DTA (Dopaminergic Therapy for Anhedonia) Study
DTA (Dopaminergic Therapy for Anhedonia) Study
The purpose of this 6-week, double-blind, placebo-controlled, crossover study is to explore
 new treatment options for people with depression who have high inflammation and anhedonia.
 Thirty-five male and female participants with depression, between the ages of 25-55 years of
 age, will be randomized to two study tracks (A and B) to receive both placebo and three doses
 of L-DOPA, given in different orders. Increases or decreases in each dose will occur
 gradually over 6 weeks of the study. Participants will complete lab tests, medical and
 psychiatric assessments, neurocognitive testing and functional MRI (fMRI) scans as part of
 the study. The total length of participation is about 2 months.
Depression is a widespread disorder (lifetime prevalence >20%). Current antidepressant
 medications are effective for many patients; however, more than 30% fail to respond. Of the
 patients that do respond to treatment, some continue to suffer with primary symptoms of
 depression like an inability to experience pleasure, called anhedonia. In this regard, one
 biological pathway that may contribute to symptoms of depression and particularly anhedonia
 is inflammation.

 The purpose of this 6-week, double-blind, placebo-controlled, crossover study is to explore
 new treatment options for people with depression who have high inflammation and anhedonia.
 Despite evidence of low dopamine function in patients with depression, the ability of
 existing dopaminergic therapies, like L-DOPA, to affect brain circuits in depression has yet
 to be explored. This study will help determine the best dose of an FDA-approved medication,
 Sinemet (L-DOPA) that might be used in the future to treat sub-groups of depressed
 individuals.

 Forty male and female participants with depression, between the ages of 25-55 years of age,
 will be randomized to two study tracks (A and B) to receive both placebo and three doses of
 L-DOPA, given in different orders. Increases or decreases in each dose will occur gradually
 over 6 weeks of the study. Participants will complete lab tests, medical and psychiatric
 assessments, neurocognitive testing and functional MRI (fMRI) scans as part of the study. The
 total length of participation is about 2 months.
Inclusion Criteria:

 -  willing and able to give written informed consent;

 -  men or women, 25-55 years of age

 -  a primary diagnosis of DSM-V MD, current, as diagnosed by the SCID-I;

 -  score >10 on the Patient Health Questionnaire [PHQ]-9

 -  off all antidepressant or other psychotropic therapy (e.g. mood stabilizers,
 antipsychotics, anxiolytics, and sedative hypnotics) for at least 4 weeks prior to
 baseline visit (8 weeks for fluoxetine)

 -  CRP ≥2 mg/L

 -  Score >/=2 on the anhedonia question of Patient Health Questionnaire [PHQ]-9

 Exclusion Criteria:

 -  history or evidence (clinical or laboratory) of an autoimmune disorder ;

 -  history or evidence (clinical or laboratory) of hepatitis B or C infection or human
 immunodeficiency virus infection; - history of any type of cancer requiring treatment
 with more than minor surgery;

 -  unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic
 disease (as determined by physical examination, EKG and laboratory testing);

 -  history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any
 type; history or current bipolar disorder; history or current gambling disorder;
 substance abuse/dependence within 6 months of study entry (as determined by SCID);

 -  active suicidal plan as determined by a score >3 on item #3 on the HAM-D; g. an active
 eating disorder (except for patients with binge eating disorder in whom binging is
 clearly associated with worsening of mood symptoms) ;

 -  a history of a cognitive disorder

 -  pregnancy or lactation;

 -  chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of
 aspirin), glucocorticoid containing medications or statins;

 -  use of NSAIDS, glucocorticoids, or statins at any time during the study;

 -  urine toxicology screen is positive for drugs of abuse,

 -  any contraindication for MRI scanning; n. intolerance, sensitivity or contraindication
 to carbidopa-levodopa (including history of narrow-angle glaucoma, melanoma, gastric
 and/or duodenal ulcers, bleeding disorders, or frequent migraines).