to placebo were compared to those remaining on escitalopram (double-blinded randomization) to assess quality of life changes as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). The Q-LES-Q-SF is designed to help assess the degree of enjoyment and satisfaction experienced during the past week across several domains: social, leisure, household, work, emotional well-being, physical, and school; it consists of 5-point rater-administered questions. Raw scores can range from 14-70, which are converted to percentage maximum possible by calculating: % Max = (Raw-minimum score)/(maximum score-minimum score). Q-LES\_Q-SF percent scores can range from 0-100, with higher scores indicating greater quality of life and satisfaction. |
Countries
United States
Participant flow
Pre-assignment details
A total of 100 participants received open-label escitalopram in Phase I. Only those who completed Phase I, met criteria for response, and were willing to continue on in the study were subsequently randomized in Phase II (n=58).
Participants by arm
| Arm | Count |
|---|---|
| Phase II: Escitalopram At the end of the initial 14-week phase, participants who responded to open-label escitalopram were randomly assigned to receive escitalopram (same dose as received in Phase I) for an additional 6 months. | 28 |
| Phase II: Placebo At the end of the initial 14-week phase, participants who responded to open-label escitalopram were randomly assigned to receive placebo for an additional 6 months. | 30 |
| Total | 58 |
Baseline characteristics
| Characteristic | Phase II: Escitalopram | Phase II: Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 28 Participants | 55 Participants |
| Age, Continuous | 37.3 years STANDARD_DEVIATION 12.4 | 31.8 years STANDARD_DEVIATION 13.5 | 33.5 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 24 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 27 Participants | 51 Participants |
| Region of Enrollment United States | 28 participants | 30 participants | 58 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 89 / 100 | 22 / 28 | 21 / 30 |
| serious Total, serious adverse events | 0 / 100 | 0 / 28 | 0 / 30 |
Outcome results
Primary
Phase II Relapse of Body Dysmorphic Disorder (BDD) Symptoms (as Measured by the BDD-YBOCS)
We compared the rate of relapse (accounting for time from randomization to relapse and censoring) by treatment arm in Phase II.
Time frame: Phase II: Biweekly for six months after randomization
Population: Intent-to-treat analysis of all 58 patients randomized to Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II: Escitalopram | Phase II Relapse of Body Dysmorphic Disorder (BDD) Symptoms (as Measured by the BDD-YBOCS) | 18 percentage of subjects who relapsed |
| Phase II: Placebo | Phase II Relapse of Body Dysmorphic Disorder (BDD) Symptoms (as Measured by the BDD-YBOCS) | 40 percentage of subjects who relapsed |
Comparison: Cox proportional hazards regression was used to compare relapse rates (accounting for censoring and time from randomization to relapse) in Phase II.p-value: 0.04895% CI: [1.01, 8.59]Regression, Cox
Secondary
Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II)
Depressive symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D), a widely used 21-item depression scale. Of the 21 items on the scale, only the first 17 are used to calculate the total score. Eight of these items are scored on a 5-point scale, ranging from 0 (not present) to 4 (severe symptom), and nine are scored from 0-2. The total score ranges from 0 to 50, where higher scores indicate a greater severity of depression and scores greater than 19 are generally considered indicative of severe depression.
Time frame: Measured bi-weekly in phase 2 from week 14 (start of randomization for relapse prevention) to week 40
Population: A total of 58 participants who had responded to open-label Escitalopram (phase 1) were randomized to receive either Escitalopram (n=28) or placebo (n=30) in the double-blind relapse prevent trial (phase 2). Some of the assessments visits were missed due to patient cancellations or study dropouts. The exact numbers analyzed are as specified below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 14 | 3.5357143 units on a scale | Standard Deviation 4.401028 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 16 | 3.8928571 units on a scale | Standard Deviation 4.1840906 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 18 | 5.2857143 units on a scale | Standard Deviation 5.5099717 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 20 | 4.8461538 units on a scale | Standard Deviation 5.5403416 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 22 | 4.2307692 units on a scale | Standard Deviation 3.5922995 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 24 | 3.625 units on a scale | Standard Deviation 3.3337862 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 26 | 3.8695652 units on a scale | Standard Deviation 4.0486176 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 28 | 4.48 units on a scale | Standard Deviation 5.0259327 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 30 | 2.85 units on a scale | Standard Deviation 3.9373381 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 32 | 2.9565217 units on a scale | Standard Deviation 3.067102 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 34 | 3.375 units on a scale | Standard Deviation 3.2412088 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 36 | 4.0416667 units on a scale | Standard Deviation 3.9943348 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 38 | 3.8181818 units on a scale | Standard Deviation 3.8623502 |
| Phase II: Escitalopram | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 40 | 4.2400000 units on a scale | Standard Deviation 4.8500859 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 34 | 4.7 units on a scale | Standard Deviation 4.5664682 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 14 | 3.3793103 units on a scale | Standard Deviation 3.3744184 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 28 | 4.4090909 units on a scale | Standard Deviation 3.4731499 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 16 | 4.2333333 units on a scale | Standard Deviation 3.9799786 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 38 | 3.4666667 units on a scale | Standard Deviation 3.8705235 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 18 | 6.3703704 units on a scale | Standard Deviation 6.4875511 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 30 | 4.5454545 units on a scale | Standard Deviation 4.0676104 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 20 | 5.4285714 units on a scale | Standard Deviation 4.7798076 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 36 | 5.4 units on a scale | Standard Deviation 5.2555735 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 22 | 3.7407407 units on a scale | Standard Deviation 3.0457106 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 32 | 4.2 units on a scale | Standard Deviation 4.007887 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 24 | 3.7727273 units on a scale | Standard Deviation 3.0539875 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 40 | 4.1578947 units on a scale | Standard Deviation 5.0250833 |
| Phase II: Placebo | Change in Depression Symptoms (HAM-D) During the Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 26 | 4.04 units on a scale | Standard Deviation 3.8457769 |
Comparison: We compared change in depression over time by randomized treatment group (Escitalopram vs. Placebo) using a random coefficient model that included terms for treatment group, time, site, and all their interactions, modeling intercepts and slopes as random effects per person.~Null hypothesis: The rate of change in depression symptom severity in the Escitalopram group will not be significantly different from the placebo group \[to be tested\].p-value: 0.093Mixed Models Analysis
Secondary
Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II)
Subjects switched to placebo were compared to those remaining on escitalopram (double-blind randomization) to assess functional impairment as measured by the Longitudinal Interval Followup Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT). The tool assesses psychosocial functioning in multiple domains, consisting of 5- to 7-point clinician administered scales that obtain information about work, household duties, student work, relationships with family and friends, recreation, life satisfaction, and global social adjustment. Scores can range from 3-22 with higher scores indicating poorer functioning.
Time frame: Measured three times throughout phase 2 of study (Weeks 14, 28 and 40)
Population: 28 in Escitalopram and 30 were randomized to Placebo after phase-1 open label. Some of the assessments visits were missed due to patient cancellations or study dropouts. The exact numbers analyzed are as specified below. Note: each participant included (28 Escitalopram, 30 placebo) was assessed at least once during phase 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase II: Escitalopram | Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 14 | 9.0000000 units on a scale | Standard Deviation 2.6943013 |
| Phase II: Escitalopram | Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 28 | 9.8000000 units on a scale | Standard Deviation 3.3040379 |
| Phase II: Escitalopram | Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 40 | 9.7600000 units on a scale | Standard Deviation 3.6887215 |
| Phase II: Placebo | Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 14 | 8.2413793 units on a scale | Standard Deviation 2.3551641 |
| Phase II: Placebo | Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 28 | 9.0000000 units on a scale | Standard Deviation 2.7961012 |
| Phase II: Placebo | Change in Functional Impairment Symptoms (LIFE-RIFT) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 40 | 8.8947368 units on a scale | Standard Deviation 3.1428002 |
Comparison: We compared change in functional impairment over time during trial phase 2 by treatment group (Escitalopram vs. Placebo) using a random coefficient model that included terms for treatment group, time, site, and all their interactions, modeling intercepts and slopes as random effects per person.~Null hypothesis: The rate of change in functional impairment in the Escitalopram group will not be significantly different from that of the placebo group \[to be tested\].p-value: 0.9766Mixed Models Analysis
Secondary
Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II)
Subjects switched to placebo were compared to those remaining on escitalopram (double-blinded randomization) to assess quality of life changes as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). The Q-LES-Q-SF is designed to help assess the degree of enjoyment and satisfaction experienced during the past week across several domains: social, leisure, household, work, emotional well-being, physical, and school; it consists of 5-point rater-administered questions. Raw scores can range from 14-70, which are converted to percentage maximum possible by calculating: % Max = (Raw-minimum score)/(maximum score-minimum score). Q-LES\_Q-SF percent scores can range from 0-100, with higher scores indicating greater quality of life and satisfaction.
Time frame: Measured three times throughout phase 2 of study (Weeks 14, 28 and 40)
Population: 28 in Escitalopram and 30 were randomized to Placebo after phase-1 open label. Some of the assessments visits were missed due to patient cancellations or study dropouts. The exact numbers analyzed are as specified below. Note: each participant included (28 Escitalopram, 30 placebo) was assessed at least once during phase 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase II: Escitalopram | Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 14 | 74.1785714 Percentage score | Standard Deviation 12.9930282 |
| Phase II: Escitalopram | Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 28 | 70.2727273 Percentage score | Standard Deviation 14.1528453 |
| Phase II: Escitalopram | Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 40 | 69.0833333 Percentage score | Standard Deviation 18.5376624 |
| Phase II: Placebo | Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 14 | 70.9259259 Percentage score | Standard Deviation 16.0166402 |
| Phase II: Placebo | Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 28 | 67.3684211 Percentage score | Standard Deviation 16.0665648 |
| Phase II: Placebo | Change in Quality of Life (Q-LES-Q-SF) Over Double-blind Relapse Prevention Phase of the Trial (Phase II) | Week 40 | 68.6470588 Percentage score | Standard Deviation 15.24361 |
Comparison: We compared change in Q-LES-Q-SF percent scores over time by randomized treatment group (Escitalopram vs. Placebo) using a random coefficient model that included terms for treatment group, time, site, and all their interactions, modeling intercepts and slopes as random effects per person.~Null hypothesis: The rate of change in Q-LES-Q-SF percent scores in the Escitalopram group will not be significantly different from that of the placebo group \[to be tested\].p-value: 0.7724Mixed Models Analysis
Secondary
Phase I Response to Escitalopram (as Measured by the BDD-YBOCS)
We calculated the proportion of patients who achieved response in Phase I, defined as a \>=30% reduction in BDD-YBOCS total score from baseline through the last phase 1 visit.
Time frame: Phase I: Weekly for weeks 1-4, biweekly from weeks 6-14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II: Escitalopram | Phase I Response to Escitalopram (as Measured by the BDD-YBOCS) | 67 percentage of subjects who responded |