cluster Posted January 9, 2011 Share Posted January 9, 2011 Leuprorelin as therapy of chronic cluster headache refractory to conventional prophylactic therapies and deep brain stimulation: open label observation M. Nicolodi 1,2 1 Interuniversity Centre of Neurochemistry and Clinical Pharmacology of Idiopathic Headache, Siena University, Siena, Italy; 2 Foundation Prevention and Therapy Primary Pain and Headache, Florence, Italy Aim To treat intractable chronic cluster. Subjects and procedure Cluster  headache  (CH),  an  extremely painful syndrome may be refractory to therapies as carbolithium, verapamil,  corticosteroids,  topiramate  and  gabapentin.  In  com- pletely refractory sufferers Deep Brain Stimulation (DBS) was used. The present observation included Group A: 67 (66 males, 1 females, mean age 42.4 ± 3.2SD) chronic CH sufferers (attacks n = 3-6/day, duration 35-67 min) previously unsuccessfully treated with  mentioned  prophylactic  medication  and  Group  B:  4  (2 females, age 29-58) chronic cluster headache sufferers (attacks n = 7-11/  day,  duration  47-110 min)  previously  unsuccessfully treated with prophylactic medications and DBS. All the enrolled subjects showed an acute abortive drug abuse: Sumatriptan in Group  A  (60-80 mg/s.c/day)  or  Tramadol  (1500 ± 5.50  SD) sometimes (38% of the days) associated with Sumatriptan (24- 42 mg/s.c/day/) in Group B. Leuprorelin 11,75 mg was given once a month in Group A, five times/month in Group B. The treatment duration in Group A was 2-3 months (mean 2.1 ± 1.0 SD). Fifty% relief was achieved during the first 14 days. Results and conclusion The benefit consisted in a complete relief for a period of 10-15 months (mean 12.1 months ± 3.2SD), fol- lowing, 18 suffers had a relapse with 2-4 attacks/ day which disappeared in a week following 1 injection of leuprorelin. The other patients had no relapse during the following 4 years. Dif- ferently Group B need more frequent administration: 5 vials/month. Nevertheless, following 6 months they have no more than 0-4 attacks/month (mean 2.8 ± 1.9 SD) versus 7-11/ month . They also use no more tramadol nor abuse sumatriptan. Patients did not reported serious adverse effects; there is no drop-out. In males, deficit of sexual desire was abolished by concomitant use of tes- tosterone 50 mg/day/orally. Source: Nicolodi M.: „Leuprorelin as therapy of chronic cluster headache refractory to conventional prophylactic therapies and deep brain stimulation: open label observation.“ In: "Abstracts of the 2nd European Headache and Migraine Trust International Congress (EHMTIC). October 28-31, 2010. Nice, France". J Headache Pain 11 (Suppl 1): S35. October 2010. http://dx.doi.org/10.1007%2Fs10194-010-0259-3 – Free full text, see PDF page 35. Summary in plain English: 67 chronic CH sufferers (attacks n = 3-6/day, duration 35-67 min) previously unsuccessfully treated with lithium, verapamil, corticosteroids, topiramate and gabapentin became completely pain free after 2 – 3 injections with Leuprorelin 11,75 mg. 49 of these 67 chronic CH sufferers have been completely pain free for more than 4 years. 18 of these 67 sufferers had a relapse 10-15 months after the treatment with 2-4 attacks/day which disappeared in a week following 1 injection of leuprorelin. Please see http://en.wikipedia.org/wiki/Leuprorelin for more information about the substance. There was a successful RCT with a single injection of 3.75 mg leuprorelin = leuprolide acetate published in 1993: Nicolodi M, Sicuteri F, Poggioni M (August 1993). "Hypothalamic modulation of nociception and reproduction in cluster headache. I. Therapeutic trials of leuprolide". Cephalalgia 13 (4): 253–7. Abstract here: http://dx.doi.org/10.1046%2Fj.1468-2982.1993.1304253.x Some of the results of this RCT from the full text: … Sixty male outpatients suffering from chronic CH who attended the Cluster Headache Unit of the Headache Centre of the University of Florence were asked to participate in the study. The diagnosis was made according to the clinical criteria of the International Headache Society (IHS) (22). The patients had been suffering from CH for at least five years. Exclusion criteria were: systemic diseases, treatment with neuroleptics or antidepressive drugs, age under 21. All the patients were partially refractory to lithium therapy which had not induced an over than 35% improvement in CH. ... Results - Therapeutic trial None of the subjects dropped out of the study. Baseline intensity, number of attacks and age of the patients were not statistically different between the leuprolide- and the placebo-treated groups. Placebo treatment did not cause any significant decrease in the mean basal values of either the number of attacks (2.1 ± 0.5 SEM) or the pain intensity (100%) throughout the treatment period (Fig. 1). Neither was any change in the course of CH pattern reported during the follow-up period. The maximum effect induced by leuprolide was a 63% decrease of the pain intensity (Fig. 2) reported during the third 10 day period after leuprolide administration. The lowest mean frequency of CH crises occurred (0.37) at this time (Fig. 2). The therapeutic effect of leuprolide began after an average of 10.1 days (range 7-15). Twelve of 30 patients who received leuprolide reported resolution of pain 17 days after drug administration. Leuprolide had no effect in 4 of 30 subjects. Fifteen of the leuprolide-treated subjects reported a general benefit which increased over time. A decrease of analgesic consumption approximately mirrored the decrease in both pain intensity and attack frequency. The mean duration of the attacks decreased from 94 min/day (range 40-150 min) to 9.4 min/day (range 0-60 min), which was the mean duration recorded during the third 10 day period after leuprolide depot. There were no differences of treatment response among age groups or patients with moderate or severe pain. The main side effect of the active treatment was a significant decrease of libido (66% on average), in comparison with the basal situation. In six of the patients treated with leuprolide the decrease of libido was minor (30% decrease in comparison with the basal values). Two of these six patients reported limited benefit of therapy (30% and 40% respectively), one reported a complete resolution of pain and three reported gradual decrease of up to 60% in pain severity. Overall, no consistent relationship between libido and pain pattern was noted. During the follow-up month the benefit produced by leuprolide persisted in 21 out of the 26 subjects who had significantly improved after active drugs. The mean duration of improvement was 3.25 months (range 1-7) Because current prophylactic treatment significantly decreases in effect during successive administrations, leuprolide was administered again to patients who had improved but relapsed. The second period of leuprolide therapy induced an amelioration similar to that of the first Gn-RH agonist administration. Does anybody here have some personal (good or bad) experience with the Leuprorelin treatment? Quote Link to comment Share on other sites More sharing options...
veggies Posted January 10, 2011 Share Posted January 10, 2011 im curious.. Quote Link to comment Share on other sites More sharing options...
CHfather Posted January 10, 2011 Share Posted January 10, 2011 Thanks for posting this, cluster. I'm always hopeful about any promising new development, in part because I figure they all add up to new insights. I hope this one works out well. I see it's for males, so it won't help my daughter. Quote Link to comment Share on other sites More sharing options...
veggies Posted January 11, 2011 Share Posted January 11, 2011 CHfather, it looks like there were only two females, but they were present so i wouldnt rule it out for your daughter! i would be curious if they were both of the 18 that relapsed but then got better with another injection. so would this work for episodic sufferers, or just chronic. i am unsure of where they are injecting this substance, maybe its a little more involved than i think. still, curious... Quote Link to comment Share on other sites More sharing options...
CHfather Posted January 11, 2011 Share Posted January 11, 2011 Thanks for pointing that out, veggies -- very thoughtful of you. I must say that for those who are obsessively interested in whatever might be happening with CH understanding and treatments (as I am), the whole document from which cluster posted this contains a bunch of pretty interesting abstracts. Nothing nearly as dramatic as what cluster posted -- I guess I just like to see anything that might promise some future possibilities. It's at http://www.springerlink.com/content/t1r43t7175100007/fulltext.pdf, and it can be searched by typing the word cluster into the search bar. Quote Link to comment Share on other sites More sharing options...
veggies Posted January 11, 2011 Share Posted January 11, 2011 i guess its true that if anyone posted a document that looked mostly legitimate, i am at the point where i would believe it just because i want it to be true.. i want to talk to my neuro about this (once i get one that isn't 80 and tells me i got CH from DOING mushrooms.) this leuprorelin does look like a magic bullet, which shouldn't exist, but i sure want it to work for me Quote Link to comment Share on other sites More sharing options...
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