Evidence map›Paper›PMID 25783757›Full record

Trial reportThe American journal of psychiatry2015

Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment.

William J Kowalczyk, Karran A Phillips, Michelle L Jobes, Ashley P Kennedy, Udi E Ghitza, Daniel A Agage, John P Schmittner, David H Epstein, Kenzie L Preston

Open access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The American journal of psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 2 pooled it
5.3field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Effects of behavioral interventions on stress reactivity in adults with substance use disorders.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2024
    Trial
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  11. Effect of the CRFPsychopharmacology · 2016
    Trial
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  13. Review
  14. An initial exploration of the daily associations between opioid use and acute suicide risk: The role of posttraumatic stress symptoms.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2026
    Article
  15. Observational
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

William J KowalczykFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Karran A PhillipsFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Michelle L JobesFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Ashley P KennedyFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Udi E GhitzaFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Daniel A AgageFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
John P SchmittnerFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
David H EpsteinFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Kenzie L PrestonFrom the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
National Institutes of Health Clinical Center · US

Funding

Real-Time Assessment of Drug Use, Along with Mental States and EnvironmentsZIADA000499 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI EPSTEIN, DAVID · 2009 to 2025
$19.9M
Prevention of Relapse in AddictionZIADA000536 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI PRESTON, KENZIE · 2009 to 2018
$9.5M
Evaluation Of Treatments Of Opioid And Cocaine DependenceZIADA000175 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI PRESTON, KENZIE · 2009 to 2016
$7.4M
EVALUATION OF TREATMENTS OF OPIOID DEPENDENCE IN HIV PATIENTSZ01DA000175 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI PRESTON, KENZIE L · 1995 to 2008
$2.3M
Intramural NIH HHS Z01 DA000175
6 · The paper itself

Abstract

objectiveThe authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action.

methodThe authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models.

resultsIn an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits.

conclusionsClonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Indexed as

CravingAdultAnalgesicsBuprenorphineClonidineDouble-Blind MethodDrug Therapy, CombinationFemaleHumansMaintenance ChemotherapyMaleMiddle AgedNarcotic AntagonistsOpiate Substitution TreatmentOpioid-Related DisordersProportional Hazards ModelsAnalgesicsBuprenorphineClonidineNarcotic Antagonists

Identifiers

PMID25783757
PMCPMC6233893
OpenAlexW2127186356

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.