The Effects of Dopamine on Reward Processing
Condition: Major Depressive Disorder (MDD)
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: amisulpride; placebo
Intervention description: single low-dose pharmacological challenge, 50 mg amisulpride; single-dose placebo capsule
Intervention MeSH terms: Amisulpride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 159.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: MDD; Major Depressive Disorder; Amisulpride

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.
    

Eligibility 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