New evidence on the pharmacological management of neuropathic pain

Alcántara Montero, A.; Sánchez Carnerero, C.I.

doi:10.1016/j.redare.2020.05.011

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MME: morphine milligram equivalents; NP: neuropathic pain; SNRI: serotonin norepinephrine reuptake inhibitors." ] ] ] "textoCompleto" => "The French Society for the Study and Treatment of Pain and the French Society of Neurology recently published its recommendations for the pharmacological management of neuropathic pain (NP).<a class="elsevierStyleCrossRef" href="#bib0005">1</a> We have found these recommendations interesting due to the methodology used and because they update the current clinical practice guidelines.<a class="elsevierStyleCrossRefs" href="#bib0010">2–5</a> To compile these recommendations, the authors performed a systematic peer review of randomized clinical trials (RCTs) with oral drugs or topical pharmacological treatments published in journals indexed in PubMed/MEDLINE and Embase from June 2013 to 18 January 2018. For studies published from 1966 to June 2013, they reviewed the most recent systematic review and meta-analysis on this topic, which was published in 2015, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence and the strength of recommendations, as well as similar inclusion criteria.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The types of NP included postherpetic neuralgia, painful diabetic and non-diabetic polyneuropathy, postamputation pain, post-traumatic/postoperative NP including plexus avulsion and complex regional pain syndrome type II, post-stroke central pain, pain from spinal cord injury, and pain associated with multiple sclerosis. Mixed nociceptive/neuropathic pain (e.g. NP from cancer and radiculopathy) was included, provided NP was analysed separately. Conditions such as complex regional pain syndrome type I, low back pain without radicular pain, fibromyalgia, and persistent idiopathic facial pain were not included, because they do not meet the current definition of NP established the International Association for the Study of Pain (IASP) (pain caused by injury or disease of the somatosensory nervous system). Trigeminal neuralgia was excluded because it generally reacts differently to pharmacological therapy.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The overall quality of the studies was considered “very high” if no bias was observed, “high” if there was only 1 or 2 biases, “moderate” if there were 3 or 4 biases and “low to very low” if there were 5 or more biases. The main sources of bias were: a poorly designed randomization sequence, lack of concealment of the randomization sequence, lack of blinding, considerable losses to follow-up, absence of an intention-to-treat analysis, trials stopped early for benefit, and selective description of outcomes.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> This classification differs slightly from that used in previous systematic reviews of treatments for NP<a class="elsevierStyleCrossRefs" href="#bib0010">2–5</a> in which “low” and “very low” quality trials were generally considered separately.These recommendations are summarized in a therapeutic algorithm based on the treatments available in France (which are similar to those in Spain) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The recommendation levels in the algorithm also took into account ease of use and long-term experience with the treatments, but did not consider costs, as these can vary from country to country and change over time. For the same reasons, the indications for the pharmacological treatments in NP proposed by the different regulatory agencies were not taken into account.<a class="elsevierStyleCrossRef" href="#bib0005">1</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Contrary to current recommendations/guidelines,<a class="elsevierStyleCrossRefs" href="#bib0010">2–5</a> we would like to highlight the main differences/novelties of this update<a class="elsevierStyleCrossRef" href="#bib0005">1</a>:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Pregabalin is proposed as an alternative to gabapentin for second-line treatment. In fact, the most recent large-scale high-quality studies have shown that pregabalin is ineffective or only weakly effective relative to placebo at doses similar to those used in routine clinical practice (generally 300 mg/day). All of these studies, including those with positive results, had very small effect sizes. A recent high-quality comparative study in chronic sciatica showed that gabapentin was significantly more effective and had fewer adverse effects than pregabalin. This is also consistent with recent meta-analyses reporting a lower number needed to harm (NNH) for pregabalin (13.9) than gabapentin (25.6). Another high-quality study reported that pregabalin lacked efficacy in acute and chronic sciatica. Finally, the COMBO trial that compared the efficacy of pregabalin or duloxetine monotherapy with the combination of these 2 drugs in painful diabetic neuropathy also reported significantly lower efficacy for pregabalin (300 mg/day) than for duloxetine (60 mg/day) in the first phase of the trial. Overall, these data suggest that the efficacy and safety of pregabalin was overestimated in the initial studies. Additionally, recent evidence has shown increasing rates of gabapentinoid abuse, and these rates appear to be higher for pregabalin than for gabapentin.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Therefore, we recommend careful monitoring of gabapentinoids. Prescribers of these drugs should be aware of high-risk populations (that is, younger patients, patients with a history of substance abuse, particularly opioids, and psychiatric comorbidities), and monitor for signs of abuse as they do with opioids.</li><li class="elsevierStyleListItem" id="lsti0010">•Based on new high-quality studies that reported positive results for botulinum toxin type A and topical lidocaine, with a good efficacy/safety ratio for both treatments, in this latest review the GRADE level of recommendation for topical lidocaine and Botulinum toxin type A has increased, and these are now recommended as first and second line treatments, respectively, for localized peripheral NP. It should be noted that in France, unlike Spain, 8% capsaicin patches are available in a limited number of pain units.<a class="elsevierStyleCrossRef" href="#bib0005">1</a></li><li class="elsevierStyleListItem" id="lsti0015">•According to recent high-quality studies, combinations of tricyclic antidepressants with opioids or with gabapentinoids are superior to monotherapy with these agents, so the authors recommend combinations of antidepressants and gabapentinoids as second-line treatment if insufficient pain relief is achieved with monotherapy. This recommendation extends to the combination of serotonin and norepinephrine reuptake inhibitor antidepressants with pregabalin, based on a large-scale, high-quality trial that provided positive results. Again, another high-quality study demonstrated the importance of combining gabapentin with morphine for the treatment of NP, although this combination is recommended as a third-line treatment, in the absence of adequate alternatives, and with the lowest possible doses.<a class="elsevierStyleCrossRef" href="#bib0005">1</a></li></ul>Therefore, we consider that periodic updates of the clinical guidelines for NP are necessary to improve our daily clinical practice and rationalize the use of all available therapeutic options. We hope these new recommendations will help improve these goals in the years to come." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Alcántara Montero A, Sánchez Carnerero CI. Nuevas evidencias sobre el manejo farmacológico del dolor neuropático. 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MME: morphine milligram equivalents; NP: neuropathic pain; SNRI: serotonin norepinephrine reuptake inhibitors." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacological and non-pharmacological treatments for neuropathic pain: Systematic review and French recommendations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Moisset" 1 => "D. Bouhassira" 2 => "J. Avez Couturier" 3 => "H. Alchaar" 4 => "S. Conradi" 5 => "M.H. 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Trillo Calvo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semerg.2019.05.008" "Revista" => array:6 [ "tituloSerie" => "Semergen" "fecha" => "2019" "volumen" => "45" "paginaInicial" => "535" "paginaFinal" => "545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31337589" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23411929/0000006700000010/v1_202012131408/S2341192920301657/v1_202012131408/en/main.assets" "Apartado" => array:4 [ "identificador" => "66474" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letter to the Director" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23411929/0000006700000010/v1_202012131408/S2341192920301657/v1_202012131408/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192920301657?idApp=UINPBA00004N"]

ISSN: 2341-1929

Revista Española de Anestesiología y Reanimación (REDAR) -the Spanish Journal of Anesthesiology and Resuscitation- is the scientific body of the Spanish Society of Anesthesiology, Resuscitation and Pain Therapy. This is a monthly journal (10 issues) that publishes scientific articles of all areas within its specialty: clinical anesthesia, resuscitation-intensive medicine and critical care, diagnosis and treatment of acute and chronic pain, urgent care and emergencies and studies on basic science and related fields. The journal accepts work in both Spanish and English.

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