Paroxetine for the prevention of depression induced by high-dose interferon alfa.
BACKGROUND
Depression commonly complicates treatment with the cytokine interferon alfa-2b. Laboratory animals pretreated with antidepressants have less severe depression-like symptoms after the administration of a cytokine. We sought to determine whether a similar strategy would be effective in humans.


METHODS
In a double-blind study of 40 patients with malignant melanoma who were eligible for high-dose interferon alfa therapy, we randomly assigned 20 patients to receive the antidepressant paroxetine and 20 to receive placebo. The treatment was begun 2 weeks before the initiation of interferon alfa and continued for the first 12 weeks of interferon alfa therapy.


RESULTS
During the first 12 weeks of interferon alfa therapy, symptoms consistent with a diagnosis of major depression developed in 2 of 18 patients in the paroxetine group (11 percent) and 9 of 20 patients in the placebo group (45 percent) (relative risk, 0.24; 95 percent confidence interval, 0.08 to 0.93). Severe depression necessitated the discontinuation of interferon alfa before 12 weeks in 1 of the 20 patients in the paroxetine group (5 percent), as compared with 7 patients in the placebo group (35 percent) (relative risk, 0.14; 95 percent confidence interval, 0.05 to 0.85). The incidence of adverse events was similar in the two groups.


CONCLUSIONS
In patients with malignant melanoma, pretreatment with paroxetine appears to be an effective strategy for minimizing depression induced by interferon alfa.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
D L
DL
Musselman
D H
DH
Lawson
J F
JF
Gumnick
A K
AK
Manatunga
S
S
Penna
R S
RS
Goodkin
K
K
Greiner
C B
CB
Nemeroff
A H
AH
Miller
D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use*; D011994:Recombinant Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017374:Paroxetine; D011994:Recombinant Proteins; D017367:Selective Serotonin Reuptake Inhibitors