Evidence map›Paper›PMID 32145041›Full record

Trial reportBritish journal of clinical pharmacology2020

Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.

Stefan Weisshaar, Laura Brandt, Brigitte Litschauer, Safoura Sheik-Rezaei, Laura Moser, Günther Nirnberger, Elisabeth Kühberger, Ulrike Bauer, Christa Firbas, Ghazaleh Gouya and 2 more

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 13 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. 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

12 authors at 4 institutions in 2 countries.

Stefan WeisshaarDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-5853-9656
Laura BrandtDepartment of Applied Psychology: Work, Education & Economy, Faculty of Psychology, University of Vienna, Vienna, Austria.
Brigitte LitschauerDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Safoura Sheik-RezaeiDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Laura MoserDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Günther NirnbergerBioconsult GmbH, Breitenfurt, Austria.
Elisabeth KühbergerG. L. Pharma GmbH, Lannach, Austria.
Ulrike BauerG. L. Pharma GmbH, Lannach, Austria.
Christa FirbasDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Ghazaleh GouyaDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Michael WolztDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-6049-1890
Gabriele FischerCenter for Public Health, Medical University of Vienna, Vienna, Austria.
Medical University of Vienna · ATGerot Lannach (Austria) · ATInfoConsult (Germany) · DEVienna University of Economics and Business · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsOral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation.

methodsIn a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated.

resultsIntravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone.

conclusionMorphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.

Indexed as

Opioid-Related DisordersSubstance Withdrawal SyndromeAnalgesics, OpioidAnimalsFemaleHumansMaleMorphineNaloxoneNarcotic AntagonistsSwineAnalgesics, OpioidMorphineNaloxoneNarcotic Antagonistsmorphinenaloxoneopioid maintenance treatmentopioid withdrawal syndromesubstance abuse-intravenous

Identifiers

PMID32145041
PMCPMC7373709
OpenAlexW3009185074

What OpenQuestion holds

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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.