Effectiveness of Escitalopram in Preventing or Reducing Depressive Symptoms in People Receiving Interleukin-2 Treatment

Melanoma is the most serious type of skin cancer, affecting nearly 54,000 people in the
United States each year. Melanomas often develop in pre-existing moles or as new moles on the
body. If left untreated, the cancerous cells can spread throughout the body. Fortunately,
melanoma can be cured if a person is diagnosed and treated early. Typical treatments include
surgery, amputation, chemotherapy, and immunotherapy. Interleukin-2 (IL-2) treatment, a type
of immunotherapy, uses the body's immune system to slow or stop the spread of cancer cells to
other parts of the body. However, IL-2 treatment is typically associated with severe side
effects, including depression, fatigue, and difficulty thinking. This study will evaluate
whether escitalopram, an antidepressant, can help improve treatment-related depressive
symptoms, reduce stress hormone levels, and increase the number of treatment cycles among
people with metastatic melanoma who are receiving IL-2 treatment.

Participation in this double-blind study will last up to 18 weeks and will include 5 to 14
study visits. Participants will complete four 1-week cycles of IL-2 treatment over a 12-week
period. Two weeks prior to starting IL-2 treatment, participants will undergo a psychiatric
interview; a computerized thinking test; questionnaires; and blood, urine, and saliva
collection. Participants will also be randomly assigned to start receiving either
escitalopram or placebo for the entire duration of the study. The dosage of escitalopram or
placebo will vary depending on the symptom severity of each participant. Immediately prior to
IL-2 treatment, participants will undergo preliminary IL-2 procedures, which will include a
medical history review, physical exam, and blood collection. These same procedures will occur
every day that the participant is in the hospital for IL-2 treatment. Participants will stay
in the hospital when receiving all four IL-2 treatment cycles. During these hospital stays,
participants will complete repeat questionnaires and computerized tasks. Blood collection
will occur at selected times as well. A follow-up visit will occur 4 weeks after the final
treatment dose of IL-2.

Inclusion Criteria:

- Diagnosed with cancer and beginning Interleukin (IL)-2 treatment

- Willing to use an effective form of birth control throughout the study if sexually
active

Exclusion Criteria:

- Diagnosed with major depression or experiencing significant depressive symptoms or a
Hamilton Rating Scale-Depression score of 18 or higher

- Brain metastases, history of a brain injury, or seizure disorders

- Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for
substance abuse or dependence within 3 months of study entry

- Suicidal, psychotic, or received psychiatric hospitalization within 12 months of study
entry

- Past or current history of schizophrenia or bipolar disorder

- Pregnant or planning on becoming pregnant within 1 to 2 years

- Evidence of untreated or poorly controlled infectious, hormone, heart, blood, kidney,
liver, or neurological disease

- Use of antidepressants, glucocorticoids, guanethidine, centrally acting
alpha-antagonists, beta-blockers, or anticonvulsants

- Clinically significant eye abnormalities

- A score lower than 28 on the Mini Mental Status Exam (MMSE)

- Prior history of severe adverse events associated with escitalopram or other selective
serotonin reuptake inhibitor (SSRI) antidepressants

- Diagnosed with type 1 or type 2 diabetes

- Any condition that might make the participant unsuitable for enrollment or that could
interfere with study participation