Aripiprazole Augmentation of SSRI Therapy in Treatment Refractory Depression

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00608543
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Our target population will have been adequately treated with one of three selective serotonin reuptake inhibitors (SSRIs; escitalopram, citalopram, or sertraline) for at least 8-12 weeks and continue to experience symptoms of depression that have prompted them to seek additional treatment. Escitalopram, citalopram, and sertraline were selected for use in this study because they are among the most commonly selected SSRIs and they are associated with a reduced likelihood of drug-drug interactions with aripiprazole. After completion of the screening process, eligible participants will be augmented with aripiprazole (5, 10, or 15 mg) for 6 weeks. Participants will continue SSRI treatment with their prescribing physician, in conjunction with study participation. Symptom severity will be assessed on a weekly basis, and cognitive and psychosocial function will be assessed at pre- and post-augmentation. We hypothesize that aripiprazole augmentation will be associated with reductions in symptom severity, and with improved performance on measures of psychosocial and cognitive function.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Aripiprazole	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Aripiprazole Augmentation of SSRI Antidepressant Therapy in Treatment Refractory Depression: Assessment of Symptom Reduction, Psychosocial Function, and Cognitive Function
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Aripiprazole augmentation This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.	Drug: Aripiprazole; varied dose (5, 10, 15 mg qd) for 6 wks; Other Names: Abilify

Outcome Measures

Primary Outcome Measures

1. Stockings of Cambridge (SOC) Mean Initial Thinking Time for 3-move Problems [baseline and 6 weeks]

   The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 3-move problems is the time (in milliseconds)taken to plan a problem solution for trials requiring 3 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment.

2. Stockings of Cambridge (SOC) Mean Initial Thinking Time for 5-move Problems [baseline and 6 weeks]

   The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 5-move problems is the time (in milliseconds) taken to plan a problem solution for trials requiring 5 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment.

3. Spatial Working Memory (SWM) Between Errors for 6-move Problems [baseline and 6 weeks]

   The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. Between errors are times the subject revisits a box in which a token was previously found; errors are calculated for 4-, 6-, and 8-box trials. Higher numbers indicate poorer performance. Errors reported are the difference between baseline and 6 weeks post-treatment.

4. Spatial Working Memory (SWM) Strategy Score [baseline and 6 weeks]

   The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. The Strategy score represents the number of times a participant begins a search with the same box for 6- and 8-box problems. Minimum score is 8 and maximum score is 56. Higher numbers indicate poorer performance. Score reported is the difference between baseline and 6 weeks post-treatment.

Secondary Outcome Measures

1. Quality of Life Enjoyment and Satisfaction Questionnaire [6 weeks]

   The Q-LES-Q general activities is designed to measure subjective satisfaction and enjoyment, as opposed to function, in various domains including physical health, feelings, work, household duties, school/course work, leisure time activities, social relations, and general activities. The raw score is converted into a percent of the maximum possible score and range from 0 to 100. Higher scores indicate greater enjoyment and satisfaction.

2. Change in Hamilton Rating Scale for Depression (HRSD - 17-item) [6 weeks]

   The HRSD 17-item scale is a clinician-administered rating scale designed to assess the severity of symptoms in patients diagnosed with depression. Scores range from 0 to 52, with higher scores indicating higher levels of depression severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-65

• Primary diagnosis of Major Depressive Disorder (MDD)

• Completion of at least 8-12 weeks (and no longer than 6 months) of treatment with escitalopram, citalopram, or sertraline, with at least 6 weeks at an adequate dose (i.e., 20 mg escitalopram; 40 mg citalopram; 150 mg sertraline)

• Hamilton Rating Scale for Depression, 17-item (HRSD17) score less than or equal to 14 and/or Clinical Global Impression - Severity (CGI-S) score less than or equal to 3

• Self-reported difficulties with cognition and/or concentration, and an Inventory for Depressive Symptomatology Clinician-Rated, 30-item (IDS-C30) item #16 (Concentration and Decision Making) score less than or equal to 2

• Ability to read and write in English (required because instructions for cognitive testing and several questionnaires are available only in English)

Exclusion Criteria:

• Presence of untreated or unstable comorbid medical condition based on physician information or evidence at examination, such as hypertension, diabetes, hypothyroidism.

• Presence of known cardiovascular disease or seizure disorder.

• Presence of other primary psychiatric disorders or conditions (including depression due to medical conditions, currently suicidal or high suicide risk, current or past psychotic disorders of any type, bipolar disorder (I, II, or Not Otherwise Specified [NOS]), schizophrenia, schizoaffective disorder, anorexia, bulimia, obsessive compulsive disorder, alcohol or substance abuse or dependence within the last 6 months)

• Presence of organic brain injury or dementia, based on a cutoff score of < 20 on the Mini Mental Status Examination (MMSE).

• Concomitant pharmacological or psychotherapeutic treatment (in addition to one SSRI as described in Inclusion Criteria) including but not limited to anxiolytics, neuroleptics, mood stabilizers

• Hospitalization for mental illness within the past year.

• For women, currently pregnant or planning to become pregnant in the next year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	752390-9119

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• Bristol-Myers Squibb

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prabha Sunderajan, Assistant Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00608543
• Other Study ID Numbers: 042004-011
• First Posted: Feb 6, 2008
• Last Update Posted: Oct 26, 2012
• Last Verified: Mar 1, 2012

• Keywords provided by Prabha Sunderajan, Assistant Professor, University of Texas Southwestern Medical Center: cognitive function; psychosocial function; augmentation; treatment refractory depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Aripiprazole

Study Results

Participant Flow

Arm/Group Title	Open-label Aripiprazole Augmentation
Arm/Group Description	Aripiprazole augmentation of existing escitalopram, citalopram, or sertraline treatment was provided to study participants at a flexible dose between 5-15 mg (based on clinical symptoms and side effects) for 6 weeks
Period Title: Overall Study
STARTED	17
COMPLETED	13
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Open-label Aripiprazole Augmentation
Arm/Group Description	Aripiprazole augmentation of existing escitalopram, citalopram, or sertraline treatment was provided to study participants at a flexible dose between 5-15 mg (based on clinical symptoms and side effects) for 6 weeks
Overall Participants	17
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.18 (7.95)
Sex: Female, Male (Count of Participants)
Female	13 76.5%
Male	4 23.5%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Stockings of Cambridge (SOC) Mean Initial Thinking Time for 3-move Problems
Description	The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 3-move problems is the time (in milliseconds)taken to plan a problem solution for trials requiring 3 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Completers; due to fact that testing occurred at pre- and post-intervention; mean represents difference between pre- and post-intervention

Arm/Group Title	Open Label Aripiprazole Augmentation
Arm/Group Description	This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.
Measure Participants	13
Mean (Standard Deviation) [milliseconds]	-4485.50 (6279.40)

2. Secondary Outcome

Title	Quality of Life Enjoyment and Satisfaction Questionnaire
Description	The Q-LES-Q general activities is designed to measure subjective satisfaction and enjoyment, as opposed to function, in various domains including physical health, feelings, work, household duties, school/course work, leisure time activities, social relations, and general activities. The raw score is converted into a percent of the maximum possible score and range from 0 to 100. Higher scores indicate greater enjoyment and satisfaction.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Study completers who completed the Q-LES-Q pre- and post-intervention; mean represents mean difference from pre- to post-intervention

Arm/Group Title	Open Label Aripiprazole Augmentation
Arm/Group Description	This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.
Measure Participants	12
Mean (Standard Deviation) [units on a scale]	0.81 (0.48)

3. Secondary Outcome

Title	Change in Hamilton Rating Scale for Depression (HRSD - 17-item)
Description	The HRSD 17-item scale is a clinician-administered rating scale designed to assess the severity of symptoms in patients diagnosed with depression. Scores range from 0 to 52, with higher scores indicating higher levels of depression severity.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Study completers who completed the HRSD pre- and post-intervention; mean represents mean difference from pre- to post-intervention

Arm/Group Title	Open Label Aripiprazole Augmentation
Arm/Group Description	This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.
Measure Participants	12
Mean (Standard Deviation) [units on a scale]	-11.42 (4.50)

4. Primary Outcome

Title	Stockings of Cambridge (SOC) Mean Initial Thinking Time for 5-move Problems
Description	The SOC is part of the CAmbridge Neuropsychological Test Automated Battery (CANTAB) and is an executive function task based on the Tower of London test that assesses spatial planning for problems with 2, 3, 4, or 5 moves. The Mean Initial Thinking Time for 5-move problems is the time (in milliseconds) taken to plan a problem solution for trials requiring 5 moves. Higher numbers indicate poorer performance. Time reported is the difference between baseline and 6 weeks post-treatment.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Completers; due to fact that testing occurred at pre- and post-intervention; mean represents difference between pre- and post-intervention

Arm/Group Title	Open Label Aripiprazole Augmentation
Arm/Group Description	This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.
Measure Participants	13
Mean (Standard Deviation) [milliseconds]	-4676.10 (8604.16)

5. Primary Outcome

Title	Spatial Working Memory (SWM) Between Errors for 6-move Problems
Description	The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. Between errors are times the subject revisits a box in which a token was previously found; errors are calculated for 4-, 6-, and 8-box trials. Higher numbers indicate poorer performance. Errors reported are the difference between baseline and 6 weeks post-treatment.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Completers because data were collected pre- and post-treatment

Arm/Group Title	Spatial Working Memory Between Errors for 6-move Problems
Arm/Group Description	This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.
Measure Participants	13
Mean (Standard Deviation) [number of errors]	-4.00 (4.67)

6. Primary Outcome

Title	Spatial Working Memory (SWM) Strategy Score
Description	The SWM task is part of the CANTAB neruopsychological test battery and is an executive function task assessing retention and manipulation of items in working memory, with the ability for assessment of perseverative (redundant) errors. The Strategy score represents the number of times a participant begins a search with the same box for 6- and 8-box problems. Minimum score is 8 and maximum score is 56. Higher numbers indicate poorer performance. Score reported is the difference between baseline and 6 weeks post-treatment.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Completers; due to fact that testing occurred at pre- and post-intervention; mean represents difference between pre- and post-intervention

Arm/Group Title	Open Label Aripiprazole Augmentation
Arm/Group Description	This is a single arm trial in which all participants recieved open label aripiprazole augmentation of their current escitalopram, citalopram or sertraline treatment.
Measure Participants	13
Mean (Standard Deviation) [units on a scale]	-3.15 (4.52)

Adverse Events

Arm/Group Title	Open-label Aripiprazole Augmentation
Arm/Group Description	Aripiprazole augmentation of existing escitalopram, citalopram, or sertraline treatment was provided to study participants at a flexible dose between 5-15 mg (based on clinical symptoms and side effects) for 6 weeks
All Cause Mortality
	Open-label Aripiprazole Augmentation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open-label Aripiprazole Augmentation
	Affected / at Risk (%)	# Events
Total	0/17 (0%)
Other (Not Including Serious) Adverse Events
	Open-label Aripiprazole Augmentation
	Affected / at Risk (%)	# Events
Total	14/17 (82.4%)
Cardiac disorders
palpitations	2/17 (11.8%)
dizziness on standing	3/17 (17.6%)
chest pain	2/17 (11.8%)
Ear and labyrinth disorders
ringing in the ears	6/17 (35.3%)
Eye disorders
blurred vision	5/17 (29.4%)
Gastrointestinal disorders
diarrhea	8/17 (47.1%)
constipation	8/17 (47.1%)
dry mouth	6/17 (35.3%)
nausea/vomiting	3/17 (17.6%)
General disorders
general malaise	8/17 (47.1%)
fatigue	13/17 (76.5%)
decreased energy	10/17 (58.8%)
Nervous system disorders
headache	14/17 (82.4%)
tremors	4/17 (23.5%)
poor coordination	6/17 (35.3%)
dizziness	5/17 (29.4%)
restlessness	12/17 (70.6%)
difficulty sleeping	13/17 (76.5%)
sleeping too much	9/17 (52.9%)
anxiety	10/17 (58.8%)
poor concentration	3/17 (17.6%)
Renal and urinary disorders
difficulty urinating	1/17 (5.9%)
painful urination	1/17 (5.9%)
frequent urination	6/17 (35.3%)
Reproductive system and breast disorders
menstrual irregularity	2/17 (11.8%)
loss of sexual desire	11/17 (64.7%)
trouble achieving orgasm	4/17 (23.5%)
trouble with erections	1/17 (5.9%)
Skin and subcutaneous tissue disorders
rash	2/17 (11.8%)
increased perspiration	6/17 (35.3%)
itching	1/17 (5.9%)
dry skin	1/17 (5.9%)

Limitations/Caveats

Note that because this is an augmentation trial, reported AEs are due to combined treatment with escitalopram, citalopram, or sertraline AND aripiprazole.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.