Effects of Paxil CR on Neural Circuits in Posttraumatic Stress Disorder (PTSD)

Effects of Paxil CR on Neural Circuits in PTSD

Posttraumatic stress disorder (PTSD) is a major public health problem in this country. It is estimated that at least one out of every seven women in our society have been the victim of childhood sexual abuse at least once before their 18th birthday. Previous studies have shown that stress is associated with damage to neurons of the hippocampus, a brain area involved in learning and memory. Also, imaging studies of brain function are consistent with dysfunction of the medial prefrontal cortex during presentation of traumatic cues. We have previously shown that serotonin reuptake inhibitor medications (paroxetine; Paxil) can change memory function and hippocampal structure in PTSD. We now propose to perform a placebo controlled study with Paxil CR (paroxetine hydrochloride controlled-release tablets), which is thought as paroxetine with less side-effects. The main purpose of this study is to determine the effects of Paxil CR on memory deficits measured with neuropsychological testing, hippocampal volume measured with a magnetic resonance imaging (MRI), medial prefrontal lobe cortical function estimated with PET, and cortisol response (reflecting the intensity of stress) in men and women with PTSD. We plan to recruit 40 subjects. After completing physical examination and evaluating neuropsychiatric history, patients will undergo an initial group of tests which includes memory testing, MRI and PET brain scan, and measurement of cortisol in their saliva. Afterwards, half will receive Paxil CR 12.5 to 62.5 mg and half will receive a placebo (sugar pill) in the beginning of the first 12 weeks as "Double Blind Phase". After 12 weeks, they will be administered memory tests, PET and MRI scan for the post-treatment phase. After this period, Paxil CR will be offered to the placebo group and followed for an additional 12 weeks. They will have final memory tests, and a MRI scan. We hypothesize that Paxil CR exerts its efficacy by acting on abnormal neural circuits, including hippocampus and prefrontal cortex, in PTSD.

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder (PTSD)
• Intervention / Treatment: Drug: placebo; Drug: paroxetine

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria for PTSD assessed by the Structured Clinical Interview for DSM IV (SCID).
• All patients with PTSD will be greater than 18 years of age, and will be required to give informed consent.
• Patients will be recruited from newspaper advertisements and fliers.
• All patients must be free of major medical illness on the basis of history and physical examination, lab testing, and electrocardiogram, and must not be actively abusing substances or alcohol.
• Patients should be free of psychotropic medications for four weeks before the study.

Exclusion Criteria:

• Pregnant and breast-feeding women will not be studied. Female subjects will be required to have a negative pregnancy test before the study. Female subjects of childbearing age will be advised to use barrier contraception for the duration of the study, in addition to other forms of contraception that they may be using.
• Serious medical or neurological illness or a hypersensitivity to paroxetine.
• Past or present steroid use.
• Electroconvulsive therapy (ECT) within the 6 months prior to study entry.
• Organic mental disorders or epilepsy
• History of head trauma
• Cerebral infectious disease or dyslexia.
• History of psychosis, schizophrenia, or eating disorders.
• Active suicidality or homicidality

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2; placebo	Drug: placebo
EXPERIMENTAL: 1; paroxetine	Drug: paroxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Function with Traumatic Reminders	PET measurement of brain activation before and after paroxetine or placebo treatment.	three months

Collaborators and Investigators

• Sponsor: Emory University

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (ACTUAL): September 1, 2007
• Study Completion (ACTUAL): September 1, 2007

Study Registration Dates

• First Submitted: May 1, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (ESTIMATE): May 6, 2008

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: PTSD; paroxetine; stress; hippocampus
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: IRB00024970