Capuron, L., Gumnick, J. F., Musselman, D. L., Lawson, D. H., Reemsnyder, A., Nemeroff, C. B., . . . Miller, A. H. (2002). Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology, 26, 643–652.

Patients were given oral paroxetine/placebo 10 mg for one week pre-interferon treatment, paroxetine/placebo 20 mg during the first week of interferon treatment, and then paroxetine/placebo 20 to 40 mg for all subsequent weeks of interferon therapy. Total length of treatment with paroxetine was 12 weeks. The study was based on the hypothesis that, as a selective serotonin reuptake inhibitor (SSRI), paroxetine may improve the neuropsychiatric and neurovegetative symptoms associated with interferon-alpha treatment.

• The study included 38 patients (paroxetine group, n = 18; placebo group, n = 20); there were equal numbers of men and women.
• Mean age was 50 years (25–74).
• Most patients were married, and approximately 50% were college educated.
• Approximately 25% of the sample had a history of major depression.
• All patients were receiving a course of interferon-alpha consisting of 20 million units/m² five days per week for four weeks, followed by eight weeks of interferon-alpha at a dose of 10 million units/m² three days per week.

• Single site
• Major academic cancer center

Patients were undergoing the active treatment phase of care.

The study was a randomized, double-blind, placebo-controlled trial.

Neurotoxicity Rating Scale (NRS) was used to measure various depressive symptoms, cognitive disturbances, and vegetative symptoms, including fatigue.

When compared with the control group, pretreatment with paroxetine was effective in preventing interferon-induced mood and cognitive symptoms, as well improving pain. Paroxetine had less effect on the development of interferon-alpha–related neurovegetative symptoms, including fatigue, as measured by the NRS. Fatigue and somatic symptoms increased in both depressed and nondepressed patients.

Across the twelve weeks of the study, seven patients from the placebo group and one patient from the paroxetine group withdrew due to severe depression or neurotoxicity.

• The study had a small sample size.
• The study used an instrument with a single item to measure fatigue.
• The study used a wide, uncontrolled paroxetine dose range.
• The study excluded patients with a diagnosis of schizophrenia or bipolar disorder; a Mini-Mental State Exam (MMSE) of 24 or less; and uncontrolled neurological, cardiovascular, endocrine, hematologic, hepatic, or renal disease.

No special training is required. There are costs related to drug acquisition.