Jump to content



Photo

Research: Duloxetine Is "genotoxic -- Causes Chromosome Damage


  • Please log in to reply
8 replies to this topic

#1 FiveNotions

FiveNotions

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 3,686 posts
  • LocationUS, East Coast
  • why_joining:
    I want my life back!

Posted 27 August 2015 - 08:29 AM

This research was done on mice. To translate the scientific lingo, the results showed that duloxetine damaged their chromosomes -- both in short-term and long-term exposure.

 

The researchers/ paper recommend testing / research on other "models" (species of animals) to see if this holds true.
 
Note: a "Micronuclei Inducer" is a substance / chemical that causes (induces) chromosome change / damage.
------------------------------
Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse
Biol. Pharm. Bull. 38, 1245–1249 (2015) [full text]

 

http://www.researchg...289a09b6b1a.pdf

Conclusion:

Our results suggest that short-term as well as cumulative damage is produced by duloxetine.

 

Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

-----------------------------------------------


#2 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 11:22 AM

Awesome FN

 

A great read. To be fair there is one report that Cymbalta does not effect the genes of red blood cells. I wonder what other dna Cymbalta effects?


#3 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 12:15 PM

Similar Ressearch

J Appl Toxicol. 2013 Sep;33(9):901-5. doi: 10.1002/jat.2859. Epub 2013 Feb 12.

Comet-FISH studies for evaluation of genetic damage of citalopram in somatic cells of the mouse.

Attia SM1, Ashour AE, Bakheet SA.

Author information

Abstract

Damage to DNA can lead to many different acute and chronic pathophysiological conditions, ranging from cancer to endothelial damage. The present study was designed to evaluate the DNA damage of an antidepressant drug, citalopram, at the recommended human doses in somatic cells of mice in vivo. Mice exposed to citalopram at varying oral doses of 12 or 24 mg kg(-1) for 7 days exhibited a significant increase in the level of DNA-strand breaking and micronuclei formation as detected by a bone marrow comet assay and micronucleus test, respectively. Furthermore, using fluorescence in situ hybridization (FISH) analysis with the centromeric mouse-satellite DNA-probe for erythrocyte micronuclei it could be shown that citalopram is aneugen as well as clastogen in somatic cells in vivo. Colchicine (COL) and mitomycin C (MMC) were used as positive controls and these compounds produced the expected responses. Both the clastogenic and the aneugenic potential of citalopram can give rise to the development of secondary tumours and abnormal reproductive outcomes. Overall, the results suggest that citalopram at the recommended human doses induces some genetic alterations, which can adversely affect the normal cellular functioning in mice. The mechanism(s) by which citalopram cause this adverse effect appear related, in part, to primary DNA strand breakage as detected by the comet assay as well as clastogenic and aneugenic events as detected by the FISH assay. Therefore, the clinical use of citalopram must be weighed against the risks of genetic damages in citalopram users.

#4 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 12:17 PM

And Another
Eur Rev Med Pharmacol Sci. 2012 Dec;16(15):2154-61.

Sister chromatid exchanges and sperm abnormalities produced by antidepressant drug fluoxetine in mouse treated in vivo.

Alzahrani HA1.

Author information

Abstract

OBJECTIVES:

The aim of this investigation was to determine the capacity of serotonin reuptake inhibitor (SSRI) antidepressant drug fluoxetine (FLX) to induce genotoxic damage in somatic and germ cells.

METHODS:

For this study, sister-chromatid exchanges (SCE's) in bone marrow cells and sperm abnormalities assays in male mice were used. The animals were organized in four groups constituted by five mice. They were orally administered with the test substance as follows: a negative control group; three groups treated with FLX (2.6, 7.8 and 13.0 mg/kg b.wt.) for 5 consecutive days. Animals were sacrificed 24h after the last treatment for analysis SCE's and left for 35 days from the first treatment for analysis sperm-shape abnormalities.

RESULTS:

The results showed that the drug was SCE and sperm abnormalities inducer. The response of this compound was dose-dependent, and showed that the highest tested dose increased about two times SCE and four times the sperm abnormalities control level. The cellular proliferation kinetics was not affected by the chemical, and the mitotic indexes were slightly diminished with the highest dose. The percentage of sperm count and sperm motility decreased (p < 0.01) with increased the dose of treatment.

#5 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 12:22 PM

And again


Food Chem Toxicol. 2013 Mar;53:281-5. doi: 10.1016/j.fct.2012.11.051. Epub 2012 Dec 8.

Citalopram at the recommended human doses after long-term treatment is genotoxic for male germ cell.

Attia SM1, Bakheet SA.


Author information

Abstract

The present study was aimed to examine if multiple oral administration of citalopram, an antidepressant drug, has any genotoxic potential on germ cells of male mice. Mice were treated with citalopram for 4 or 8 weeks at the doses of 6, 12 and 24 mg/kg/day and were sacrificed 24 h after the last dose. Multiple exposures to 12 and 24 mg/kg/day citalopram significantly increased sperm DNA strand breaks (14.0 and 16.0, respectively, compared to the concurrent control of 6.8 at week 4 and 15.2 and 20.7, respectively, compared to the concurrent control of 7.2 at week 8) and aberrant primary spermatocytes (6.6% and 7.6%, respectively, compared to the control of 2.8% at week 4 and 7.4% and 8.4%, respectively, compared to the control of 3.2% at week 8) as well as oxidative DNA damage (2.7 and 3.1, respectively, compared to the control of 1.6 at week 4 and 3.3 and 3.9, respectively, compared to the control of 1.7 at week 8). Overall, this study provides that citalopram at the recommended human doses after long-term treatment is genotoxic for mouse germ cells. Thus, male patients receiving citalopram may stand at higher risk for abnormal reproductive outcomes, particularly in the reproductive ages.

#6 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 12:25 PM

Oh Yea, another one.

Mutat Res. 2012 Oct 9;748(1-2):17-20. doi: 10.1016/j.mrgentox.2012.06.004. Epub 2012 Jun 29.

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster.

Gürbüzel M1, Oral E, Kizilet H, Halici Z, Gulec M.

Author information


Abstract

This study evaluated different concentrations of selective serotonin-reuptake inhibitors (citalopram and sertraline) for genotoxicity by use of the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for the multiple wing hairs (mwh) and flare (flr³) genes were treated with these two compounds. Two recessive markers were located on the left arm of chromosome 3, i.e. 'multiple wing hairs' (mwh) in map position 0.3 and 'flare-3' (flr³) at 38.8, while the centromere was located in position 47.7. SMART is based on the loss of heterozygosity, which may occur through various mechanisms, such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and non-disjunction. Genetic changes occurring in somatic cells of the wing's imaginal discs, cause the formation of mutant clones on the wing blade. The results of this study show that citalopram had a genotoxic effect in the Drosophila SMART. Sertraline, however, did not show any genotoxic effect in balancer heterozygous wings. This study concluded that more information is needed to be certain regarding the mutagenic effects of sertraline.

#7 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 12:43 PM

Build-up of SSRI in the thalamus with time.

https://www.ncbi.nlm...pubmed/10625123

#8 fishinghat

fishinghat

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 10,629 posts
  • LocationMissouri

Posted 27 August 2015 - 01:49 PM

Well my digging found 17 articles on the damaging effects of ssri and snri on chromosomes/dna and or nerve cells. They covered 7 different drugs with citalopram (Celexa) getting the worse reviews and sertraline Zoloft) the best.

 

If anybody is interested in any of these let me know.


#9 FiveNotions

FiveNotions

    God-like

  • Active Members
  • PipPipPipPipPipPipPipPip
  • 3,686 posts
  • LocationUS, East Coast
  • why_joining:
    I want my life back!

Posted 27 August 2015 - 01:57 PM

Anyone who wonders what the hell is happening to Western Civilization need look no further than what these drugs do to us ... we're being destroyed by the drug companies .... each individual life damaged, combined, doth a society / civilization make ... :angry: 





0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users