Effects of Cognitive Behavioral Therapy on Brain Serotonin Activity in People With Depression

Phase 2

Completed

Conditions: Depression

Interventions: Drug: ADAM SPECT plus No Therapy
Drug: ADAM SPECT plus Cognitive Therapy

Registration Number: NCT00641108

Lead Sponsor: University of Pennsylvania

Brief Summary: This study will examine changes in brain serotonin activity in people with depression before and after they receive cognitive behavioral therapy.

Detailed Description: Depression is a serious illness that affects almost 19 million adults in the United States each year. Common symptoms of depression include persistent feelings of anxiety, guilt, or hopelessness; irregular sleep and appetite patterns; lethargy; disinterest in previously enjoyed activities; excessive irritability and restlessness; suicidal thoughts; and inability to concentrate. A person's depression can be attributed to a variety of causes, including biological and genetic factors, environmental influences, or developmental experiences. Among biological factors, a recently researched possible cause is the altered activity of specialized areas on brain nerve cells called serotonin receptors, which have been found to be at reduced levels in people with depression. The hormone serotonin is known to naturally influence mood, making depression treatments that aim to increase levels of serotonin important. Treatment for depression with cognitive behavioral therapy (CBT), which teaches ways to modify thoughts and behaviors that contribute to depression, may help in raising brain serotonin levels and in improving depressive symptoms. This study will examine changes in brain serotonin activity using single photon emission computed tomography (SPECT) imaging in people with depression before and after they receive CBT. The study will also use SPECT imaging to compare brain serotonin activity of non-depressed healthy participants with that of depressed participants.

Participation in this study will last between 12 and 14 weeks. All participants will first undergo an initial evaluation that will include questions about medical history, a physical exam, a blood draw, a urine test, and an electrocardiogram (ECG). Participants will then undergo an ADAM (a selective radioligand for SPECT imaging) SPECT scan. During the ADAM SPECT scan visit, participants will undergo an injection of the ADAM, an ECG, blood pressure monitoring, and a 60-minute SPECT scan. If necessary, participants may also be asked to have a magnetic resonance imaging (MRI) brain scan after completing the SPECT scan.

Depressed participants will then attend at least once weekly CBT sessions for 12 weeks. During the 45-minute sessions, participants will meet with a therapist to learn ways to adjust thoughts and behaviors that may be adding to their depression. After completing the 12 weeks of CBT, all participants will be re-evaluated by a study doctor and, if still in good health, will undergo a repeat ADAM SPECT scan.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

DSM-IV diagnosis of major depressive disorder (MDD)
Drug naive from prior psychotropic medication for more than 6 months before study entry
Hamilton-Depression (HAM-D) 17 score greater than or equal to 16
Woman of childbearing age with a negative pregnancy test within 48 hours of scanning

Exclusion Criteria

DSM-IV Axis I diagnosis other than MDD
Use of psychotropic medication within 6 months of study entry
History of bipolar disorder
Current alcohol or drug abuse/dependence within 6 months of study entry
History of sensitivity or intolerance to s-citalopram
Medical contraindication to the use of s-citalopram
Unstable medical condition (e.g., angina pectoris, untreated hypertension)
Pregnant or nursing
Woman of childbearing potential not using a medically acceptable form of birth control
Actively suicidal or requiring hospitalization
Requiring additional psychotropic drug therapy
History of transient ischemic attacks
History of cerebral infarction (including lacunar infarct with symptoms more than 24 hours in duration)
History of Binswanger's disease or a history of hypertensive encephalopathy
History of intracranial hemorrhage
History of head trauma with loss of consciousness
History of encephalitis
History of extended exposure to known neurotoxin (e.g., cyanide, carbon monoxide)
Uncontrolled metabolic disorder (e.g., thyroid disease, diabetes mellitus)
History of cognitive impairment other than major depressive episode
History of normal pressure hydrocephalus
History of cancer metastatic to the central nervous system
History of Parkinson's or other basal ganglia disease
History of Guillain-Barré syndrome (chronic or relapsing polyneuropathy)
Inability to undergo an MRI scan

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	ADAM SPECT plus No Therapy	Healthy subjects without depression will undergo ADAM SPECT scans.
ADAM SPECT	ADAM SPECT plus Cognitive Therapy	Participants with depression will undergo ADAM SPECT scans and cognitive behavioral therapy.

Primary Outcome Measures