The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: Preliminary findings

Dominique Musselman, Erica B. Royster, Ming Wang, Qi Long, Lisa M. Trimble, Tara K. Mann, Daniel S. Graciaa, Marcia D. McNutt, N. S.Freda Auyeung, Lindsay Oliver, David H. Lawson, Andrew H. Miller

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1921-1928
Number of pages8
JournalNeuropsychopharmacology
Volume38
Issue number10
DOIs
StatePublished - Sep 2013

Keywords

  • adrenocorticotropin (ACTH)
  • depression
  • escitalopram
  • interleukin-2
  • interleukin-6
  • melanoma

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: Preliminary findings'. Together they form a unique fingerprint.

  • Cite this

    Musselman, D., Royster, E. B., Wang, M., Long, Q., Trimble, L. M., Mann, T. K., Graciaa, D. S., McNutt, M. D., Auyeung, N. S. F., Oliver, L., Lawson, D. H., & Miller, A. H. (2013). The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: Preliminary findings. Neuropsychopharmacology, 38(10), 1921-1928. https://doi.org/10.1038/npp.2013.85