Neurotrophic Factors and Depression (Lex/BDNF)

Blood Levels of Neurosteroids and Neurotrophic Factors in Normal Controls and in Patients With Major Depression

Study intended to determine if there are baseline differences in serum neurosteroid levels and neurotrophic factor (BDNF) levels in healthy controls vs unmedicated depressed subjects, and whether the levels of these change with antidepressant treatment. Study also intended to determine if baseline neurosteroid/ BDNF levels, and the change in these levels with =treatment, are correlated with clinical antidepressant response to escitalopram (Lexapro).

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Drug: Placebo; Drug: Escitalopram

Detailed Description

The study was approved by the UCSF Committee on Human Research, and all participants gave informed consent. The depressed subjects began treatment with placebo for one week, followed by escitalopram for eight weeks (10 mg per day x 4 weeks, followed by 20 mg per day x 4 weeks, as tolerated) in a double-blind, fixed-order, within-subject cross-over manner. The depressed subjects and the psychiatric rater were unaware of the study design and the sequence and duration of treatments. Depressed and control subjects underwent venipuncture to obtain blood for assays. The controls underwent venipuncture once, and the depressed subjects had venipuncture just prior to beginning active escitalopram treatment and again after 8 weeks of escitalopram treatment. Blood was also collected at Weeks 4 and 8 of treatment in the depressed subjects for assay of citalopram and citalopram metabolites, to gauge medication compliance. Finally, depression severity and global clinical change were assessed in the depressed subjects at Baseline and at the end of Week 8 of escitalopram treatment.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF
    • San Francisco, California, United States, 94143-0984
      • University of California San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Male subjects with unipolar Major Depressive Disorder (DSM-IV) with a minimum score of 22 on the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) who were medication-free for at least 6 weeks, were enrolled. Fifteen individually age-matched (+ 3 years) healthy male controls with no history of psychiatric illness were also enrolled. Subjects' ages ranged from 22- 55 y.o. (mean + S.D.= 41.4 + 8.75 y.o.). All subjects were required to pass a urine toxicology screen (assessing the presence of drugs of abuse) on the day of testing.

Exclusion Criteria:

Individuals with co-morbid panic disorder were excluded, since they may poorly tolerate typical starting doses of antidepressants , and individuals with co-morbid post-traumatic stress disorder were excluded, since they may have neuroendocrine regulatory responses different from those of depressed subjects without PTSD. Exclusion criteria for both groups included recent (within 6 months) alcohol or drug abuse as defined by DSM-IV criteria, concurrent psychotherapeutic interventions, poor medical health or abnormal clinical labs, active suicidality, and use of medications that could interfere with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
EXPERIMENTAL: Escitalopram	Drug: Escitalopram; SSRI antidepressant; Other Names: Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum BDNF levels	Baseline, week 4, week 8
Serum allopregnanolone levels	Baseline, week 4, week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Montgomery-Asberg Depression Rating Scale	baseline, week 4, week 8
Clinical Global Impression	Baseline, week 4, week 8

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Owen M Wolkowitz, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (ACTUAL): December 1, 2006
• Study Completion (ACTUAL): November 1, 2008

Study Registration Dates

• First Submitted: December 19, 2008
• First Submitted That Met QC Criteria: December 19, 2008
• First Posted (ESTIMATE): December 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 22, 2008
• Last Update Submitted That Met QC Criteria: December 19, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Depression; BDNF; allopregnanolone; neurotrophic factor; neurosetroid
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; 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: H3097-19671-08