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. 2025 Apr 23:6:1536584.
doi: 10.3389/fpain.2025.1536584. eCollection 2025.

Recognition and treatment of attention deficit-hyperactivity disorder in patients with treatment-resistant burning mouth syndrome: a retrospective case study

Kaori Takahashi #  1 , Satoshi Kasahara #  2   3 , Miwako Takahashi  4 , Taito Morita  2 , Naoko Sato  5 , Toshimitsu Momose  6 , Ko Matsudaira  2   7 , Shin-Ichi Niwa  8 , Kanji Uchida  2 , Toshiyuki Handa  1 , Tatsuya Ichinohe  1 , Ken-Ichi Fukuda  9
Affiliations

Recognition and treatment of attention deficit-hyperactivity disorder in patients with treatment-resistant burning mouth syndrome: a retrospective case study

Kaori Takahashi et al. Front Pain Res (Lausanne). .

Abstract

Introduction: Burning mouth syndrome (BMS) is an idiopathic oral pain disorder characterized by burning sensations and dysesthesia, often complicated by psychosocial factors and psychiatric comorbidities, necessitating a multidisciplinary approach. BMS, classified as nociplastic pain (NcplP), frequently involves central sensitization. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, is commonly comorbid with NcplP, and ADHD-targeted treatment has shown efficacy in NcplP management. However, the role of ADHD diagnosis and treatment on BMS and associated brain function abnormalities remains unexplored. Therefore, we aimed to investigate the prevalence of ADHD comorbidity and its assessment using ADHD scales and the therapeutic efficacy of an ADHD-focused algorithm, including pre- and post-treatment cerebral blood flow single-photon emission computed tomography (SPECT) results, in patients with treatment-resistant BMS referred from the outpatient clinic of dental psychosomatic specialists at a tertiary care institution for multidisciplinary treatment.

Methods: We retrospectively analyzed data from 14 patients with treatment-resistant BMS who received multidisciplinary care, including psychiatric evaluation and SPECT imaging. Clinical assessments included the Conners' Adult ADHD Rating Scale (CAARS-S and CAARS-O), Pain Numerical Rating Scale, Hospital Anxiety and Depression Scale, and Pain Catastrophizing Scale. Algorithm-based pharmacotherapy using ADHD-effective medications (methylphenidate, atomoxetine, guanfacine, aripiprazole, venlafaxine, and duloxetine) was administered.

Results: ADHD was diagnosed in 13 patients (92.9%), with 57.2% exhibiting borderline or clinical-level symptoms. Clinically significant improvements were observed in all clinical scales among the 10 patients who completed algorithm-based treatment. Brain perfusion SPECT identified hypoperfusion in the frontal lobe and hyperperfusion in the perigenual anterior cingulate cortex, insular cortex, posterior cingulate gyrus, and precuneus in 90% of cases, with improvements noted following treatment.

Conclusions: ADHD is frequently comorbid in patients with treatment-resistant BMS, and ADHD-targeted pharmacotherapy may help alleviate pain, cognitive dysfunction, and brain perfusion abnormalities. These findings suggest that ADHD screening, diagnosis, and multidisciplinary management involving psychiatrists could play a crucial role in optimizing clinical outcomes in patients with BMS.

Keywords: attention deficit hyperactivity disorder; burning mouth syndrome; frontal hypoperfusion; methylphenidate; multidisciplinary approach; nociplastic pain; precuneal hyperperfusion; single-photon emission computed tomography.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

A flowchart outlines a stepwise treatment strategy for managing coexisting burning mouth syndrome and ADHD. The pathway begins with MP (methylphenidate) and progresses sequentially to ATX (atomoxetine), GF (guanfacine), APZ (aripiprazole), and VFX/DTX (venlafaxine/duloxetine) if insufficient improvement or intolerable side effects occur. Each step includes the option to assess for "sufficient improvement" or to proceed to the next treatment. Contraindications for each medication are indicated in parallel pathways, directing toward usual treatment if a medication cannot be used. Solid arrows indicate progression, while dashed arrows represent alternate paths due to contraindications.
Figure 1
Algorithm for pharmacological management of patients with BMS and comorbid ADHD. ADHD, attention-deficit/hyperactivity disorder; APZ, aripiprazole; ATX, atomoxetine; DXT, duloxetine hydrochloride; GF, guanfacine; MP, methylphenidate; VFX, venlafaxine hydrochloride.
Six box plots compare pre- and post-treatment scores for different clinical measures. Panels (A) to (C) show significant reductions in maximum, minimum, and average Numerical Rating Scale (NRS) pain scores. Panels (D) and (F) show significant decreases in HADS-A (anxiety) and PCS (pain catastrophizing) scores. Panel (E) shows no significant change in HADS-D (depression) scores. Asterisks indicate statistically significant differences. Each box plot displays median, interquartile range, and outliers. The data suggest treatment led to reduced pain intensity, anxiety, and catastrophizing, but not a significant change in depression.
Figure 2
Changes in pain intensity and related symptoms pre- and post-treatment. Panels (A–F) illustrate the changes in pain NRS maximum, pain NRS minimum, pain NRS average, HADS-A, HADS-D, and PCS scores, respectively, pre- and post-treatment. *P < 0.05. HADS-A/D, hospital anxiety and depression scale anxiety and depression; NRS, numerical rating scale; PCS, Pain Catastrophizing Scale.
Four rows of brain SPECT images labeled (A) to (D) show axial, coronal, and sagittal views of cerebral perfusion with a color scale indicating normalized counts per voxel from 0 (black) to 60 (red). Red arrows highlight regions of hypoperfusion, particularly in panels (A), (B), and (D), most notably in the parietal and occipital lobes. Panel (C) shows relatively preserved perfusion without marked abnormalities. The anterior-posterior orientation is marked in (A), and lateralization is indicated as right (R) and left (L). The images compare perfusion patterns across different conditions or timepoints.
Figure 3
Representative cerebral blood flow SPECT images before treatment. Voxel values are normalized to average counts-per-voxel, with a cerebellar reference count of 50. The color bar represents count values ranging from 0 to 60. Panels (A–C) show images from patients #4, #5, and #12, respectively (all with a CGI-S score of 5), exhibiting focal hyperperfusion in the perigenual anterior cingulate cortex (crossbar) and the insular cortex (red arrows), alongside hypoperfusion in other frontal regions. Panel (D) displays images from patient #6 (CGI-S score of 2), who exhibited preserved CBF in the frontal and parietal lobes. The sagittal and axial views on the left indicate focal hyperperfusion, while the central axial views highlight increased perfusion in the insular cortex. The sagittal and axial views on the right show perfusion in the precuneus and posterior cingulate cortex. SPECT, single-photon emission computed tomography; CGI-S, clinical global impression severity; ant, anterior; R right; L, left.
A reference chart titled "Behavioral Characteristics of ADHD in Pain Management" outlines common behaviors observed in individuals with ADHD that may impact pain treatment. These include inattention, boredom, procrastination, reliance on others, disorganization, forgetfulness, fidgeting, hyperactivity, excessive talking, impulsiveness, anger control issues, over-involvement with others, and a strong dislike of waiting. The list emphasizes how these traits can affect communication, adherence to treatment, and clinical interactions. The chart is designed as a take-home message to support healthcare professionals in recognizing and addressing ADHD-related behaviors during pain management.
Figure 4
Behavioral characteristics of ADHD in pain management. ADHD, attention-deficit/hyperactivity disorder.
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