Clinical Trial of Propranolol for Seasonal Affective Disorder
Condition: Seasonal Affective Disorder; Healthy
MeSH terms: Mood Disorders; Seasonal Affective Disorder
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      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.
    

Intervention name(s): Propranolol
Intervention type(s): Drug
Intervention MeSH terms: Propranolol
Primary purpose: Treatment
Keywords: Season; Light; Propranolol; Photoperiod; Pharmacokinetics; Circadian Rhythm; Seasonal Rhythm; Seasonal Affective Disorder; Pineal Gland; Suprachiasmatic Nucleus; Healthy Volunteer; HV; Winter Depression; SAD