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The Effects of Dopamine on Reward Processing

Sponsor
Mclean Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01253421
Collaborator
National Institute of Mental Health (NIMH) (NIH)
159
Enrollment
1
Location
4
Arms
51
Duration (Months)
3.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of a single low dose of the D2/D3 antagonist amisulpride on reward processing. More generally, this study will test the role of dopamine (a naturally occurring brain chemical) in depression.

Hypotheses:

Administration of a single low dose of the D2/D3 antagonist amisulpride will (1) improve performance in a behavioral task assessing learning from feedback and (2) boost activation in reward-related brain regions.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Through an integration of a functional magnetic resonance imaging (fMRI) approach coupled with a pharmacological challenge, the goal of the current study will be to investigate the role of dopamine in MDD. Participants in this research will include 36 MDD subjects and 36 demographically matched healthy participants recruited from the community by Dr. Pizzagalli's laboratory at McLean Hospital's Center for Depression, Anxiety and Stress Research. This study will include two sessions:

  • The first session will involve a diagnostic interview, and a series of questionnaires and assessments.

  • The second session will take place at the McLean Hospital's Neuroimaging Center, and include the administration of a low-dose of amisulpride (50 mg capsule) or placebo, followed by an fMRI brain scan and administration of two behavioral tasks.

Study Design

Study Type:
Interventional
Actual Enrollment :
159 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
There were two groups of subjects: currently experiencing a major depressive episode, or normal health controls. The groups were matched for age, gender, and race. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo.There were two groups of subjects: currently experiencing a major depressive episode, or normal health controls. The groups were matched for age, gender, and race. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo.
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
The Effects of Dopamine on Reward Processing
Study Start Date :
Feb 1, 2012
Actual Primary Completion Date :
May 1, 2016
Actual Study Completion Date :
May 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: MDD-amisulpride

Subjects experiencing a current episode of major depression who are randomized to receive amisulpride

Drug: amisulpride
single low-dose pharmacological challenge, 50 mg amisulpride
Other Names:
  • Solian

    		•
    Placebo Comparator: MDD-placebo

    Subjects experiencing a current episode of major depression who are randomized to receive placebo

    Drug: placebo
    single-dose placebo capsule
    Active Comparator: HC-amisulpride

    Subjects having no history of mental disorder (healthy controls, HC) who are randomized to receive amisulpride

    Drug: amisulpride
    single low-dose pharmacological challenge, 50 mg amisulpride
    Other Names:
  • Solian

    		•
    Placebo Comparator: HC-placebo

    Subjects having no history of mental disorder who are randomized to receive placebo

    Drug: placebo
    single-dose placebo capsule

    Outcome Measures

    Primary Outcome Measures

    1. Effect on PST Reward Learning [administered after scan]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on the ability to learn from rewards during a Probabilistic Selection Task (PST). A higher effect size indicates greater ability to learn from reward trials.

    2. Effect on PST Penalty Learning [administered after scan]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on the ability to learn from penalties during a Probabilistic Selection Task (PST). A higher effect size indicates greater ability to learn from penalty trials.

    3. Effect on Caudate Response to Cues [Scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on caudate activation after presentation of a cue. Positive values indicate an increase in activation relative to baseline.

    4. Effect on NAcc Response to Cues [Scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on nucleus accumbens (NAcc) activation after presentation of a cue. Positive values indicate an increase in activation relative to baseline.

    5. Putamen Response to Cues [Scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on putamen activation after presentation of a cue. Positive values indicate an increase in activation relative to baseline.

    6. Effect on Caudate Response to Reward [During scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on caudate activation after Reward outcomes. Positive values indicate an increase in activation relative to baseline.

    7. Effect on NAcc Response to Reward [During scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on nucleus accumbens (NAcc) activation after reward outcomes. Positive values indicate an increase in activation relative to baseline.

    8. Effect on Putamen Response to Reward [During scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on putamen activation (beta) after reward outcomes. Positive values indicate an increase in activation relative to baseline.

    Secondary Outcome Measures

    1. Effect on Caudate-dACC Connectivity After Reward [During scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on functional connectivity between caudate and dorsal anterior cingulate cortex (dACC) in response to reward outcomes

    2. Effect on NAcc-MCC Connectivity After Reward [During scan session]

      This statistic shows the effect (beta) that the combination of diagnosis and drug has on functional connectivity between nucleus accumbens (NAcc) and mid-cingulate cortex (MCC) in response to reward outcomes.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Inclusion Criteria for subjects with Major Depressive Disorder (MDD):

    1. Diagnostic and Statistical Manual of Mental Disorders (DSM IV) diagnostic criteria for MDD, diagnosed with the use of the Structured Clinical Interview for DSM Disorders (SCID);

    2. Written informed consent;

    3. Both genders and all ethnic origins, age between 18 and 45;

    4. A baseline score > 16 on the Hamilton Rating Scale for Depression (HRSD) 17-item version;

    5. Right-handed.

    6. Absence of any psychotropic medications for at least 2 weeks:

    • 6 weeks for fluoxetine,

    • 6 months for neuroleptics,

    • 2 weeks for benzodiazepines,

    • 2 weeks for any other antidepressants.

    Inclusion Criteria for Control Subjects:

    1. Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (SCID-I/NP);

    2. Written informed consent;

    3. Both genders and all ethnic origins, age between 18 and 45;

    4. Right-handed;

    5. Absence of any medications for at least 3 weeks;

    6. Absence of pregnancy.

    Exclusion Criteria:
    • Exclusion Criteria for All Subjects:

    1. Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment;

    2. Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, intrauterine device, s/p tubal ligation, or partner with vasectomy);

    3. Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological or hematologic disease;

    4. Lifetime history of seizure disorder;

    5. Lifetime history or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of alcohol abuse within the last 12 months, which is permissible for MDD subjects); eating disorders, post-traumatic stress disorder (lifetime PTSD is exclusionary for control subjects, PTSD within the last 24 months is exclusionary for MDD subjects); simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD;

    6. More than five instances of lifetime cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine);

    7. Use of dopaminergic drugs (including methylphenidate) within the last 6 months;

    8. Lifetime history or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status Examination at the screening visit;

    9. Lifetime history of adverse drug reactions or allergy to the study drug (amisulpride);

    10. Patients with mood congruent or mood incongruent psychotic features;

    11. Current use of other psychotropic drugs;

    12. Clinical or laboratory evidence of hypothyroidism;

    13. Patients with a lifetime history of electroconvulsive therapy (ECT);

    14. Patients with renal insufficiency;

    15. Failure to meet standard MRI safety requirements

    16. Electrolytes, blood urea nitrogen, creatinine: outside the normal range (also ruling out renal insufficiency);

    17. Liver function tests above 1.5 times the upper normal;

    18. Corrected QT interval (QTc) interval in EKG above 450 ms or EKG indicative of arrhythmia or cardiac conduction abnormalities;

    19. Diabetes with poor glucose control;

    20. Cardiac disease, bradycardia less than 55 bpm, hypokalemia, congenital prolongation of QT interval or on-going treatment with a medication likely to induce one of these conditions.

    21. Currently in cognitive-behavioral therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 McLean Hospital Belmont Massachusetts United States 02478

    Sponsors and Collaborators

    • Mclean Hospital
    • National Institute of Mental Health (NIMH)

    Investigators

    • Principal Investigator: Diego A Pizzagalli, PhD, McLean Hospital, Harvard University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Diego A. Pizzagalli, Director, Center for Depression, Anxiety and Stress Research, Mclean Hospital
    ClinicalTrials.gov Identifier:
    NCT01253421
    Other Study ID Numbers:
    • 2010-P001568
    • R01MH068376
    First Posted:
    Dec 3, 2010
    Last Update Posted:
    Apr 27, 2018
    Last Verified:
    Apr 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Diego A. Pizzagalli, Director, Center for Depression, Anxiety and Stress Research, Mclean Hospital
    MDD
    Major Depressive Disorder
    Amisulpride
    Additional relevant MeSH terms:
    Depressive Disorder
    Depression
    Depressive Disorder, Major
    Amisulpride

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited at McLean Hospital (Belmont, MA) and Massachusetts General Hospital (MGH; Boston, MA) between February, 2012, and September, 2015. The study was advertised using flyers, and on a number of internet bulletin boards available to the general public. Study visits were conducted in research facilities at McLean Hospital.
    Pre-assignment Detail An assessment visit was conducted prior to the drug-challenge visit. Subjects had a diagnostic interview (SCID) and preliminary physical exam, provided a blood sample for lab tests, and completed surveys, to determine eligibility. Those meeting eligibility criteria were scheduled for a drug+scanning visit where randomization occurred.
    Arm/Group Title All Participants Prior to Randomization MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description All Participants went through Assessment, prior to randomization. Subjects experiencing a current episode of major depression who are randomized to receive amisulpride Subjects experiencing a current episode of major depression who are randomized to receive placebo Subjects having no history of mental disorder who are randomized to receive amisulpride Subjects having no history of mental disorder who are randomized to receive placebo
    Period Title: Assessment and Scheduling
    STARTED 159 0 0 0 0
    Eligible After Screening Visit 85 0 0 0 0
    Returned for Drug+Scanning Visit 60 0 0 0 0
    COMPLETED 60 0 0 0 0
    NOT COMPLETED 99 0 0 0 0
    Period Title: Assessment and Scheduling
    STARTED 0 15 14 16 15
    Received Drug Challenge 0 15 14 16 15
    COMPLETED 0 15 14 16 14
    NOT COMPLETED 0 0 0 0 1

    Baseline Characteristics

    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo Total
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo Total of all reporting groups
    Overall Participants 15 14 16 14 59
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    27.20
    (8.6)
    25.8
    (5.35)
    25.3
    (25.3)
    24.7
    (24.7)
    26
    (6.79)
    Sex: Female, Male (Count of Participants)
    Female
    12
    80%
    6
    42.9%
    11
    68.8%
    9
    64.3%
    38
    64.4%
    Male
    3
    20%
    8
    57.1%
    5
    31.3%
    5
    35.7%
    21
    35.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    20%
    1
    7.1%
    3
    18.8%
    0
    0%
    7
    11.9%
    Not Hispanic or Latino
    12
    80%
    13
    92.9%
    12
    75%
    14
    100%
    51
    86.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    6.3%
    0
    0%
    1
    1.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    1
    6.3%
    0
    0%
    1
    1.7%
    Asian
    2
    13.3%
    2
    14.3%
    0
    0%
    5
    35.7%
    9
    15.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    6.7%
    2
    14.3%
    3
    18.8%
    3
    21.4%
    9
    15.3%
    White
    11
    73.3%
    9
    64.3%
    10
    62.5%
    6
    42.9%
    36
    61%
    More than one race
    1
    6.7%
    1
    7.1%
    1
    6.3%
    0
    0%
    3
    5.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    6.3%
    0
    0%
    1
    1.7%
    Region of Enrollment (Count of Participants)
    United States
    15
    100%
    14
    100%
    16
    100%
    14
    100%
    59
    100%
    Educ-yrs (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    15.6
    (2.06)
    16.6
    (2.90)
    16.2
    (2.13)
    16.5
    (1.52)
    16.2
    (2.18)
    Menstrual phase (Count of Participants)
    Follicular
    1
    6.7%
    2
    14.3%
    6
    37.5%
    3
    21.4%
    12
    20.3%
    Luteal
    4
    26.7%
    1
    7.1%
    1
    6.3%
    3
    21.4%
    9
    15.3%
    Unknown
    7
    46.7%
    3
    21.4%
    4
    25%
    3
    21.4%
    17
    28.8%
    HRSD (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    16.4
    (3.37)
    18.4
    (5.09)
    1.0
    (1.58)
    0.5
    (0.66)
    9.37
    (8.997)
    MDD SCID rating (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.9
    (.27)
    2.9
    (.27)
    1
    (0)
    1
    (0)
    1.93
    (.99)
    # MDEs (Episodes) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Episodes]
    2.75
    (2.667)
    4.79
    (3.490)
    3.74
    (3.230)
    Length_MDE (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    20.50
    (16.53)
    14.00
    (18.982)
    16.17
    (17.771)
    Patients with comorbid anxiety disorder (Count of Participants)
    Has comorbid Anxiety Disorder
    3
    20%
    6
    42.9%
    0
    0%
    0
    0%
    9
    15.3%
    No comorbid Anxiety Disorder
    9
    60%
    8
    57.1%
    16
    100%
    14
    100%
    47
    79.7%
    Unknown
    3
    20%
    0
    0%
    0
    0%
    0
    0%
    3
    5.1%
    Patients with past anxiety disorder (Count of Participants)
    Yes
    3
    20%
    6
    42.9%
    0
    0%
    0
    0%
    9
    15.3%
    No
    9
    60%
    8
    57.1%
    16
    100%
    14
    100%
    47
    79.7%
    Unknown
    3
    20%
    0
    0%
    0
    0%
    0
    0%
    3
    5.1%
    TCI Total (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    87.97
    (13.992)
    94.2
    (17.78)
    103.9
    (13.99)
    105.9
    (14.53)
    97.97
    (16.417)
    TCI NS-1 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    27.760
    (5.4779)
    29.385
    (5.3000)
    34.200
    (5.7595)
    35.857
    (5.8159)
    31.814
    (6.4070)
    TCI NS-2 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    19.60
    (4.137)
    20.85
    (6.053)
    22.93
    (4.698)
    22.79
    (5.860)
    21.54
    (5.258)
    TCI NS-3 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    23.873
    (6.9297)
    25.231
    (8.8615)
    26.667
    (5.5891)
    26.571
    (4.3273)
    25.581
    (6.5084)
    TCI NS-4 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    16.73
    (3.973)
    18.77
    (3.468)
    20.07
    (5.311)
    20.64
    (4.551)
    19.04
    (4.555)
    BIS attention-1 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    10.393
    (2.3053)
    9.929
    (1.9400)
    9.620
    (1.9879)
    11.000
    (2.3205)
    10.225
    (2.1500)
    BIS cognitive instability (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    5.143
    (1.7913)
    5.536
    (1.9852)
    4.467
    (1.1255)
    5.857
    (1.5619)
    5.237
    (1.6800)
    BIS motor-1 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    12.714
    (2.6144)
    12.786
    (2.9136)
    12.133
    (2.2636)
    12.071
    (2.9733)
    12.421
    (2.6454)
    BIS perseverance (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    6.643
    (1.5984)
    6.857
    (1.6104)
    6.847
    (1.4426)
    7.693
    (1.9408)
    7.007
    (1.6593)
    BIS self control (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    11.071
    (3.2455)
    10.429
    (3.0813)
    11.067
    (3.6345)
    12.357
    (3.2959)
    11.228
    (3.3113)
    BIS cognitive complexity (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    9.786
    (2.0069)
    10.161
    (2.9509)
    9.933
    (2.3442)
    10.554
    (2.4143)
    10.105
    (2.4016)
    BIS Attention-2 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    15.536
    (3.6187)
    15.464
    (2.7767)
    14.087
    (2.8332)
    16.857
    (3.2548)
    15.461
    (3.2078)
    BIS Motor-2 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    19.357
    (3.2959)
    19.643
    (3.5865)
    18.980
    (2.8016)
    19.764
    (3.7056)
    19.428
    (3.2791)
    BIS Non-planning-2 (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    20.857
    (4.1668)
    20.589
    (5.2638)
    21.000
    (5.7446)
    22.911
    (4.1459)
    21.333
    (4.8528)
    MASQ total (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    173.727
    (14.2367)
    174.077
    (18.5448)
    92.350
    (16.0618)
    88.571
    (12.4389)
    131.476
    (44.6597)
    MASQ GDA (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    21.800
    (6.2244)
    23.385
    (6.7520)
    14.200
    (3.3209)
    12.071
    (1.9793)
    17.772
    (6.8060)
    MASQ GDD (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    41.960
    (7.7346)
    39.538
    (7.2872)
    14.533
    (3.6029)
    14.214
    (2.9136)
    27.375
    (14.5034)
    MASQ AA (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    21.880
    (2.9644)
    23.385
    (4.4260)
    19.417
    (3.3643)
    17.643
    (1.1507)
    20.534
    (3.7852)
    MASQ AD (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    88.087
    (9.1143)
    87.769
    (6.9180)
    44.200
    (8.4448)
    44.643
    (9.6764)
    65.795
    (23.5064)
    RSES_Total (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    26.36
    (4.802)
    26.36
    (5.988)
    14.14
    (3.891)
    14.33
    (4.633)
    21.86
    (7.651)
    Defeat Scale (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    38.09
    (6.700)
    35.55
    (9.720)
    5.88
    (3.182)
    5.25
    (5.392)
    23.66
    (17.049)
    BDI-II (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    24.40
    (8.423)
    27.91
    (7.877)
    1.31
    (2.387)
    1.51
    (3.131)
    13.54
    (13.828)
    SHPS total (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    32.753
    (4.6489)
    32.450
    (7.5103)
    21.293
    (5.6623)
    23.714
    (7.4258)
    27.534
    (8.0970)
    SHPS-low (Count of 'low' responses (1 or 2)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Count of 'low' responses (1 or 2)]
    7.667
    (1.3452)
    6.857
    (1.0995)
    6.400
    (1.8439)
    6.571
    (2.9013)
    6.879
    (1.9293)
    AES (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    43.45
    (7.063)
    42.14
    (4.786)
    59.53
    (4.856)
    60.86
    (4.400)
    51.63
    (10.218)
    Current smokers (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Past smokers (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    1
    7.1%
    0
    0%
    0
    0%
    1
    1.7%
    Current drinkers (Count of Participants)
    Count of Participants [Participants]
    4
    26.7%
    6
    42.9%
    5
    31.3%
    4
    28.6%
    19
    32.2%
    Drinks in past 24hrs (equivalent shot/can/glasses) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [equivalent shot/can/glasses]
    0.29
    (0.469)
    0.46
    (0.519)
    0.36
    (0.497)
    0.29
    (0.469)
    0.35
    (0.480)
    Usual caffeine (mg) (milligrams) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams]
    124.35
    (74.162)
    176.50
    (87.444)
    82.93
    (77.308)
    64.75
    (41.139)
    111.05
    (111.05)
    Caffeine today (mg) (milligrams) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams]
    81.23
    (83.400)
    102.88
    (108.938)
    32.13
    (32.335)
    67.23
    (67.268)
    69.44
    (79.159)

    Outcome Measures

    1. Primary Outcome
    Title Effect on PST Reward Learning
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on the ability to learn from rewards during a Probabilistic Selection Task (PST). A higher effect size indicates greater ability to learn from reward trials.
    Time Frame administered after scan

    Outcome Measure Data

    Analysis Population Description
    Reward-learning results are missing for 7 subjects
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 14 12 15 11
    Mean (Standard Deviation) [Effect size (Beta)]
    0.6271
    (0.15608)
    0.7575
    (0.1676)
    0.823
    (0.1228)
    0.7545
    (0.1828)
    2. Primary Outcome
    Title Effect on PST Penalty Learning
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on the ability to learn from penalties during a Probabilistic Selection Task (PST). A higher effect size indicates greater ability to learn from penalty trials.
    Time Frame administered after scan

    Outcome Measure Data

    Analysis Population Description
    Penalty-learning results are missing for 7 subjects
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 14 12 15 11
    Mean (Standard Deviation) [Effect size (Beta)]
    0.2428
    (0.1800)
    0.29
    (0.2056)
    0.2207
    (0.20225)
    0.2391
    (0.14618)
    3. Primary Outcome
    Title Effect on Caudate Response to Cues
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on caudate activation after presentation of a cue. Positive values indicate an increase in activation relative to baseline.
    Time Frame Scan session

    Outcome Measure Data

    Analysis Population Description
    Data are missing for 8 subjects due to poor MRI quality.
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 13 11 16 11
    Mean (Standard Deviation) [Effect size (Beta)]
    0.2231
    (0.42189)
    -0.0391
    (0.32792)
    -0.0938
    (0.57788)
    0.0582
    (0.30318)
    4. Primary Outcome
    Title Effect on NAcc Response to Cues
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on nucleus accumbens (NAcc) activation after presentation of a cue. Positive values indicate an increase in activation relative to baseline.
    Time Frame Scan session

    Outcome Measure Data

    Analysis Population Description
    Data are missing for 8 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 13 11 16 11
    Mean (Standard Deviation) [Effect size (Beta)]
    0.2446
    (0.38546)
    0.0736
    (0.38694)
    0.1356
    (0.51800)
    0.2182
    (0.55236)
    5. Primary Outcome
    Title Putamen Response to Cues
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on putamen activation after presentation of a cue. Positive values indicate an increase in activation relative to baseline.
    Time Frame Scan session

    Outcome Measure Data

    Analysis Population Description
    Data are missing for 9 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 13 11 16 10
    Mean (Standard Deviation) [Effect size (Beta)]
    0.4969
    (0.41086)
    0.3955
    (0.36653)
    0.4169
    (0.41839)
    0.3808
    (0.42303)
    6. Primary Outcome
    Title Effect on Caudate Response to Reward
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on caudate activation after Reward outcomes. Positive values indicate an increase in activation relative to baseline.
    Time Frame During scan session

    Outcome Measure Data

    Analysis Population Description
    Data are missing for 9 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 12 11 16 11
    Mean (Standard Deviation) [Effect size (Beta)]
    0.5783
    (1.0104)
    -0.2673
    (0.1575)
    -0.33
    (1.243)
    0.1955
    (0.1101)
    7. Primary Outcome
    Title Effect on NAcc Response to Reward
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on nucleus accumbens (NAcc) activation after reward outcomes. Positive values indicate an increase in activation relative to baseline.
    Time Frame During scan session

    Outcome Measure Data

    Analysis Population Description
    Data are missing for 10 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 13 10 16 10
    Mean (Standard Deviation) [Effect size (Beta)]
    0.9377
    (0.1357)
    0.1578
    (0.8534)
    0.4018
    (1.2619)
    0.954
    (1.0833)
    8. Primary Outcome
    Title Effect on Putamen Response to Reward
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on putamen activation (beta) after reward outcomes. Positive values indicate an increase in activation relative to baseline.
    Time Frame During scan session

    Outcome Measure Data

    Analysis Population Description
    Data are missing for 9 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 13 11 16 10
    Mean (Standard Deviation) [Effect size (Beta)]
    0.6338
    (0.8394)
    0.1709
    (0.7996)
    -0.14
    (1.2282)
    0.436
    (0.6689)
    9. Secondary Outcome
    Title Effect on Caudate-dACC Connectivity After Reward
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on functional connectivity between caudate and dorsal anterior cingulate cortex (dACC) in response to reward outcomes
    Time Frame During scan session

    Outcome Measure Data

    Analysis Population Description
    Data missing for 8 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 14 11 13 13
    Mean (Standard Deviation) [Effect size (Beta)]
    0.3628
    (0.4057)
    0.3881
    (0.3415)
    0.2992
    (0.49098)
    0.6192
    (0.4270)
    10. Secondary Outcome
    Title Effect on NAcc-MCC Connectivity After Reward
    Description This statistic shows the effect (beta) that the combination of diagnosis and drug has on functional connectivity between nucleus accumbens (NAcc) and mid-cingulate cortex (MCC) in response to reward outcomes.
    Time Frame During scan session

    Outcome Measure Data

    Analysis Population Description
    Data missing for 8 subjects due to poor MRI quality
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    Measure Participants 14 11 13 13
    Mean (Standard Deviation) [Effect size (Beta)]
    0.4375
    (0.4163)
    0.324
    (0.4992)
    0.4846
    (0.6279)
    0.4877
    (0.5070)

    Adverse Events

    Time Frame Full study duration (2012-2015)
    Adverse Event Reporting Description
    Arm/Group Title MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Arm/Group Description Subjects experiencing a current episode of major depression who received amisulpride Subjects experiencing a current episode of major depression who received placebo Subjects having no history of mental disorder who received amisulpride Subjects having no history of mental disorder who received placebo
    All Cause Mortality
    MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/14 (0%) 0/16 (0%) 0/14 (0%)
    Serious Adverse Events
    MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/14 (0%) 0/16 (0%) 0/14 (0%)
    Other (Not Including Serious) Adverse Events
    MDD-amisulpride MDD-placebo HC-amisulpride HC-placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/14 (0%) 0/16 (0%) 0/14 (0%)

    Limitations/Caveats

    The choice of a 50-mg dose of amisulpride was based on animal work showing low doses potentiate striatal dopamine release, have strong hedonic effects, and increase the incentive value of environmental cues. Higher doses may have different results.

    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.

    Results Point of Contact

    Name/Title Diego Pizzagalli, Ph.D.
    Organization McLean Hospital
    Phone 617-855-4230
    Email dap@mclean.harvard.edu
    Responsible Party:
    Diego A. Pizzagalli, Director, Center for Depression, Anxiety and Stress Research, Mclean Hospital
    ClinicalTrials.gov Identifier:
    NCT01253421
    Other Study ID Numbers:
    • 2010-P001568
    • R01MH068376
    First Posted:
    Dec 3, 2010
    Last Update Posted:
    Apr 27, 2018
    Last Verified:
    Apr 1, 2018