Dopaminergic Therapy for Depression with Anhedonia

Overseen By Bobbi Woolwine, CCRC

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Antidepressants, Psychotropics, NSAIDs, Statins

Disqualifiers: Autoimmune, Cancer, Cardiovascular, Psychotic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

19 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking all antidepressant or other psychotropic medications (like mood stabilizers, antipsychotics, anxiolytics, and sedative hypnotics) for at least 4 weeks before starting the trial (8 weeks for fluoxetine).

What data supports the effectiveness of the drug Carbidopa Levodopa for depression with anhedonia?

Research shows that Carbidopa Levodopa is effective in treating Parkinson's disease by improving symptoms and quality of life. While this is not directly related to depression with anhedonia, it suggests the drug can positively affect conditions involving dopamine, a brain chemical linked to mood and pleasure. ^{1 2 3 4 5}

Is dopaminergic therapy with Carbidopa Levodopa safe for humans?

Research on Carbidopa Levodopa, primarily used for Parkinson's disease, indicates it is generally safe for humans, with most adverse effects related to the infusion system or surgical procedures rather than the drug itself. ^{1 2 6 7 8}

How does the drug Carbidopa Levodopa differ from other treatments for depression with anhedonia?

Carbidopa Levodopa is unique because it targets dopamine levels in the brain, which is a different approach compared to typical antidepressants that often focus on serotonin. This drug is traditionally used for Parkinson's disease to manage dopamine deficiency, and its use for depression with anhedonia is novel, as it may help address dopamine-related symptoms in this condition. ^{1 8 9 10 11}

What is the purpose of this trial?

This trial tests L-DOPA, a medication that boosts dopamine, in people with depression who have high inflammation and can't feel pleasure. The goal is to see if increasing dopamine can improve their mood and ability to feel pleasure. L-DOPA is used to treat motor symptoms in Parkinson's disease by increasing dopamine levels in the brain.

Research Team

Jennifer Felger, PhD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for men and women aged 25-55 with depression, specifically those experiencing anhedonia (loss of pleasure) and high inflammation. Participants must have a certain score on the PHQ-9 questionnaire, not be on antidepressants or other psychotropic drugs for at least 4 weeks, and have no history of significant medical conditions or substance abuse.

Inclusion Criteria

You have a score of 10 or more on the PHQ-9.

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

I am between 25 and 55 years old.

Exclusion Criteria

urine toxicology screen is positive for drugs of abuse,

pregnancy or lactation;

I am not taking NSAIDs, glucocorticoids, or statins during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive both placebo and three doses of L-DOPA in a double-blind, placebo-controlled, crossover study

6 weeks

Weekly visits for dose adjustments and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Carbidopa Levodopa
• Placebo

Trial Overview The study tests Carbidopa Levodopa's effectiveness against anhedonia in depressed individuals with high inflammation. Over six weeks, participants will receive varying doses of L-DOPA and placebos in different sequences to assess changes in their condition through lab tests, assessments, neurocognitive testing, and brain scans.

Participant Groups

Group I: Placebo followed by Carbidopa Levodopa Experimental Treatment 2 Interventions

Participants will receive first placebo, and then Carbidopa Levodopa (L-DOPA) at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day.

Group II: Carbidopa Levodopa followed by Placebo Experimental Treatment 2 Interventions

Participants will receive first Carbidopa Levodopa at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day; and then placebo.

Carbidopa Levodopa is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Approved in United States as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Approved in Canada as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Approved in Japan as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Levodopa, particularly in the form of levodopa-carbidopa intestinal gel, is crucial for providing continuous dopaminergic stimulation, which is essential in the treatment of Parkinson's disease.

Studies highlight the efficacy and safety of this treatment, showing improvements in the quality of life for patients undergoing long-term therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Levodopa: the story continues]. Titova, NV., Katunina, EA.[2016]

Levodopa/carbidopa gel (Duodopa®) has been shown to significantly improve motor symptoms in advanced Parkinson's disease, with 10 out of 11 studies reporting improvements that met clinically important differences on the Unified Parkinson's Disease Rating Scale (UPDRS) III.

The treatment also enhances quality of life, as all studies assessing this aspect reported improvements that met clinically important differences, although most adverse events were related to the infusion system rather than the drug itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodopa® treatment for advanced Parkinson's disease: a review of efficacy and safety. Nyholm, D.[2013]

In a study of 34 patients with advanced Parkinson's disease who were intolerant to L-DOPA, a higher proportion of carbidopa (25%) was preferred by most patients and helped reduce gastrointestinal and psychiatric side effects associated with L-DOPA.

While increasing carbidopa improved side effects, the overall improvement in disability was modest, indicating that while the combination may enhance tolerability, it does not significantly enhance the effectiveness of L-DOPA in treating Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbidopa dosage modifies L-dopa induced side effects and blood levels of L-dopa and other amino acids in advanced parkinsonism. Bermejo Pareja, F., Martinez-Martin, P., Muradas, V., et al.[2019]

A study involving 20 patients with Parkinson's disease confirmed that the combination of L-dopa with a peripheral aromatic amino acid decarboxylase inhibitor (benserazide or carbidopa) is the most effective treatment available, allowing for an 80% reduction in L-dopa dosage.

Switching between the two formulations, Madopar and Sinemet, can help maintain efficacy and prevent loss of effectiveness during long-term treatment, as both achieve similar plasma levels of L-dopa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The combined treatment of Parkinson's disease with L-dopa plus decarboxylase inhibitors (carbidopa, benserazide) (author's transl)]. Podiwinsky, F., Mentasti, M., Riederer, P., et al.[2013]

In a double-blind study involving 28 patients with chronic schizophrenia, L-dopa treatment (up to 1250 mg daily) showed significant improvement in symptoms according to nurse assessments, despite psychiatrist and psychologist ratings indicating only minor changes.

The study lasted six weeks and all participants continued their regular neuroleptic medication, suggesting that L-dopa may enhance treatment outcomes in schizophrenia when combined with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double blind trial of L-dopa in chronic schizophrenia. Buchanan, FH., Parton, RV., Warren, JW., et al.[2017]

In a study involving 29 patients with Parkinson's disease, Sinemet-CR demonstrated a high effectiveness rate of 80%, particularly improving symptoms like rigidity, hypokinesia, and tremor over a treatment duration of 3 months.

The treatment was found to be safe, with only 6 cases reporting negative side effects, supporting its recommendation for broader use in managing Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of the Sinemet-CR preparation in treating Parkinson's disease]. Artem'ev, DV., Damulin, IV., Iakhno, NN.[2016]

In 1984, the average use of L-dopa-containing drugs in Sweden was 1.46 defined daily doses per 1,000 inhabitants, indicating a strong correlation with the prevalence of Parkinson's disease, the primary condition treated with these medications.

The county of Gävleborg showed an exceptionally high usage rate of 2.34 DDD per 1,000 inhabitants, prompting further investigation into local factors that may influence this increased utilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Swedish county with unexpectedly high utilization of anti-parkinsonian drugs. Aquilonius, SM., Hartvig, P.[2019]

In a study of 60 Parkinsonism patients, the combination of levodopa with G31,406 showed potential benefits due to its anticataleptic effects, likely linked to its anticholinergic and dopaminergic actions.

The study aimed to assess not only the efficacy of these drug combinations but also the side effects and their impact on depression commonly experienced by Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The L-dopa sparing effect of G 31,406 in the treatment of parkinson's disease. Couto, B., Oliveira, C., Mattos, JP., et al.[2013]

Carbidopa (CD) significantly accumulates in the rat hypothalamus and striatum after administration, with peak levels observed one hour post-injection, indicating its ability to penetrate the brain and potentially influence dopamine metabolism.

At higher doses, carbidopa can inhibit dopamine formation in the brain, particularly in the hypothalamus, while also affecting the levels of other metabolites, suggesting a complex interaction between carbidopa and levodopa in the treatment of conditions like Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum. Kaakkola, S., Tuomainen, P., Wurtman, RJ., et al.[2019]

Levodopa therapy revolutionized the treatment of Parkinson's disease (PD) after its effectiveness was confirmed in 1967, despite initial inconsistent results, but it also introduced significant side effects like dyskinesias and motor fluctuations.

The addition of dopa decarboxylase inhibitors, such as carbidopa, in the 1970s improved symptom control and reduced side effects, leading to more effective long-term management of PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History of levodopa and dopamine agonists in Parkinson's disease treatment. Tolosa, E., Martí, MJ., Valldeoriola, F., et al.[2019]

Levodopa is the primary treatment for Parkinson's disease, working by restoring dopamine release from damaged brain cells, which helps alleviate symptoms.

While effective, levodopa can cause side effects like dyskinesia due to its action on brain receptors, and using peripheral decarboxylase inhibitors can help reduce nausea associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of some aspects of the pharmacology of levodopa. Morris, JG.[2014]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Levodopa: the story continues]. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Duodopa® treatment for advanced Parkinson's disease: a review of efficacy and safety. [2013]

3. Denmark pubmed.ncbi.nlm.nih.gov

Carbidopa dosage modifies L-dopa induced side effects and blood levels of L-dopa and other amino acids in advanced parkinsonism. [2019]

4. Austria pubmed.ncbi.nlm.nih.gov

[The combined treatment of Parkinson's disease with L-dopa plus decarboxylase inhibitors (carbidopa, benserazide) (author's transl)]. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Double blind trial of L-dopa in chronic schizophrenia. [2017]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The use of the Sinemet-CR preparation in treating Parkinson's disease]. [2016]

7. Denmark pubmed.ncbi.nlm.nih.gov

A Swedish county with unexpectedly high utilization of anti-parkinsonian drugs. [2019]

8. Mexico pubmed.ncbi.nlm.nih.gov

The L-dopa sparing effect of G 31,406 in the treatment of parkinson's disease. [2013]

9. Austria pubmed.ncbi.nlm.nih.gov

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

History of levodopa and dopamine agonists in Parkinson's disease treatment. [2019]

11. Australia pubmed.ncbi.nlm.nih.gov

A review of some aspects of the pharmacology of levodopa. [2014]