Treatment of Major Depression With St. John's Wort (Hypericum)
A Placebo Controlled Clinical Trial of a Standardized Extract of Hypericum Perforatum in Major Depressive Disorder
2 other identifiers
interventional
N/A
1 country
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Dec 1998
Typical duration for not_applicable
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 1998
CompletedFirst Submitted
Initial submission to the registry
March 31, 2000
CompletedFirst Posted
Study publicly available on registry
April 3, 2000
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2001
CompletedApril 8, 2014
March 1, 2006
March 31, 2000
April 7, 2014
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Feighner Research Institute
San Diego, California, 92121, United States
Stanford Univ School of Medicine
Stanford, California, 94305, United States
Harbor-UCLA Rsch and Education Inst
Torrance, California, 90502, United States
Univ of South Florida College of Med
Tampa, Florida, 33613, United States
Emory Mood and Anxiety Disorders Clinical Trials Program
Atlanta, Georgia, 30329, United States
McLean Hospital
Belmont, Massachusetts, 02478, United States
Eastside Comprehensive Medical Services
New York, New York, 10021, United States
Duke Univ Med Ctr
Durham, North Carolina, 27710, United States
Univ of Cincinnati Medical Ctr
Cincinnati, Ohio, 45267, United States
Univ of Texas Southwestern Med Ctr
Dallas, Texas, 75235, United States
Seattle Clinical Research Center
Seattle, Washington, 98104, United States
Dean Foundation for Hlth Rsch and Education
Middleton, Wisconsin, 53562, United States
Related Publications (6)
Hypericum Depression Trial Study Group; Davidson JR, Gadde KM, Fairbank JA, Krishnan KRR, Califf RM, Binanay C, Parker CB, Pugh N, Hartwell TD, Vitiello B, Ritz L, Severe J, Cole JO, de Battista C, Doraiswamy PM, Feighner JP, Keck P, Kelsey J, Lin KM, Londborg PD, Nemeroff CB, Schatzberg AF, Sheehan DV, Srivastava RK, Taylor L, Trivedi MH, Weisler RH. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002 Apr 10;287(14):1807-14. doi: 10.1001/jama.287.14.1807.
PMID: 11939866RESULTVitiello B, Shader RI, Parker CB, Ritz L, Harlan W, Greenblatt DJ, Gadde KM, Krishnan KR, Davidson JR. Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial. J Clin Psychopharmacol. 2005 Jun;25(3):243-9. doi: 10.1097/01.jcp.0000162801.72002.85.
PMID: 15876903RESULTChen JA, Vijapura S, Papakostas GI, Parkin SR, Kim DJ, Cusin C, Baer L, Clain AJ, Fava M, Mischoulon D. Association between physician beliefs regarding assigned treatment and clinical response: re-analysis of data from the Hypericum Depression Trial Study Group. Asian J Psychiatr. 2015 Feb;13:23-9. doi: 10.1016/j.ajp.2014.12.002. Epub 2014 Dec 9.
PMID: 25544195DERIVEDGrobler AC, Matthews G, Molenberghs G. The impact of missing data on clinical trials: a re-analysis of a placebo controlled trial of Hypericum perforatum (St Johns wort) and sertraline in major depressive disorder. Psychopharmacology (Berl). 2014 May;231(9):1987-99. doi: 10.1007/s00213-013-3344-x.
PMID: 24232445DERIVEDSarris J, Fava M, Schweitzer I, Mischoulon D. St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry. 2012 Nov;45(7):275-8. doi: 10.1055/s-0032-1306348. Epub 2012 May 16.
PMID: 22592504DERIVEDChen JA, Papakostas GI, Youn SJ, Baer L, Clain AJ, Fava M, Mischoulon D. Association between patient beliefs regarding assigned treatment and clinical response: reanalysis of data from the Hypericum Depression Trial Study Group. J Clin Psychiatry. 2011 Dec;72(12):1669-76. doi: 10.4088/JCP.10m06453. Epub 2011 Oct 4.
PMID: 22053942DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jonathan Davidson
Duke Univ Med Ctr
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Sponsor Type
- NIH
Study Record Dates
First Submitted
March 31, 2000
First Posted
April 3, 2000
Study Start
December 1, 1998
Study Completion
July 1, 2001
Last Updated
April 8, 2014
Record last verified: 2006-03