title: The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: preliminary findings.
abstract: Interleukin (IL)-2, a T-cell cytokine used to treat malignant melanoma, can induce profound depression. To determine whether pretreatment with the antidepressant escitalopram could reduce IL-2-induced neuroendocrine, immune, and neurobehavioral changes, 20 patients with Stage IV melanoma were randomized to either placebo or the serotonin reuptake inhibitor, escitalopram (ESC) 10-20 mg/day, 2 weeks before, and during IL-2 treatment (720 000 units/kg Q8 h × 5 days (1 cycle) every 3 weeks × 4 cycles). Generalized estimation equations were used to examine HPA axis activity (plasma ACTH and cortisol), immune activation (plasma IL-6), and depressive symptoms (Hamilton Depression Rating Scale (HDRS) score). Tolerance of IL-2 treatment (concomitant medications required) and adherence (number of IL-2 doses received) were also assessed. Both the groups (ESC (n=9), placebo (n=11)) exhibited significant IL-2-induced increases in plasma cortisol, IL-6, and depressive symptoms (p<0.05), as well as a temporal trend for increases in plasma ACTH (p=0.054); the effects of age and treatment were not significant. Higher plasma ACTH concentrations were associated with higher depressive symptoms during cycles 1-3 of IL-2 therapy (p<0.01). Although ESC had no significant effects on ACTH, cortisol, IL-6, tolerance of, or adherence to IL-2, ESC treatment was associated with lower depressive symptoms, ie, a maximal difference of ∼3 points on the HDRS, which, though not statistically significant (in part, due to small sample size), represents a clinically significant difference according to the National Institute for Health and Clinical Excellence guidelines. A larger sample size will establish whether antidepressant pretreatment can prevent IL-2-induced neurobehavioral changes.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Miami Leonard H. Miller School of Medicine, Miami, Florida 33146,, USA. dmusselman@med.miami.edu
authors.forename: Dominique
authors.initials: D
authors.lastname: Musselman
authors.forename: Erica B
authors.initials: EB
authors.lastname: Royster
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Trimble
authors.forename: Tara K
authors.initials: TK
authors.lastname: Mann
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Graciaa
authors.forename: Marcia D
authors.initials: MD
authors.lastname: McNutt
authors.forename: N S Freda
authors.initials: NS
authors.lastname: Auyeung
authors.forename: Lindsay
authors.initials: L
authors.lastname: Oliver
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D055118:Medication Adherence; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000523:psychology; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000970:Antineoplastic Agents; D007376:Interleukin-2; D015850:Interleukin-6; D015283:Citalopram; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone