Combining a Dopamine Agonist and Selective Serotonin Reuptake Inhibitor for Treatment of Depression: A Double-Blind, Randomized Study
Pramipexole
+ Escitalopram
Mental Disorders+3
+ Behavioral Symptoms
+ Depression
Treatment Study
Summary
Study start date: June 1, 2004
Actual date on which the first participant was enrolled.Despite the availability of a wide range of antidepressant drugs, 30% to 40% of patients with major depression fail to respond to first-line antidepressant (e.g., selective serotonin reuptake inhibitors \[SSRIs\]) treatment, despite adequate dosage, duration, and compliance. Furthermore, these medications may take weeks to months to achieve their full effects, and in the meantime, patients continue to suffer from their symptoms and continue to be at risk of self-harm as well as harm to their personal and professional lives. Thus, there is a clear need to develop novel and improved therapeutics for treatment-resistant major depression that are more effective and have a rapid onset of action. Preclinical and clinical studies suggest that antidepressants with a combined mechanism of action (e.g., combination of a selective serotonin-reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor) may be more effective than either agent alone in achieving remission (Nelson et al 2004). Thus, it stands to reason that other combinations of antidepressants with other mechanisms of action when combined may have a synergistic effect that is superior to an antidepressant with a single mechanism of action. Preclinical and clinical studies suggest that the dopaminergic system may play a major role in the pathophysiology of depression. Preclinical studies suggest synergistic antidepressant effects with the combination of a SSRI and a selective D3 receptor agonist in animal models of depression. Similarly, preliminary clinical studies suggest synergism with combination treatment that affects the serotonin and dopamine systems. Together, these data suggests that treatments which affect the serotonin and dopamine systems will be more effective than agents which use a single mechanism. We propose to compare the combination of a selective dopaminergic agonist and a SSRI in patients with treatment-resistant major depression. To our knowledge, this will be the only controlled double-blind study to date that will examine the efficacy of a serotonin and dopamine combination given from the start of treatment. Patients, ages 18 years or older, with a diagnosis of major depression (without psychotic features), will be randomized to the combination of a selective dopaminergic receptor agonist and a SSRI or either drug alone for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater remission rate using specified criteria. Approximately 115 patients with acute major depression will be enrolled in the study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.39 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 65 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
INCLUSION CRITERIA: 1. Male or female subjects, 18 to 65 years of age. 2. Female subjects of childbearing potential must be using a medically accepted means of contraception. 3. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document. 4. Subjects must fulfill DSM-IV criteria for Major Depression (296.33) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P. 5. Subjects must have an initial score of greater than or equal to 20 on the MADRS at Visit 1 and Visit 2. 6. Subjects must not have a greater than a 25% decrease in the MADRS total scores during washout (between Visits 1 and 2). 7. Current or past history of lack of response to at least one adequate antidepressant trial (SSRI) operationally defined using the Antidepressant Treatment History Form (ATHF) (Sackeim 2001b). If this criteria has not been met, a four-week prospective trial of a standard antidepressant (at the patients' and clinicians' discretion) may be given. Subjects are excluded if greater than four failed antidepressant trials for the current major depressive (adequate dose and duration as defined by the ATHF). 8. Current major depressive episode of at least 4 weeks duration. EXCLUSION CRITERIA: 9. Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder or bipolar disorder as defined in the DSM-IV. 10. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months. 11. Previously failed to respond to an adequate trial (dose and duration) of escitalopram. 12. Female subjects who are either pregnant or nursing. 13. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 14. Subjects with uncorrected hypothyroidism or hyperthyroidism. 15. Subjects with one or more seizures without a clear and resolved etiology. 16. Previous treatment with pramipexole. 17. Treatment with a reversible MAOI within 2 weeks prior to Visit 2. 18. Treatment with fluoxetine within 5 weeks prior to Visit 2. 19. Treatment with any other concomitant medication not allowed (Appendix A) 7 days prior to study Visit 2. 20. Treatment with clozapine or ECT within 3 months prior to study Visit 2. 21. Judged clinically to be an acute suicidal risk. 22. Psychotherapy will not be permitted during the study.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.3 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
Active ComparatorGroup III
Active ComparatorStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, United StatesSee the location