Protocol Number: 01-M-0175

Title:

Treatment of Winter Depression with Pharmacological Suppression of Melatonin Secretion

Number:

01-M-0175

Summary:

The purpose of this study is to determine what dose of a new timed-release tablet of the drug propranolol will reduce secretion of the hormone melatonin in healthy volunteers. This study will also determine whether suppressing melatonin will improve depressive symptoms in people with seasonal affective disorder (SAD).

SAD (sometimes referred to as winter depression) is a condition in which people experience depression as a result of seasonal variations in light. Human brains have a circadian pacemaker that regulates many body functions. As the seasons change and light duration varies, the circadian pacemaker regulates seasonal behavior by transmitting a signal of day length to the pineal gland, which secretes the hormone melatonin. Melatonin secretion increases in the winter as the duration of light decreases. Evidence suggests that the melatonin signal of seasonal change is present in people with SAD but not in healthy volunteers; thus there is a possibility that seasonal changes which influence the duration of melatonin secretion control the course of illness in individuals with SAD. This study will determine whether propranolol can shorten the duration of melatonin secretion and mimic the effect of summer days to improve symptoms of depression in people with SAD.

Healthy volunteers will be admitted to the hospital for about 2 days. The volunteers will receive either propranolol or placebo (an inactive pill) before going to bed and upon awakening. Blood samples will be collected at various times throughout the study.

Participants with SAD will be interviewed periodically on an outpatient basis to determine the onset of depression in the fall or winter. Two weeks after depressive symptoms arise, participants will begin treatment with either propranolol or placebo. At the beginning of the treatment, participants will be hospitalized for about 2 days and will have blood collected at various times. During the hospital stay, participants will continue treatment with either propranolol or placebo in the morning and at night; all participants will receive propranolol at some point during the study. Participants will be interviewed weekly for 4 weeks.

Premenopausal women with or without SAD will keep a record of their menstrual cycles and will use a urine test kit to identify the time of ovulation during the month before and after admission to the hospital.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

Men and non-pregnant women non-smokers of all ethnic backgrounds between the ages of 18 to 50 who are free of major medical illness and who agree and are medically able to abstain from alcohol and all drugs, to adhere to a regular sleep schedule, and to limit caffeine-intake to less than or equal to 2 cups of coffee per day for at least two weeks (prescription drugs, 4 weeks) before, and for 4 weeks during the treatment period are eligible to participate.

Healthy volunteers will also be free of major psychiatric illness.

Patients will meet the criteria of Rosenthal et al. (1982) for Seasonal Affective Disorder.

EXCLUSION CRITERIA

Patients will be ineligible for participation if they are currently being treated with an antidepressant drug.

Women who are pregnant or breast feeding will not participate.

Individuals who have a major medical illness or who are unable to abstain from nicotine, alcohol and all drugs for at least two weeks (prescription drugs 4 weeks) and to limit caffeine-intake to less than or equal to 2 cups per day of coffee before the study and during the study will not participate.

Individuals with cardiac valve disease will be excluded.

Individuals with histories of these illnesses or conditions will specifically be excluded from participating: asthma, bronchospastic disease, obstructive pulmonary disease, coronary artery disease, congestive heart failure, A-V block, peripheral vascular disease, diabetes, thyrotoxicosis, severe allergic reactions, and sinus bradycardia.

Subjects older than 50 will be excluded.

Patients who report that they have been previously treated with a beta adrenergic receptor antagonist will be excluded.

Individuals who have unusual or irregular sleep schedules or who work on shifts will be excluded from participating.

Special Instructions: Currently Not Provided

Keywords:

Season

Light

Propranolol

Photoperiod

Pharmacokinetics

Circadian Rhythm

Seasonal Rhythm

Seasonal Affective Disorder

Pineal Gland

Suprachiasmatic Nucleus

Recruitment Keywords:

Healthy Volunteer

HV

Winter Depression

Seasonal Affective Disorder

SAD

Conditions:

Seasonal Affective Disorder

Healthy

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Atenolol reduces plasma melatonin concentration in man

Mammalian pineal melatonin: a clock for all seasons

Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/28/2004