Psychopharmacology of Fear-Potentiated Startle in Humans
Condition: Healthy
Study type: Observational

Summary: 
      The purpose of this study is to understand the effects of the drug alprazolam (Xanax ) on
      anxiety.

      To understand the effect of anxiety-relieving drugs on fear and anxiety, researchers often
      have participants anticipate unpleasant stimuli. Anticipating unpleasant stimuli increases or
      potentiates a simple reflex called the startle reflex. The so-called fear-potentiated startle
      reflex (FPS) effect may be blocked or reduced by anxiety-relieving drugs. Evidence suggests
      that the FPS can be mediated by two mechanisms that regulate the phasic- and sustained
      enhancement of startle. This study will elicit phasic and sustained FPS in participants by
      having them anticipate moderately painful stimuli that are administered predictably and
      unpredictably. The main goal of this study is to assess the affect of alprazolam on the
      phasic and sustained enhancement of startle.

      This study comprises two pilot experiments and a main study. Participants in the study will
      be screened with a psychiatric history, physical examination, electrocardiogram (EKG), and
      blood and urine tests. Participants will four testing sessions separated by 5 to 10 days. At
      each session, participants will be given one of two doses of alprazolam, diphenhydramine, or
      placebo (an inactive pill). Questionnaires and other tests will be performed.
    

Detailed description: 
      Objective:

      Recent breakthroughs in biomedical research have not improved the ability to identify
      successful pharmacological treatments derived from novel candidate compounds. This is partly
      due to the inability of the existing scientific approach to translate candidate anxiolytics
      identified through the drug discovery process into efficient psychopharmacological treatment
      of patients. A new drug development approach urgently needs to be implemented to improve
      predictability and efficiency in translating the basic science explosion into validated drug
      targets. A key approach to improve the selection of candidate anxiolytics for clinical trials
      is to fill the gap between animal models and clinical studies in patients by implementing
      tests in healthy humans with a predictive validity of subsequent clinical efficacy. As a step
      towards this goal, we developed integrative experimental models of fear and anxiety in
      non-clinical subjects. We now use these models to identify the anxiolytic and anxiogenic
      properties of various compounds. The current specific objectives are to 1) further test the
      psychopharmacological validity of the model using recognized anxiolytics (the SSRI
      citalopram), 2) test the properties of compounds that are hypothesized to be anxiolytic or
      anxiogenic (e.g., oxytocin, arginine vasopressin, hydrocortisone) and 3) examine the time
      course of the anxiolytic effect of the benzodiazepine alprazolam on FPS.

      Study population:

      Medically and psychiatrically healthy males and females ages 18 to 45.

      Design:

      The study examines fear and anxiety elicited by unpleasant electric shock delivered
      predictably and unpredictably, respectively. The following drugs will be tested:

      1) Citalopram, 2) oxytocin and arginine vasopressin, 3) hydrocortisone, 4) alprazolam.

      Outcome measures:

      The primary outcome measure is the startle reflex. Secondary measures include the skin
      conductance response, the heart rate, and subjective measures of anxiety.
    

Keywords: SSRI; Anxiety; Stress; Citalopram; Benadryl; Diphenhydramine; Startle; Fear-Potentiated Startle; Fear; Normal Volunteers; Healthy Volunteers; HV