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The Effects of Dopamine on Reward Processing

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ClinicalTrials.gov Identifier: NCT01253421
Recruitment Status : Completed
First Posted : December 3, 2010
Results First Posted : January 18, 2018
Last Update Posted : April 27, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Diego A. Pizzagalli, Mclean Hospital

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
Major Depressive Disorder (MDD) Drug: amisulpride Drug: placebo 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 Type : Interventional  (Clinical Trial)
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.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Dopamine on Reward Processing
Study Start Date : February 2012
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Dopamine
U.S. FDA Resources

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 Name: 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 Name: Solian
Placebo Comparator: HC-placebo
Subjects having no history of mental disorder who are randomized to receive placebo
Drug: placebo
single-dose placebo capsule



Primary Outcome Measures :
  1. Effect on PST Reward Learning [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01253421


Locations
United States, Massachusetts
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

Publications:
Responsible Party: Diego A. Pizzagalli, Director, Center for Depression, Anxiety and Stress Research, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01253421     History of Changes
Other Study ID Numbers: 2010-P001568
R01MH068376 ( U.S. NIH Grant/Contract )
First Posted: December 3, 2010    Key Record Dates
Results First Posted: January 18, 2018
Last Update Posted: April 27, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
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, Mclean Hospital:
MDD
Major Depressive Disorder
Amisulpride

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Dopamine
Sultopride
Sulpiride
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Antidepressive Agents, Second-Generation
Antidepressive Agents