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. Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or – Free full text, see PDF page 35.

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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.