Brief report
Use of antidepressants in the treatment of chronic orofacial pain caused by temporomandibular disorders: A randomized controlled clinical trial
Uso de antidepresivos en el tratamiento del dolor orofacial crónico causado por trastornos temporomandibulares: un ensayo clínico controlado y aleatorizado
Bruno Macedo de Sousaa, Antonio López-Valverdeb, Francisco Carameloc, Maria Joao Rodriguesa, Nansi López-Valverdeb,
Corresponding author
a Institute for Occlusion and Orofacial Pain Faculty of Medicine, University of Coimbra, Coimbra, Portugal
b Department of Surgery, University of Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
c Laboratory of Biostatistics and Medical Informatics, Coimbra, Institute for Clinical and Biomedical Research (iCBR), School of Medicine, University of Coimbra, Coimbra, Portugal
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[ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Antonio" "apellidos" => "López-Valverde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Francisco" "apellidos" => "Caramelo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Maria Joao" "apellidos" => "Rodrigues" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:4 [ "nombre" => "Nansi" "apellidos" => "López-Valverde" "email" => array:1 [ 0 => "nlovalher@usal.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Institute for Occlusion and Orofacial Pain Faculty of Medicine, University of Coimbra, Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Surgery, University of Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Laboratory of Biostatistics and Medical Informatics, Coimbra, Institute for Clinical and Biomedical Research (iCBR), School of Medicine, University of Coimbra, Coimbra, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Uso de antidepresivos en el tratamiento del dolor orofacial crónico causado por trastornos temporomandibulares: un ensayo clínico controlado y aleatorizado" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1243 "Ancho" => 1675 "Tamanyo" => 151863 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow chart of progress through the phases of the study according to the CONSORT statement 2010.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Temporomandibular disorders (TMDs) are a generic term that encompasses clinical conditions affecting the muscles of mastication, the temporomandibular joint (TMJ) and associated structures, resulting from a series of alterations of the masticatory system. The main symptom is pain, localized in the area of the masticatory muscles and/or in the preauricular area with a prevalence of 31.1% for adults and 11.3% for children.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The etiology is multifactorial (parafunctions, clenching of teeth, stress, etc.) and continuous pain is frequently associated with comorbid pathologies such as anxiety, depression and insomnia, with patients sometimes presenting different degrees of moderate to severe depression.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> It is known that both chronic pain and depression share common neurochemical substrates and similar dysfunctional alterations, and drugs that regulate pain by interrupting or reducing the release of neurotransmitters in the synapse between first and second order neurons are targets for their treatment. These situations could explain the role of serotonin reuptake inhibitors (SRIs) and tricyclic antidepressants (TCAs) in pain control and release.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although the use of TCAs as the treatment of choice for depression has been decreasing and more tolerable drugs, such as SSRIs, have been introduced, many clinicians use amitriptyline or its metabolite nortriptyline, at low doses, as first-line treatment for persistent myofascial pain (PMP), as it decreases both pain intensity and muscle tenderness.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There are few studies that analyze the efficacy of TCAs and ISRs in the treatment of chronic orofacial pain (COP) in TMDs. Studies comparing their efficacy with that of occlusal splints are also scarce, so the aim of our study was to compare the efficacy of these drugs in patients with COP.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A randomized controlled clinical trial (RCT) was designed according to CONSORT guidelines at the University Hospital of the Faculty of Medicine of the University of Coimbra (Portugal). It started in March 2021 and ended in July 2022. The research, in accordance with the 1975 Declaration of Helsinki, revised in 2000, was approved by the Ethics Committee of the Center (protocol number 013-CE-2020. ClinicalTrials.gov: ID <a href="ctgov:NCT04777838">NCT04777838</a>).</p><p id="par0030" class="elsevierStylePara elsevierViewall">A sample of 64 adult patients (42 women) with COP<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>18 years old treated at the Hospital and University Center of Coimbra (Portugal) who presented PMP in the masticatory muscles for more than 6 months, excluding pregnant women, patients with serious diseases, those who had received previous treatment for PMP and those who reported adverse effects to treatment with Citalopram and/or Amitriptyline. Pain intensity was assessed at baseline and at 3, 6 and 9 weeks using the visual analog scale (VAS). The sample size was calculated by repeated measures ANOVA, with 3 groups and 4 measurement times, with a power of 80% and a significance level of 0.05. A correlation of 0.5 between repeated measures and an effect size of 0.35 was incorporated. GPower 3.1.9.7 was used to calculate the sample, yielding a requirement of 18 subjects per group. Considering a dropout rate of 10%, the sample size was adjusted to 20 subjects per group. Participants were randomly assigned (Randomize.net) to three groups: Group 1 (control) of 22 patients who received a Michigan-type nighttime occlusal splint; Group 2 of 21 patients who received 10<span class="elsevierStyleHsp" style=""></span>mg of citalopram (Generis®, Generis Farmaceutica, Portugal) per day and Group 3 of 21 patients who received 25<span class="elsevierStyleHsp" style=""></span>mg of amitriptyline (Generis®, Generis Farmaceutica, Portugal) per day.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Absolute and relative frequency measures were used for gender distribution. Age-related statistics included mean and standard deviation. Fisher's exact test was used for sex, and the Kruskal–Wallis test was used for age. Initial assessment of normality was calculated using the Shapiro–Wilk test. The mean, standard deviation and confidence intervals of the VAS data were described at four different time points in the three groups. The normality of VAS was assessed using the Shapiro–Wilk test. To assess differences between groups, with respect to VAS, confidence intervals were used along with a repeated measures ANOVA test. Tukey's test was used for comparisons between groups.</p><p id="par0040" class="elsevierStylePara elsevierViewall">All statistical calculations were performed using IBM® SPSS® v28, maintaining a predefined significance level of 5%.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">There were no dropouts, so data from 64 subjects were available to evaluate the results.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study flow chart has been described according to the CONSORT guidelines and reported in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. The discrepancy between the three outcome assessors (BMS, AL-V, NL-V) was <85% (Cohen's kappa coefficient (<span class="elsevierStyleItalic">κ</span>)).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In sociodemographic aspect, the control group had 8 men and mean age of 36 years and the Amitriptyline and Citalopram groups had 7 men and mean age of 39 and 40 years respectively.</p><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> describe the statistical results of the variables analyzed.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents the mean, standard deviation and confidence intervals. These statistics relate to pain assessment by VAS at multiple time points and in the context of the three groups. The tabulation provides an overview of pain assessment over time.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Relevant differences were observed in the measurements throughout the evaluation time (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) and also between groups (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007). A fine observation detected a relevant difference between patients treated with amitriptyline and the control group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007). No differences were found between the groups treated with citalopram and control (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.058) or between those treated with amitriptyline and citalopram (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.692).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The results of our study showed that antidepressants, especially tricyclics (amitriptyline) in a single nightly dose of 25<span class="elsevierStyleHsp" style=""></span>mg, are effective in reducing COP caused by TMDs.</p><p id="par0080" class="elsevierStylePara elsevierViewall">It is known that TMDs are a pathology associated with physical and psychological factors and that stress can trigger or worsen them, and reciprocally, the prolongation in time of the symptomatology of these disorders, worsens the psychological state of the patients suffering from them. A recent meta-analysis of a sample of 3678 subjects found that patients with myofascial pain showed a higher incidence and severity of anxiety/depression than patients with other signs of TMD.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Kindler et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> on a sample of 3006 participants found an association between depressive symptoms and joint pain, such that subjects with depressive symptoms had a higher risk of joint pain, recommending that depressive and anxiety symptoms be taken into account when instituting therapy for TMD pain. Some studies have recommended for the treatment of these pathologies, the combination of non-invasive therapies (pharmacotherapy, cognitive-behavioral therapy, occlusal devices, etc.), although most of them initially recommend non-steroidal anti-inflammatory drugs together with muscle relaxants and, in chronic cases, benzodiazepines or antidepressants; however, despite the close relationship between chronic pain and depression, it is known that the analgesic effect of antidepressants is independent of their beneficial properties on mood, although they have been shown to effectively reduce chronic pain.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Amitriptyline is considered the gold standard of analgesic antidepressants, being the drug with the most clinical evidence. The results of our study coincided with those of Rizzatti-Barbosa et al.,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> who demonstrated the efficacy of amitriptyline in TMD pain, and those of Plesh et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> who investigated the efficacy of low doses of amitriptyline (10–30<span class="elsevierStyleHsp" style=""></span>mg) in the treatment of chronic TMD pain; however, our study included a sample of 22 patients, with follow-ups at 3, 6 and 9 weeks, which is superior to that of the studies by Rizzatti-Barbosa et al. and Plesh et al. with reduced samples and short follow-ups. A double-blind RCT compared the analgesic efficacy of amitriptyline at doses of 25, 50 and 75<span class="elsevierStyleHsp" style=""></span>mg, finding that maximum analgesic potency occurred at the 75<span class="elsevierStyleHsp" style=""></span>mg dose, despite the risk of adverse effects.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> In our study, with a safety dose (25<span class="elsevierStyleHsp" style=""></span>mg per day), we found no serious side effects, only some patients complained of dry mouth.</p><p id="par0090" class="elsevierStylePara elsevierViewall">We highlight a series of limitations: the degree of anxiety or depression and the socioeconomic conditions of the patients included were not previously assessed. On the other hand, the patients, who were not hospitalized, were beyond the control of the evaluators in terms of possible analgesic self-medication or other drugs that could alter the results.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">Despite the above limitations, we found significant improvement in all groups over 9 weeks. However, the group treated with occlusal splint was the least clinically relevant and the group treated with amitriptyline showed the longest lasting improvement. This drug at a dose of 25<span class="elsevierStyleHsp" style=""></span>mg per day would be a good option in patients suffering from chronic pain due to TMDs.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Authors’ contributions</span><p id="par0100" class="elsevierStylePara elsevierViewall">Conceptualization, B.M.S. and M.J.R.; methodology, B.M.S.; software, F.C.; validation, N.L.-V.; formal analysis, F.C.; investigation, B.M.S. and M.J.R.; writing—original draft preparation, A.L.-V.; writing—review and editing, A.L.-V.; and N.L.-V.; supervision, N.L.-V. All authors have read and agreed to the published version of the manuscript.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Institutional review board statement</span><p id="par0105" class="elsevierStylePara elsevierViewall">The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Center with protocol number 013-CE-2020.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Informed consent statement</span><p id="par0110" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all subjects involved in the study.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">No funding.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres2203494" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1848942" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2203493" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1848941" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Institutional review board statement" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Informed consent statement" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 13 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-10-28" "fechaAceptado" => "2024-02-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1848942" "palabras" => array:4 [ 0 => "Orofacial pain" 1 => "Temporomandibular disorders" 2 => "Antidepressants" 3 => "Randomized clinical trial" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1848941" "palabras" => array:4 [ 0 => "Dolor orofacial" 1 => "Trastornos temporomandibulares" 2 => "Antidepresivos" 3 => "Ensayo clínico aleatorizado" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Temporomandibular disorders (TMDs) are a common pathology, associated with pain in the facial territory and with associated psychological disorders, such as anxiety and depression. The aim of this study was to evaluate the efficacy of antidepressants in the treatment of pain associated with TMD.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Sixty four patients suffering from chronic orofacial pain, randomly distributed in 3 groups: control group treated with night splint, group treated with 10<span class="elsevierStyleHsp" style=""></span>mg/day of citalopram and group treated with 25<span class="elsevierStyleHsp" style=""></span>mg/day of amitriptyline. Pain intensity was assessed, randomly, by a single blinded evaluator, according to the VAS at baseline and after one, three, six and nine weeks.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All groups showed a reduction of pain throughout the period of time evaluated, however, the group treated with amitriptyline showed the best pain reduction results 3.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.5, 1.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.4 and 0.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.3 at 3, 6 and 9 weeks, respectively.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Low doses of amitriptyline appear to be a good therapeutic option in patients with TMDs suffering from chronic orofacial pain.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los trastornos temporomandibulares (TTM) son una patología frecuente, asociada a dolor en el territorio facial y a trastornos psicológicos asociados, como ansiedad y depresión. El objetivo de este estudio fue evaluar la eficacia de los antidepresivos en el tratamiento del dolor asociado a los TTM.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Un total de 64 pacientes con dolor orofacial crónico, distribuidos aleatoriamente en tres grupos: grupo control, tratado con férula nocturna; grupo tratado con 10<span class="elsevierStyleHsp" style=""></span>mg/día de citalopram, y grupo tratado con 25<span class="elsevierStyleHsp" style=""></span>mg/día de amitriptilina. La intensidad del dolor fue evaluada, aleatoriamente, por un único evaluador ciego, según la EVA al inicio del estudio y después de una, tres, seis y nueve semanas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Todos los grupos mostraron una reducción del dolor a lo largo del periodo de tiempo evaluado; sin embargo, el grupo tratado con amitriptilina mostró los mejores resultados de reducción del dolor: 3,3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1,5, 1,5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1,4 y 0,9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1,3 a las 3, 6 y 9<span class="elsevierStyleHsp" style=""></span>semanas, respectivamente.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Las dosis bajas de amitriptilina parecen ser una buena opción terapéutica en pacientes con TTM que sufren dolor orofacial crónico.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1243 "Ancho" => 1675 "Tamanyo" => 151863 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow chart of progress through the phases of the study according to the CONSORT statement 2010.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 923 "Ancho" => 1675 "Tamanyo" => 72969 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The graph shows the variation over time in the mean and 95% confidence interval of pain assessed with the VAS.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">95% confidence intervals are presented between brackets.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Initial \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Week 3 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Week 6 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Week 9 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bite splint \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.9 (1.3) [5.4, 6.5] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.9 (2.1) [3.0, 4.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.4 (2.2) [2.4, 4.4] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1 (2.3) [2.1, 4.2] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amitriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.4 (2.3) [4.4, 6.5] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.3 (1.5) [2.6, 4.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 (1.4) [0.8, 2.1] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9 (1.3) [0.3, 1.5] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Citalopram \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.4 (1.7) [5.4, 6.2] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.7 (1.6) [2.9, 4.4] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.0 (1.4) [1.4, 2.6] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4 (1.4) [0.7, 2.0] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3595848.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Statistics (mean, standard deviation, and 95% confidence intervals) of the Visual Analog Scale for pain for the three groups over time.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An update on temporomandibular disorders (TMDs) and headache" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. 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