A Glutamate Transporter GLT1, in the Treatment of Bipolar Disorder
Status:
Withdrawn
Trial end date:
2009-09-15
Target enrollment:
Participant gender:
Summary
This study examines if Ceftriaxone, an antibiotic, will improve symptoms of depression in
Bipolar Disorder.
Purpose: This study will examine whether the drug ceftriaxone can help patients with bipolar
depression during short-term treatment of symptoms such as depressed mood, psychomotor
retardation (slowed down thinking and movements), and problems with sleep. Recent studies
suggest that abnormalities in the brain levels of the chemical glutamate may be involved in
causing depression. Ceftriaxone increases a protein in the brain called GLT1, which is
responsible for regulating brain levels of glutamate.
People between 18 and 65 years of age with bipolar disorder who are currently in a depressive
episode of at least 4 weeks but no longer than 12 months duration may be eligible for this
study.
Participants are admitted to the NIH Clinical Center for about 10 weeks. During the first 1
to 2 weeks, they are evaluated and tapered off any antidepressant or mood stabilizers they
have been taking. They remain free of all medication for 2 weeks and are then randomly
assigned to take either ceftriaxone or placebo for 6 weeks. The study drugs are given
intravenously (through a vein) every day. To minimize discomfort, patients are given a PICC
line - a tube that is inserted in a vein in the arm and remains there for the duration of
drug treatment. This prevents the need for repeated intravenous injections.
Patients have a physical examination at the beginning and at the end of the study and two
electrocardiograms (ECG) during the study. They are evaluated periodically with a series of
psychiatric rating scales to determine the effects of the study drug on mood and thinking and
they have periodic blood tests to assess their health status.
In addition, patients are asked to undergo a lumbar puncture (spinal tap) twice during the
study to collect a sample of cerebrospinal fluid (CSF, the fluid that bathes the brain and
spinal cord). The CSF is examined to try to understand how brain chemicals are related to
depression and to the effects of ceftriaxone. A local anesthetic is given and a needle is
inserted in the space between the bones in the lower back where the CSF circulates below the
spinal cord. A small amount of fluid is collected through the needle. This test is optional.
At the end of the study patients are offered free treatment for up to 3 months with standard
medications for bipolar depression and a referral to a community physician for long-term
treatment will be made.