Netherlands symptoms and conditions

Clinical trial of montelukast in the Netherlands.

I noticed two things:

1. The researcher states that sides effects are 10%.
2. The researcher will not allow patients to also take drugs which are metabolized by CYP2C8 because montelukast inhibits that as proved by in vitro (test tube) studies. American studies in vitro said yes montelukast is an inhibitor but in vivo (in people) that it didn't happen. I was always confused by that and would still like to know more
.
******

I was just asked by Dr. ???, if these European reports lead to change in product information in these countries. I did post that I thought that we should try to find that out. I don't have access to that information. But I do see that the Netherlands did require that depression be added to the product information. It doesn't say the date but Merck agreed.

Artie wanted to tell us about the blood brain barrier. Where are you Artie?

The report says:

In three of the cases a positive dechallenge was seen.The fact that the patients (except for one) did not suffer from depressive symptoms before they started montelukast, the short latency, and recovery after withdrawal of the drug all strengthen our hypothesis that depressive symptoms are an ADR related to the use of montelukast. According to the Marketing Authorisation Holder of montelukast, depression will be added to the product information.

Mechanism: The mechanism of montelukast-induced depressive symptoms is unknown. However, montelukast has earlier been associated with adverse drug reactions such as abnormal dreaming, nightmares, hallucinations, agitation with aggressive behavior, irritability and restlessness, which suggests that montelukast can penetrate the blood brain barrier and exert an effect in the brain .

From the Netherlands 2006.

This is the html version of the file http://www.lareb.nl/documents/kwb_2006_4_montel.pdf.

Page 1
Nederlands Bijwerkingen Centrum LarebMei 2007Montelukast and depressive symptomsIntroductionMontelukast (Singulair®)is a leukotriene receptor antagonist available on the Dutchmarket since 1998. It is indicated for the treatment ofasthma as combination therapy forpatients with light to moderate forms of chronic asthma which cannot be adequately controlledby inhalation corticosteroids and short-acting ß-agonists. For asthma patients for whommontelukast is indicated as asthma treatment it can also relieve symptoms of seasonal allergicrhinitis. Montelukast is also indicated in asthma prevention, if exercise-inducedbronchoconstriction is the main factor

Reports On September 20, 2006 the database of the Netherlands Pharmacovigilance Centre Lareb contained four reports of depressive reactions associated with theuse of montelukast.Patient A is a female aged 55 who used montelukast 10 mg once daily for asthma associated with COPD. Concomitant medication included ipratropiumbromideinhalation, salmeterol inhalation, fluticasone inhalation, acetylcysteine, budesonide nose spray and desloratadine. Two weeks after montelukast therapy was initiated the patient experienced nightmares, a depressive symptoms, fatigue and increased dyspnoea. When montelukast was withdrawn, the first three symptoms resolved. It is not known if the dyspnoea resolved. The reporting pneumonologist stated that the increased dyspnoea also could be a sign of progressing COPD. Patient B, reported by a pneumonologist, is a female aged 39 who used montelukast 10 mg once daily for asthma. Concomitant medication included salmeterol/fluticasone inhalation, mebeverine and psyllium seed. One week afterstarting montelukast treatment the patient experienced chest discomfort, malaise,depressive symptoms and dizziness. Montelukast was withdrawn, patient outcomeis unknown. Patient C, reported by a pharmacist, is a male aged 46 who used montelukast 10mg once daily for asthma. Concomitant medication included omeprazole,salbutamol inhalation and budesonide/formoterol inhalation. Six days after starting montelukast treatment the patient got in a depressed state. The patient continued to use montelukast for four weeks but the depression did not resolve. When montelukast was withdrawn, the patient recovered. Patient D, reported by a pharmacist, is a female aged 59 who used montelukast 10mg once daily for mild to moderate asthma. Concomitant medication included mometasone nose spray, salmeterol/fluticason inhalation, oxazepam and paroxetine. Three days after starting treatment with montelukast the patient experienced insomnia and aggravation of her depression. When montelukast was withdrawn the symptoms resolved.

Page 2
Nederlands Bijwerkingen Centrum LarebMei 2007 Other sources of information drugs are known to cause depressive symptoms. However montelukasthas not been associated with depressive symptoms earlier . A Medline searchbased on the MeSH terms montelukast, leukotriens, depressive disorder and mood disorders did not yield any relevant publication. DatabasesOn September 20, 2006 the database of the Netherlands Pharmacovigilance Centre Lareb contained four reports of depression associated with the use ofmontelukast (ROR 2.1 95% CI 0.8 - 5.7). The same day the database of the WHO contained 3466 reports on montelukast, 43 of these concerned depression (ROR1.2 95% CI 0.9 – 1.6)MechanismThe mechanism of montelukast-induced depressive symptoms is unknown.However montelukast has earlier been associated with adverse drug reactions such as abnormal dreaming, nightmares, hallucinations, agitation with aggressive behavior, irritability and restlessness, which suggests that montelukast can penetrate the blood brain barrier and exert an effect in the brain .Discussion and conclusionLareb received four reports of depressive symptoms in patients using montelukast.Possible confounding includes that asthma itself has been associated with the development of depression . Inhalated corticosteroids can also exert effects onthe central nervous system. Fluticason in combination with salmeterol which isused by patients A, B and D, is associated with hyperactivity and irritability where as budesonide, which is used by patient C also has been associated with depression . The latency of montelukast-induced depressive symptoms variesfrom 3-14 days. In three of the cases a positive dechallenge was seen.The fact that the patients (except for one) did not suffer from depressive symptomsbefore they started montelukast, the short latency, and recovery after withdrawal ofthe drug all strengthen our hypothesis that depressive symptoms are an ADRrelated to the use of montelukast. According to the Marketing Authorisation Holderof montelukast, depression will be added to the product information.

A report from the Netherlands discusses depression. I had failed to notice that the report stated that in three cases the onset of the depression after taking Singulair was from 3-14 days.

Discussion and conclusion
Lareb received four reports of depressive symptoms in patients using montelukast.Possible confounding includes that asthma itself has been associated with the development of depression . Inhalated corticosteroids can also exert effects on the central nervous system. Fluticason in combination with salmeterol which is used by patients A, B and D, is associated with hyperactivity and irritability whereas budesonide, which is used by patient C also has been associated with depression .
----------------------------------------------------------------------------------------------------------

The latency of montelukast-induced depressive symptoms varies from 3-14 days.
-----------------------------------------------------------------------------------------------------------
In three of the cases a positive dechallenge was seen. The fact that the patients (except for one) did not suffer from depressive symptoms before they started montelukast, the short latency, and recovery after withdrawal of the drug all strengthen our hypothesis that depressive symptoms are an ADR
related to the use of montelukast.

According to the Marketing Authorisation Holder of montelukast, depression will be added to the product information.

For those who need some "scientific" documentation to take to their doctors regarding the adverse side effects of Singular - montelukast. This reports from the Netherlands in 2002 does a good job of explaining side effects found in the clinical studies versus those found in post marketing reports. I am disturbed to hear reports that patients are either afraid to talk to their doctors for fear of being ridiculed or their doctors are dismissive of their complaints.

So here is one worth printing for your files.

http://www.lareb.nl/documents/kwb_2002_3_monte.pdf.

I am 35 yrs old. My son was born 7/2/6 I got the Mirena inserted on 8/31/06. Right after I had my son. My body doesn't react well to the birth control pill and did not want to get pregnant. My Gyn said there is a slow release of hormone so I wouldn't even notice any changes. My period was off but I just had my son. In March I went to my primary and she put me on Zoloft since I was experiencing anxiety, a constant flush, and insomnia (kinda feel like your going crazy at certain times of day). I never had these before giving birth (and its not the stress of my son). They did blood work it came back fine. I took yoga, acupuncture and Zoloft, nothing is working 18 months later I went to my primary office and seen a nurse practitioner and she said take the Mirena out-she herself had certain side effects that I had. My Gyn says that is not the cause, it could be the Zoloft. How confusing is all this. I am really considering having it removed soon. I want to feel myself again. I'm sure my husband does too. Anyone with info. on after the Mirena is removed and how I might feel would be helpful. At least I have idea what might lie ahead even though every one is different.I am so glad I found this site. Ladies take care of yourselves. There will be happiness again.