At a glance
ClinicalIndex Comparison Record- ✓Age 18–65 years
- ✓DSM-IV diagnosis of Major Depression confirmed by SCID-P structured interview
- ✓HDRS ≥18 at baseline
- ✓For Phase II entry: prior response to total sleep deprivation (≥40% HAM-D6 reduction) followed by depressive relapse
- ✕Uncontrolled hypertension: SBP ≥140 and/or DBP ≥90 on 3+ readings in drug-free period
- ✕Sleep apnea/hypopnea index >15 episodes per minute
- ✕Psychotic features, schizophrenia, or other psychotic disorder
- ✕Current anxiety disorders (GAD, panic, PTSD)
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
An Investigation of a Pharmacologic Strategy to Bring About Rapid (Next Day) Antidepressant Effects
In Brief
A Phase 2 clinical trial evaluating Yohimbine hydrochloride and Placebo for Depression, Involutional and Major Depresssion. Completed, enrolled 11 participants across 1 site.
Detailed Summary
This study examines if Yohimbine, when given during the sleep cycle, will improve symptoms of depression within a matter of hours. Purpose: This study will examine whether the drug yohimbine, given at a specific time during the sleep cycle, produces chemical changes in the brain similar to those that occur with sleep deprivation. It will also see if yohimbine can induce rapid (next day) antidepressant effects in patients with major depression. Total sleep deprivation for 36 hours improves mood in most patients with major depression in a matter of hours, but the response is usually short-lived. Understanding the chemical changes that occur in the body during sleep deprivation may help in the development of a rapidly acting antidepressant.Patients with major depressive disorder between 18 and 65 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, and blood and urine tests. Participants are hospitalized at the NIH Clinical Center for the study, as follows: Drug-free period: Patients are tapered off their anti-depression medications and remain drug-free for 1 week before beginning study phase 1. Study phase 1: Patients undergo sleep deprivation for 36 hours. Those whose depression improves with sleep deprivation initially and then worsens continue to phase 2. The day after sleep deprivation, patients undergo a lumbar puncture (spinal tap). For this test, a local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle. Study phase 2: Patients spend 1 night in the sleep lab. A catheter (plastic tube) is placed in a vein in each arm-one to give yohimbine and the other to draw blood samples. A small monitor cuff is placed on a finger to measure the patient's blood pressure and blood oxygen levels during the night. While asleep, the patient receives a dose of yohimbine or placebo, given over 3 minutes. A lumbar puncture is done the following morning. Patients receive no medications for 6 days, and then the sleep lab procedure is repeated. Patients who received yohimbine in the previous experiment are switched to placebo, and those who were given placebo are switched to yohimbine.
Study Details
Timeline
Interventions
Participants receive yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep.
Participants receive an inactive equivalent of yohimbine 0.125 mg/kg administered over 3 minutes during REM sleep.