Treatment of Major Depression With St. John's Wort (Hypericum)

April 7, 2014 updated by: National Institute of Mental Health (NIMH)

A Placebo Controlled Clinical Trial of a Standardized Extract of Hypericum Perforatum in Major Depressive Disorder

The purpose of this trial is to study the acute efficacy and safety of a standardized extract of the herb Hypericum perforatum (St. John's Wort), called hypericum for purposes of this trial, in the treatment of patients with major depression.

Clinical depression is a serious medical disorder that can be debilitating and can lead to suicide. There is growing public interest in claims that hypericum may be an effective treatment for depression. Although it is widely prescribed in Europe, no studies of its long-term use have been conducted, and published studies have treated different types of patients and have used several different doses. The toxicity and side effects of hypericum appear to be substantially less than those of standard tricyclic antidepressant medications, and thus hypericum may be more acceptable to patients. In addition, the cost is significantly less than standard antidepressant medications. Published studies assessed acute efficacy and lasted between 4 and 12 weeks (most being 4-6 weeks). The longer-term effects of hypericum have not been evaluated. There is a need for a large-scale, controlled clinical trial to assess whether Hypericum has a significant therapeutic effect in patients with clinical depression.

Patients are assigned randomly (like tossing a coin) to receive St. John's wort, Sertraline (Zoloft), or a placebo (sugar pill) for 8 weeks. This is a double-blind study, meaning neither the patient nor the doctor will know which treatment is being assigned. Patients who respond well to the treatment will continue on the assigned treatment for an additional 4 months. Patients will have regular follow-up visits to monitor their symptoms and any side effects they experience.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This trial will determine the acute antidepressant efficacy of a standardized extract of hypericum (St. John's Wort) for the treatment of major depressive disorder.

For this trial, the primary efficacy analysis will be evaluated at 8 weeks. For observational purposes, a 4-month double blind continuation (6 months total treatment) in treatment responders would enable an approximation of the effectiveness of maintenance treatment with this medication. No published studies have included a selective serotonin re-uptake inhibitor (SSRI) comparator. While this trial will not compare the efficacy of hypericum to an SSRI, having an SSRI arm of sertraline (Zoloft) will allow an evaluation of the validity of the trial.

336 eligible patients will be randomly assigned to double-blind treatment with hypericum, sertraline, or placebo following a one-week placebo lead-in period (between screening and baseline). All treatment groups will consist of 112 patients and will be followed for an eight-week period. Treatment responders will be continued on the randomly assigned treatment arm for an additional 18 weeks.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92121
        • Feighner Research Institute
      • Stanford, California, United States, 94305
        • Stanford Univ School of Medicine
      • Torrance, California, United States, 90502
        • Harbor-UCLA Rsch and Education Inst
    • Florida
      • Tampa, Florida, United States, 33613
        • Univ of South Florida College of Med
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory Mood and Anxiety Disorders Clinical Trials Program
    • Massachusetts
      • Belmont, Massachusetts, United States, 02478
        • McLean Hospital
    • New York
      • New York, New York, United States, 10021
        • Eastside Comprehensive Medical Services
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Univ Med Ctr
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Univ of Cincinnati Medical Ctr
    • Texas
      • Dallas, Texas, United States, 75235
        • Univ of Texas Southwestern Med Ctr
    • Washington
      • Seattle, Washington, United States, 98104
        • Seattle Clinical Research Center
    • Wisconsin
      • Middleton, Wisconsin, United States, 53562
        • Dean Foundation for Hlth Rsch and Education

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Major depression assessed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID; First et al, 1995)
  • Minimum score greater than or equal to 20 on the 17-item Hamilton Depression (HAM-D) Scale at screen and at baseline
  • GAF of 60 or less (moderate symptoms) at screen and at baseline
  • HAM-D cannot decrease by 25% or more between screening and baseline
  • Capacity to give informed consent and to follow study procedures.
  • Abstinence or effective method of contraception throughout the study

Exclusion Criteria:

  • Scores greater than 2 on the "suicide" item of HAM-D, or history of suicide attempt(s) in the past 12 months
  • Current suicidal or homicidal risk, as determined by the investigator
  • Women of childbearing age who are pregnant, planning pregnancy in the next 6 months, breast-feeding, or not using medically acceptable means of birth control (hormonal treatment such as birth control pill, injection or implant, IUD, or double barrier of condom and diaphragm together is acceptable; primary use of condom, sponge or diaphragm alone (single barrier) is not acceptable because these may carry a higher rate of failure when used alone
  • Clinically significant liver disease (such as hepatitis, cirrhosis, etc); or clinically significant elevation of liver enzyme tests (two times the upper limit of normal; asymptomatic Gilbert's syndrome is not an exclusion). 4. Serious or unstable medical illness. 5. History of seizure disorder (other than febrile).
  • Any of the following DSM-IV diagnoses by SCID: current (within past 6 months) alcohol or other substance abuse disorder; schizophrenia, schizo-affective, or other psychotic disorder; bipolar disorder; current panic disorder or obsessive compulsive disorder; history of psychotic features of affective disorder (mood congruent or incongruent)
  • Clinical or laboratory evidence of untreated or unstable thyroid disorder
  • Failed to respond to at least two adequate antidepressant trials (defined as 6 weeks or more treatment with either greater than or equal to 150 mg imipramine, or tricyclic equivalent), or greater than or equal to 60 mg of phenelzine, or MAOI equivalent, or greater than or equal to 100 mg of sertraline, or its SSRI equivalent
  • Have taken sertraline or any form of hypericum during this current episode of depression at any dose level, daily, for at least one month, within the past 6 months
  • Current (within past 6 months) use of other prescription or non-prescription drugs, including anticonvulsants and other medications with significant psychotropic properties, antiretroviral medications, cyclosporine, digoxin, coumadin, dietary supplements, natural remedies, and botanical preparations (eg, hypericum, kava, valerian)
  • Have had other investigational drugs within 30 days or other psychotropic medication within 21 days of baseline (6 weeks for fluoxetine)
  • Known allergy or hypersensitivity to the study medications
  • Positive drug urine screen
  • Have been in psychotherapy for 2 months or less at the time of enrollment into the study
  • Receiving psychotherapies which are specifically designed to treat depression, eg, interpersonal psychotherapy during the study period
  • Mental retardation or cognitive impairment, or any disorder that might interfere with their ability to consent or follow study procedures and requirements

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Mental Health (NIMH)

Collaborators

National Center for Complementary and Integrative Health (NCCIH)

Investigators

  • Principal Investigator: Jonathan Davidson, Duke Univ Med Ctr

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1998

Study Completion (Actual)

July 1, 2001

Study Registration Dates

First Submitted

March 31, 2000

First Submitted That Met QC Criteria

March 31, 2000

First Posted (Estimate)

April 3, 2000

Study Record Updates

Last Update Posted (Estimate)

April 8, 2014

Last Update Submitted That Met QC Criteria

April 7, 2014

Last Verified

March 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N01 MH70007
  • DSIR CT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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