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Pretreatment neurophysiological and clinical characteristics of placebo responders in treatment trials for major depression

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Abstract

Rationale

High placebo response rates are a confound in treatment trials for major depressive disorder (MDD). A method for prospective identification of placebo responders could enhance the efficiency of clinical trials.

Objective

The objective was to identify the neurophysiological, symptomatic, and cognitive characteristics of subjects who were likely to respond to placebo in clinical trials for MDD.

Methods

Fifty-one subjects with MDD were treated in clinical trials with either fluoxetine (n=24) or venlafaxine (n=27) versus placebo. All subjects underwent pretreatment assessment with quantitative electroencephalographic (QEEG) power and cordance, as well as symptom ratings and neuropsychological testing. After a 1-week single-blind placebo lead-in, subjects were randomized to double-blind placebo controlled treatment with a medication or placebo. At the end of 8 weeks, the blind was broken and treatment response assessed. Response was defined by a final Hamilton Depression Rating Scale score of ≤10.

Results

Of the medication-treated and placebo-treated subjects, 52% (13/25) and 38% (10/26) responded. Placebo responders had lower pretreatment frontocentral cordance in the theta frequency band than all other subjects (P<0.006) and medication responders in particular (P<0.004). Placebo responders also had faster cognitive processing time, as assessed by neuropsychological testing, and lower reporting of late insomnia (P<0.03). Exploratory examination of a multiple variable model for predicting placebo response was conducted using logistic regression, in which these three pretreatment measures accurately identified 97.6% of eventual placebo responders.

Conclusions

These findings suggest that combined clinical, neurophysiological, and cognitive assessments of prospective subjects for clinical trials may be useful for identifying MDD subjects who are likely to show robust response to placebo. Prospective validation of these results in a larger, independent sample of subjects is necessary to establish the reliability and usefulness of this method for prospective identification of placebo responders.

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Acknowledgments

This work was supported by Research Scientist Development Award K02-MH01165 and grant R01-MH40705 from the National Institute of Mental Health to Dr Leuchter, and Career Development Award K08-MH01483 from the National Institute of Mental Health to Dr Cook. We also wish to acknowledge the grant support of Eli Lilly and Company, Inc. and Wyeth-Ayerst Laboratories, Inc. in conducting this study.

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Authors and Affiliations

  1. UCLA NPI, 760 Westwood Plaza, Suite 37-452, Los Angeles, CA, 90024-1759, USA

    Andrew F. Leuchter

  2. UCLA NPI, 760 Westwood Plaza, Suite 37-432, Los Angeles, CA, 90024-1759, USA

    Melinda Morgan

  3. UCLA NPI, 760 Westwood Plaza, Suite 37-451, Los Angeles, CA, 90024-1759, USA

    Ian A. Cook

  4. UCLA NPI, 760 Westwood Plaza, Suite 37-439, Los Angeles, CA, 90024-1759, USA

    Jennifer Dunkin

  5. UCLA NPI, 760 Westwood Plaza, Suite 37-431, Los Angeles, CA, 90024-1759, USA

    Michelle Abrams

  6. 26314 NE 37th Avenue, Ridgefield, WA, 98642, USA

    Elise Witte

Authors
  1. Andrew F. Leuchter
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  2. Melinda Morgan
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  3. Ian A. Cook
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  4. Jennifer Dunkin
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  5. Michelle Abrams
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  6. Elise Witte
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Corresponding author

Correspondence to Andrew F. Leuchter.

Additional information

From the Laboratory of Behavioral Pharmacology, UCLA Neuropsychiatric Institute, and the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA.

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Leuchter, A.F., Morgan, M., Cook, I.A. et al. Pretreatment neurophysiological and clinical characteristics of placebo responders in treatment trials for major depression. Psychopharmacology 177, 15–22 (2004). https://doi.org/10.1007/s00213-004-1919-2

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  • DOI: https://doi.org/10.1007/s00213-004-1919-2

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