Evidence map›Paper›PMID 29601316›Full record

Trial reportJournal of clinical psychopharmacology2018

Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive Disorder Halted Due to Intolerability.

Bashkim Kadriu, Shiwen Yuan, Cristan Farmer, Allison C Nugent, Marc S Lener, Mark J Niciu, Minkyung Park, Aaron Yazdian, Elizabeth D Ballard, Fritz A Henn and 3 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of clinical psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. 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

13 authors at 1 institution in 2 countries.

Bashkim Kadriu
Shiwen Yuan
Cristan Farmer
Allison C Nugent
Marc S Lener
Mark J Niciu
Minkyung Park
Aaron Yazdian
Elizabeth D Ballard
Fritz A Henn
Ioline D Henter
Lawrence T Park
Carlos A Zarate
National Institute of Mental Health · US

Funding

Glutamatergic Modulators--Rapid Sustained AntidepressantZ01MH002857 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MANJI, HUSSEINI K · 2005 to 2008
$621k
Intramural NIH HHS Z01 MH002857Intramural NIH HHS Z99 MH999999
6 · The paper itself

Abstract

backgroundSome glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission.

methodsThis randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200-400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Quantitative insulin sensitivity check index, as well as concomitant imaging measures (electroencephalography, proton magnetic resonance spectroscopy, magnetoencephalography), were used as potential surrogate markers of target (KATP channel) engagement.

resultsThe study was halted due to severe adverse effects. Given the small sample size, statistical evaluation of the effect of diazoxide on Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not pursued. Visual inspection of the quantitative insulin sensitivity check index test revealed no evidence of target engagement.

conclusionsAlthough the results are negative, they are an important addition to the literature in this rapidly changing field.

Indexed as

AdultAgedCross-Over StudiesDepressive Disorder, Treatment-ResistantDiazoxideDose-Response Relationship, DrugDouble-Blind MethodEarly Termination of Clinical TrialsFemaleGlutamic AcidHumansMajor Depressive DisorderMaleMiddle AgedPotassium ChannelsPsychiatric Status Rating ScalesDiazoxideGlutamic AcidPotassium Channels

Identifiers

PMID29601316
PMCPMC5903962
OpenAlexW2795038067

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.