Rapid Antidepressant Effects of Yohimbine in Major Depression
Status:
Completed
Trial end date:
2009-08-01
Target enrollment:
Participant gender:
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.