Risk of Drug Dependance Associated with use of Triptans and Ergot Derivatives. Neuromuscular Dentistry an Alternative to Drugs

A recent article (PubMed abstract below) in the European Journal of Clinical Pharmacology made the following conclusions “These findings confirm the hypothesis that triptans and ergot derivatives are associated with an increased risk of drug dependence”
The study looked at ” triptans (almotriptan, eletriptan, naratriptan, sumatriptan, and zolmitriptan) as well as ergot derivatives used in acute migraine” Positive cases were defined as “as those reports corresponding to “drug abuse,” “physical or mental drug dependence,” and “pharmacodependence,” while non cases were defined as all remaining patients. There were a total of 309,178 reports in the database with drug dependence accounting for 0.8% (2,489) of the reports. The study reported “The risk of dependence was similar for triptans and ergot derivatives and did not differ from that of benzodiazepines”

The use of Neuromuscular Dentistry (http://www.ihateheadaches.org) to treat migraines without excessive drug use can eliminate some of the risks of drug abuse. While the percentage of patients abusing these drugs is small it does represent a significant risk. The risk of death is very low with triptans. The Triptan Cardiovascular Safety Expert Panel of the American Headache Society made the following conclusions:

‘1. Chest symptoms occurring during use of triptans are usually nonserious and usually not attributed to ischemia (deficiency of blood flow).
2. While serious cardiovascular adverse events have occurred after use of triptans, their incidence in clinical trials and clinical practice appears to be extremely low.
3. The cardiovascular risk-benefit profile of triptans favors their use in the absence of contraindications.
Most clinical trials and clinical practice data on triptans are derived from patients without known coronary artery disease.
These data support the conclusion that, in patients at low risk of coronary artery disease, triptans can be prescribed confidently without the need for prior cardiac status evaluation.”

The American Headache Society does warn about Serotonin Syndrome and triptans do increase this risk. They have an excellent patient information page that should be read by patients utilizing Triptans for treating migraines with any of these three different classes of medication: Selective serotonin reuptake inhibitors (SSRIs), Monoamine oxidase inhibitors (MAOIs) and Tricyclic antidepressants (TCAs). The information page is available at: http://www.achenet.org/education/patients/SSRIsTriptansandSerotoninSyndrome.asp The following is is how the American Headache Society defines Serotonin Syndrome:

“SSRIs, Triptans and Serotonin Syndrome: What is the Risk of Serotonin Syndrome in Migraine?”
“The serotonin syndrome (SS) is an acute, sometimes serious and potentially fatal adverse drug reaction. It is due to medications that increase serotonergic activity throughout the body and nervous system. Serotonin syndrome, by definition, is a group of symptoms presenting as mental changes, autonomic nervous system malfunction, and neuromuscular complaints. Patients may present with confusion, agitation, diarrhea, sweating, shivering, hypertension, fever, increased white blood cell count, incoordination, marked increase in reflexes, muscle jerks, tremor, extreme stiffness, seizures and even coma. The severity of changes ranges from mild to fatal.has an excellent patient education page on Serotonin Syndrome.”

The Food and Drug Administration (FDA) issued an alert in 2006, based on 27 case reports regarding serotonin syndrome resulting from use of either a selective serotonin-reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) with a triptan drug for migraine. It is important to note that this was a small number of cases and large numbers of patients have benefitted from these drug combinations.

A recent study in Headache (Pubmed abstract below) “Triptan Use as a Function of Cardiovascular Risk. A Population-Based Study” examined use of triptans in patients with cardiovascular disease and concluded “Triptan use is lower in those with vs without CV risk, suggesting that doctors and/or patients fear using triptans in individuals at risk to CVD.” It is interesting to note that there was significant less use of triptans in migrainers with diabetes, hypertension and among smokers.nother study

Another study “Treatment choices and patterns in migraine patients with and without a cardiovascular risk profile.” published in Cephalgia reported that “Differences in treatment choices and patterns between migraine patients with and without a known cardiovascular risk profile reveal a certain reticence in prescribing vasoconstrictive antimigraine drugs to patients at cardiovascular risk.”

A final study (pubMed abstract below) “Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From The Norwegian Mother and Child Cohort Study.” in Headache reported on the effects of triptans on Pregnancy and happily reported no evidence of congenital malformations associated with triptan use. They did show increases in premature birth and uterine changes. “Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus , and blood loss >500 mL during labor.” They conclude “Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malformations. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters.”

The overall safety record of the triptans is very good though there are some concerns about safety for certain classes of patients. Neuromuscular Dentistry can treat many patients with Migraines, Chronic Daily Headaches and Tension-Type (ETTH) headaches and frequently eliminate the need for drug therapy and associated risks. Neuromuscular Dentistry works by affecting the trigeminal nrvous system. It is the trigeminovascular system responsible for most migraines. See http://www.ihateheadaches.org for more information on Neuromuscular /dentistry and Migraines.

PUBMED ABSTRACTS FOLLOW:PUB
Eur J Clin Pharmacol. 2009 Dec 19. [Epub ahead of print] Drug dependence associated with triptans and ergot derivatives: a case/non-case study.
Beau-Salinas F, Jonville-Béra AP, Cissoko H, Bensouda-Grimaldi L, Autret-Leca E.

Department of Pharmacology, CHRU of Tours, Bretonneau Hospital, Regional Centre of Pharmacovigilance, 2 boulevard Tonnellé, 37 044, Tours Cedex 9, France, f.beau-salinas@chu-tours.fr.
INTRODUCTION: The aim of this case/non-case study was to assess and compare the risk of drug dependence associated with different migraine-specific drugs, i.e., ergot derivatives and triptans, using the French pharmacovigilance database. METHODS: Reports on drug side effects recorded in this database between January 1985 and June 2007 were analyzed, and triptans (almotriptan, eletriptan, naratriptan, sumatriptan, and zolmitriptan) as well as ergot derivatives used in acute migraine were examined. For all reports, cases were defined as those reports corresponding to “drug abuse,” “physical or mental drug dependence,” and “pharmacodependence,” whereas “non-cases” were defined as all the remaining SED reports. The method’s reliability was assessed by calculating the risk associated with a negative (amoxicillin) and a positive (benzodiazepines) control. The risk of dependence associated with each drug and control was evaluated by calculating the odds ratio (OR) with a confidence interval of 95%. RESULTS: Among the 309,178 reports recorded in the database, drug dependence accounted for 0.8% (2,489) of the reports, with 10.9% (449) involving a triptan, and 9.33% (332) an ergot derivative. The risk of dependence was similar for triptans and ergot derivatives and did not differ from that of benzodiazepines. In the triptan group, the risk (odds ratio [95% CI]) ranged from 10.3 [4.8-22.3] for sumatriptan to 21.5 for eletriptan [10.1-45.6], while in the ergot derivative group, it ranged from 12 [8-17.9] for ergotamine to 20.6 [8-53] for dihydroergotamine. CONCLUSIONS: These findings confirm the hypothesis that triptans and ergot derivatives are associated with an increased risk of drug dependence.
PMID: 20024536 [PubMed – as supplied by publisher]

Headache. 2009 Dec 21. [Epub ahead of print] Triptan Use as a Function of Cardiovascular Risk. A Population-Based Study.
Bigal ME, Golden W, Buse D, Chen YT, Lipton RB.

From the Merck Research Laboratories, Whitehouse Station, NJ, USA (M.E. Bigal); Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA (M.E. Bigal, D. Buse, and R.B. Lipton); Department of Outcomes Research, Merck Inc., Whitehouse Station, NJ, USA (W. Golden and Y.-T. Chen); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA (R.B. Lipton); The Montefiore Headache Center, Bronx, NY, USA (R.B. Lipton).
(Headache 2009;**:**-**) Aim.- To estimate the proportion of individuals with migraine using triptan therapy as a function of their cardiovascular (CV) profile and disease severity. Methods.- As a part of the American Migraine Prevalence and Prevention study, we identified migraineurs representative of the U.S. adult population. Triptan use was estimated as a function of presence of CV disease (CVD), of CV risk factors, and by level of migraine-related disability. Results.- Our sample consists of 6102 individuals with migraine. Compared with migraineurs without risk factors for CVD, triptans were significantly less likely to be used in individuals with diabetes (11.5% vs 18.3%, OR = 0.6, 95% CI = 0.5-0.7), hypertension (14.8%, OR = 0.8, 0.7-0.9) and by smokers (12.9%, OR = 0.7, 0.6-0.8). Similar findings were seen for individuals with established CVD. As contrasted to individuals without CVD, those with myocardial infarct (8.5% vs 18.5%, OR = 0.4, 0.3-0.7), stroke (7%, OR = 0.6, 0.3-0.9) and heart surgery (9.3%, OR = 0.5, 0.4-0.7) were less likely to use triptans. Use of triptan increased as a function of disability regardless of CVD status or presence of CV risk factors. Conclusion.- Triptan use is lower in those with vs without CV risk, suggesting that doctors and/or patients fear using triptans in individuals at risk to CVD. Furthermore, triptan use in those with established CVD increases with headache-related disability, suggesting that patients and providers balance risks and benefits. Additional and analytical data are needed on the safety of triptans in the setting of CVD risk. This study has not assessed adequacy of care.
PMID: 20039953 [PubMed – as supplied by publisher]

Cephalalgia. 2009 Mar;29(3):322-30.
Treatment choices and patterns in migraine patients with and without a cardiovascular risk profile.
Wammes-van der Heijden EA, Tijssen CC, Egberts AC.

Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
Treatment patterns in migraine patients with cardiovascular risk factors are largely unknown. A retrospective observational study was conducted to characterize the baseline cardiovascular risk profile of new users of specific abortive migraine drugs, and to investigate treatment choices and patterns in patients with and without a known cardiovascular risk profile. New users of a triptan, ergotamine or Migrafin (n = 36,839) from 1 January 1990 to 31 December 2006 were included. Approximately 90% of all new users did not have a clinically recognized cardiovascular risk profile. The percentage of new users with a cardiovascular risk profile did not differ between new users of a triptan, ergotamine or Migrafin and also did not change during the study period of 17 years. Differences in treatment choices and patterns between migraine patients with and without a known cardiovascular risk profile reveal a certain reticence in prescribing vasoconstrictive antimigraine drugs to patients at cardiovascular risk.
PMID: 19220314 [PubMed – indexed for MEDLINE]

Headache. 2010 Jan 28. [Epub ahead of print] Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From The Norwegian Mother and Child Cohort Study.
Nezvalová-Henriksen K, Spigset O, Nordeng H.

From the Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Norway (K. Nezvalová-Henriksen and H. Nordeng); Department of Clinical Pharmacology, St Olav’s University Hospital, Trondheim, Norway (O. Spigset); Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway (O. Spigset); The Division for Mental Health, National Institute of Health, Oslo, Norway (H. Nordeng).
(Headache 2010;**:**-**) Objective.- To evaluate the safety of triptan therapy during pregnancy. Background.- Information on the safety of triptan therapy during pregnancy is scarce and only available for sumatriptan, naratriptan, and rizatriptan. No associations with congenital malformations have been detected so far, but one study found a significant association between sumatriptan exposure during pregnancy and prematurity. Methods.- The study population consisted of 69,929 pregnant women and their newborn children for whom data on drug exposure and pregnancy outcome were available. Information on triptan therapy and potential socio-demographic and medical confounding factors was obtained from the Norwegian Mother and Child Cohort Study. Information on congenital malformations and other adverse pregnancy outcomes was obtained from the Norwegian Medical Birth Registry. The datasets were linked via the women’s personal identification number. Pearson’s chi(2) tests and logistic regression analyses were used to identify associations between triptan therapy and pregnancy outcome. Results.- No significant associations between triptan therapy during the first trimester and major congenital malformations (unadjusted OR: 1.0; 95% CI 0.8-1.3, adjusted OR: 1.0; 95% CI 0.7-1.2) or other adverse pregnancy outcomes were found. Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1-1.9, adjusted OR: 1.4; 95% CI 1.1-1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1-1.5, adjusted OR: 1.3; 95% CI 1.1-1.5). Conclusions.- Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malformations. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters. Although the present findings are reassuring, confirmation in independent studies is warranted.
PMID: 20132339 [PubMed – as supplied by publisher]