Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 14573318 · doi:10.1016/s0006-3223(03)00173-2
What was done
Twenty-six patients with malignant melanoma were randomized in a double-blind design to receive either paroxetine or placebo, initiated 2 weeks prior to interferon (IFN)-alpha therapy and continued for the first 12 weeks of treatment. Blood levels of tryptophan (TRP), kynurenine (KYN), and neopterin (an immune activation marker) were measured at baseline and at 2, 4, and 12 weeks of IFN-alpha treatment, alongside structured assessments for depression, anxiety, and neurotoxicity.
What was found
The abstract reports no exact numerical values or effect sizes. Across all patients, IFN-alpha therapy was accompanied by significant increases in KYN, neopterin, and the KYN/TRP ratio regardless of treatment arm. Among placebo-treated patients, those who developed major depression showed significantly larger increases in KYN and neopterin and more prolonged decreases in TRP compared with nondepressed patients; TRP decreases also correlated with depressive, anxious, and cognitive symptoms (but not somatic or neurovegetative symptoms). In paroxetine-treated patients, no correlations were observed between these biological markers and clinical symptom measures.
Why it matters
This study provides clinical trial evidence that immune-driven indoleamine-2,3-dioxygenase activation and resulting tryptophan depletion contribute to interferon-induced psychiatric symptoms, and demonstrates that SSRIs can blunt these behavioral effects without reversing the underlying metabolic shift.
Limits
The sample size is very small (26 patients divided into two arms), limiting statistical power and subgroup analyses. The abstract does not provide exact point estimates, variance, or p-values, and the findings in melanoma patients receiving high-dose IFN-alpha may not generalize to other inflammatory conditions or general major depressive disorder.
Cited by
- supports Interferon-alpha treatment activates indoleamine 2,3-dioxygenase (IDO), shifting tryptophan metabolism away from serotonin and into kynurenine.