Major DepressionPhase 2NCT00086307
Lexapro and Pramipexole and to Treat Major Depression
A Phase 2 study testing Pramipexole and Escitalopram in people with Major Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study compares the effectiveness of the combination of antidepressants: Lexapro and Pramipexole, with the effectiveness of each antidepressant alone. Purpose: Patients between 18 and 65 years of age with Major Depressive Disorder without psychotic features may be eligible for this 9-week study. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depression
- What is being tested?
- Pramipexole and Escitalopram
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to Mar 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects, 18 to 65 years of age.
- Female subjects of childbearing potential must be using a medically accepted means of contraception.
- Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
- 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.
- Subjects must have an initial score of greater than or equal to 20 on the MADRS at Visit 1 and Visit 2.
- Subjects must not have a greater than a 25% decrease in the MADRS total scores during washout (between Visits 1 and 2).
- 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).
- Current major depressive episode of at least 4 weeks duration.
Who cannot join
- Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder or bipolar disorder as defined in the DSM-IV.
- Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months.
- Previously failed to respond to an adequate trial (dose and duration) of escitalopram.
- Female subjects who are either pregnant or nursing.
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
- Subjects with uncorrected hypothyroidism or hyperthyroidism.
Show all 14Show fewer
- Subjects with one or more seizures without a clear and resolved etiology.
- Previous treatment with pramipexole.
- Treatment with a reversible MAOI within 2 weeks prior to Visit 2.
- Treatment with fluoxetine within 5 weeks prior to Visit 2.
- Treatment with any other concomitant medication not allowed (Appendix A) 7 days prior to study Visit 2.
- Treatment with clozapine or ECT within 3 months prior to study Visit 2.
- Judged clinically to be an acute suicidal risk.
- Psychotherapy will not be permitted during the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Combining a Dopamine Agonist and Selective Serotonin Reuptake Inhibitor for Treatment of Depression: A Double-Blind, Randomized Study
This study compares the effectiveness of the combination of antidepressants: Lexapro and Pramipexole, with the effectiveness of each antidepressant alone.
Purpose: Patients between 18 and 65 years of age with Major Depressive Disorder without psychotic features may be eligible for this 9-week study. Candidates must currently be in a major depressive episode of at least 4 weeks' duration, have failed to respond to treatment with an SSRI (Prozac, Zoloft, Paxil, Luvox, Celexa), and not have failed to respond to more than four antidepressants for the current episode. Candidates are screened with a physical examination, psychiatric evaluation, blood tests, review of vital signs, height and weight measurements, electrocardiogram (ECG), urine test for illegal drugs, and pregnancy test for women.
Read more
Participants are tapered off antidepressants or other medications prohibited during the study and remain drug-free for 1 week before starting treatment. They are then randomly assigned to take pramipexole and escitalopram, pramipexole alone, or escitalopram alone for 6 weeks. During the study, participants come to the clinic eight times for health assessments and symptoms assessments, which include a check of vital signs and rating scales for depression and anxiety, adverse events, and sexual functioning. Blood and urine samples are collected periodically to monitor health, detect pregnancy in women, and detect illicit drug use.
At the end of the 6-week treatment period, participants have a physical examination, ECG, blood test, and check of vital signs. Short-term anti-depressant treatment is offered, and plans are made for long-term treatment.
Atendemos pacientes de habla hispana.
...
Read the detailed description
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.
- Conditions
- Major Depression
- Being tested
- Pramipexole, Escitalopram
- Keywords
- Pramipexole, Escitalopran, Antidepressant, Dopaminergic Receptor Agonist, Depression, Major Depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PramipexoleDrug
Pramipexole will be titrated so patients receive the following medication three times per day during the weeks noted: .125 milligrams (mg) in week 1, .250 mg in week 2, .5 mg in week 3, and .75 mg in weeks 4 to 6.
EscitalopramDrug
Escitalopram will be started at 10 mg/day and patients will continue on this throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Pramipexole | Active comparator | Patients receive pramipexole and placebo. The dosage of pramipexole is 0.125 milligrams (mg) three times per day in the first week, 0.250 mg three times per day in the second week, 0.5 mg three times per day in the third week, and 0.75 mg three times per day in the fourth week and thereafter. Receives: Drug: Pramipexole |
| Escitalopram | Active comparator | Patients receive escitalopram and placebo. The dosage of escitalopram is 10 milligrams (mg) per day. Receives: Drug: Escitalopram |
| Escitalopram and Pramipexole | Experimental | Patients receive escitalopram and pramipexole. The dosage of escitalopram is 10 milligrams (mg) per day. The dosage of pramipexole is 0.125 mg three times per day in the first week, 0.250 mg three times per day in the second week, 0.5 mg three times per day in the third week, and 0.75 mg three times per day in the fourth week and thereafter. Receives: Drug: Pramipexole; Drug: Escitalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery Asberg Depression Rating Scale (MADRS)
The Montgomery Asberg Depression Rating Scale (MADRS) is a 10 item scale for assessing the severity of depression. Items are rated on a scale of 0 to 6, so the maximum score is 60 and the minimum is 0, where 60 is the most severe depression. Scores of 18 or greater are generally considered to indicate a moderate level of depression.
Measured: Weekly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2004 (estimated)
- Study startJun 2004
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Carlos Zarate, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Carlos A Zarate, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00086307
- Sponsor's protocol ID
- 040227
- Other IDs
- 04-M-0227
- Status last verified
- Jan 2013
- First submitted
- 29 Jun 2004
- Last updated
- 28 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Agnoli A, Ruggieri S, Casacchia M. Restatement and prospectives of ergot alkaloids in clinical neurology and psychiatry. Pharmacology. 1978;16 Suppl 1:174-88. doi: 10.1159/000136818. No abstract available.
PubMed 347463Anderson IM. SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability. Depress Anxiety. 1998;7 Suppl 1:11-7.
PubMed 9597346Agren H, Mefford IN, Rudorfer MV, Linnoila M, Potter WZ. Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF. J Psychiatr Res. 1986;20(3):175-93. doi: 10.1016/0022-3956(86)90002-6.
PubMed 2430098
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining a Dopamine Agonist and Selective Serotonin Reuptake Inhibitor for Treatment of Depression: A Double-Blind, Randomized Study
- ClinicalTrials.gov ID
- NCT00086307
- Acronym / sponsor ID
- 040227
- Conditions
- Major Depression
- Keywords
- Pramipexole, Escitalopran, Antidepressant, Dopaminergic Receptor Agonist, Depression, Major Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Jun 2004
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 30 Jun 2004 (estimated)
- Results
- Posted 12 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study compares the effectiveness of the combination of antidepressants: Lexapro and Pramipexole, with the effectiveness of each antidepressant alone.
Purpose: Patients between 18 and 65 years of age with Major Depressive Disorder without psychotic features may be eligible for this 9-week study. Candidates must currently be in a major depressive episode of at least 4 weeks' duration, have failed to respond to treatment with an SSRI (Prozac, Zoloft, Paxil, Luvox, Celexa), and not have failed to respond to more than four antidepressants for the current episode. Candidates are screened with a physical examination, psychiatric evaluation, blood tests, review of vital signs, height and weight measurements, electrocardiogram (ECG), urine test for illegal drugs, and pregnancy test for women.
Participants are tapered off antidepressants or other medications prohibited during the study and remain drug-free for 1 week before starting treatment. They are then randomly assigned to take pramipexole and escitalopram, pramipexole alone, or escitalopram alone for 6 weeks. During the study, participants come to the clinic eight times for health assessments and symptoms assessments, which include a check of vital signs and rating scales for depression and anxiety, adverse events, and sexual functioning. Blood and urine samples are collected periodically to monitor health, detect pregnancy in women, and detect illicit drug use.
At the end of the 6-week treatment period, participants have a physical examination, ECG, blood test, and check of vital signs. Short-term anti-depressant treatment is offered, and plans are made for long-term treatment.
Atendemos pacientes de habla hispana.
...
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pramipexole | Active comparator | Drug: PramipexolePatients receive pramipexole and placebo. The dosage of pramipexole is 0.125 milligrams (mg) three times per day in the first week, 0.250 mg three times per day in the second week, 0.5 mg three times per day in the third week, and 0.75 mg three times per day in the fourth week and thereafter. |
| Escitalopram | Active comparator | Drug: EscitalopramPatients receive escitalopram and placebo. The dosage of escitalopram is 10 milligrams (mg) per day. |
| Escitalopram and Pramipexole | Experimental | Drug: Pramipexole, Drug: EscitalopramPatients receive escitalopram and pramipexole. The dosage of escitalopram is 10 milligrams (mg) per day. The dosage of pramipexole is 0.125 mg three times per day in the first week, 0.250 mg three times per day in the second week, 0.5 mg three times per day in the third week, and 0.75 mg three times per day in the fourth week and thereafter. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female subjects, 18 to 65 years of age.
- Female subjects of childbearing potential must be using a medically accepted means of contraception.
- Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
- 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.
- Subjects must have an initial score of greater than or equal to 20 on the MADRS at Visit 1 and Visit 2.
Key exclusion criteria (14 listed)
- Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder or bipolar disorder as defined in the DSM-IV.
- Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months.
- Previously failed to respond to an adequate trial (dose and duration) of escitalopram.
- Female subjects who are either pregnant or nursing.
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PramipexolePramipexole will be titrated so patients receive the following medication three times per day during the weeks noted: .125 milligrams (mg) in week 1, .250 mg in week 2, .5 mg in week 3, and .75 mg in weeks 4 to 6. | Drug | Escitalopram and Pramipexole, Pramipexole |
| EscitalopramEscitalopram will be started at 10 mg/day and patients will continue on this throughout the study. | Drug | Escitalopram, Escitalopram and Pramipexole |
Primary outcome
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: Weekly
The Montgomery Asberg Depression Rating Scale (MADRS) is a 10 item scale for assessing the severity of depression. Items are rated on a scale of 0 to 6, so the maximum score is 60 and the minimum is 0, where 60 is the most severe depression. Scores of 18 or greater are generally considered to indicate a moderate level of depression.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 347463Agnoli A, Ruggieri S, Casacchia M. Restatement and prospectives of ergot alkaloids in clinical neurology and psychiatry. Pharmacology. 1978;16 Suppl 1:174-88. doi: 10.1159/000136818. No abstract available.
- Background: PubMed 9597346Anderson IM. SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability. Depress Anxiety. 1998;7 Suppl 1:11-7.
- Background: PubMed 2430098Agren H, Mefford IN, Rudorfer MV, Linnoila M, Potter WZ. Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF. J Psychiatr Res. 1986;20(3):175-93. doi: 10.1016/0022-3956(86)90002-6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos A Zarate, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pramipexole and Escitalopram in people with Major Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery Asberg Depression Rating Scale (MADRS) (time frame: Weekly). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00086307, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2013.