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.

Condition	Treatment or Intervention
Major depression	Drug: Sertraline  Drug: Hypericum perforatum (St. John's wort)

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

Inclusion Criteria: 1. Major depression assessed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID; First et al, 1995); 2. Minimum score greater than or equal to 20 on the 17-item Hamilton Depression (HAM-D) Scale at screen and at baseline; 3. GAF of 60 or less (moderate symptoms) at screen and at baseline; 4. HAM-D cannot decrease by 25% or more between screening and baseline; 5. Capacity to give informed consent and to follow study procedures.

• Not breast-feeding
• Abstinence or effective method of birth control / contraception including oral contraceptives during the study
• Not pregnant

Exclusion Criteria:

Exclusion Criteria: 1. Higher than "2" on the "suicide" item of HAM-D, or history of suicide attempt(s) in the past 12 months, or who, in the investigator's judgment, poses a current suicidal or homicidal risk. 2. 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. 3. 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). 6. Any of the following DSM-IV diagnoses by SCID: a) current (within past 6 months) alcohol or other substance abuse disorder; b) schizophrenia, schizo-affective, or other psychotic disorder; c) bipolar disorder; d) current panic disorder or obsessive compulsive disorder; e) history of psychotic features of affective disorder (mood congruent or incongruent). 7. Clinical or laboratory evidence of untreated or unstable thyroid disorder. 8. Patients who have 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. 9. Patients who, during this current episode of depression, have taken sertraline or any form of hypericum, at any dose level, daily, for at least one month, within the past 6 months. 10. 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). 11. Patients who have had other investigational drugs within 30 days or other psychotropic medication within 21 days of baseline (6 weeks for fluoxetine). 12. Patients with a known allergy or hypersensitivity to the study medications. 13. Positive drug urine screen. 14. Patients who have been in psychotherapy for 2 months or less at the time of enrollment into the study. Patients who are receiving psychotherapies which are specifically designed to treat depression, eg, interpersonal psychotherapy during the study period. 15. Patients with mental retardation or cognitive impairment, or any disorder that might interfere with their ability to consent or follow study procedures and requirements.

California
      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
Florida
      Univ of South Florida College of Med, Tampa,  Florida,  33613,  United States
Georgia
      Emory Mood and Anxiety Disorders Clinical Trials Program, Atlanta,  Georgia,  30329,  United States
Massachusetts
      McLean Hospital, Belmont,  Massachusetts,  02478,  United States
New York
      Eastside Comprehensive Medical Services, New York,  New York,  10021,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      Univ of Cincinnati Medical Ctr, Cincinnati,  Ohio,  45267,  United States
Texas
      Univ of Texas Southwestern Med Ctr, Dallas,  Texas,  75235,  United States
Washington
      Seattle Clinical Research Center, Seattle,  Washington,  98104,  United States
Wisconsin
      Dean Foundation for Hlth Rsch and Education, Middleton,  Wisconsin,  53562,  United States

Study chairs or principal investigators

Jonathan Davidson,  Principal Investigator,  Duke Univ Med Ctr   

Study ID Numbers:  N01-MH-70007A
Record last reviewed:  July 2000
Last Updated:  October 13, 2004
Record first received:  March 31, 2000
ClinicalTrials.gov Identifier:  NCT00005013
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08