This study will evaluate the effectiveness of the experimental drug, Org 24448, for
short-term treatment of depression. It will examine the effects of the drug on symptoms, such
as low mood and persistent sadness, poor sleep and appetite, poor motivation and lack of
enjoyment of things people normally enjoy, negative thinking, and feeling slowed down or
having trouble concentrating. It will also assess whether the drug improves cognitive
function, especially memory.
Patient with major depression who do not have a serious, unstable medical illness and who are
21 to 55 years of age may be eligible for this study. Candidates are screened with a
psychiatric and medical history, diagnostic interview, physical examination,
electrocardiogram, blood tests and, for women, a pregnancy test.
Participants are tapered off anti-depression drugs (and any other medications not allowed on
the study) over a 3-week period and then begin a 2-week drug-free period. During these 2
weeks they have an electroencephalogram (EEG) with light stimulation, and those whose EEG
indicates a seizure disorder are excluded from the study. Also at the beginning of the
drug-free period they begin taking a placebo ("sugar pill") twice a day. After 2 weeks on
placebo, some patients begin treatment with Org 24448, while others remain on placebo. They
continue the medication for 8 weeks, during which time they have a weekly check of vital
signs, blood and urine tests, and rating scales for depression and anxiety. Level of
functioning is evaluated twice during the study. After 8 weeks of treatment, patients have a
physical exam, electrocardiogram (ECG), EEG, blood tests, and begin to come off the study
drug, tapering the medication over a week.
In addition to the above procedures, some patients undergo the following tests during the
2-week drug-free period and again toward the end of the 8-week medication phase:
- Neuropsychological testing, including measurements of cognitive abilities such as
memory, attention, problem-solving, and language skills.
- Positron emission tomography (PET): This nuclear medicine test provides information
about different brain regions. The patient lies on a table in the PET scanner (similar
to a computed tomography (CT) scanner), with a mask placed over his or her face that
helps keep the head still. A sugar fluid with a radioactive material attached to it is
injected into a catheter (plastic tube) that has been inserted into a vein in the
patient's arm. The scanner detects ...