Persistent idiopathic dentoalveolar pain (PIDAP) is a type of disease that, despite affecting thousands of people globally, negatively impacts patients\' quality of life because of its unknown cause. Notably, the disease has a high prevalence rate and is primarily prone to middle-aged and senior individuals. Efforts have been made to gain the understanding needed for the accurate diagnosis and prompt treatment of PIDAP cases. This case report discusses the challenges faced in diagnosing and managing PIDAP after dental implants. The present study involved the case of a 62-year-old male patient, previously operated on for an implant at position #11, who suffered from chronic pain but no specific cause could be identified. We used an evaluation strategy to gain insights into the patient\'s illness, including antibiotic treatment, crown replacement, and continued pain. We prescribed nortriptyline 10 mg, and there was an improvement. This finding suggests that nortriptyline 10 mg QHS eliminates chronic pain.

OBJECTIVE: This study aims to quantitatively analyse nortriptyline\'s analgesic potency, safety and tolerability.
METHODS: Systematic review and meta-analysis.
METHODS: The systematic search was conducted in Scopus, Web of Science and PubMed in February 2023.
METHODS: Clinical trials evaluating the efficacy of nortriptyline in reducing pain scores (open-label studies and comparisons of nortriptyline with placebo or other analgesics) in different pain types were included.
METHODS: The data extraction procedure and the screening phases were carried out based on predetermined eligibility criteria. To pool the data, the standardised mean difference (SMD) and standardised mean change (SMC) methods, along with random-effect and fixed-effect meta-analysis, were used. The risk of bias was assessed using the Cochrane Collaboration method, and the Grading of Recommendations Assessment, Development and Evaluation criteria were used to measure the certainty of the results.
RESULTS: 14 of the initial 648 studies were eventually imported. Nortriptyline was reported to significantly reduce pain severity in chronic low back pain, painful symptoms in major depressive disorder, neuropathy, chronic pelvic pain and neuropathic corneal pain. However, it was not superior to placebo in fibromyalgia and knee osteoarthritis. In comparison to placebo and various alternative analgesics, the pooled SMD for lowering pain scores was 0.43 (0.23-0.64) and -0.18 (-0.39 to 0.03), respectively. In the pretreatment and post-treatment analyses, the pooled SMC was -1.20 (-1.48 to -0.93). Although constipation and xerostomia were the most commonly reported side effects, all references indicated that the adverse events were well tolerated at the administered dosages.
CONCLUSIONS: While nortriptyline is effective in some chronic pains, such as neuropathies, it lacks efficacy in some other chronic pains, such as fibromyalgia and osteoarthritis. Nortriptyline is well tolerated when administered in doses intended for its analgesic effects. Moreover, several studies suggested that the analgesic effects of nortriptyline are comparable to those of amitriptyline and gabapentin.

OBJECTIVE: Cytisine serves as an affordable smoking cessation aid with acceptable safety profile. However, data comparing its efficacy and safety to standard therapies are limited. We aimed to examine efficacy and safety of cytisine compared to nortriptyline, which is the only approved smoking-cessation medication in Thailand.
METHODS: A 12-month, multicentre, randomized, double-blinded, placebo-controlled trial was conducted. Participants aged ≥20 years who smoked ≥10 cigarettes/day were randomly assigned to receive a 25-day cytisine or a 12-week nortriptyline treatment course. Brief interventions (BI) for smoking cessation were provided to all participants. The primary outcome was biochemically verified continuous abstinence rate (CAR) at 12 months. Additionally, self-reported abstinence, verified by exhaled carbon monoxide (CO) ≤ 10 ppm, was collected at 2 weeks, 1, 3, 6 and 12 months to assess both CAR and 7-day point prevalence abstinence rate (PAR).
RESULTS: A total of 1086 participants were recruited and randomized into cytisine (n = 540) and nortriptyline (n = 546) groups. The 12-month CAR was 12.22% for cytisine and 9.52% for nortriptyline. The relative difference was 0.03 (95% confidence interval [CI]; -0.01 to 0.06) and the relative risk was 1.28 (95% CI; 0.91-1.81). No differences were observed in secondary outcomes between both groups. The incidence of adverse effects from cytisine appeared to be lower than that of nortriptyline.
CONCLUSIONS: At 12 months, cytisine plus BI was as effective as nortriptyline plus BI for smoking cessation. The adverse events for both cytisine and nortriptyline were minimal and well-tolerated.

OBJECTIVE: Migraine, as a primary headache disorder, stands as one of the primary causes of disability worldwide. Consequently, prophylactic treatments are highly recommended for individuals experiencing recurrent migraine episodes. Our study aimed to compare the efficacy and safety profiles of venlafaxine and nortriptyline in the prophylactic management of migraine.
METHODS: In this single-center, randomized, double-blind clinical trial, 210 migraine patients were allocated into two groups in a 1:1 ratio. One group received venlafaxine (37.5 mg, orally twice daily), while the other group administered nortriptyline (25 mg, orally once daily). A neurologist documented (1) headache intensity using the Visual Analog Scale (VAS) and 6-point Behavioral Rating Scale (BRS-6), (2) headache frequency (per month), and (3) headache duration (in hours) of participants on days 0, 45, and 90 of the intervention.
RESULTS: Following the 90-day intervention, a significant decrease was observed in VAS, BRS-6, frequency, and duration of headaches within both groups (all with p-values <0.001). No difference in VAS, BRS-6, or headache durations was observed between the two groups after 45 and 90 days of treatment (all p-values > 0.05). Although the headache frequency exhibited no difference between the groups after 45 days (p-value = 0.097), a significantly lower frequency in the venlafaxine group was observed at day 90 of the intervention (p-value = 0.011). The reductions in attack parameters in the 0-45- and 0-90-day intervals did not meet statistical significance between the two groups (p-values > 0.05). 77.0 % of the participants in the venlafaxine group and 79.2 % in the nortriptyline group experienced a minimum of 50 % improvement in all attack parameters. Venlafaxine demonstrated a statistically significant lower incidence of adverse reactions in comparison to nortriptyline (p-value = 0.005). A total of 33 adverse drug reactions were documented in the venlafaxine group and 53 in the nortriptyline group, with insomnia observed in the former and xerostomia in the latter as the most prevalent side effects.
CONCLUSIONS: Venlafaxine and nortriptyline demonstrate clinically significant and comparable therapeutic efficacy for migraine patients in reducing the intensity, frequency, and duration of headache attacks. Venlafaxine may be preferred to nortriptyline in the context of migraine preventive treatment under comparable conditions due to its lower incidence of adverse effects.

BACKGROUND: Consensus-guidelines for prescribing antidepressants recommend that clinicians should be vigilant to match antidepressants to patient\'s medical history but provide no specific advice on which antidepressant is best for a given medical history.
OBJECTIVE: For patients with major depression who are in psychotherapy, this study provides an empirically derived guideline for prescribing antidepressant medications that fit patients\' medical history.
METHODS: This retrospective, observational, cohort study analyzed a large insurance database of 3,678,082 patients. Data was obtained from healthcare providers in the U.S. between January 1, 2001, and December 31, 2018. These patients had 10,221,145 episodes of antidepressant treatments. This study reports the remission rates for the 14 most commonly prescribed single antidepressants (amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, sertraline, trazodone, and venlafaxine) and a category named \"Other\" (other antidepressants/combination of antidepressants). The study used robust LASSO regressions to identify factors that affected remission rate and clinicians\' selection of antidepressants. The selection bias in observational data was removed through stratification. We organized the data into 16,770 subgroups, of at least 100 cases, using the combination of the largest factors that affected remission and selection bias. This paper reports on 2,467 subgroups of patients who had received psychotherapy.
RESULTS: We found large, and statistically significant, differences in remission rates within subgroups of patients. Remission rates for sertraline ranged from 4.5% to 77.86%, for fluoxetine from 2.86% to 77.78%, for venlafaxine from 5.07% to 76.44%, for bupropion from 0.5% to 64.63%, for desvenlafaxine from 1.59% to 75%, for duloxetine from 3.77% to 75%, for paroxetine from 6.48% to 68.79%, for escitalopram from 1.85% to 65%, and for citalopram from 4.67% to 76.23%. Clearly these medications are ideal for patients in some subgroups but not others. If patients are matched to the subgroups, clinicians can prescribe the medication that works best in the subgroup. Some medications (amitriptyline, doxepin, nortriptyline, and trazodone) always had remission rates below 11% and therefore were not suitable as single antidepressant therapy for any of the subgroups.
CONCLUSIONS: This study provides an opportunity for clinicians to identify an optimal antidepressant for their patients, before they engage in repeated trials of antidepressants.
CONCLUSIONS: To facilitate the matching of patients to the most effective antidepressants, this study provides access to a free, non-commercial, decision aid at http://MeAgainMeds.com.
CONCLUSIONS:  Policymakers should evaluate how study findings can be made available through fragmented electronic health records at point-of-care. Alternatively, policymakers can put in place an AI system that recommends antidepressants to patients online, at home, and encourages them to bring the recommendation to their clinicians at their next visit.
CONCLUSIONS:  Future research could investigate (i) the effectiveness of our recommendations in changing clinical practice, (ii) increasing remission of depression symptoms, and (iii) reducing cost of care. These studies need to be prospective but pragmatic. It is unlikely random clinical trials can address the large number of factors that affect remission.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Room tilt illusion (RTI) is a rare and transient perceptual disturbance in which an individual perceives their surroundings as having been rotated or tilted, usually at 90 or 180 degrees. Primarily linked with vestibular disorders and neurological lesions, this report details the only reported occurrence of the RTI phenomena in nortriptyline use for treatment-refractory depression. The patient developed RTI six days after starting the medication and the disturbance resolved after medication cessation. Although the mechanism behind such a phenomenon with medication use has not been elucidated, its etiology may rest on the effect of tricyclic antidepressants on the vestibulo-thalamo-cortical system and visual-vestibular integration. Clinicians should be aware of the potential for such a medication-induced perceptual disturbance, especially in the workup for more serious etiologies in elderly patients with co-morbidities.

UNASSIGNED: The QRS complex duration is commonly used to prognosticate severity, predict outcomes, and indicate treatment in overdose. However, literature to support this practice is mixed in tricyclic antidepressant overdoses and absent in non-tricyclic antidepressant overdoses. Our objective was to assess the validity of QRS complex duration as a prognostic marker in overdose.
UNASSIGNED: This was a secondary analysis of cases reported to the Toxicology Investigators Consortium between January 1, 2010, and December 31, 2022. Cases were assessed to determine the six xenobiotics most associated with QRS complex prolongation. All cases involving these six xenobiotics, regardless of QRS complex duration, constituted the study cohort. Inclusion criteria were cases of patients older than 12 years old with single-xenobiotic exposures. Clinical outcomes evaluated were seizure, ventricular dysrhythmia, metabolic acidosis, and death.
UNASSIGNED: Of 94,939 total cases, diphenhydramine, amitriptyline, bupropion, quetiapine, nortriptyline, and cocaine were most associated with QRS complex prolongation. Inclusion criteria were met by 4,655 cases of exposure to these xenobiotics. QRS complex prolongation was associated with increased odds ratio of seizure in all included xenobiotics, of ventricular dysrhythmia in all included xenobiotics except nortriptyline, and of metabolic acidosis or death in all included xenobiotics except nortriptyline and quetiapine. A normal QRS complex duration had a negative predictive value of greater than or equal to 93.0 percent of developing metabolic acidosis and 98.0 percent of developing a ventricular dysrhythmia or death from the xenobiotics studied.
UNASSIGNED: This study demonstrates that patients with QRS complex prolongation from all six xenobiotics studied had an increased prevalence and odds of developing severe outcomes. Furthermore, patients who did not develop QRS complex prolongation were unlikely to develop a ventricular dysrhythmia, metabolic acidosis, or death. These findings were noted in six xenobiotics that mechanistically can cause QRS complex prolongation through sodium channel or gap junction inhibition.
UNASSIGNED: Identification of patients at risk for severe outcomes after overdose can be aided by measuring the QRS complex duration. If prospectively validated, these outcomes have implications on risk stratification, disposition level of care, and appropriateness of treatments.

UNASSIGNED: To compare the efficacy of Duloxetine and Nortriptyline in alleviating the symptoms of severity, anxiety, depression and quality of life in patients with functional dyspepsia (FD).
UNASSIGNED: We conducted a single-blinded 3-month trial of Duloxetine 20-30 mg daily in 20 patients and Nortriptyline 25 mg daily in 25 FD patients. The primary outcome measure was the severity of FD symptoms by Gastrointestinal symptoms rating scale. Secondary measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Nepean Dyspepsia Index. the patients were measured in 3 stages.
UNASSIGNED: 45 patients with FD with a mean age of 37.18 ± 10.62 years participated in the study. The severity of symptoms was significantly lower in the Nortriptyline group than in the Duloxetine group after three months (p = 0.031). The level of anxiety (p = 0.049), depression (p = 0.045) and quality of life (p = 0.046) improved significantly after three months in the Duloxetine group compared to Nortriptyline. Mediation analysis using linear regression revealed a significant mediator role for anxiety. This mediation analysis revealed a 21.13% reduction in anxiety in the Duloxetine group.
UNASSIGNED: While both medications demonstrated efficacy, Nortriptyline appeared to be superior in symptom reduction. Duloxetine exhibited more advantages compared to Nortriptyline in addressing anxiety and depression and enhancing the overall quality of life. Also, Duloxetine may have a noteworthy impact, contributing to a 20% reduction in FD symptoms by lowering anxiety levels.
UNASSIGNED: https://en.irct.ir/trial/65512.

X is a 22-month-old White male infant with a complex medical history, including diagnoses of FBXO11 mutation, hypotonia, restrictive lung disease and mild intermittent asthma, laryngotracheomalacia, obstructive sleep apnea (OSA), feeding difficulties with a history of aspiration, gastroesophageal reflux disease (GERD), and developmental delays. X\'s medical presentation has resulted in multiple prior medical admissions for respiratory failure due to acute illnesses, procedures and treatments including gastrojejunostomy (GJ) tube dependence, supraglottoplasty to reshape tissues of the upper larynx, and the use of biphasic positive airway pressure (BiPAP) at night and room air during the day when he is at baseline. In addition, he has nocturnal events characterized by significant agitation, screaming, crying, body stiffening and limb movements with pauses in breathing, mouth breathing, restless sleep, and difficulty waking in the morning with concomitant daytime fatigue despite above treatments for OSA. There is no history of congenital heart disease or sudden unexplained death. Family history is noncontributory because parents are negative for the FBXO11 variant.X\'s sleep disruption has led to significant sleep deficits for both X and his caregivers, who spend much of the night strategizing on how to console him. X has undergone several sleep studies, starting when X was aged 4 months, at several children\'s hospitals across the nation to determine the cause of his chronic sleep disturbance, which yielded limited information and treatment success. As an infant, X received a medical workup and was subsequently treated with a proton pump inhibitor (PPI) for reflux. At 12 months, he was diagnosed with disordered sleep with myoclonic jerks and started on melatonin and gabapentin for involuntary movements. At 13 months, gabapentin was weaned back because of intolerance, and at 15 months, nortriptyline and clonidine were started because of worsening symptoms to target potential neuropathic pain. While most of his symptoms were at night, he had occasional daytime screaming episodes, particularly when experiencing illness. Gabapentin and clonidine were stopped because nortriptyline seemed most effective.At 17 months, the results from a sleep study led to a diagnosis of night terrors, and several clinicians agreed that X\'s sleep disruption was behavioral in nature. At this time, an infant mental health consultant met with a sleep psychologist on the family\'s behalf to support family in considering systematic desensitization therapy to increase tolerance to wearing his BiPAP mask, as well as other behavioral and sleep hygiene strategies, which were tried on several occasions and again, resulted in limited improvement in functioning.At 19 months, X\'s multidisciplinary team reconsidered a night terror diagnosis after a failed trial of clonazepam and pursued a differential diagnosis of periodic limb movement disorder (PLMD). X trialed gabapentin again, but this time only a nighttime dose, per sleep medicine and psychiatry recommendation. While this brought some temporary relief from nighttime distress, despite increasing to the highest dose for age and weight (15 mg/kg/dose), this became less effective, and he was weaned off at 22 months. He had been on iron supplementation since age 6 months and received an iron infusion at 22 months because of persistently low ferritin levels and PLMD in sleep.At 24 months, X was briefly trialed on levetiracetam. While no evidence for seizures on EEG was present, this medication was chosen for involuntary movements and genetic risk for seizures. However, this medication was not useful. At 25 months, an evaluation with a movement disorder physiatrist resulted in a diagnosis of nocturnal paroxysmal dystonia, and he was started on baclofen, which has provided some, but not complete relief to nighttime symptoms. Parents are reporting he has more \"good nights\" than \"bad nights,\" but \"bad nights\" come in stretches of a few days in length with no known trigger or relief.Most recently, X was evaluated by general genetics. Whole exome sequencing (WES) was pursued which revealed a pathogenic de novo variant in FBXO11 and provides a likely cause for his neurodevelopmental phenotype. However, he has some features not explained by FBX011; thus, reanalysis of his WES was performed and revealed a de novo variant of uncertain significance in RAF1. Because pathogenic variants in RAF1 have been associated with dilated cardiomyopathy and Noonan spectrum disorder, it was recommended that X be followed periodically in a cardiac genetics clinic. Family is well connected into the FBXO11 community, including supportive Facebook groups. Parents have shared that they do not feel X\'s breathing issues and pain fit with the phenotype of other children with FBXO11 mutations.X is also enrolled in a medical child care program to facilitate development and social-emotional functioning and receives learning, speech, occupational, physical, and feeding therapy while in attendance. Despite periods of absence due to contracting numerous viral illnesses over the past several months, X continues to make progress across developmental therapies and happily engages when at the program.What additional diagnostic tests and treatment should be considered to better understand X\'s medical and behavioral presentation? What are the implications of chronic sleep deprivation and stress on the behavior and development of infant with X\'s profile? What are important psychosocial considerations because it relates to children with medical complexity (CMC), particularly for X and his family to support caregiver, family, and X\'s quality of life and overall well-being?