-
PloS One 2023Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals.
METHODS
We searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups.
RESULTS
Twenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd's ratio for amitriptyline versus placebo (OR = 7.41; [95% CI, 4.54 to 12.12]). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent.
DISCUSSION
The large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (<100 participants) decreased heterogeneity between studies, but may also have reduced our ability to detect rare events. Future studies should focus on older people, as they are more susceptible to anticholinergic ADRs.
REGISTRATION
PROSPERO: CRD42020111970.
Topics: Adult; Aged; Humans; Amitriptyline; Cholinergic Antagonists
PubMed: 37018325
DOI: 10.1371/journal.pone.0284168 -
Cardiovascular Toxicology Sep 2022Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies...
Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.
Topics: Amitriptyline; Arrhythmias, Cardiac; Diphenhydramine; Electrocardiography; Flecainide; Humans; Long QT Syndrome; Methadone; Mirtazapine; Poison Control Centers; Retrospective Studies; Risk Factors; Tachycardia, Ventricular; Torsades de Pointes; Trazodone; Ventricular Fibrillation
PubMed: 35930218
DOI: 10.1007/s12012-022-09764-4 -
Pharmacopsychiatry Mar 2024CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on...
INTRODUCTION
CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status.
METHODS
Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PC, PC) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine.
RESULTS
There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram.
DISCUSSION
PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.
Topics: Humans; Cytochrome P-450 CYP2D6; Venlafaxine Hydrochloride; Amitriptyline; Pharmacogenetics; Sertraline; Risperidone; Escitalopram; Cytochrome P-450 CYP2C19; Genotype
PubMed: 38354747
DOI: 10.1055/a-2248-6924 -
Cureus Aug 2023Introduction A common dental problem is the fear of pain during needle prick for giving local anesthesia (LA). The needle prick pain during dental procedures...
Introduction A common dental problem is the fear of pain during needle prick for giving local anesthesia (LA). The needle prick pain during dental procedures often varies with sex and age. Perception of pain depends on various factors, which can be psychological and biological. This perception of pain may change the behavior of patients toward dental treatments. Traditionally, lidocaine gel formulation was utilized before the parenteral dosage form. The lidocaine gel formulation is considered the drug of choice for LA in dental surgery. Currently, amitriptyline has been utilized in dental practice because of its beneficial pharmacology. Hence, the present study has been undertaken to compare the anesthetic ability of amitriptyline as an intraoral topical anesthetic agent with lidocaine gel. Methods This study was a comparative clinical study between two medications' anesthetic properties. This study included 120 patients indicated for bilateral orthodontics (the subdivision of dentistry that emphasizes identifying necessary interventions for the malocclusion of teeth) procedures. All the subjects were divided into amitriptyline and lidocaine groups. Both anesthetic gels were applied at separate sites before the injection of LA. The time of the onset of anesthesia was noted and analyzed. Patients were selected on the basis of inclusion and exclusion criteria. Individuals aged 18 to 30 years who were systemically healthy and orthodontically indicated for bilateral premolar extraction were included in this study. Again, patients with a history of neurological disorders and allergies to amitriptyline and lidocaine were excluded from the current study. Results Significant differences emerged between groups at five and 10 minutes, with amitriptyline-induced partial numbness (36.7% and 6.7%). At 40 and 45 minutes, both groups showed varied partial and complete numbness, with amitriptyline leading to partial recovery (23.3% and 73.3% complete numbness, 23.3% partial recovery) and lidocaine resulting in partial recovery (81.7%). When comparing the visual analog scale (VAS) scores, both groups exhibited a similar simultaneous effect at 15 minutes. Nonetheless, amitriptyline displayed significantly lower scores at 25 and 35 minutes (p < 0.001) in comparison to lidocaine. Similar observations were made when controlling for pain intensity. Conclusion It was concluded that amitriptyline holds both anesthetic and analgesic properties. Nevertheless, this study was unable to generalize the study findings because of the small sample size and being a single-center study. However, the VAS scores of anesthetic and analgesic pharmacodynamics properties of amitriptyline were statistically significantly lower than lidocaine, particularly at 25 and 35 minutes. Additionally, amitriptyline-induced anesthetic and analgesic pharmacology, especially pharmacokinetics properties, depends on the location and pattern of pain.
PubMed: 37581201
DOI: 10.7759/cureus.43405 -
Rheumatology (Oxford, England) May 2021There are signs that antidepressants and anticonvulsants are being prescribed more often for OA patients, despite limited evidence. Our objectives were to examine...
OBJECTIVES
There are signs that antidepressants and anticonvulsants are being prescribed more often for OA patients, despite limited evidence. Our objectives were to examine prescription rates and time trends for antidepressants and anticonvulsants in OA patients, to assess the percentage of long-term prescriptions, and to determine patient characteristics associated with antidepressant or anticonvulsant prescription.
METHODS
A population-based cohort study was conducted using the Integrated Primary Care Information database. First, episodic and prevalent prescription rates for antidepressants (amitriptyline, nortriptyline and duloxetine) and anticonvulsants (gabapentinoids) in OA patients were calculated for the period 2008-17. Logistic regression was used to assess which patient characteristics were associated with prescriptions.
RESULTS
In total, 164 292 OA patients were included. The prescription rates of amitriptyline, gabapentin and pregabalin increased over time. The increase in prescription rates for pregabalin was most pronounced. Episodic prescription rate increased from 7.1 to 13.9 per 1000 person-years between 2008 and 2017. Amitriptyline was prescribed most (15.1 episodic prescriptions per 1000 person-years in 2017). Prescription rates of nortriptyline and duloxetine remained stable at 3.0 and 2.0 episodic prescriptions per 1000 person-years, respectively. For ≤3% of patients with incident OA, medication was prescribed long-term (≥3 months). In general, all medication was prescribed more frequently for older patients (except duloxetine), women, patients with OA in ≥2 joints, patients with spinal OA and patients with musculoskeletal disorders.
CONCLUSION
Prescription rates of amitriptyline, gabapentin and pregabalin increased over time. Since there is little evidence to support prescription in OA, caution is necessary when prescribing.
Topics: Aged; Analgesics; Anticonvulsants; Antidepressive Agents; Depressive Disorder; Drug Prescriptions; Female; Gabapentin; Humans; Male; Middle Aged; Osteoarthritis; Practice Patterns, Physicians'; Pregabalin
PubMed: 33175150
DOI: 10.1093/rheumatology/keaa544 -
Journal of Investigative Medicine : the... Feb 2024As more states legalize cannabinoid products for recreational use and medicinal purposes, the prevalence of cannabinoid hyperemesis syndrome has become increasingly... (Review)
Review
As more states legalize cannabinoid products for recreational use and medicinal purposes, the prevalence of cannabinoid hyperemesis syndrome has become increasingly common. Yet, it remains unrecognized to many healthcare providers along with the most efficacious treatments. Cannabinoid hyperemesis syndrome most often presents with episodic vomiting secondary to chronic daily cannabis use over several months to years. Patients often complain of nausea and abdominal pain that is improved by taking hot showers or baths. Symptoms are alleviated with the cessation of cannabis use over a period of 6-12 months. Treatment for acute attacks often consists of parenteral benzodiazepines in the inpatient setting. Long-term management and prevention of further attacks are aided by tricyclic antidepressants such as amitriptyline with a dose range of 50-200 mg/d. Once a patient is in remission, amitriptyline can be tapered slowly. As cannabis becomes more widely available and accepted in the continental United States, so must education on the diagnosis of cannabinoid hyperemesis syndrome and treatment strategies.
Topics: Humans; Cannabis; Cannabinoid Hyperemesis Syndrome; Prevalence; Amitriptyline; Vomiting
PubMed: 37997432
DOI: 10.1177/10815589231217495 -
Journal of Hazardous Materials Sep 2023To investigate the catalytic mechanism and mass transfer efficiency in the removal of amitriptyline using an electro-peroxide process, a CuFeO-modified carbon cloth...
To investigate the catalytic mechanism and mass transfer efficiency in the removal of amitriptyline using an electro-peroxide process, a CuFeO-modified carbon cloth cathode was prepared and utilized in a reaction unit. The results demonstrated a remarkable efficacy of the system, achieving 91.0% amitriptyline removal, 68.3% mineralization, 41.2% mineralization current efficiency, and 0.24 kWh/m energy consumption within just five minutes of treatment. The study revealed that the exposed Fe atoms of the ferrite nanoparticles, with a size of 22.7 nm and 89.7% crystallinity, functioned as mediators to bind the adsorbed O atoms. The 3d, 3d, and 3d orbitals of Fe atoms interacted with the 2p orbital of O atoms of HO and O to form σ and π bonds, facilitating the adsorption-activation of HO and O into hydroxyl radicals. These hydroxyl radicals (∼ 1.15 × 10 mol/L) were distributed at the cathode-solution interface and rapidly consumed along the direction of liquid flow. The flow-through cathode design improved the mass transfer of aqueous O and in-situ generated HO, leading to an increased yield of hydroxyl radicals, as well as the contact time and space between hydroxyl radicals and amitriptyline. Ultimately, this resulted in a higher degradation efficiency of the system.
PubMed: 37343407
DOI: 10.1016/j.jhazmat.2023.131604 -
Journal of Clinical PsychopharmacologyClozapine, a second-generation antipsychotic medication, is mainly indicated for managing treatment-resistant schizophrenia. Among all the nonthreatening adverse effects... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation and Comparison of the Effectiveness of Atropine Eye Drops, Ipratropium Bromide Nasal Spray, and Amitriptyline Tablet in the Management of Clozapine-Associated Sialorrhea in Patients With Refractory Schizophrenia: A Randomized Clinical Trial.
PURPOSE
Clozapine, a second-generation antipsychotic medication, is mainly indicated for managing treatment-resistant schizophrenia. Among all the nonthreatening adverse effects of clozapine, sialorrhea is a stigmatizing complication occurring in approximately 31.0% to 97.4% of patients. In this study, 2 topical agents (atropine eye drop and ipratropium nasal spray) and a systemic medication (amitriptyline) were compared simultaneously for the management of clozapine-associated sialorrhea.
METHODS
We conducted a randomized, single-blinded, non-placebo-controlled clinical trial from June 2022 to January 2023. Eligible patients were randomly allocated into 3 mentioned groups. Patients were monitored for sialorrhea weekly based on scales, including the Toronto Nocturnal Hypersalivation Scale, Clinical Global Impression-Improvement, and Clinical Global Impression-Severity for 1 month. Possible adverse drug reactions and adherence were also recorded.
RESULTS
Twenty-four patients, including 6, 10, and 8 individuals in ipratropium bromide nasal spray, atropine eye drop, and amitriptyline groups, completed the study, respectively. The cohort's demographic, baseline clinical, and sociocultural characteristics were comparable among the 3 groups. Within-group comparisons, between times baseline and week 4, demonstrated that significant differences were in groups atropine and amitriptyline based on Toronto Nocturnal Hypersalivation Scale, in 3 groups based on Clinical Global Impression-Improvement, and also in only-atropine group based on Clinical Global Impression-Severity. Likewise, between-group comparisons showed that atropine was significantly more effective in clozapine-associated sialorrhea management than amitriptyline and ipratropium, in the first 2 weeks and second 2 weeks of study, respectively. Regarding safety, the interventions were tolerated relatively well.
CONCLUSIONS
Conclusively, atropine is more efficacious than amitriptyline, within the first 2 weeks of study and also relative to ipratropium, overall. As time effect was significant between atropine and amitriptyline, according to analysis of covariance test, further investigation with longer follow-up duration would be prudent. In addition, expanding patient population with larger sample size should be conducted for more precision.
Topics: Humans; Amitriptyline; Antipsychotic Agents; Atropine; Clozapine; Ipratropium; Nasal Sprays; Schizophrenia; Schizophrenia, Treatment-Resistant; Sialorrhea; Tablets
PubMed: 38100776
DOI: 10.1097/JCP.0000000000001786 -
Indian Journal of Pharmacology 2023Escitalopram, fluoxetine, and amitriptyline are the drugs commonly used in the treatment of depression. The pharmacoeconomic evaluation of these drugs becomes relevant...
INTRODUCTION
Escitalopram, fluoxetine, and amitriptyline are the drugs commonly used in the treatment of depression. The pharmacoeconomic evaluation of these drugs becomes relevant as they are prescribed for a long period of time, and depression causes a significant economic burden. The cost-minimization study would contribute to bringing down the annual treatment costs, leading to better medication adherence and ultimately better patient outcomes.
MATERIALS AND METHODS
All drug prices are mentioned in Indian National Rupee (INR). All expenses are based on 2022 pricing. No cost discounting was used because all expenditures were calculated over a year. We considered hypothetical scenarios where the patient was prescribed the lowest possible dose for depression, an equivalent antidepressant dose, a defined daily dose, and the maximum acceptable therapeutic dose for depression.
RESULTS
Annual average treatment costs of amitriptyline, escitalopram, and fluoxetine in patients with depression at baseline with equivalent dosing as mono-drug therapy were 2765.53, 2914.78, and 1422.72 rupees (INR), respectively. Savings were high when the patient was shifted to fluoxetine from either escitalopram or amitriptyline. The savings from switching to fluoxetine were 50.66% and 56.42% from escitalopram and amitriptyline, respectively.
CONCLUSION
The choice of an antidepressant depends on multiple aspects, among which the cost of treatment plays a crucial role. Among the drugs compared, fluoxetine seems to offer greater value for money. The study emphasizes that selective serotonin reuptake inhibitors are the most commonly prescribed antidepressants not only because of their favorable pharmacological profile but also because of their affordability.
Topics: Humans; Fluoxetine; Amitriptyline; Escitalopram; Depression; Antidepressive Agents; Health Care Costs
PubMed: 37929407
DOI: 10.4103/ijp.ijp_854_22 -
JCI Insight Feb 2021TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced synaptopathy. The effects were...
TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced synaptopathy. The effects were consistent with regeneration of cochlear synapses that we observed in vitro after synaptic loss due to kainic acid-induced glutamate toxicity and were elicited by administration of TrkB agonists, amitriptyline, and 7,8-dihydroxyflavone, directly into the cochlea via the posterior semicircular canal 48 hours after exposure to noise. Synaptic counts at the inner hair cell and wave 1 amplitudes in the auditory brainstem response (ABR) were partially restored 2 weeks after drug treatment. Effects of amitriptyline on wave 1 amplitude and afferent auditory synapse numbers in noise-exposed ears after systemic (as opposed to local) delivery were profound and long-lasting; synapses in the treated animals remained intact 1 year after the treatment. However, the effect of systemically delivered amitriptyline on synaptic rescue was dependent on dose and the time window of administration: it was only effective when given before noise exposure at the highest injected dose. The long-lasting effect and the efficacy of postexposure treatment indicate a potential broad application for the treatment of synaptopathy, which often goes undetected until well after the original damaging exposures.
Topics: Amitriptyline; Animals; Auditory Threshold; Cochlea; Cochlear Nerve; Coculture Techniques; Disease Models, Animal; Evoked Potentials, Auditory, Brain Stem; Flavones; Hair Cells, Auditory, Inner; Hearing Loss, Noise-Induced; Membrane Glycoproteins; Mice; Mice, Inbred CBA; Protein-Tyrosine Kinases; Regeneration; Synapses
PubMed: 33373328
DOI: 10.1172/jci.insight.142572