Efficacité et tolérance du tramadol dans les douleurs néoplasiques

Résumé

Afin de comparer l’effet antalgique et la tolérance du tramadol et de la buprénorphine, 60 patients (44 hommes, 16 femmes, âge moyen 61,4 ans) tous présentant des tumeurs à un stade avancé, ont été traités, par voie orale, dans un essai contrôlé croisé avec séquences randomisées.

Les patients ont pris les deux traitements, chaque molécule pendant une semaine, avec une fenêtre thérapeutique de 24 heures entre les deux.

Le tramadol a été prescrit à une dose orale quotidienne de 300mg, et la buprénorphine en sublingual à 0,6 mg/jour. L’état général a été évalué (à l’aide de l’échelle de Karnofsky) ainsi que l’intensité de la douleur, avant et dans les 4 heures suivant la prise des deux médicaments. Chaque patient a également rempli un livret d’évaluation quotidien afin de recueillir le niveau de la douleur une heure après la prise, l’évolution de la douleur au cours de la journée et son intensité par rapport à celle de la journée précédente. Ils ont également évalué la durée et la qualité du sommeil.

L’échelle de Karnofsky a révélé peu d’écarts entre les deux traitements, mais toutes les autres variables ont montré une nette amélioration de la douleur, indiquant ainsi l’effet antalgique significatif des deux molécules.

La buprénorphine et le tramadol ont produit un effet analgésique comparable, mais l’amélioration avec le tramadol était significative dans les 60 minutes suivant la prise (p < 0,05 par rapport à l’évaluation initiale) et plus forte (p < 0,05 aux 2ème, 4ème, 6ème et 7ème jours par rapport à la buprénorphine).

A la fin du traitement par le tramadol, une amélioration du sommeil a également été constatée, tant au niveau quantitatif que qualitatif (tous deux p < 0,05). L’évaluation finale a été largement en faveur du tramadol, en ce qui concerne l’efficacité (p < 0,05) et la tolérance (p < 0,01).

De ce fait, le tramadol a été mieux toléré, provoquant des effets indésirables moins nombreux et moins forts que la buprénorphine, amenant un seul patient à interrompre le traitement par rapport à 18 patients sous buprénorphine.

English Abstract

Opioid analgesics represent one of the most important tools in a sequential pharmacological approach to oncological pain relief. They are recommended by the WHO when nonsteroidal anti-inflammatory drugs (NSAIDs) no longer provide adequate analgesia.

However, the use of opioids is limited because of their numerous and often severe adverse effects. This aspect of opioids has motivated continuous research projects aimed at discovering drugs that can provide maximum pain relief but with improved tolerability.

Tramadol is a new, centrally acting analgesic with a dual mechanism of action. It shows a selective interaction with μ receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release.

From a pharmacokinetic standpoint, tramadol offers high bioavailability, with similar patterns after oral or parenteral administration (half-life 5 to 7 hours, time to peak plasma concentration 3.1 hours, and approximately 20% plasma protein binding).

Although the efficacy of tramadol is comparable to that of other drugs with similar modes of action, the incidence of side effects such as constipation and respiratory depression is lower. The frequency of euphoria and dysphoria is negligible, resulting in little risk of abuse or dependence.

It therefore seemed appropriate to further investigate the efficacy and tolerability of tramadol, defined as having only weak potency, in comparison with a widely used opioid, in oncological pain. Buprenorphine was selected as an opioid with a potency equivalent to half that of morphine, but with tolerability that is partially limited by the fact that it frequently gives rise to adverse reactions considered typical of stronger opioids.

To compare the analgesic effect and tolerability of tramadol and buprenorphine, 60 patients (44 men, 16 women; average age 61.4 years), all presenting with advanced tumours, were treated orally in a controlled crossover trial with randomised sequences.

Patients took both drugs, each for a week, with a 24-hour washout period between treatments.

Tramadol was prescribed at the daily dose of 300mg, orally, and buprenorphine at 0.6 mg/day, as a sublingual preparation.

Assessments were made of Karnofsky performance status and severity of pain before and during the 4 hours after taking the 2 drugs. Each patient also completed a daily diary recording the severity of pain 1 hour after the dose, the evolution of pain during the day and its severity compared with that on the previous day. They also assessed the duration and quality of sleep.

The Karnofsky index changed little with either treatment, but all other variables showed worthwhile improvement, indicating the significant analgesic effect of both drugs.

Buprenorphine and tramadol had a similar analgesic effect, although the improvement with the test drug was significant within 1 hour of administration (p < 0.05 compared with baseline) and more marked (p < 0.05 on day 2 compared with buprenorpine).

At the end of tramadol treatment, sleep had also improved, both quantitatively and qualitatively (both p < 0.05). The final assessment was significantly in favour of tramadol as regards efficacy (p < 0.05) and patient acceptability (p < 0.01).

Thus, tramadol was better tolerated than buprenorphine, and caused fewer and milder adverse reactions. Only 1 patient discontinued tramadol, compared with 18 using reference therapy. Tramadol, although theoretically less potent, nevertheless brought about as much pain relief as the comparator opioid.

In conclusion, for this class of drug, tramadol provides an excellent balance between efficacy and tolerability, confirming preliminary studies.