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Sertraline Compared With Hypericum Perforatum (St.John's Wort) in Treating Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00066859
Recruitment Status : Completed
First Posted : August 7, 2003
Last Update Posted : November 29, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:

RATIONALE: Antidepressants such as sertraline and the herb hypericum perforatum (St. John's wort) may be effective in treating mild to moderate depression. It is not yet known which treatment is more effective in improving depression in patients who have cancer.

PURPOSE: This randomized phase III trial is studying how well sertraline works compared to St. John's wort in treating mild to moderate depression in patients with solid tumors.

Condition or disease Intervention/treatment Phase
Depression Unspecified Adult Solid Tumor, Protocol Specific Drug: Zoloft 50 mg Dietary Supplement: St. John's Wort 600 mg Phase 3

Detailed Description:


  • Compare the change in depression severity in cancer patients with mild to moderate depression treated with sertraline vs Hypericum perforatum.
  • Compare the severity of somnolence, nausea, and insomnia in patients treated with these regimens.
  • Compare the impact of these regimens on fatigue in these patients.
  • Correlate hyperforin concentrations with change in depression severity in patients treated with Hypericum perforatum.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to level of depression (mild vs moderate), concurrent radiotherapy (yes vs no), and TNM stage (I, II, or III vs IV). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral sertraline daily.
  • Arm II: Patients receive oral Hypericum perforatum daily. In both arms, treatment continues for 4 months in the absence of unacceptable toxicity.

Measurements of depression, somnolence, nausea, insomnia, fatigue, and hyperforin concentration are assessed at baseline, and at 1, 2, and 4 months.

PROJECTED ACCRUAL: A maximum of 250 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Phase III Double-Blind Randomized Trial Comparing Sertraline (Zoloft) And Hypericum Perforatum (St. John's Wort) In Cancer Patients With Mild To Moderate Depression
Study Start Date : March 2004
Actual Primary Completion Date : April 2005
Actual Study Completion Date : November 2005

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Arm 1: Sertraline (Zoloft) 50 mg
Zoloft 50 mg by mouth daily for 1 week if tolerated dose may be increased to 100 mg daily for 4 months
Drug: Zoloft 50 mg
Zoloft 50 mg by mouth daily for 1 week if tolerated dose may be increased to 100 mg daily for 4 months
Other Names:
  • Sertraline
  • Zoloft

Active Comparator: Arm 2 - St. John's Wort 600mg
St. John's wort 600 mg daily for 1 week. If tolerated dose may be increased to 900 mg daily for four months.
Dietary Supplement: St. John's Wort 600 mg
St. John's wort 600 mg daily for 1 week, if tolerated. Dose may be increased to 900 mg daily for 4 months.
Other Name: Hypericum perforatum

Primary Outcome Measures :
  1. Depression severity as measured by Hamilton Depression rating scale. [ Time Frame: 4 months ]
    To compare the change in depression severity in cancer patients with mild to moderate depression on sertraline and St. John's wort.

Secondary Outcome Measures :
  1. Somnolence, nausea, and insomnia as assessed by the NCI Common Toxicity Criteria. The Epworth Sleepiness Scale will also be used to assess somnolence. [ Time Frame: 4 months ]
  2. Fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. [ Time Frame: 4 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Mild or moderate depression as determined by the following criteria (see Section 7.1 and 8.0)
  • Mild : HRSD score 10-14; moderate: HRSD score 15-19 (Appendix IV)
  • At least 2 of nine symptoms of depression on the PHQ (Appendix V)
  • At least one of the nine PHQ symptoms must be either depressed/irritable mood or anhedonia
  • Histologically or cytologically documented solid tumor, lymphoma, or primary or metastatic brain tumor > 6 months from radiation with stable disease or no evidence of disease.
  • Concurrent cancer chemotherapy with sertraline or St. John's wort is not allowed, therefore patients must have no plan for chemotherapy for 4 months
  • Prior chemotherapy is allowed, but patients must be >4 weeks from prior chemotherapy except >6 weeks from prior mitomycin-C or nitrosourea
  • Patients receiving Rituxin, Herceptin, Erbitux, Interferon, etc. are eligibile for this study while under treatment.
  • Prior or concurrent radiation is allowed except brain irradiation for brain metastases or primary brain tumor. Must be > 6 months from radiation with stable disease or no evidence of disease.
  • Age > 18 years
  • ECOG performance status 0 -1 (Appendix III)
  • Life expectancy >4 months
  • Required initial laboratory values (within 3 days of registration): hemoglobin >10 g/dl and bilirubin <1.5 mg/dl, negative pregnancy test
  • Signed protocol specific informed consent prior to registration
  • Patient recruitment this study will be done through the out patient clinic. The research PI or designee including clinic physician, resident, research nurse or research assistant will review medical information to determine or verify protocol eligibility either at the time the patient is being seen in the clinic for a routine visit/consult or prior to the patient's clinic visit.


  • A patient will be excluded if he/she is (a) judged to be severely depressed using the following criteria: HRSD score 20 or more or a positive score on PHQ item i (suicidal ideation) or (b) judged not to be depressed by a score of 9 or less on the HRSD or fewer than two PHQ items scored positively. A patient who is found to be severely depressed or suicidal, either on initial screening or during the trial will be referred for appropriate treatment.
  • Psychotic symptoms, dementia, marked agitation requiring medication
  • Current or previous alcohol or drug dependence
  • Hematologic malignancy (i.e., leukemias, multiple myeloma)
  • Planned chemotherapy in the next 4 months
  • Antidepressant or St. John's wort use in the last 4 weeks
  • Current or planned use of erythropoietin (Procrit®, Aranesp®)
  • Current or planned use of theophylline, warfarin (except for central line prophylaxis), protease inhibitors used to treat AIDS, digoxin, cyclosporin, benzodiazepines (such as diazepam, alprazolam, etc), calcium-channel blockers (such as diltiazem, nifedipine, etc), coenzyme A reductase inhibitors (cholesterol lowering agents), macrolide antibiotics (such as azithromycin, erythromycin, clarithromycin, etc), griseofulvin, phenobarbital, phenytoin, rifampin, rifabutin, ketoconazole, fluconazole, itraconazole, corticosteroids, grapefruit juice, or other naturopathic/herbal products that could interfere with St. John's wort (call study chairman with questions).
  • Pregnant or nursing women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00066859

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United States, California
Bay Area Tumor Institute
Oakland, California, United States, 94609-3305
United States, Georgia
Regional Radiation Oncology Center at Rome
Rome, Georgia, United States, 30165
United States, Illinois
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
United States, North Carolina
CCOP - Southeast Cancer Control Consortium
Goldsboro, North Carolina, United States, 27534-9479
High Point Regional Hospital
High Point, North Carolina, United States, 27261
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
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Principal Investigator: Antonius A. Miller, MD Wake Forest University Health Sciences
Study Chair: Edward G. Shaw, MD Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences Identifier: NCT00066859    
Other Study ID Numbers: REBACCCWFU-98101
U10CA081851 ( U.S. NIH Grant/Contract )
First Posted: August 7, 2003    Key Record Dates
Last Update Posted: November 29, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Wake Forest University Health Sciences:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
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Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs