Nathan Huneke

It was a real privilege to be invited to present on treatment-resistance in anxiety disorders at the Psychiatry Masterclass 2025 at the Conrad Dubai. Many thanks to the organising and scientific committees for inviting me!

It was great to be there with such excellent speakers!

Excellent @liviaasan.bsky.social, well done!

Our new Insights article out now in European Neuropsychopharmacology

We argue that poor control conditions in digital therapeutics trials risk misleading efficacy claims.

Let’s raise the bar for DTx trial design.

🔗 authors.elsevier.com/a/1l-8p,L21E...

@ecnp.eu
#DTx #MentalHealth #ClinicalTrials

It was great to present on placebo and nocebo effects in depressive and anxiety disorders in an educational update session at the ECNP Congress. Many thanks to the educational committee for inviting me! @ecnp.eu

YouTube video by SFB-TRR 289 "Treatment Expectation" Webinar: Nathan Huneke - Toward improved understanding of placebo effects in psychiatric disorders

🎥 Two new #SFB289 #webinars are uploaded on our YouTube channel! 🎥

In September 2025, @nathanhuneke.bsky.social presented his work on placebo effects in psychiatric disorders: youtu.be/Z1pyhXSV5RE

Great to collaborate on this with @hvansteenbergen.bsky.social! We found evidence that endogenous opioids mediate attentional broadening after receiving rewards.

Really enjoyed the opportunity to present at the SFB289 webinar!

Great to be part of this

Pramipexole augmentation for the acute phase of treatment-resistant, unipolar depression: a placebo-controlled, double-blind, randomised trial in the UK In this trial involving participants with treatment-resistant depression, pramipexole augmentation of antidepressant treatment, at a target dose of 2·5 mg, demonstrated a reduction in symptoms relativ...

Our new study published in TheLancetPsych! We found that pramipexole augmentation substantially reduced depressive symptoms in patients with treatment-resistant depression over 48 weeks of treatment. This is an important advance in how we treat depression! 1/6
www.thelancet.com/journals/lan...

Timely article!

Negative Effects During Placebo Treatment This study compares premature study termination rates in placebo groups of high-quality randomized clinical trials across 9 major psychiatric disorders, focusing on total dropouts, dropouts due to adv...

Editorial accompanies jamanetwork.com/journals/jam...

Understanding Placebo Mechanisms to Reduce Attrition in Psychiatric Trials Placebo responses in psychiatric trials are clinically significant and variable.1 When placebo response is large, the assay sensitivity of a clinical trial can be impacted, meaning that it can potenti...

Our thoughts on missing data, statistics and placebo effects in psychiatric trials.

Thanks Samuele Cortese and Marco Solmi!

jamanetwork.com/journals/jam...

Very important initiative!

Expectancy Effects, Blinding Integrity, and Placebo Response in Psychiatric Disorders This narrative review discusses the impact of expectancy effects and functional unblinding on treatment responses in randomized clinical trials of treatments in psychiatry.

Our new review in JAMA Psychiatry: "Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders"

jamanetwork.com/journals/jam...

Thanks to co-first author Guil Fusetto-Veronesi; and to Samuele Cortese, David Baldwin, Matt Garner

🧵👇

Expectancy Effects, Blinding Integrity, and Placebo Response in Psychiatric Disorders This narrative review discusses the impact of expectancy effects and functional unblinding on treatment responses in randomized clinical trials of treatments in psychiatry.

Check out the paper and let us know what you think!

jamanetwork.com/journals/jam...

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalized Anxiety AbstractBackground. Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed b

3. We should develop readouts that are resistant to expectation effects (e.g. psychophysics, network connectivity). Experimental medicine models appear resistant to expectation effects, & could be used to develop such readouts academic.oup.com/ijnp/article... journals.sagepub.com/doi/abs/10.1...

2. Statistical methods to 'account for' or 'correct for' expectation effects in RCTs exist but need testing and validating. Gathering data as in recommendation 1 would allow us to do this.

We make the following recommendations:

1. We should systematically record blinding integrity for patients and for clinician raters, and if it fails, why. This would allow us to explore the above question.

If blinding fails in active arms in RCTs w/ larger drug-placebo separation, that might be OK, as an effective treatment might unblinds patients/raters. BUT, if blinding failure in placebo arms drives the difference (maybe through 'disappointment'/'know'-cebo/'lessebo') then that would be a concern.

The relationship between blinding integrity and medication efficacy in randomised‐controlled trials in patients with anxiety disorders: A systematic review and meta‐analysis Background Blinding is thought to minimise expectancy effects and biases in double-blind randomised-controlled trials (RCTs). However, whether blinding integrity should be assessed and reported rema...

Our recent work shows blinding integrity is rarely measured in psychiatric RCT's. Yet, signals suggest a potential relationship between functional unblinding and greater drug-placebo separation - perhaps due to lower placebo effect onlinelibrary.wiley.com/doi/full/10.... jaacap.org/article/S089...

i.e. higher expectations = higher treatment efficacy. Treatment effects are larger in open-label trials compared with the same treatment given double-blind. Despite this, effect of functional unblinding on estimates of efficacy has been little explored, partly due to lack of data

'Response to treatment' results from 3 broad effects: non-specific effects, placebo-specific effects (expectations, associative learning, maybe unblinding effects...), and the improvement specifically attributable to the treatment itself. These effects appear to be additive:

In this narrative review we discuss how expectancy effects and functional unblinding can impact treatment and placebo responses in RCT's treatments in psychiatry.

We finish with recommendations for the field. Here is a summary:

Expectancy Effects, Blinding Integrity, and Placebo Response in Psychiatric Disorders This narrative review discusses the impact of expectancy effects and functional unblinding on treatment responses in randomized clinical trials of treatments in psychiatry.

Our new review in JAMA Psychiatry: "Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders"

jamanetwork.com/journals/jam...

Thanks to co-first author Guil Fusetto-Veronesi; and to Samuele Cortese, David Baldwin, Matt Garner

🧵👇

🧠 Help Us Understand Pain Perception in FND! 🧠

Looking for volunteers with & without #FND for a study in London @kingsioppn.bsky.social. Single lab visit testing pain perception with electrical stimulation.

Interested? Please message me: Livia.Asan@kcl.ac.uk ✉️

Thanks for sharing!

Of course!

Why academia is sleepwalking into self-destruction. My editorial @brain1878.bsky.social If you agree with the sentiments please repost. It's important for all our sakes to stop the madness
academic.oup.com/brain/articl...

#Pubmed problems being reported

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