Wastewater-based epidemiology (WBE) is proposed as a cost-effective approach to objectively monitor the antidepressant use but it requires more accurate correction factors (CF) than what had been used in previous studies. Amitriptyline is a popular prescription medicine for treating depression and nerve pain, which could be prone to misuse and need monitoring. The CF of amitriptyline employed in previous WBE studies varied from 10 to 100, leading to substantial disparities between WBE estimates and expected mass of antidepressants in wastewater. Hence, this study aimed to take amitriptyline as a case study and refine the CF by correlating mass loads measured in wastewater from 12.2 million inhabitants collected during the 2016 Census with corresponding annual sales data. The triangulation of WBE data and sales data resulted in a newly-derived CF of 7, which is significantly different from the CF values used in previous studies. The newly derived CF was applied to a secondary, multi-year (2017 to 2020) WBE dataset for validation against sales data in the same period, demonstrating the estimated amitriptyline use (380 ± 320 mg/day/1000 inhabitants) is consistent with sales data (450 ± 190 mg/day/1000 inhabitants). When we applied the new CF to previous studies, the wastewater consumption loads matched better to prescription data than previous WBE estimations. The refined CF of amitriptyline can be used in future WBE studies to improve the accuracy of the consumption estimates.

OBJECTIVE: To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment\'s effectiveness in patients diagnosed with burning mouth syndrome (BMS).
BACKGROUND: Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making.
METHODS: This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05).
RESULTS: Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response.
CONCLUSIONS: AMT may be effective in BMS management for most patients.

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.

The author reports a 19-year-old woman suffering from repeated episodes of non-bloody vomiting for 18 months. All routine and special investigations were normal. She was labeled as a case of cyclic vomiting syndrome (CVS), and she developed insomnia after the initiation of amitriptyline as a prophylactic treatment. The case was reported to increase awareness regarding the importance of monitoring medication side effects among clinicians when using different classes of medications to treat CVS.

BACKGROUND: Acute presentations of acquired exotropia or divergent alignment of either or both eyes are commonly observed following intracranial vascular events, trauma, orbital, and endoscopic sinus surgeries.
METHODS: The reported case is about a 16-year-old previously healthy Tamil female who presented to the emergency department with a few hours of reduced responsiveness. With the only clue in the history being about a family conflict the previous day, the examination revealed a noticeable exotropia along with a constellation of anticholinergic findings: a low Glasgow Coma Score, mydriasis, tachycardia, floppy limbs, exaggerated reflexes, and a palpable urinary bladder. Amitriptyline overdose leading to significant neurological involvement was suspected, and she was immediately offered urine alkalinization. Resources for urine and blood toxicological studies were not available. The patient gained consciousness 24 hours later and confirmed an overdose of ten amitriptyline tablets. Exotropia, a unique manifestation of this patient\'s neurotoxicity, spontaneously resolved in 36 hours.
CONCLUSIONS: The reported case is about an uncommon clinical finding of exotropia seen in a common toxicological emergency: acute amitriptyline overdose. The importance of having a wide knowledge of various clinical presentations of drug toxicities is highlighted here, as any delay in diagnosis or initiation of life-saving measures could have resulted in fatal consequences.

Cyclic vomiting syndrome is a benign, chronic, functional gastrointestinal pathology that manifests clinically with intense nausea and vomiting interspersed with asymptomatic periods. Its diagnosis is made according to the Rome IV criteria, which require the presence of at least 2 episodes of vomiting in the past 6 months or 3 or more episodes in the past year, with the corresponding exclusion of secondary causes that can explain the vomiting. We present the case of a 44-year-old man who consulted for intermittent nausea and vomiting of 1 year evolution with hydroelectrolytic repercussion and multiple emergency consultations. The diagnosis of cyclic vomiting syndrome was made and treatment with amitriptyline was started due to its neuromodulatory effect to prevent the recurrence of episodes. After 6 months of establishing it, the patient is asymptomatic.

Painful post-traumatic trigeminal neuropathy (PPTTN) can result from iatrogenic injury to one or more branches of the trigeminal nerve during oral surgical procedures such as tooth extractions. Like other chronic neuropathic pain conditions, PPTTN can significantly alter the patient\'s quality of life, especially when pharmacological treatment is ineffective or not tolerated. As such, new treatment options have been investigated, including local injections of botulinum toxin type A (BTX-A). A 29-year-old woman presented to our tertiary orofacial pain clinic for evaluation of chronic electric shock-like pain attacks and severe allodynia in the territory of the right inferior alveolar nerve and buccal nerve following right mandibular third molar extraction 3 years prior. Following several failed attempts at classic pharmacological management (including carbamazepine, venlafaxine, duloxetine, pregabalin, clonazepam, and amitriptyline), BTX-A injections were administered in the vicinity of the right mental nerve. This treatment provided significant improvement in the patient\'s condition and overall quality of life with no significant adverse effects. Because both neuropathies were significantly improved by remote BTX-A injections, this case report provides preliminary clinical evidence supporting spinopetal transport of BTX-A, as shown in animal models, as an underlying pathophysiological mechanism of BTX-A-mediated analgesia.

Utilizing pharmacogenomics (PGx) and integrating drug-induced phenoconversion to guide opioid therapies could improve the treatment response and decrease the occurrence of adverse drug events. Genetics contribute to the interindividual differences in opioid response. The purpose of this case report highlights the impact of a PGx-informed medication safety review, assisted by a clinical decision support system, in mitigating the drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively) that increase the risk of an inadequate drug response and adverse drug events (ADEs). This case describes a 69-year-old female who was referred for PGx testing for uncontrolled chronic pain caused by osteoarthritis and neuropathy. The clinical pharmacist reviewed the PGx test results and medication regimen and identified several (DGIs and DDGIs, respectively) at Cytochrome P450 (CYP) 2C19 and CYP2D6. The recommendations were to: (1) switch tramadol to buprenorphine transdermal patch, an opioid with lower potential for ADEs, to mitigate a CYP2D6 DDGI; (2) gradually discontinue amitriptyline to alleviate the risk of anticholinergic side effects, ADEs, and multiple DDGIs; and (3) optimize the pregabalin. The provider and the patient agreed to implement these recommendations. Upon follow-up one month later, the patient reported an improved quality of life and pain control. Following the amitriptyline taper, the patient experienced tremors in the upper and lower extremities. When the perpetrator drug, omeprazole, was stopped, the metabolic capacity was no longer impeded; the patient experienced possible amitriptyline withdrawal symptoms due to the rapid withdrawal of amitriptyline, which was reinitiated and tapered off more slowly. This case report demonstrates a successful PGx-informed medication safety review that considered drug-induced phenoconversion and mitigated the risks of pharmacotherapy failure, ADEs, and opioid misuse.

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.

BACKGROUND: Reduced consciousness has a wide variety of possible causes, not infrequently being toxic in nature. An intoxication might be obvious, but in this paper an unexpected case with a tricyclic antidepressant is presented.
METHODS: A 76-year-old caucasian female was found unconscious. Primary diagnostic evaluation, including a negative drugs of abuse test, did not give direction to any clear cause. Yet an intraventricular conductive disorder with widening of the QRS complex and electroencephalogram abnormalities did suggest a possible drug effect. Heteroanamnestic information led to the suspicion of an amitriptyline intoxication, which was confirmed by further laboratory analysis. The patient remained comatose for several days. High concentrations of amitriptyline indicated a large overdose of amitriptyline and, in combination with a cytochrome P450 2D6 poor metabolizer status, could explain the long persistence of her comatose state.
CONCLUSIONS: We present a tricyclic antidepressant intoxication, where the patient is thought to have taken a large amount of amitriptyline at once, which, in combination with a cytochrome P450 2D6 poor metabolizer status, led to an unusual long persistence of her coma.