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Pharmakologische Interventionen zur Behandlung von Phantomschmerzen

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Abstract

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Background

Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable and disabling. Various medications have been studied in the treatment of phantom pain. Presently there is uncertainty in the optimal pharmacologic management of PLP. 

Objectives

This review aims to summarize the evidence of effectiveness of pharmacologic interventions in treating PLP.

Search methods

We searched the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS) Trials Register, the Cochrane Controlled Trials Register (CENTRAL, The Cochrane Library), MEDLINE and EMBASE up to September 2011 for randomised and quasi‐randomised trials comparing pharmacologic treatment with placebo, another active treatment, or no treatment.

Selection criteria

We included randomised and quasi‐randomised trials studying the effectiveness of pharmacologic interventions in patients with established PLP. The outcomes considered were change in pain intensity, function, mood, sleep, quality of life, satisfaction and adverse effects.

Data collection and analysis

Three review authors independently assessed the methodologic quality of the studies and extracted the data. We reported continuous and dichotomous data on change in pain intensity, function, mood/depression scores, sleep, quality of life, satisfaction for each study, where available. Because of the wide variability in the studies, we did not perform a meta‐analysis for all the interventions and outcomes but we attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results and described adverse effects. We assessed clinical heterogeneity by making qualitative comparisons in terms of the populations, interventions, outcomes/outcome measures and methods.

Main results

From 583 references/publications, we selected 13 studies involving 255 participants. Six groups of medications were reviewed, namely, N‐methyl D‐aspartate (NMDA) receptor antagonists, antidepressants, anticonvulsants, anaesthetics, opioids, and calcitonin. Ten studies were of high quality and three were of moderate quality based on both Jadad and Van Tulder criteria. Because of the wide variation (heterogeneity) in the pharmacologic interventions, outcome measures, analyses, reporting of results, duration of follow‐ups and study designs, it was not possible to pool the results for most of the interventions and outcomes. Morphine (oral and intravenous) was effective in decreasing pain intensity in the short‐term with reported adverse effects being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems. The NMDA receptor antagonists, ketamine and dextromethorphan but not memantine, had analgesic effects. The adverse effects of ketamine were more serious and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety. The results for gabapentin in terms of pain relief were conflicting but combining the results showed a trend towards benefit. Gabapentin, however, did not improve function, depression score and sleep quality. Side effects experienced were somnolence, dizziness, headache and nausea. Amitryptiline was not effective in PLP with dry mouth and dizziness as side effects based on one study. The findings for calcitonin and anaesthetics were variable. Adverse effects of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes.

Authors' conclusions

The short‐ and long‐term effectiveness of opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and anaesthetics for clinically relevant outcomes that include pain, function, mood, sleep, quality of life, satisfaction and adverse effects remains unclear. Morphine, gabapentin and ketamine demonstrate trends towards short‐term analgesic efficacy. Memantine and amitriptyline were ineffective for PLP. Results, however, are to be interpreted with caution as these were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long‐term efficacy and safety outcomes. The direction of efficacy of calcitonin, anaesthetics and dextromethorphan need further clarification. Larger and more rigorous randomised controlled trials are needed to make stronger recommendations about which medications would be useful for clinical practice.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Laienverständliche Zusammenfassung

Medikamente zur Behandlung von Phantomschmerzen bei Patienten mit fehlenden Gliedmaßen

Verschiedene Medikamente wurden gegen Phantomschmerzen eingesetzt, aber die Behandlung bleibt nach wie vor unbefriedigend. Ob Opioide, N‐Methyl‐D‐Aspartat (NMDA)‐Rezeptor‐Antagonisten (z.B. Ketamin, Memantin, Dextromethorphan), Antikonvulsiva, Antidepressiva, Calcitonin und Anästhetika wirksam sind bei der Verbesserung der Ergebnisse, wie Schmerzen, Funktion, Stimmung, Schlaf, Lebensqualität, Zufriedenheit und Sicherheit, in der kurz‐ und langfristigen Anwendung, bleibt weiterhin ungewiss. Morphin, Gabapentin und Ketamin bewirken eine kurzfristige Schmerzlinderung, die Ergebnisse basierten aber meist auf kleinen Studien. Die Ergebnisse für Calcitonin und Anästhetika waren unterschiedlich. Erhebliche Unterschiede in den Medikamenten, Methoden, Designs, Endpunkten, Endpunktmaßen, der Nachbeobachtung, den Analysen und Berichten / Präsentation der Ergebnisse machten es schwierig, Ergebnisse für die Interventionen und Endpunkte zu kombinieren. Die Ergebnisse sind mit Vorsicht zu interpretieren, da diese auf einigen wenigen Studien mit einer kleinen Anzahl von Studienteilnehmern basieren und Daten über die langfristige Wirksamkeit und Sicherheit fehlen. Studien von guter Qualität mit ausreichender Fallzahl, längerer Nachbeobachtung und mit patientenrelevanten Endpunkten sind notwendig, um sicherere Empfehlungen machen zu können und somit eine gute Beratung über die beste Schmerzlinderung bei dieser Patientenpopulation zu ermöglichen.