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Konum: MODA-KADIKÖY --İSTANBUL Hastalık:CROHN İlaç:NALTREXONE(LDN)
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 Tarih: Cmt May 21, 2011 6:52 am Mesaj konusu: |
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LDN İLE İLGİLİ BİR MAKALE ....
ASLI http://www.stlouisgastro.com/client_files/file/Naltrexone-Side-Effects-and-Efficacy-in-GI-Disorders.pdf ADRESİNDE DİR
Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders
Ploesser J, Weinstock LB, Thomas E
International Journal of Pharmaceutical Compounding; March 2010
Abstract
Use of low dose naltrexone has been advocated for a variety of medical problems. Only a few
articles published in peer reviewed journals have documented side effects of low dose
naltrexone. The purpose of this study was to determine the frequency of adverse effects of low
dose naltrexone in patients who have been treated for a variety of gastrointestinal disorders. The
secondary purpose was to determine global efficacy in a retrospective survey. Patients (206)
from a single gastroenterologist’s clinical practice who had been prescribed naltrexone were
mailed a survey to evaluate the side effects and efficacy of naltrexone. Patients had either
irritable bowel syndrome without evidence for small intestinal bacterial overgrowth, irritable
bowel syndrome with evidence of small intestinal bacterial overgrowth, chronic idiopathic
constipation, or inflammatory bowel disease. Patients with diarrhea were given 2.5 mg daily,
constipation 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily. In the patients
who returned the survey, 47/121 (38.8%) had no side effects. Of the 74/121 (61.2%) patients
who had side effects, 58 had one or more neurological complaints, and 32 had one or more
gastrointestinal side effects. In the patients with side effects, 24/74 (32.4%) had short lived
symptoms. Low dose naltrexone was terminated owing to side effects in 20/74 patients (27.0%).
In 13 patients with idiopathic irritable bowel syndrome, 2 were markedly improved, 5 were
moderately improved, 2 were unchanged, and 3 were markedly worse. In 85 patients with
irritable bowel syndrome-small intestinal bacterial overgrowth, 15 were markedly improved, 32
were moderately improved, 11 were mildly improved, 23 were unchanged, 3 were moderately
worse, and 1 was markedly worse. In 12 patients with chronic constipation, 7 were markedly
improved, 1 was moderately improved, 3 were mildly improved, and 1 was unchanged. Two of 8
patients with inflammatory bowel disease were markedly improved, 1 was moderately improved,
1 was mildly improved, and 4 were unchanged. Low dose naltrexone frequently has side effects
but in most is tolerable. It appears to be helpful for a number of patients with gastrointestinal
disorders.
Introduction
Naltrexone is U.S. Food and Drug Administration (FDA)-approved for relapse prevention of
alcohol dependence, and it plays a role in relapse prevention of narcotic abuse.1-2 The dose of
oral naltrexone for these purposes is 50 mg daily.
Use of low dose naltrexone (LDN) (1.75 to 4.5 mg daily) has been advocated on the Internet
for a variety of medical problems.3 Only a few articles on LDN or ultra-LDN have been
published in peer reviewed journals.4-6 A recent review elucidated the potential mode of action
including immune-modulation and anti-inflammatory processes.7 Manipulation of opioid
receptors has potential application in gastrointestinal disorders. Opioid neurons exhibit tonic
restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. Antiinflammatory
effects are also desirable for both inflammatory bowel disease and irritable bowel
syndrome (IBS).
Naltrexone is a water soluble compound which crosses the blood brain barrier, and this
increases the potential for neurologic side effects. Reported adverse effects of standard dose
naltrexone include anxiety, nervousness, confusion, drowsiness, hallucinations, skin crawling,
blurred vision, muscle or joint pain, vomiting, diarrhea, stomach pain, liver disease, and skin
rash. There were no significant adverse reactions using ultra-LDN (0.5 mg) in one study.4 Recent
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FDA approval of subcutaneously injected methylated formulation, methylnaltrexone (Relistor),
allows for safe use of this compound in patients who are on narcotics. Methylnaltrexone is
effective for opioid-induced constipation by reversing peripheral opioid receptors.8
At this point in time, methylnaltrexone is not available in oral formulation and thus the role of
oral LDN needs to be further defined. The purpose of this study was to determine the frequency
of adverse effects of LDN in patients who have been treated for a variety of gastrointestinal (GI)
disorders. The secondary purpose was to determine global efficacy in a retrospective survey.
Material and Methods
LDN was compounded in 2.5-mg and 4.5-mg capsules. The source of naltrexone was
Spectrum Chemical Manufacturing Corporation. Compounding began by first calculating the
ingredient filling constants. Ingredients other than naltrexone included microcrystalline cellulose
as a filler and some food color powder to assure proper blending of powders. Formulas for
batches of 100 and 300 capsules were calculated using the filling constants; and powders were
mixed using an electronic mortar and pestle. The final powder mixture was then placed into
empty size #3 gelatin capsules which were locked into capsule machines. Once the capsules were
appropriately packed, the capsule tops were locked onto the capsule bottoms.
Patients from a single gastroenterologist’s clinical practice who had been prescribed
naltrexone in a two-year period were mailed a letter asking if they would participate in a survey
to evaluate the side effects and efficacy of naltrexone. If they did not return the survey they were
called once to remind them to fill out the survey. The majority of the patients had received
prescriptions in the previous six months.
Patients (206) with the following GI conditions were given prescriptions for LDN: IBS
without evidence for small intestinal bacterial overgrowth (SIBO) (i.e., patients with a normal
lactulose breath test), IBS with evidence of SIBO (using naltrexone as a second phase of
treatment in efforts to improve motility and reduce inflammation), chronic idiopathic
constipation, and patients with inflammatory bowel disease. Patients with diarrhea were given
2.5 mg daily, constipation 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily.
In the survey they were asked about the duration and dose of naltrexone administered. They
were asked if they had any of the following side effects: trouble sleeping, nightmares or vivid
dreams, jitteriness, nervousness, dizziness, headache, drowsiness, anxiety, vomiting, decrease in
appetite, diarrhea, stomach pain, muscle pain, nausea, or other symptoms. They were asked if the
side effects improved with continued use of the naltrexone and if they had to stop using
naltrexone because of a side effect. If they were no longer taking naltrexone, they were asked
what made them stop taking it: condition improved, unacceptable side effects, or the medicine
did not work. They were asked if their overall GI symptoms were markedly improved,
moderately improved, slightly improved, unchanged, slightly worse, moderately worse, or
markedly worse. If they had SIBO, they were asked if they needed to take another antibiotic
since being placed on naltrexone.
Results
Surveys were returned by 121/206 (58.7%) of the patients. The mean age (±1 standard
deviation) was 53.0 ±16.8. Of these 92 women and 29 men, 85 had IBS with SIBO, 14 had
idiopathic IBS, 12 had slow transit chronic constipation, 8 had inflammatory bowel disease
(Crohn’s disease in 4 and ulcerative colitis in 4), and 2 had small bowel pseudoobstruction. The
daily dose of naltrexone was 2.5 mg in 67, 5.0 mg in 46, and 4.5 mg in 8 patients.
In the patients who returned the survey, 47/121 (38.8%) had no side effects. Of the 74/121
(61.2%) patients who had side effects, 58 had one or more neurological complaints, and 32 had
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one or more GI side effects. The profile of the side effects is shown in the accompanying Table.
In the patients with side effects, 24/74 (32.4%) had short-lived symptoms. In twenty of the 74
patients (27.0%), naltrexone was terminated owing to side effects. The rest of the patients were
able to tolerate the side effects. The frequency of side effects for the group treated with 2.5 mg
compared with the group treated with 5.0 mg daily differed in three symptoms, respectively:
1. Anxiety (11.9 vs. 21.7%)
2. Muscle pain (4.5 vs. 15.2%)
3. Diarrhea (6.0 vs. 13.0%)
The efficacy of naltrexone was determined a global assessment of overall clinical improvement:
.. Markedly improved
.. Moderately improved
.. Mildly improved
.. Unchanged
.. Mildly worse
.. Moderately worse
.. Markedly worse
Naltrexone was used to supplement stable existing therapy in IBD patients or act as sole
treatment in the cases of IBS-SIBO and idiopathic IBS. Patients with chronic constipation were
treated with LDN alone or as an adjunct to other partially effective medications.
Of the 13 patients with idiopathic IBS (3 with diarrhea, 5 with constipation, and 5 with
alternating bowel habits), the results were:
.. 2 (15.3%) were markedly improved
.. 5 (38.5%) were moderately improved
.. 2 (15.3%) were unchanged
.. 3 (23.1%) were markedly worse
Of the 3 that were worse, the results were:
.. 1 had IBS-constipation
.. 2 had IBS-alternating bowel habits
The 85 patients with IBS-SIBO were treated for a mean of 14.2 weeks (58 with 2.5 mg and 27
with 2.5 mg twice daily LDN), with the following results:
.. 15 (17.6%) were markedly improved
.. 32 (37.6%) were moderately improved
.. 11 (12.9%) were mildly improved
.. 23 (27.0%) were unchanged
.. 3 (3.5%) were moderately worse
.. 1 (1.2%) were markedly worse
A second course of antibiotics were administered in 38% of these patients during the 14 weeks to
retreat recurrent symptoms of SIBO.
LDN (2.5 mg twice daily) was administered for a mean of 10.8 weeks in 12 patients with
chronic constipation. Of these patients, the results were:
.. 7 (58.3%) were markedly improved
.. 1 (8.3%) was moderately improved
4
.. 3 (25.0%) were mildly improved
.. 1 (8.3%) was unchanged
Eight patients with inflammatory bowel disease (4 Crohn’s and 4 ulcerative colitis) were
treated with 4.5 mg naltrexone daily for a mean of 16.8 weeks, with the following results:
.. Two were markedly improved
.. 1 was moderately improved
.. 1 was mildly improved
.. 4 were unchanged
Two of those who stated they were unchanged were in clinical remission prior to starting
naltrexone.
Discussion
The current study shows that side effects of LDN occurred frequently (61%) and led to
cessation of the treatment in a quarter of those with adverse effects. The retrospective nature of
the study and incomplete return of the surveys would likely bias the frequency to a higher
number of adverse effects. There are few studies that have evaluated side effects of LDN. In 40
multiple sclerosis patients treated with 3.0 mg naltrexone, 3 reported having trouble
concentrating and 1 reported having fatigue.6 In 42 IBS patients treated with ultra-LDN (0.5 mg),
no side effects were reported.4
There is theoretic value to use of LDN in GI disorders, but few articles have been published.
One study of 50 mg naltrexone to affect GI motility failed to show efficacy in treatment of
constipation in IBS.9 In an open-label study, 89% of 17 Crohn's disease exhibited a response to
LDN (4.5 mg daily), and 67% achieved a remission (P <0.001).6 In another open-label study, 42
IBS patients participated and received ultra-LDN (0.5 mg daily).4 During treatment, the mean
weekly number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 (P = 0.011).
In the present study, the global responses to LDN appeared to show promise in IBS, IBSSIBO,
chronic constipation, and inflammatory bowel disease. The nature of this study did not
allow for quantitative analysis. Retrospective nature and incomplete data collection further
reduced the conclusions that can be reached. Further study appears to be warranted to determine
the efficacy of LDN in GI diseases.
Conclusion
LDN is not without potential for side effects. Future use of methylnaltrexone may be better
tolerated since it does not cross the blood brain barrier.
References
1. Garbutt JC. The state of pharmacotherapy for the treatment of alcohol dependence. J Subst
Abuse Treat 2009; 36(1): S15–S23.
2. Adi Y, Juarez-Garcia A, Wang D et al. Oral naltrexone as a treatment for relapse prevention
in formerly opioid-dependent drug users: A systematic review and economic evaluation.
Health Technol Assess 2007; 11(6): iii–iv, 1–85.
3. [No author listed.] Low dose naltrexone. [Low Dose Naltrexone Website.] December 20,
2009. Available at: www.lowdosenaltrexone.org. Accessed March 30, 2009.
4. Kariv R, Tiomny E, Grenshpon R et al. Low-dose naltrexone for the treatment of irritable
bowel syndrome: A pilot study. Dig Dis Sci 2006; 51(12): 2128–2133.
5. Smith JP, Stock H, Bingaman S et al. Low-dose naltrexone therapy improves active Crohn's
disease. Am J Gastroenterol 2007; 102(4): 820–828.
6. Gironi M, Martinelli-Boneschi F, Sacerdote P et al. A pilot trial of low-dose naltrexone in
primary progressive multiple sclerosis. Mult Scler 2008; 14(8): 1076–1083.
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7. Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med
Hypotheses 2009; 72(3): 333–337.
8. Thomas J, Karver S, Cooney GA et al. Methylnaltrexone for opioid-induced constipation in
advanced illness. N Engl J Med 2008; 358(22): 2332–2343.
9. Foxx-Orenstein AE, Camilleri M, Szarka LA et al. Does co-administration of a non-selective
opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipationpredominant
irritable bowel syndrome? A randomized controlled trial. Neurogastroenterol
Motil 2007; 19(10): 821–830.
Table. Side Effects of Low Dose Naltrexone in 121 Patients.
Number
of Participants Percentage of Participants
Neurological Side Effects with Side Effects with Side Effects
Anxiety 19 15.7
Drowsiness 14 11.6
Headache 14 11.6
Dizziness 13 10.7
Insomnia 10 8.3
Muscle pain 10 8.3
Vivid dreams 6 5.0
Mood change 4 3.3
Trouble concentrating 2 1.7
Gastrointestinal Side Effects
Nausea 15 12.4
Abdominal pain 14 11.6
Diarrhea 10 8.3
Anorexia 10 8.3
Other Side Effects
Rash 1 0.1
Hot flashes 1 0.1
Weight gain 1 0.1
_________________
"Low Dose Naltrexone (LDN) may well be the most important therapeutic breakthrough in over fifty years. It provides a new, safe and inexpensive method of medical treatment by mobilizing the natural defenses of one's own immune system.
........... " — David Gluck, MD
ÇEVİRİSİ.:...............
"Düşük Doz naltrekson (LDN) de en önemli tedavi atılım elli yıl içinde olabilir. Bu kişinin kendi bağışıklık sisteminin doğal savunma seferber ederek tıbbi tedavi, güvenli ve ucuz yeni bir yöntem sağlar.LDN önemli sağlık maliyetlerini azaltır ve hastalıkların geniş bir dizi tedavi artırır........
Naltroxene (LDN = Low Dose
Naltrexone)..(ETHYLEX -VIVITROL-NEMEKSİN=Muadili NALTREXONE)
OKUNUŞLARI:Naltrekson,Naltrexone,Naltreksone
http://www.barsakforum.com/naltrexone-tedavisi-crohn-da-vt58.html?highlight=naltroxen |
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