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| Maribel Márquez*, Silvia Guzman and Herman Soto | |
| Clinical Departament, HS Pharmaeconomic studies, Distrito Federal 09360, Mexico, USA | |
| Corresponding Author : | Márquez M Pharmacoeconomics coordinator HS Pharmaeconomic studies Distrito Federal, Distrito Federal Mexico, USA Tel: 52 5526362946 E-mail: maribel.marquez@health-solutions.mx |
| Received September 23, 2015; Accepted November 16, 2015; Published November 20, 2015 | |
| Citation: Márquez M, Guzman S, Soto H (2015) Systemic Review on the Use of Diclofenac/B Complex as an Anti-Inflammatory Treatment with Pain Relief Effect for Patients with Acute Lower Back Pain. J Pain Relief 4:216. doi:10.4172/21670846.1000216 | |
| Copyright: © 2015 Márquez M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
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Objective: the goal of this paper is to perform a systematic review on the use of diclofenac/B complex indicated for acute low back pain, compared to other available therapies for low back pain.
Material and Methods: The systematic review was performed on the following databases: Medline/Pubmed, Cochrane Library (CENTRAL), EMBASE, Imbiomed,LILACS, Artemisa and Nieto Editores, up until February 14th, 2015. A manual searchwas also performed on Google search. Key words were used under the MeSH terminology (Medical Subject Headings): low back pain, lumbago, diclofenac/vitamin B, non-steroidal anti-inflammatory, diclofenac, ibuprofen, naproxen, treatment. Study: Selection was performed by two investigators experts on the subject, selecting those studies with relevant information for the goal of this review.
Results: We found 261 studies with potential interest. Finally, 2 studies were selected, 1 clinical trial and a systematic review. The systematic review by Roelofs et al. (2011), which was done with Cochrane Collaboration and had as a goal to evaluate the effects of NDAIS´s and COX-2 inhibitors on non-specific low back pain treatment and to evaluate which NSAID´s was the most effective. The other selected study was a clinical trial performed by Mibielli et al. in 2009, a randomized study, double-blinded,with parallel groups, that included patients that received diclofenac and B complex andthe other arm received only diclofenac.
Conclusion: Diclofenac/B complex has a pain relief effect, anti-inflammatory and synergic neuro-regenerative effect, and this efficiency has been evaluated in several clinical studies where the administration of diclofenac plus vitamins B1, B6 and B12 decreases pain quicker, apart from being a safe drug.
| Keywords |
| Systemic review; Diclofenac/B complex; Acute lower back pain |
| Introduction |
| Pain is the most frequent cause of medical consults. The International Association for the Study of Pain (Asociación Internacional para el Estudio del Dolor) has defined pain as “a sensitive and emotionally unpleasant experience associated with real or potential tissue damage”. Perception of pain depends on a neuronal sensitivity system (pain receptors) and afferent nervous pathways that respond to tissue stimuli on such receptors [1]. |
| Chronic pain is a public health problem. It has been suggested that this health problem affects 25 to 29% of general population worldwide. In Mexico, we lack information on the prevalence of chronic pain; however, the National Institute of Social Security, reports that 5% of diseases attended by first contact physicians, are painful by definition [2]. |
| Nowadays a drug exists that combines the anti-neuritic effect of B complex (vitamins B1, B6 and B12) with the anti-inflammatory effect of diclofenac to achieve pain relief effect useful for neurological and neuropathic diseases [3]. |
| Low back pain can be defined as pain or soreness on the lower back, between the inferior border of the last ribs and the inferior crease of the gluteal area, that frequently has a neuritic component with or without expansion to one or both legs, it may involve ostheomuscular and ligament structures, with or without functional limitations that may complicate a daily life and even cause work absenteeism [4]. |
| Low back pain represents an important public health problem in occidental societies due to its elevated prevalence, high impact, magnitude and socio-economic repercussions; it affects labour age population and generates an increase in resource use and work day losses. It is estimated that 60.7% of adults have an episode of lumbar pain syndrome in their lives [5] and there is evidence that it represents one of the main causes of physical limitations in people under 45 years of age. In Mexico, the National Institute of Social Security (IMSS, by its letters in Spanish) reports that low back pain constitutes the eight causes of family medicine consults, registering a total of 907,552 consults at the first level of medical attention [6]. |
| There are several clinical practice guidelines (CPG) for low back pain, (Table 1) according to the recommendations regarding its treatment, it is suggested the use of acetaminophen as a first line drug and the use of NSAID´s as a second line drug, specifically the use of diclofenac, ibuprofen and naproxen [4,7-11]. |
| Given the importance of this disease, the goal of this paper is to perform a systematic review on the use of the association B complex and diclofenac indicated for acute low back pain, compared to other available therapies for this disease, which are recommended on clinical practice guidelines. |
| Materials and Methods |
| To perform a systematic review, the research question for the search of clinical studies was: does the association of B complex and diclofenac [diclofenac 75 mg/B complex (cyanocobalamin 1 mg, thiamine 100 mg y pyridoxine 100 mg)] is better for pain relief in patients with acute lower pain than other non-steroid anti-inflammatory agents (specifically ibuprofen, diclofenac and naproxen) as a monotherapy? |
| Research strategy |
| Study search was performed on the following databases: Medline/ Pubmed, Cochrane Library (CENTRAL), EMBASE, Imbiomed, LILACS, Artemisa and Nieto Editores, up until February 14th, 2015. A manual search was also performed on Google search. Key words were used under the MeSH terminology (Medical Subject Headings): low back pain, lumbago, diclofenac/vitamin b, non-steroidal antiinflammatory, diclofenac, ibuprofen, naproxen, treatment. Language filters were used (English and Spanish), clinical trials, meta-analysis and systematic reviews, as long as they were adequate to use on our database. |
| Study Selection |
| Study selection was performed by two investigators experts on the subject, selecting those studies with relevant information for the goal of this review; clinical studies, systematic reviews and/or meta-analysis were selected, which evaluated the comparison to monotherapy for acute low back pain. The selection only included studies with complete texts, excluding editorial letters and publication abstracts, as well as those with chronic low back pain, patients that received other additional medications different from those relevant to this study and those performed in children. Discrepancies were resolved by mutual discussion. The agreement between the two reviewers for selection and validity assessment of trials was scored by kappa coefficient. |
| Data extraction from individual studies |
| The context of all selected studies was obtained on an initial database with the goal of deciding if the obtained data was comparable or not, for a possible meta-analysis. |
| Quality of the studies evaluation |
| In the selected studies, the complete text was searched to ensure that it fulfilled the required information from the clinical studies by the Consolidated Standards of Reporting Trial from 2010 and by the PRISMA Declaration for the systematic reviews and meta-analysis [12]. |
| Results |
| Study selection |
| With the search algorithm (Table 1), we found 261 studies with potential interest. After eliminating repeated studies and after reading all abstracts, it was decided to review a total of 9 texts, which were analysed for their subsequent evaluation. Finally, 2 studies were selected, 1 clinical trial and 1 systematic review. Agreement between two reviewers for study selection was 0.87 and the kappa value shown concordance important. |
| Study characteristics |
| The systematic review by Roelofs et al. from 2011 [13], which was done by Cochrane Collaboration and had as a goal to evaluate the effects of NDAIS´s and COX-2 inhibitors (meloxicam 7.5/day and 15 mg/day, valdecoxib 40mg/day, etoricoxib 60 mg/day) on non-specific low back pain treatment and to evaluate which NSAID´s was the most effective; patients over 18 years of age were evaluated that required pain treatment that was caused by non-specific low back pain with or without sciatic pain. They included 65 clinical trials with a total of 11,327 patients (Tables 2-4). |
| The other selected study was a clinical trial performed by Mibielli et al. in 2009 [14], a randomized study, double-blinded, with parallel groups, that included 187 patients that received diclofenac (50 mg) and B complex (thiamine, pyridoxine and cyanocobalamin [50 mg/50 mg/1 mg] twice a day and 185 patients that received diclofenac 50mg twice a day. |
| Quality of the studies |
| Regarding the systematic review performed by Roelofs et al, it fulfilled all the suggested items by the PRISMA Declaration, and it’s worth mentioning that because it is a document from the Cochrane Collaboration, whose strict method is the most adequate. The clinical trial elaborated by Mibielli, according to the CONSORT items, the title was not identified as a clinical trial, and the study registry name was not specified, while the other items are all described within the document. For these reason we can conclude that both studies have adequate quality. |
| Discussion |
| For treatment of low back pain, NSAID’s are the most prescribed drugs worldwide. NSAID’s are mildly effective for short term treatment in patients with low back pain, both acute and chronic, however they are more effective than drugs such as acetaminophen, opioids or muscle relaxants, and comparing NSAID’s with the new COX-2 inhibitors, these last ones are equally effective but are associated with less adverse effects, particularly gastric ulcer and renal damage [13]. |
| Several studies have reported that thiamine, pyridoxine and cyanocobalamin have an important role for the adequate function of the central nervous system, the myelin cover and other cell structures, it is essential for nutrition, axonal transport, neural excitability and neurotransmitter synthesis, and combined with diclofenac they present a synergic action in ostheomuscular diseases and pain management [3,15,16]. The mechanisms are currently unknown, it has been proposed that the antihyperalgesic mechanisms of B vitamins include its ability to increase afferent inhibitory control of nociceptive neurons at the spinal cord [17], to improve sensory nerve conduction velocity [18] and to reduce neuronal hyperexcitability by altering sodium currents in injured dorsal root ganglia [19]. Moreover, the individual administration of thiamine and pyridoxine produce antinociception in acetic acid-induced pain or pain induced by supramaximal electrical stimulation of afferent C fibers, in the last years it has been postulated that B vitamins induced antinociception could result from activation of opioid receptors or nitric oxide release [20]. |
| The indication of low back pain in the association diclofenac/B complex obeys the clinical effects that have been reported from the pain relief effect related to the synthesis and metabolism of neurotransmitters such as acetylcholine, gamma-aminobutyric acid, dopamine and serotonin, that participate in their liberation from the pre-synaptic membrane, as well as the synthesis of sphingolipids that constitute the myelin cover, which translates into a pain relief effect [3], these studies are experimental in pre-clinic phase but evaluate different kind of pain, not specifically low back pain [17,18,20-22]. Respect to low back pain, a double-blind randomised, placebo-controlled study clinical study that examine the efficacy and safety intramuscular vitamin B12, showed a statistically significant difference in favour of the active treatment both for visual analogic scale (VAS) and Disability Questionnaire (DQ) and decreasing the consumption of paracetamol [23]. Another clinical trial that studied combination of B vitamins and diclofenac was performed by Kunt et al., studying 53 patients with acute low back pain reporting good or excellent results in pain management in 77.4% and moderate effects in 15.1% [24], however the language of this study is Germany by this reason not is included in this paper. |
| It is worth mentioning that there are several published studies that could not be included in this systematic review given that even though they study patients with low back pain, it was not possible to obtain the complete version of such studies and they are in different languages to Spanish or English. However the evaluated results indicate an improvement in pain with a combination of diclofenac with thiamine, pyridoxine and cyanocobalamin, such studies are described here: Vetter et al, evaluated 256 patients with low back pain comparing diclofenac versus diclofenac with vitamin B1, B6 and B12, to determine if the duration of treatment was shortened with the addition of B complex, and all the results were evaluated with the Hoppe Pain Questionnaire (HPQ) (this questionnaire evaluate different aspects of the perceived pain on a 7 point Likert scale, comprises 4 primary scales: pain suffering, pain anxiety, pain sharpness and pain rhythm) [25]; and showed superiority of diclofenac with vitamin B1, B6 and B12; they documented adverse effects in 39 patients, 14 of which required to stop treatment [26]. Also Bruggemann et al studied in 418 patients the clinical efficiency of diclofenac with B complex for a maximum period of 3 week compared to diclofenac. The evaluation from the HPQ and other additional data related to pain intensity indicated better results with the combination therapy; regarding safety there was no statistically significant difference between both groups [27]. However, given the perception of clinical practice and published work [28,29] it looks like the response to NSAID’s varies amongst individuals, which makes indication and evaluation of response to these drugs to be individualized, and thus the selection of the drugs will depend fundamentally on the patients characteristics, the NSAID’s profile and the physician experience with their use [30]. |
| Although the previously described studies have showed beneficial effects of using diclofenac/B complex, we notice that there are very few published studies that evaluate it for low back pain, a chronic disease that affects patient’s life quality and that the probability for generalpopulation to suffer it is high. |
| Apart from these studies, the combination of diclofenac with thiamine, pyridoxine and cyanocobalamin was also evaluated in patients with fractures or surgeries of the lower extremities. The first study was a pilot clinical trial where the combination B complex with diclofenac was evaluated; the pain was evaluated with a visual analogue scale that showed a significant decrease at 12, 24, 36 and 48 hours postsurgery, and in general drugs were well tolerated [31]. The second study was performed by Ponce et al., and it evaluated the combination of diclofenac and B complex in 122 patients with acute lower pain from a fracture or surgery of lower extremities showing a significant decrease of pain compared to diclofenac, which means that adding B complex increases pain relief effect of diclofenac [32]. |
| This favourable evidence of the use of diclofenac/B complex could indicate that given the beneficial results of its use in the population, it could be feasible to search for a better clinical scenario to be able to use, and thus be able to evaluate the effects of diclofenac/B complex in different pain scenarios for which it may be indicated. |
| For the studies selected from this systematic review, in the paper performed by Roelofs et al. included the trials performed by Vetter and Bruggemann (previously described). However, considering the sample size of patients treated in both studies, regarding the total sample from all studies, they weren’t able to find statistically significant differences for the combination of diclofenac and vitamins B1, B6 and B12. |
| Respect to the study by Mibielli et al, corroborates the mayor pain relief effect of diclofenac while combined with thiamine, pyridoxine and cyanocobalamin. |
| In this work we also reviewed the CPG for other therapeutic indications of diclofenac/B complex, however only the general use of NSAID’s is recommended in certain diseases such as neck pain or arm pain; in cases of neuropathies the use of NSAID’s associated with tricyclic antidepressants, and for fibromyalgia the use of NSAID’s associated to other drugs. However, none of the CPG suggests the use of diclofenac/B complex, and we could neither find clinical studies that evaluate the indications we previously mentioned. For alcoholic neuropathies only the use of Vitamin B is recommended, but not diclofenac; for radiculitis physical therapy is recommended, and for carpel tunnel syndrome the treatment is surgery. |
| Conclusion |
| We can conclude that diclofenac/B complex has a pain relief effect, anti-inflammatory and synergic neuro-regenerative effect, and this efficiency has been evaluated in several clinical studies where the administration of diclofenac plus vitamins B1, B6 and B12 decreases pain quicker, apart from being a safe drug. Nevertheless, the evidence in literature that seem to favour the use of diclofenac/B complex is slim and does not fulfil with the adequate quality regarding the obtained benefits in patients that use it for the approved indications. We suggest increasing scientific data to conclude more on the use of diclofenac/B complex for low back pain. |
| Declaration of Interests |
| The authors declare no competing interest, but this study was funded by Merck Serono. |
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| Table 1 | Table 2 | Table 3 | Table 4 |
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| Figure 1 |
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