The effective perospirone augmentation with clonazepam for treatment-resistant burning mouth syndrome: A case report.

Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61-year-old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51-year-old woman complained of a burning sensation along with oral dryness and crumb-like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb-like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS.

Dental conditions in patients with medically unexplained oral symptoms.

Background/purpose: Dentists sometimes struggle with treating patients with unexplained symptoms, known as oral psychosomatic disorders, that do not improve with conventional treatment. Oral psychosomatic disorders do not fit the definition of psychosomatic diseases in internal medicine. To ensure appropriate dental treatment, it is important for general dentists to distinguish between oral psychosomatic disorders and psychosomatic diseases. However, relevant evaluation methods have not yet been developed. The DMFT index is widely used as an indicator of the caries status. The purpose of this study was to compare the DMFT index scores of patients with oral psychosomatic. Materials and methods: The DMFT scores of 2202 patients with oral psychosomatic disorders, 145 psychiatric inpatients, and 3940 general dental patients were statistically compared. The DMFT of patients with oral psychosomatic disorders was further compared based on the presence or absence of psychiatric history and disease. Results: The median DMFT scores of oral psychosomatic disorder patients, psychiatric inpatients, and general dental patients were 16, 22, and 10, respectively, showing a significant difference. No significant differences were found in the DMFT scores based on the presence or absence of psychiatric history in oral psychosomatic disorder patients. Conclusion: The intraoral environment of patients with oral psychosomatic disorders was worse than that of general dental patients but better than that of psychiatric inpatients. General dentists could suspect psychiatric and oral psychosomatic disorders based on the state of patients' oral environment.

Case series of drug-induced open bite: Extrapyramidal symptoms related to psychotropic medications.

Introduction: Drug-induced open bite is one of the extrapyramidal symptoms with abnormal tonus of muscles and is rarely recognized in dentistry. This is a retrospective case study to investigate clinical characteristics including detailed complaints in patients with drug-induced open bite. Methods: Of the outpatients who first visited the psychosomatic dental clinic at the Tokyo Medical and Dental University Hospital between September 2013 and September 2022, the patients diagnosed with drug-induced open bite were involved in this study. The clinical characteristics including sex, age, detailed complaints, duration of illness, abnormal findings, psychotropic medications, and other medications that were taken at the first examination, psychiatric comorbidities, the duration of psychiatric diseases, and other medical histories were collected retrospectively by reviewing their medical chart. Results: Drug-induced open bite was found in 11 patients [women: 7, men: 4, median of age: 49 (36.5, 53) years old]. Difficulty in eating especially chewing was the major complaint (9/11, 81.6%) with the duration of illness as 48.0 (16.5, 66) months. Various degrees of open bite were observed. While some showed no occlusal contact on frontal teeth, some showed occlusal contact only on the second molars; moreover, the jaw showed a horizontal slide in a few patients. Three cases could be followed up for prognosis; while in one case the drug-induced open bite improved with 6 months of follow-up, two cases did not improve, and one showed extrusion of molars. All of them had psychiatric comorbidities with the most common diagnosis being schizophrenia (n = 5) and depression (n = 5) followed by insomnia (n = 1) and autism spectrum disorder (n = 1) including duplicated diagnosis. Nine patients (81.6%) had been undergoing treatment with antipsychotics of which three patients were also taking antidepressants. Discussion: Although a drug-induced open bite is a rare symptom, prudent medical interviews about symptoms, psychiatric comorbidities, and psychotropic medication history besides oral assessment are necessary to provide a precise diagnosis and appropriate management in collaboration between dentists and psychiatrists.

A case with burning mouth syndrome followed by dementia with Lewy bodies: a case report.

Burning mouth syndrome (BMS) is characterized by persistent oral burning sensations without corresponding organic findings. Dementia with Lewy bodies (DLB) is a common type of dementia and generally presents visual hallucination and parkinsonism as motor dysfunction besides cognitive decline. In this case report, we present a case in which DLB emerged during the treatment for BMS, with a relatively positive outcome for BMS. A 74 years-old female complained of burning pain in her mouth and a subsequent decrease in food intake. Following a diagnosis of BMS, pharmacotherapy was initiated. BMS was much improved with mirtazapine 15 mg and aripiprazole 1.0 mg, leading to the restoration of her food intake by day 180. However, BMS flared up again triggered by deteriorating physical condition of herself and that of her husband. With aripiprazole 1.5 mg and amitriptyline 25 mg, her BMS gradually improved by day 482. However, by day 510, an increase in anxiety was noted, accompanied by the occasionally misidentification of her husband on day 566. Her cognitive impairment and disorientation were also reported by her husband on the day 572, she was then immediately referred to a neurologist specialized dementia and diagnosed with DLB on the day 583. Her treatment was adjusted to include the prescription of rivastigmine which was titrated up to 9.0 mg. Considering the potential impact of amitriptyline on cognitive function, it was reduced and switched to mirtazapine; however, her oral sensations slightly got worse. Following the consultation with her neurologist, amitriptyline 10 mg was reintroduced and aripiprazole was discontinued on day 755. Remarkably, BMS gradually improved without deteriorating DLB. This case indicated the reaffirmed necessity of careful interviews for changes in daily life not only with the patients but also with their families through the medical assessments. It highlights the vigilance regarding potential cognitive decline underlying or induced as an adverse event especially when treating elderly patients with BMS. While the interaction between BMS and DLB remains unclear, this case underscores the importance of prudent diagnosis and constructing collaboration with specialists in managing BMS with the early phase of DLB.

Case Report: Auditory Hallucination Induced by Amitriptyline for the Treatment of Atypical Odontalgia.

Auditory hallucination is usually associated with psychiatric diseases and organic brain illness. It was rarely found as adverse events of antidepressants. Amitriptyline is considered as one of the first line medications for the psychopharmacotherapy of chronic pain including atypical odontalgia (AO) which shows chronic tooth pain without corresponding abnormalities. Anticholinergic adverse events induced by amitriptyline are usually bearable and not critical since the prescription dose is very low for the patients with AO. This is a first case report about the AO patients who showed auditory hallucination by the low dose of amitriptyline. A 43-years-old female, housewife, complained chronic toothache following dental procedures and was diagnosed as AO. Amitriptyline was initially prescribed 25 mg and gradually increased up to 60 mg with the improvement of AO symptoms in 7 months. Although the temporary recurrence was observed following to the retreatment of prosthodontic dental procedures, it improved in a few weeks. Therefore, the dose of amitriptyline was decreased, and the continuation dose was set 30 mg. In 24 months, the AO symptoms were very much improved; however, she reported that she had been heard the voices at midnight for a year. The voices were neighborhoods' and talking about the noise troubles she had claimed before. She had not realized that the voices were auditory hallucination since they were heard only at midnight infrequent and not bothering her daily life. At the time she reported auditory hallucination, she worried whether organic brain diseases are hiding because the frequency of voices was increased and sometimes occurred in daytime. The adverse event of amitriptyline was suspected since she had never had psychotic symptoms before. Amitriptyline was decreased and continued with the dose of 25 mg. Magnetic resonance imaging and psychiatric consultation revealed no abnormality of brain and in psychiatric aspects. After final prosthodontic treatment, the amitriptyline was discontinued in 30 months. Two months after the discontinuation, auditory hallucination was almost disappeared with no recurrence of AO. The present case report suggests that amitriptyline has possibility to induce auditory hallucination even in conventional dose throughout the treatment of chronic pain including AO.

The intra-articular injection of RANKL-binding peptides inhibits cartilage degeneration in a murine model of osteoarthritis.

We recently found that the receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4 stimulated the differentiation of both chondrocytes and osteoblasts. OP3-4 is also shown to inhibit cartilage degeneration. To clarify whether the peptide can inhibit cartilage degeneration without stimulating bone formation, we first performed a proliferation assay using C3H10T1/2 (the murine mesenchymal stem cell line), which is the common origin of both chondrocytes and osteoblasts. The RANKL-binding peptides, OP3-4 and W9, promoted cellular proliferation at 24 and 48 h, respectively. Next, we injected both peptides into the intra-articular space of the knee joints of mice with monosodium-iodoacetate (MIA)-induced osteoarthritis to clarify the effects of the peptides on cartilage tissue. Twenty-five nine-week-old male C57BL/6J mice received injections of vehicle, or the same molar amount of W9, OP3-4, or a control peptide (which could not stimulate osteoblast differentiation) on days 7, 14, and 21 after the injection of MIA. The mice were sacrificed on day 28. The histomorphometric analyses revealed that both peptides inhibited the degeneration of cartilage without enhancing bone formation activity. Our data suggest that the stimulation of mesenchymal cell proliferation by the RANKL-binding peptides might lead to the inhibition of cartilage degeneration.

Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.

Both W9 and OP3-4 were known to bind the receptor activator of NF-κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide-induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3-4 accelerated BMP-2-induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL-binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP-2-induced bone regeneration by the RANKL-binding peptides.