Lexapro and Pramipexole and to Treat Major Depression

Phase 2

Completed

Conditions: Major Depression

Interventions: Drug: Escitalopram
Drug: Pramipexole

Registration Number: NCT00086307

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief 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. 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.

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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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Escitalopram	Escitalopram	Patients receive escitalopram and placebo. The dosage of escitalopram is 10 milligrams (mg) per day.
Pramipexole	Pramipexole	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.
Escitalopram and Pramipexole	Escitalopram	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.
Escitalopram and Pramipexole	Pramipexole	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.

Primary Outcome Measures

Name	Time	Method
Montgomery Asberg Depression Rating Scale (MADRS)	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.

Secondary Outcome Measures