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Pharmaceutics Jan 2024retracted the article "Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats" [...].
retracted the article "Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats" [...].
PubMed: 38276524
DOI: 10.3390/pharmaceutics16010152 -
Oman Medical Journal Nov 2023This study sought to determine the confidence level of mental health practitioners in Oman regarding the use of antidepressants during pregnancy and breastfeeding,...
OBJECTIVES
This study sought to determine the confidence level of mental health practitioners in Oman regarding the use of antidepressants during pregnancy and breastfeeding, assess their knowledge and need for further training in this area, and examine their current prescribing patterns and preferences.
METHODS
A questionnaire-based survey was conducted from May to June 2017 among all practitioners in the psychiatry specialty, including medical officers authorized to prescribe medications, at the Behavioral Medicine Department of Sultan Qaboos University Hospital and Al Masarra Hospital.
RESULTS
Forty-two practitioners (response rate = 89.4%) responded to the questionnaire. Of them, 10 (23.8%) had no experience, while 30 (71.4%) had experience in prescribing antidepressants during both pregnancy and breastfeeding periods. Twenty-seven (64.3%) respondents felt that they were confident in prescribing antidepressants for women during their perinatal period, while 30.0% were neutral. Moreover, 35 (83.3%) participants expressed the need for more training in this area. Furthermore, 34 (81.0%) believed that more training in perinatal psychiatry should be included in the psychiatry curriculum. There was no consistent prescribing pattern (either prescribing or avoiding) among our participating practitioners during the first trimester of pregnancy and breastfeeding periods. The drug of choice in the first trimester of pregnancy was fluoxetine preferred by approximately 85.0% of the practitioners, but avoided by 10.0% of practitioners in the same period. This was followed by amitriptyline (50.0% vs. 23.0%), sertraline (50.0% vs. 9.0%), imipramine (28.0% vs. 84.0%). During breastfeeding, the drug of choice for approximately 74.0% of the practitioners was paroxetine, but avoided by 15.0% of practitioners. This was followed by sertraline (50.0% vs. 8.0%). The most common reasons for prescription during pregnancy were safety, evidence-based practice, and low teratogenicity. For breastfeeding, the main reasons for prescription were low levels of the drug in breast milk, safety, and evidence-based practice. On the other hand, high teratogenicity, neonatal side effects, limited data, and lack of evidence were among the most common reasons behind avoiding prescribing during pregnancy, while high levels of breast milk, neonatal side effects, limited evidence, and safety concerns were the most common reasons during the breastfeeding period.
CONCLUSIONS
There was inconsistency among mental health practitioners in making prescription decisions and in their prescribing patterns.
PubMed: 38264515
DOI: 10.5001/omj.2023.123 -
Frontiers in Psychiatry 2023Burning mouth syndrome (BMS) is characterized by persistent oral burning sensations without corresponding organic findings. Dementia with Lewy bodies (DLB) is a common...
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.
PubMed: 38260804
DOI: 10.3389/fpsyt.2023.1329171 -
Diabetes Research and Clinical Practice Dec 2023Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant...
Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant curtailment of functionality and quality of life. Patients may present with unremitting burning, aching or "electric-shock" type pains in their feet, legs and later, in the hands. Conventional management approaches must focus not only on pain relief, but also on concurrent sleep problems, mood disorders and functionality. The mainstay of treatment is pharmacotherapy. Most current international guidelines recommend a choice of four drugs: amitriptyline, duloxetine, pregabalin or gabapentin, as initial treatment for PDN. Recent evidence from the OPTION-DM trial demonstrated that these drugs and their combinations have equivalent efficacy. Moreover, combination treatment provided significant pain relief to patients with inadequate response to the maximum tolerated dose of monotherapy. PDN refractory to pharmacotherapy can be treated with capsaicin 8% or high frequency spinal cord stimulation.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Quality of Life; Duloxetine Hydrochloride; Pain
PubMed: 38245323
DOI: 10.1016/j.diabres.2023.110765 -
Environmental Toxicology and... Mar 2024Interaction of nanoplastics (NPls) with other environmental contaminants could affect their uptake by the organisms and their toxicity. Thus, the present study aims to...
Interaction of nanoplastics (NPls) with other environmental contaminants could affect their uptake by the organisms and their toxicity. Thus, the present study aims to investigate the polystyrene NPls (44 nm) interaction with the antidepressant amitriptyline (AMI) and its toxicity to Danio rerio embryos. A similar toxicological profile for NPls + AMI exposure was found for most of the evaluated endpoints, comparing with AMI single exposure, showing that the presence of NPls did not modulate the AMI toxicity. However, the behavioral assessment showed a different pattern with hypoactivity for the NPls + AMI exposure (NPls - hyperactivity; AMI - no effect). Interaction effects between NPls and AMI were also found in the protein contents (antagonism) and in the total glutathione content (synergism). This study highlights the complexity and unpredictability of NPls interaction with pharmaceuticals, important for an accurate environmental risk assessment and for the developing of effective strategies and interventions against plastic pollution.
Topics: Animals; Amitriptyline; Zebrafish; Microplastics; Water Pollutants, Chemical; Polystyrenes
PubMed: 38244879
DOI: 10.1016/j.etap.2024.104372 -
Neurotherapeutics : the Journal of the... Jan 2024While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex...
While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex phenotype that precludes neonatal-onset epilepsy. In the present work, the clinical features of three patients carrying a de novo KCNQ2 Y141N (n = 1) or G239S variant (n = 2) respectively, are described. All three patients had a mild global developmental delay, with prominent language deficits, and strong activation of interictal epileptic activity during sleep. Epileptic seizures were not reported. The absence of neonatal seizures suggested a GoF effect and prompted functional testing of the variants. In vitro whole-cell patch-clamp electrophysiological experiments in Chinese Hamster Ovary cells transiently-transfected with the cDNAs encoding Kv7.2 subunits carrying the Y141N or G239S variants in homomeric or heteromeric configurations with Kv7.2 subunits, revealed that currents from channels incorporating mutant subunits displayed increased current densities and hyperpolarizing shifts of about 10 mV in activation gating; both these functional features are consistent with an in vitro GoF phenotype. The antidepressant drug amitriptyline induced a reversible and concentration-dependent inhibition of current carried by Kv7.2 Y141N and G239S mutant channels. Based on in vitro results, amitriptyline was prescribed in one patient (G239S), prompting a significant improvement in motor, verbal, social, sensory and adaptive behavior skillsduring the two-year-treatment period. Thus, our results suggest that KCNQ2 GoF variants Y141N and G239S cause a mild DD with prominent language deficits in the absence of neonatal seizures and that treatment with the Kv7 channel blocker amitriptyline might represent a potential targeted treatment for patients with KCNQ2 GoF variants.
Topics: Infant, Newborn; Cricetinae; Animals; Humans; Amitriptyline; Cricetulus; CHO Cells; Gain of Function Mutation; Epilepsy; Phenotype; Seizures; KCNQ2 Potassium Channel
PubMed: 38241158
DOI: 10.1016/j.neurot.2023.10.006 -
Neurology and Therapy Apr 2024In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2-4 prior preventive migraine treatment failures. This post hoc...
INTRODUCTION
In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2-4 prior preventive migraine treatment failures. This post hoc analysis evaluated the efficacy of eptinezumab across the 24-week placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure type.
METHODS
DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously every 12 weeks. Changes from baseline in MMDs and percentages of patients with ≥ 50% reduction from baseline in MMDs (≥ 50% migraine responder rates [MRRs]) were summarized in subgroups of patients defined by prior treatment failure type. Subgroups were not mutually exclusive and included patients for whom topiramate, beta blockers (metoprolol, propranolol), amitriptyline, and/or flunarizine had failed.
RESULTS
Across Weeks 1-12 in all subgroups, patients treated with eptinezumab experienced greater reductions from baseline in MMDs than those receiving placebo (reductions ranged from 4.5-5.5 vs 1.6-2.4, respectively), with larger reductions over Weeks 13-24. Similarly, ≥ 50% MRRs were consistently higher with eptinezumab than placebo and increased following a second infusion.
CONCLUSION
In all subgroups, regardless of prior preventive treatment failure type, eptinezumab demonstrated greater reductions in MMDs and higher MRRs compared with placebo.
TRIAL REGISTRATION
ClinicalTrials.gov (Identifier: NCT04418765).
PubMed: 38236314
DOI: 10.1007/s40120-023-00575-5 -
Medicine Jan 2024There are studies on the effect of low-dose amitriptyline on pain control, but there is a lack of studies on the use of amitriptyline for chronic pain and the factors...
There are studies on the effect of low-dose amitriptyline on pain control, but there is a lack of studies on the use of amitriptyline for chronic pain and the factors associated with the prescription of traditional doses. We used a national sample cohort of patients aged ≥ 18 years who were prescribed amitriptyline along with chronic pain, without psychiatric disorders, between 2002 to 2015. We categorized the prescriptions into 2 groups according to the daily dose: low doses (≤25 mg) and traditional doses (>25 mg). Multivariable logistic regression models were used to identify factors associated with traditional dose prescriptions. Among 177,769 prescriptions for amitriptyline, 15,119 (8.5%) were prescribed for chronic pain. The prevalence of prescriptions and proportion of traditional doses of amitriptyline tended to decrease during the study period. Male sex (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.13); age 65-80 years (OR 1.12, 95% CI 1.08-1.16), especially ≥ 80 years (OR 1.55, 95% CI 1.45-1.65); headaches (OR 1.18, 95% CI 1.10-1.27), receiving medical aids (OR 2.58, 95% CI 2.46-2.71); and being prescribed benzodiazepines or zolpidem concomitantly (OR 1.10, 95% CI 1.06-1.15) were significantly associated with traditional dose prescriptions of amitriptyline. Although traditional dose prescriptions of amitriptyline have been declining, close monitoring is still required in the presence of the above-mentioned factors.
Topics: Humans; Male; Cross-Sectional Studies; Amitriptyline; Chronic Pain; Benzodiazepines; Headache
PubMed: 38181253
DOI: 10.1097/MD.0000000000036790 -
BMJ Open Dec 2023Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
Adverse drug events associated with nortriptyline compared with paroxetine and alternative medications in an older adult population: a retrospective cohort study in Southern California.
OBJECTIVE
Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
DESIGN
Retrospective cohort study.
SETTING
The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California.
PARTICIPANTS
Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018.
MAIN OUTCOME MEASURES
HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities.
RESULTS
Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin.
CONCLUSIONS
Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.
Topics: Humans; Aged; Paroxetine; Nortriptyline; Citalopram; Fluoxetine; Sertraline; Venlafaxine Hydrochloride; Amitriptyline; Duloxetine Hydrochloride; Retrospective Studies; Escitalopram; Gabapentin; Drug-Related Side Effects and Adverse Reactions; Syncope
PubMed: 38154883
DOI: 10.1136/bmjopen-2023-076028 -
The Journal of Pharmacology and... Jan 2024Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal...
Assessing Dose- and Sex-Dependent Antinociceptive Effects of Cannabidiol and Amitriptyline, Alone and in Combination, and Exploring Mechanism of Action Involving Serotonin 1A Receptors.
Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal approach to pain and sociocultural changes have renewed interest in cannabinoid use, particularly cannabidiol (CBD), for pain. The tricyclic antidepressant amitriptyline (AT) is approved for use in pain-related syndromes, alone and within a multimodal approach. Therefore, we investigated sex- and dose-dependent effects of CBD and AT antinociception in the 2.5% formalin inflammatory pain model. Male and female C57BL/6J mice were pretreated with either vehicle, CBD (0.3-100 mg/kg), or AT (0.1-30 mg/kg) prior to formalin testing. In the acute phase, CBD induced antinociception after administration of 30-100 mg/kg in males and 100 mg/kg in females and in the inflammatory phase at doses of 2.5-100 mg/kg in males and 10-100 mg/kg in females. In the acute phase, AT induced antinociception at 10 mg/kg for all mice, and at 0.3 mg/kg in males and 3 mg/kg in female mice in the inflammatory phase. Combining the calculated median effective doses of CBD and AT produced additive effects for all mice in the acute phase and for males only in the inflammatory phase. Use of selective serotonin 1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635) maleate (0.1 mg/kg) before co-administration of CBD and AT reversed antinociception in the acute and partially reversed antinociception in the inflammatory phase. Administration of AT was found to enhance cannabinoid receptor type 1mRNA expression only in female mice. These results suggest a role for serotonin and sex in mediating cannabidiol and amitriptyline-induced antinociception in inflammatory pain. SIGNIFICANCE STATEMENT: Inflammatory pain is an important component of both acute and chronic pain. We have found that cannabidiol (CBD) and amitriptyline (AT) show dose-dependent, and that AT additionally shows sex-dependent, antinociceptive effects in an inflammatory pain model. Additionally, the combination of CBD and AT was found to have enhanced antinociceptive effects that is partially reliant of serotonin 1A receptors and supports the use of CBD within a multimodal approach to pain.
Topics: Mice; Male; Female; Animals; Cannabidiol; Serotonin; Amitriptyline; Chronic Pain; Receptor, Serotonin, 5-HT1A; Mice, Inbred C57BL; Serotonin Antagonists; Analgesics; Formaldehyde
PubMed: 38129125
DOI: 10.1124/jpet.123.001855