The Effects of Dopamine on Reward Processing

NCT01253421 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2010-P001568R01MH068376
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder (MDD)

Keywords

MDD; Major Depressive Disorder; Amisulpride

Outcome Measures

Primary Outcomes (8)

• Effect on PST Reward Learning

  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.

  administered after scan

• Effect on PST Penalty Learning

  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.

  administered after scan

• Effect on Caudate Response to Cues

  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.

  Scan session

• Effect on NAcc Response to Cues

  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.

  Scan session

• Putamen Response to Cues

  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.

  Scan session

• Effect on Caudate Response to Reward

  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.

  During scan session

• Effect on NAcc Response to Reward

  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.

  During scan session

• Effect on Putamen Response to Reward

  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.

  During scan session

Secondary Outcomes (2)

• Effect on Caudate-dACC Connectivity After Reward

  During scan session

• Effect on NAcc-MCC Connectivity After Reward

  During scan session

Study Arms (4)

MDD-amisulpride

ACTIVE COMPARATOR

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

Drug: amisulpride

MDD-placebo

PLACEBO COMPARATOR

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

Drug: placebo

HC-amisulpride

ACTIVE COMPARATOR

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

Drug: amisulpride

HC-placebo

PLACEBO COMPARATOR

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

Drug: placebo

Interventions

amisulpride DRUG

single low-dose pharmacological challenge, 50 mg amisulpride

Also known as: Solian

HC-amisulpride; MDD-amisulpride

placebo DRUG

single-dose placebo capsule

HC-placebo; MDD-placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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);
• Written informed consent;
• Both genders and all ethnic origins, age between 18 and 45;
• A baseline score \> 16 on the Hamilton Rating Scale for Depression (HRSD) 17-item version;
• Right-handed.
• Absence of any psychotropic medications for at least 2 weeks:
• weeks for fluoxetine,
• months for neuroleptics,
• weeks for benzodiazepines,
• weeks for any other antidepressants.
• 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);
• Written informed consent;
• Both genders and all ethnic origins, age between 18 and 45;
• Right-handed;
• Absence of any medications for at least 3 weeks;

You may not qualify if:

• Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment;
• 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);
• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological or hematologic disease;
• Lifetime history of seizure disorder;
• More than five instances of lifetime cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine);
• Use of dopaminergic drugs (including methylphenidate) within the last 6 months;
• Lifetime history or current diagnosis of dementia, or a score of \< 26 on the Mini Mental Status Examination at the screening visit;
• Lifetime history of adverse drug reactions or allergy to the study drug (amisulpride);
• Patients with mood congruent or mood incongruent psychotic features;
• Current use of other psychotropic drugs;
• Clinical or laboratory evidence of hypothyroidism;
• Patients with a lifetime history of electroconvulsive therapy (ECT);
• Patients with renal insufficiency;
• Failure to meet standard MRI safety requirements
• Electrolytes, blood urea nitrogen, creatinine: outside the normal range (also ruling out renal insufficiency);

Sponsors & Collaborators

• Mclean Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (2)

• Admon R, Kaiser RH, Dillon DG, Beltzer M, Goer F, Olson DP, Vitaliano G, Pizzagalli DA. Dopaminergic Enhancement of Striatal Response to Reward in Major Depression. Am J Psychiatry. 2017 Apr 1;174(4):378-386. doi: 10.1176/appi.ajp.2016.16010111. Epub 2016 Oct 24.

  PMID: 27771973 BACKGROUND

• Liu Y, Admon R, Mellem MS, Belleau EL, Kaiser RH, Clegg R, Beltzer M, Goer F, Vitaliano G, Ahammad P, Pizzagalli DA. Machine Learning Identifies Large-Scale Reward-Related Activity Modulated by Dopaminergic Enhancement in Major Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):163-172. doi: 10.1016/j.bpsc.2019.10.002. Epub 2019 Oct 22.

  PMID: 31784354 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Amisulpride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and 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.

Results Point of Contact

• Title: Diego Pizzagalli, Ph.D.
• Organization: McLean Hospital

dap@mclean.harvard.edu

617-855-4230

Study Officials

• Diego A Pizzagalli, PhD

  McLean Hospital, Harvard University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Depression, Anxiety and Stress Research

Model Details: 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.

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 3, 2010
• Study Start: February 1, 2012
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: April 27, 2018
• Results First Posted: January 18, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)