Evidence map›Paper›PMID 28640990›Full record

Trial reportThe Journal of clinical psychiatry

Opiate Antagonists Do Not Interfere With the Clinical Benefits of Stimulants in ADHD: A Double-Blind, Placebo-Controlled Trial of the Mixed Opioid Receptor Antagonist Naltrexone.

Thomas J Spencer, Pradeep Bhide, Jinmin Zhu, Stephen V Faraone, Maura Fitzgerald, Amy M Yule, Mai Uchida, Andrea E Spencer, Anna M Hall, Ariana J Koster and 1 more

Registry-linked trialOpen access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical psychiatry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01673594 (Prevention of Stimulant-Induced Euphoria With an Opioid Receptor Antagonist), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01673594 phase4completednot on this map

Prevention of Stimulant-Induced Euphoria With an Opioid Receptor Antagonist

TypeinterventionalSponsorMassachusetts General HospitalRan2012 to 2015Enrolled37ConditionsADHD, Stimulant-Induced EuphoriaArmsSODAS MPH, Naltrexone
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Thomas J SpencerMassachusetts General Hospital, 55 Fruit St, Warren 705, Boston, MA, 02144. spencer@helix.mgh.harvard.edu.
Pradeep BhideDepartment of Neuroscience, Florida State University, Tallahassee, Florida, USA.
Jinmin ZhuDepartment of Neuroscience, Florida State University, Tallahassee, Florida, USA.
Stephen V FaraoneDepartment of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York, USA.
Maura FitzgeraldPediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Amy M YulePediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mai UchidaPediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Andrea E SpencerPediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Anna M HallPediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ariana J KosterPediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Joseph BiedermanPediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harvard University · USSUNY Upstate Medical University · US

Funding

AACAP Physician Scientist Program in Substance UseK12DA000357 · NIDA · AMERICAN ACADEMY-CHILD/ADOLESCENT PSYCH · PI Kevin M. Gray · 1998 to 2026
$29.1M
Longitudinal Family/Molecular Genetic Study to Validate Research Domain CriteriaR01MH101519 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI FARAONE, STEPHEN V, GLATT, STEPHEN J · 2014 to 2018
$3.5M
NIDA NIH HHS K12 DA000357NIMH NIH HHS R01 MH101519
6 · The paper itself

Abstract

objectiveMethylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD).

methodsWe conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015. Spheroidal Oral Drug Absorption System (SODAS) methylphenidate was administered twice daily, was titrated to approximately 1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with a test dose of immediate-release methylphenidate. The primary outcome measure was the Adult ADHD Investigator Symptom Report Scale (AISRS).

resultsThirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS methylphenidate and randomly assigned to naltrexone 50 mg or placebo. Thirty-one subjects completed the study through week 3, and 25 completed through week 6. Throughout 6 weeks of blinded naltrexone and open methylphenidate treatment, the coadministration of naltrexone with methylphenidate did not interfere with the clinical effectiveness of methylphenidate for ADHD symptoms. Additionally, the combination of naltrexone and methylphenidate did not produce an increase in adverse events compared with methylphenidate alone.

conclusionsOur findings provide support for the concept of combining opioid receptor antagonists with stimulants to provide an effective stimulant formulation with less abuse potential.

trial registrationClinicalTrials.gov identifier: NCT01673594​.

Indexed as

AdolescentAdultAttention Deficit Disorder with HyperactivityCentral Nervous System StimulantsDelayed-Action PreparationsDouble-Blind MethodDrug Therapy, CombinationEuphoriaFemaleHumansMaleMethylphenidateNaltrexoneNarcotic AntagonistsYoung AdultCentral Nervous System StimulantsDelayed-Action PreparationsMethylphenidateNaltrexoneNarcotic Antagonists

Identifiers

PMID28640990
PMCPMC6438372
OpenAlexW2684636976

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.