• Compare the change in depression severity as measured by Hamilton Depression rating scale at 4 months
  

• Compare the severity of somnolence, nausea, and insomnia at 4 months
  
• Compare the impact of therapy at 4 months
  
• Correlate the hyperforin concentrations with the change in depression severity at 4 months
  

OBJECTIVES:

• 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.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor

  • No hematologic malignancy (e.g., leukemia, lymphoma, or multiple myeloma)

• Diagnosis of mild to moderate depression

  • No severe depression or suicidal ideation
• No psychotic symptoms, dementia, or marked agitation requiring medication
• No brain metastases or primary brain tumor

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 4 months

Hematopoietic

• Hemoglobin greater than 10 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior or concurrent alcohol abuse or drug dependence

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent epoetin alfa (e.g., Procrit® or Aranesp®)

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
• No concurrent chemotherapy

Endocrine therapy

• No concurrent corticosteroids

Radiotherapy

• Prior or concurrent radiotherapy allowed except brain irradiation for brain metastases or primary brain tumor

Surgery

• Not specified

Other

• More than 4 weeks since prior antidepressants or Hypericum perforatum
• No concurrent warfarin (central line prophylaxis allowed)

• No concurrent administration of any of the following:

  • Theophylline
  • Protease inhibitors used to treat AIDS
  • Digoxin
  • Cyclosporine
  • Benzodiazepines (e.g., diazepam or alprazolam)
  • Calcium-channel blockers (e.g., diltiazem or nifedipine)
  • Coenzyme A reductase inhibitors (cholesterol-lowering agents)
  • Macrolide antibiotics (e.g., azithromycin, erythromycin, or clarithromycin)
  • Griseofulvin
  • Phenobarbital
  • Phenytoin
  • Rifampin
  • Rifabutin
  • Ketoconazole
  • Fluconazole
  • Itraconazole
  • Grapefruit juice
  • Naturopathic/herbal products that would interfere with Hypericum perforatum