Zusammenfassung
Der neuropathische Schmerz entsteht per definitionem durch eine Funktionsstörung peripherer afferenter und/oder efferenter oder zentraler
Axone unabhängig von deren Ursache. Etablierte medikamentöse Therapieverfahren mit
trizyklischen Antidepressiva und Ionenkanalblockern erreichen bei numbers-needed-to-treat
zwischen 2 und 3,7 nur bei bis zu 50 % der Patienten eine suffiziente Schmerzkontrolle.
Der Einsatz von Opioiden bei neuropathischen Schmerzen im Rahmen einer eskalierenden
Therapiestrategie wurde bisher kontrovers diskutiert. Neuere Studien zeigen eine Wirksamkeit
von Opiaten und Opioiden bei dieser Indikation, die der der etablierten Medikamente
ebenbürtig ist. Die hier dargestellte Analyse von acht randomisierten und kontrollierten
Untersuchungen mit oraler Gabe von Opioiden und Opiaten ergab eine mittlere number-needed-to-treat
von 2,98 (Standardabweichung 0,93). Viele Studien konnten eine Verbesserung der Alltagsfunktionen
unter der Therapie nachweisen, im Gegensatz zu trizyklischen Antidepressiva scheint
es nicht zu einer kognitiven Beeinträchtigung zu kommen. Damit stellen Opioide und
Opiate eine wichtige therapeutische Option zur erfolgreichen Behandlung neurogener
Schmerzsyndrome dar. Spezifische Therapiekomplikationen müssen beachtet werden. Der
Patient muss über Vor- und Nachteile des Therapiekonzeptes aufgeklärt werden, einschließlich
dem substanzbedingten Auftreten einer körperlichen Abhängigkeit. Das bei den meisten
Patienten zu beobachtende Auftreten unerwünschter Wirkungen mit Übelkeit, Obstipation,
Sedierung, Schwindel und Juckreiz bei unterschiedlich starker Ausprägung muss ggf.
therapeutisch gemildert werden. Diese führen deutlich häufiger als bei Therapien mit
trizyklischen Antidepressiva oder Ionenkanalblockern zum Therapieabbruch. Dabei liegen
die Abbruchquoten bei Patienten mit neuropathischen Schmerzen niedriger als bei anderen
Schmerzindikationen, was am ehesten an den im Vergleich deutlich niedrigeren Tagesdosen
mit Äquivalenzdosen zwischen 15 und 40 mg Morphin pro Tag liegt. Eine Toleranzentwicklung
mit Wirkverlust und subsequenter Dosissteigerung wurde bei Patienten mit neuropathischen
Schmerzen bisher nicht beobachtet. Patienten mit Suchtanamnese sind für diesen Therapieansatz
wegen des prinzipiellen Suchtpotenzials nicht geeignet und müssen im Vorfeld zuverlässig
identifiziert werden. Geeigneten Patienten mit neuropathischen Schmerzen darf damit
auch nach Kriterien der evidence-based medicine die Anwendung von Opiaten und Opioiden
nicht vorenthalten werden.
Abstract
Neuropathic pain is defined as a pain initiated or caused by a primary lesion or dysfunction
in the peripheral and/or central nervous system independent of the single cause. Accepted
pharmacological therapy with tricyclic antidepressants and ion-channel-blocker enable
satisfactory pain control only in up to 50 % of patients considering the numbers-needed-to-treat
between 2 und 3.7. The use of opioids in an escalating therapeutic strategy in neuropathic
pain is controversially discussed. Recent studies demonstrate an efficacy of opioids
in these patients, which is similar to established drugs. In this analysis of eight
randomized controlled trials with oral opioids a mean number-needed-to-treat of 2.98
was found (standard error 0.93). Many of these studies showed an improvement of disability
und social funcitoning scores. In contrast to tricyclic antidepressants no impact
on cognitive function was found. Therefore opioids are an important option for the
successful therapy of neuropathic pain syndroms. Specific issues in the use of opioids
must be observed. The patient must give informed consent to advantages and disadvantages
of this approach, including the physical dependency which is immanent in opioids.
Side effects like nausea, constipation, sedation, dizziness and pruritus occur in
most patients to variable degree and must be treated if necessary. They cause discontinuation
of therapy more frequently than tricyclic antidepressants or ion-channel-blocker.
Overall the discontinuation rate is lower than in other pain syndromes treated with
opioids, which is most likely due to the lower mean daily dosages of an equivalent
of 15 to 40 mg morphine necessary. The development tolerance with loss of efficacy
and subsequent increase in dose was not observed in patients with neuropathic pain.
Patients with a history of addiction must be excluded from the use of opioids before
therapy is initiated. Therapy with opioids should not be withhold from suitable patients
with neuropathic pain as also criteria of evidence-based medicine support their use.
Literatur
- 1 Merskey H, Bogduk N. Classification of Chronic Pain, Second Edition, IASP Task Force
on Taxonomy. Seattle; IASP Press 1994: 209-214
- 2
Sindrup S H, Jensen T S.
Efficacy of pharmacological treatments of neuropathic pain: an update and effect related
to mechanisms of drug action.
Pain.
1999;
83
389-400
- 3
Arnér S, Meyerson B A.
Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain.
Pain.
1988;
33
11-23
- 4
Haddox J D.
The use of opioids for the treatment of chronic pain. A consensus statement from the
American Academy of pain medicine and the American pain society.
Clin J Pain.
1997;
13
6-8
- 5
Sorgatz H, Hege-Scheuing G, Kopf A. et al .
Langzeitanwendung von Opioiden bei nichttumorbedingten Schmerzen.
Deutsches Ärzteblatt.
2002;
99
A2180-2185
- 6
Watson C P, Babul N.
Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia.
Neurology.
1998;
50
1837-1841
- 7
Harati Y, Gooch C, Swenson M. et al .
Double-blind randomized trial of tramadol for the treatment of the pain of diabetic
neuropathy.
Neurology.
1998;
50
1842-1846
- 8
Sindrup S H, Andersen G, Madsen C. et al .
Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind,
controlled trial.
Pain.
1999;
83
85-90
- 9
Sindrup S H, Madsen C, Brosen K, Jensen T S.
The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite
levels.
Clin Pharmacol Ther.
1999;
66
636-641
- 10
Huse E, Larbig W, Flor H, Birbaumer N.
The effect of opioids on phantom limb pain and cortical reorganization.
Pain.
2001;
90
47-55
- 11
Harke H, Gretenkort P, Ladleif H U. et al .
The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine
and sustained-release morphine in patients pretreated with spinal cord stimulation:
a double-blinded randomized study.
Anesth Analg.
2001;
92
488-495
- 12
Raja S N, Haythornthwaite J A, Pappagallo M. et al .
Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled
trial.
Neurology.
2002;
59
1015-1021
- 13
Maier C, Hildebrandt J, Klinger R. et al, MONTAS Study Group .
Morphine responsiveness, efficacy and tolerability in patients with chronic non-tumor
associated pain - results of a double-blind placebo-controlled trial (MONTAS).
Pain.
2002;
97
223-233
- 14
Göbel H, Stadler T.
Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study
versus clomipramine with or without levomepromazine.
Drugs.
1997;
53, Suppl 2
34-39
- 15
Cherny N I.
Opioid analgesics. Comparative features and prescribing guidelines.
Drugs.
1996;
51
713-737
- 16
Benedetti F, Vighetti S, Amanzio M. et al .
Dose-response relationship in nociceptive and neuropathic pain.
Pain.
1998;
74
205-211
- 17
Ventafridda V, Ripamonti C, Conno F de. et al .
Antidepressants increase availability of morphine in cancer patients.
Lancet.
1987;
1
1204
- 18
Ventafridda V, Bianchi M, Ripamonti C. et al .
Study on the effects of antidepressant drugs on the nociceptive action of morphine
and on plasma morphine in rat and man.
Pain.
1990;
43
155-162
- 19
Thomsen A B, Becker N, Eriksen J.
Opioid rotation in chronic non-malignant pain patients.
Acta Anaesthesiol Scand.
1999;
43
918-923
- 20
Arkinstall W, Sandler A, Goughnour B. et al .
Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized,
placebo-controlled clinical trial.
Pain.
1995;
62
169-178
- 21
Lloyd R S, Costello F, Eves M J. et al .
The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination
dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the
hips.
Curr Med Res Opin.
1992;
13
37-48
- 22
Moulin D E, Iezzi A, Amireh R. et al .
Randomised trial of oral morphine for chronic non-cancer pain.
Lancet.
1996;
20
143-147
- 23
Simpson R K, Edmondson E A, Constant C F, Collier C.
Transdermal fentanyl as treatment for chronic low back pain.
J Pain Symptom Manage.
1997;
14
218-224
- 24
Hale M E, Fleischmann R, Salzmann R. et al .
Efficacy and safety of controlled-release versus immediate-release oxycodone: randomized,
double-blind evaluation in patients with chronic back pain.
The Clinical Journal of Pain.
1999;
15
179-183
- 25
McQuay H J, Tramèr M, Nye B A. et al .
A systematic review of antidepressants in neuropathic pain.
Pain.
1996;
68
217-227
- 26
McQuay H, Carroll D, Jadad A R. et al .
Anticonvulsant drugs for management of pain: a systematic review.
BMJ.
1995;
311
1047-1052
- 27
Dole V P.
Narcotic addiction, physical dependence and relapse.
N Engl J Med.
1972;
286
988-992
- 28
Adriaensen H, Vissers K, Noorduin H, Meert T.
Opioid tolerance and dependence: an inevitable consequence of chronic treatment.
Acta Anaesth Belg.
2003;
54
37-47
- 29 South S M, Smith M T. Analgesic tolerance to opioids. IASP Pain Clinical Updates
2001 Vol IX/5
- 30
Medina J L, Diamond S.
Drug dependency in patients with chronic headache.
Headache.
1977;
17
12-14
- 31
Perry S, Heidrich G.
Management of pain during debridement: a survey of US burn units.
Pain.
1982;
13
267-280
- 32
Winkelmüller M, Winkelmüller W.
Long-term effects of continuous intrathekal opioid treatment in chronic pain of non-malignant
etiology.
Neurosurg.
1996;
85
458-467
- 33
France R D, Urban B J, Keefe F J.
Long-term use of narcotic analgesics in chronic pain.
Soc Sci Med.
1984;
19
1379-1382
- 34
Tennant F, Robinson D, Sagherian A, Seecof R.
Chronic opioid treatment of intractable, non-malignant pain.
NIDA Res Monogr.
1988;
81
174-180
- 35
Zenz M, Strumpf M, Tryba M.
Long-term oral opioid therapy in patients with chronic nonmalignant pain.
J Pain Symptom Manage.
1992;
7
69-77
- 36
Dellemijn P L, Duijn H van, Vanneste J AL.
Prolonged treatment with transdermal fentanyl in neuropatic pain.
J Pain Symptom Manage.
1998;
16
220-229
- 37
Schulzeck S, Gleim M, Maier C.
Morphintabletten bei chronischen nicht-tumorbedingten Schmerzen.
Anaesthesist.
1993;
42
545-556
- 38
Way W L.
Basic mechanisms in narcotiv tolerance and physical dependence.
Ann NY Acad Sci.
1978;
311
61-68
- 39 American Psychiatric Association .Diagnostic and statistical manual of mental disorders. Washington
DC; American Psychiatric Association 1994
- 40
American Society of Addiction Medicine .
Public policy statement on definitions related to the use of opioids in pain treatment.
J Addict Dis.
1998;
17
129-133
- 41
Fishbain D A, Rosomoff H L, Rosomoff R S.
Drug abuse, dependence and addiction in chronic pain patients.
Clin J Pain.
1992;
8
77-85
- 42
Regier D A, Myers J K, Kramer M. et al .
The NIMH Epidemiologic Catchment Area program. Historical context, major objectives,
and study population characteristics.
Arch Gen Psychiatry.
1984;
41
934-941
- 43
Zacny J, Bigelow G, Compton P. et al .
College on problems of drug dependence taskforce on prescription opioid non-medical
use and abuse: position statement.
Drug and Alcohol Dependence.
2003;
69
215-232
- 44
Portenoy R K, Foley K M.
Chronic use of opioid analgesics in non-malignant pain: report of 38 cases.
Pain.
1986;
25
171-186
- 45
American Academy of Pain and the American Pain Society .
The use of opioids for the treatment of chronic pain: a consensus statement from the
American Academy of Pain and the American Pain Society.
Clin J Pain.
1997;
13
6-8
- 46
Abreu M E, Bigelow G E, Fleisher L, Walsh S L.
Effecte of intravenous injection speed on responses to cocaine and hydromorphone in
humans.
Psychopharmacology.
2001;
154
76-84
- 47
Roset P N, Farre M, Torre R de la. et al .
Modulation of rate of onset and intensity of drug effects reduces abuse potential
in healthy males.
Drug Alcohol Depend.
2001;
64
285-298
- 48
Weissman D E, Haddox J D.
Opioid pseudoaddiction - an iotragenic syndrome.
Pain.
1989;
46
363-366
- 49
Portenoy R K.
Chronic opioid therapy in non-malignant pain.
J Pain Symptom Manage.
1990;
5
S46-S62
- 50 Schug S A, Large R G. Opioids for Chronic Noncancer Pain. Pain - Clinical updates
1995, Volume III, Issue 3. International association for the study of pain.
- 51
Jamison R N.
Comprehensive treatment and outcome assessment for chronic opioid therapy in nonmalignant
pain.
J Pain Symptom Manage.
1996;
11
231-241
- 52
Nedeljkovic S S, Wasan A, Jamison R N.
Assessment of efficacy of long-term opioid therapy in pain patients with substance
abuse potential.
Clin J Pain.
2002;
18
S39-S51
Privatdozent Dr. med. Stefan Braune
Neurozentrum Prien
Bernauer Straße 12
83209 Prien
Email: braune@neurozentrum-prien.de