Adding the substance P blocker aprepitant to standard topical eczema treatment provided no additional improvement in disease severity, itch, or scratching compared to topical treatment alone.
No additive effectDespite substance P's known role in itch and skin inflammation, blocking it with aprepitant for 7 days added no measurable benefit to standard topical eczema treatment in this 39-patient trial.
What the researchers found
Adding the substance P antagonist aprepitant (80 mg/day for 7 days) to standard topical treatment provided no additional benefit over topical treatment alone in adults with moderate-to-severe atopic dermatitis. Both the aprepitant group (n=19) and the control group (n=20) showed improvements in disease severity (SCORAD), itch (pruritus), and scratching movements, but aprepitant did not enhance these improvements. This negative result suggests that blocking substance P via the NK-1 receptor does not meaningfully reduce eczema symptoms beyond what standard topical therapy achieves.
Why it matters
Substance P is a neuropeptide involved in itch signaling, inflammation, and the stress response in the skin. Because atopic dermatitis involves intense itching and can worsen with stress, blocking substance P seemed like a rational therapeutic approach. This study's negative result is important because it helps redirect research away from NK-1 receptor antagonism as a standalone strategy for eczema and toward other mechanisms that may be more effective for treating the itch-scratch cycle.
The numbers in context
n=39 (19 aprepitant, 20 control) · 80 mg/day aprepitant for 7 days · No significant difference in SCORAD, pruritus, or scratching between groups
How the study worked
This open randomized trial assigned 39 adults with moderate-to-severe atopic dermatitis to either aprepitant (80 mg/day orally for 7 days) plus standardized topical treatment (moderately strong steroid and moisturizer) or topical treatment alone. Outcomes included SCORAD (a validated disease severity score), pruritus intensity, and objectively measured scratching movements.
Who was studied
39 adults with moderate-to-severe atopic dermatitis randomized to aprepitant plus topical treatment or topical treatment alone
What this study cannot tell us
The study was open-label (not blinded), which could introduce bias in subjective outcome assessments like itch severity. The sample size of 39 is small and may have been underpowered to detect modest effects. The 7-day treatment duration is very short — substance P blockade may require longer treatment to show effects. The dose of 80 mg/day was chosen based on anti-emetic use and may not be optimal for dermatological applications.
How to read the evidence
This is a randomized controlled trial, but its evidence is limited by the open-label design (no blinding), small sample size, and very short 7-day treatment period. The negative result is informative but not definitive — the study may have been underpowered or the treatment duration insufficient.
When this study was published
Published in 2018, this study predates the widespread adoption of newer eczema treatments like JAK inhibitors. The negative result for substance P blockade remains relevant as researchers continue exploring neuropeptide-targeted therapies for chronic itch conditions.
The bigger picture
The itch-scratch cycle in atopic dermatitis involves multiple neuropeptides and neural pathways, not just substance P. This negative result aligns with a broader pattern in dermatology where single-target neuropeptide blockers have struggled to make a clinical impact in chronic itch conditions. More recent approaches — like JAK inhibitors (e.g., baricitinib, upadacitinib) and IL-4/IL-13 blockers (dupilumab) — have shown much greater success by targeting the immune pathways driving eczema, rather than the itch signal itself.
Questions still open
- Would a longer duration of aprepitant treatment (weeks rather than 7 days) or higher doses produce different results?
- Is substance P more important in acute itch flares versus chronic eczema, and would a different study design better capture its contribution?
- Could blocking multiple neuropeptides simultaneously (substance P, CGRP, and others) be more effective than targeting substance P alone?
Common questions
What is substance P and why was it tested for eczema?
Does this mean neuropeptides aren't important in eczema itch?
Read the original research
Substance P Antagonist Aprepitant Shows no Additive Effect Compared with Standardized Topical Treatment Alone in Patients with Atopic Dermatitis.
Acta dermato-venereologica, 98(3), 324-328
Citation
Lönndahl, Louise; Holst, Mikael; Bradley, Maria; Killasli, Hassan; Heilborn, Johan; Hall, Martin A; Theodorsson, Elvar; Holmberg, Jadwiga; Nordlind, Klas. (2018). Substance P Antagonist Aprepitant Shows no Additive Effect Compared with Standardized Topical Treatment Alone in Patients with Atopic Dermatitis.. Acta dermato-venereologica, 98(3), 324-328. https://doi.org/10.2340/00015555-2852