Clinical Trial of Propranolol for Seasonal Affective Disorder
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Seasonal Affective Disorder; Healthy
Intervention: Propranolol (Drug)
Phase: Phase 2
Sponsored by: National Institute of Mental Health (NIMH)
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.
Official title: Treatment of Winter Depression With Pharmacological Suppression of Melatonin Secretion
Study design: Treatment
Symptoms of seasonal affective disorder (SAD) in humans resemble seasonal changes that occur
in animals. Moreover, in both humans and animals, the occurrence of these changes is
regulated by light. In animals the circadian pacemaker regulates seasonal behavior by
transmitting a signal of daylength to other sites in the organism. This signal is expressed,
reciprocally, in the duration of nocturnal melatonin secretion, which is longer in winter and
shorter in summer. Sites distal to the pineal that regulate seasonal behavior read and
respond to this melatonin signal of change of season. In a longitudinal study, we showed
that a homologous melatonin signal of change of season is present in patients with SAD but
not in healthy volunteers. In light of the animal models, this finding raises the
possibility that seasonal changes in duration of melatonin secretion govern the course of
illness in patients with SAD. If so, then an intervention that shortens the duration of
melatonin secretion in winter and thereby mimics the effect of summer days should improve
symptoms of winter depression. To test this hypothesis, we propose to administer
propranolol, a beta-adrenergic receptor blocking medication that is frequently prescribed for
the treatment of hypertension, to patients with SAD in the winter. We will administer
propranolol at a time of night when it would suppress and shorten the duration of melatonin
secretion and then ascertain whether this intervention improves depression. A unique feature
of this parallel-design, controlled clinical trial is that propranolol, when administered at
a time of day when melatonin is not secreted, can serve as its own active placebo.
Minimum age: 18 Years.
Maximum age: 50 Years.
- 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
Patients will be ineligible for participation if they are currently being treated with an
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.
Locations and Contacts
Harvard University, Boston, Massachusetts 02115, United States
Arendt J, Bojkowski C, Franey C, Wright J, Marks V. Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab. 1985 Jun;60(6):1166-73.
Starting date: May 2001
Ending date: January 2007
Last updated: February 24, 2007