Drug Therapy to Treat Minor Depression

Pharmacotherapy for Minor Depression

This 6-month study will compare the effectiveness of citalopram (Celexa®), hypericum (St. John's Wort), and placebo for the treatment of minor depression.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Drug: Citalopram; Drug: St. John's Wort; Drug: Placebos

Detailed Description

Minor depression is highly prevalent, causes substantial morbidity and disability, presents a serious risk factor for the development of major depressive disorder, yet is under recognized and under treated. Researchers have determined that patients with minor depression frequently seek treatment from general practitioners and are often treated with prescription antidepressants. There is a need to evaluate the effectiveness of St. John's Wort in the management of minor depression. If the proposed study demonstrates the efficacy of St. John's Wort and/or citalopram, it will suggest treatment paradigms that can be tested and applied in primary care settings.

Subjects participated in a 12-week double-blind randomized study comparing St. John's Wort, citalopram, and placebo. Subjects were recruited through clinical referrals and community advertising. Data were obtained at the baseline visit (just prior to randomization) and at postrandomization visits conducted at 2-week intervals for the next 12 weeks, for a modified intent-to-treat sample consisting of all 73 subjects with at least 1 post-randomization visit (evaluable sample).

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh, Western Psychiatric Institute and Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Minor Depression symptoms for at least 6 months
• Endorse one of the DSM-IV "A" criteria for MDD and at least one other symptom of MDD or endorse both of the "A" criteria for MDD
• Global Assessment of Functioning (GAF) score < 70
• Short form health survey (SF-36) social functioning score <= 75% or an emotional role functioning score <= 67%
• HAM-D-17 score 10-17, inclusive
• Minor depression symptoms for at least 6 months

Exclusion Criteria:

• Major depressive disorder (MDD) or dysthymia within the past year or in partial remission of MDD
• At least a 12-week course of either citalopram at a minimum or 40 mg/day or St. John's Wort at a minimum of 900 mg/day during the current episode of depression
• Previous intolerance to either citalopram or St. John's Wort or history of nonresponse to either citalopram at a minimum of 40 mg/day or St. John's Wort at a minimum of 900 mg/day for at least 12 weeks
• Unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease
• Uncontrolled seizure disorder
• The following DSM-IV diagnoses: organic mental disorders; substance use disorders, including alcohol, active within the last year or patients with a positive urine drug screen; schizophrenia; delusional disorder; psychotic disorders not elsewhere classified; bipolar disorder; bereavement; adjustment disorder; antisocial personality disorder; panic disorder, social phobia, generalized anxiety disorder (GAD), or obsessive compulsive disorder (OCD). Patients may have a lifetime diagnosis of an anxiety disorder as long as it is not current.
• Mood-congruent or mood-incongruent psychotic features
• Psychotropic drugs
• Hypothyroidism
• Investigational psychotropic drugs within the last year
• Positive toxicology screen
• Medications metabolized by the CYP3A4 system, where induction of this system poses a risk to the medical stability of the patient
• Pregnancy or refusal to use a medically accepted method of contraception
• Serious suicide or homicide risk
• Psychotherapy beginning less than 3 months ago

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: citalopram; Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.	Drug: Citalopram; Established Selective Serotonin Reuptake Inhibitor antidepressant; Other Names: Celexa, Cipramil
Experimental: St. John's Wort; Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.	Drug: St. John's Wort; Natural extract from the St. John's Wort plant.; Other Names: Hypericum
Placebo Comparator: Placebo; Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.	Drug: Placebos; Placebo pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)	We expect that subjects with minor depression treated for 12 weeks with St. John's Wort or citalopram will have significantly greater reduction in depressive symptom severity than those treated with placebo. This will be measured by blind ratings on the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) which has a total score range from 0 to 84 with 0 being not depressed at all and 84 being the most depressed. The change will be calculated by subtracting the Week 12 score from the Baseline score.	Change from Baseline to Week 12
Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment	We expect that subjects treated for Minor Depression for 12 weeks with either St. John's Wort or citalopram will have similar safety profiles to subjects treated with placebo, and will not differ by more than 20% in rates of adverse side effects (e.g., nausea, headache, insomnia, hypersomnia, diarrhea) from subjects treated with placebo. This was measured by the number of adverse events (physical symptoms) emerging or worsening during 12 weeks of treatment.	Change from Baseline to Week 12

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Mental Health (NIMH); National Center for Complementary and Integrative Health (NCCIH); Office of Dietary Supplements (ODS)

Publications and helpful links

Helpful Links

• Click here to view the "Treatment for Minor Depression" NIH news release.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: November 8, 2002
• First Submitted That Met QC Criteria: November 12, 2002
• First Posted (Estimate): November 13, 2002

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Minor Depression; St. John's Wart
• 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: R01MH061758 (U.S. NIH Grant/Contract); DSIR AT-SO (NorthShore LIJ Health System); R01MH061757 (U.S. NIH Grant/Contract); R01MH061394 (U.S. NIH Grant/Contract)