Evidence map›Paper›PMID 27712113›Full record

Trial reportThe American journal of drug and alcohol abuse2017

Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study.

Matthew J Erlendson, Nicole D'Arcy, Ellen M Encisco, Jeffrey J Yu, Lorena Rincon-Cruz, Gary Peltz, J David Clark, Larry F Chu

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

Trial report in The American journal of drug and alcohol abuse, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pharmacological therapies for management of opium withdrawal.The Cochrane database of systematic reviews · 2018
    Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Serotonin ReceptorInternational journal of environmental research and public health · 2022
    Article
  7. Review
  8. Opioid misuse in gastroenterology and non-opioid management of abdominal pain.Nature reviews. Gastroenterology & hepatology · 2018
    Review
  9. Review
  10. A Flawed Design Produces Flawed Results.Journal of addiction medicine
    Article
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

8 authors at 1 institution in 1 country.

Matthew J Erlendsona Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Nicole D'Arcya Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Ellen M Enciscoa Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Jeffrey J Yua Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Lorena Rincon-Cruza Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Gary Peltza Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
J David Clarka Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Larry F Chua Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA.
Stanford University · US

Funding

Prevention of neonatal opioid withdrawal syndromeR01HD070795 · NICHD · STANFORD UNIVERSITY · PI PELTZ, GARY A · 2012 to 2020
$6.1M
Opiate-Induced Tolerance &Hyperalgesia in Pain PatientsK23GM071400 · NIGMS · STANFORD UNIVERSITY · PI CHU, LAWRENCE F · 2004 to 2008
$653k
Understanding the Effects of Chronic Opioids Therapy in HumansK02DA033348 · NIDA · STANFORD UNIVERSITY · PI CHU, LAWRENCE F · 2013 to 2017
$633k
NICHD NIH HHS R01 HD070795NIDA NIH HHS K02 DA033348NIGMS NIH HHS K23 GM071400
6 · The paper itself

Abstract

backgroundTreatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective.

objectivesThis double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect.

methodsAt timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15.

resultsComparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333.

conclusionsPretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal.

Indexed as

Cross-Over StudiesDouble-Blind MethodDrug SynergismHealthy VolunteersHumansHydroxyzineIsoquinolinesMaleMorphineNaloxonePalonosetronQuinuclidinesSubstance Withdrawal SyndromeYoung AdultHydroxyzineIsoquinolinesMorphineNaloxonePalonosetronQuinuclidinesantihistamine, 5HT3 antagonisthydroxyzineopioid withdrawalPalonosetron

Identifiers

PMID27712113
PMCPMC5728104
OpenAlexW2515933403

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.