Influence of Escitalopram on Fear Conditioning

Pharmacologic Influence of Escitalopram on the Reduction of Fear Acquisition and Triggered Renewal During Fear Conditioning: a Model for the Prevention and Persistence of Learned Fear and Anxiety in Response to Trauma and Stress

The purpose of the study is to learn how differences in learning under mildly-stressful circumstances may be changed by taking an antidepressant medication. This medication is called Lexapro (Escitalopram). The investigators will also examine the impact of any anxiety, depression, and stress related symptoms on learning processes. The investigators will also look at the response of these symptoms to Lexapro.

Study Overview

• Status: Completed
• Conditions: Fear Conditioning
• Intervention / Treatment: Drug: Escitalopram

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female outpatients 18 to 75 years of age
2. Must have no current DSM-IV Axis I diagnosis as measured by the SCID (Structured Clinical Interview for DSM-IV-TR axis 1 disorders) with a trained study investigator. Past history of anxiety disorders, major depressive episodes or substance abuse disorders at least six months prior to baseline are not exclusionary.

Exclusion Criteria:

1. Patients will be excluded from entry into the study for current serious medical conditions or other conditions deemed likely to result in surgery or hospitalization.
2. Patients with a history of trauma resulting in head injury related seizures, or with epilepsy (except a prior history of febrile seizures of infancy which are not exclusionary).
3. Pregnant or lactating women or those of childbearing potential not using medically accepted forms of contraception will be excluded.
4. Concurrent use of other antidepressants, benzodiazepines or antipsychotic medications.
5. Patients with a history of hypersensitivity to escitalopram are excluded.
6. Individuals must have discontinued MAO inhibitors more than 14 days before starting study drug.
7. Additional contraindicated drugs during the study are pimozide, furazolidine, isocarboxazid, lazabemide, and St. John's Wort.
8. Participants meeting DSM-IV or SCID criteria for a substance use disorder in the last six months other than nicotine dependence and those with a positive toxicology screen at baseline consistent with evidence of current substance abuse or dependence as determined by clinical interview.
9. A lifetime history of Bipolar or any psychotic disorder is excluded.
10. Current claustrophobia is exclusionary.
11. Patients currently taking any narcotic will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active medication; Escitalopram 10mg/day	Drug: Escitalopram; Escitalopram 10mg/day or matched pill placebo
Placebo Comparator: Placebo; Matched pill placebo	Drug: Escitalopram; Escitalopram 10mg/day or matched pill placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4	Three-way interaction between group (active vs. placebo), CS (+ vs. -), and trials (1 - 4). CS+ refers to the conditioned stimulus associated with the unconditioned stimulus (electric shock). Higher numbers reflect higher skin conductance response to the CS+ (conditioned stimulus). CS- refers to the stimulus not associated with the unconditioned stimulus. Higher numbers reflect higher skin conductance response to a CS-. Square-root transformed skin conductance conditioned response are reported for trials 1 to 4 of the Early Extinction Phase.	Day 2 of Fear Conditioning Paradigm (15 to 18 days post medication initiation)
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5	Three-way interaction between group (active vs. placebo), CS (+ vs. -), and trials (1 - 5). CS+ refers to the conditioned stimulus associated with the unconditioned stimulus (electric shock). Higher numbers reflect higher skin conductance response to the CS+ (conditioned stimulus). CS- refers to the stimulus not associated with the unconditioned stimulus. Higher numbers reflect higher skin conductance response to a CS-. Square-root transformed skin conductance conditioned response are reported for trials 1 to 5 of the Acquisition Phase.	Baseline on Day 1 of Fear Conditioning Paradigm (14 to 17 days post medication initiation)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Naomi M Simon, M.D., M.Sc., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: July 12, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 2011

Study Record Updates

• Last Update Posted (Estimate): June 11, 2014
• Last Update Submitted That Met QC Criteria: June 5, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: 2008-P-001314