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Acta Anaesthesiologica Taiwanica :... Dec 2014Tolerance to and dependence on the analgesic effect of opioids is a pharmacological phenomenon that occurs after their prolonged administration. (Comparative Study)
Comparative Study
INTRODUCTION
Tolerance to and dependence on the analgesic effect of opioids is a pharmacological phenomenon that occurs after their prolonged administration.
OBJECTIVE
The aim of this study was to evaluate the protective effects of ceftriaxone and amitriptyline on the development of morphine-induced tolerance and dependence.
METHODS
In this study, 18 groups (9 groups each for tolerance and dependency tests) of mice (n = 8) received saline [10 mL/kg, intraperitoneally (i.p.)], morphine (50 mg/kg, i.p.), ceftriaxone (50 mg/kg, i.p., 100 mg/kg, i.p., and 200 mg/kg, i.p.), amitriptyline (5 mg/kg, i.p., 10 mg/kg, i.p., and 15 mg/kg, i.p.), or a combination of ceftriaxone (50 mg/kg, i.p.) and amitriptyline (5 mg/kg, i.p.) once per day for 4 days for investigation and comparison of the effects of ceftriaxone and amitriptyline on the prevention of dependency and tolerance to morphine. Tolerance was assessed with administration of morphine (9 mg/kg, i.p.) and using the hot plate test on the 5(th) day. In dependency tests, withdrawal symptoms were assessed on the 4(th) day for each animal 30 minutes after the administration of naloxone (4 mg/kg, i.p.; 2 hours after the last dose of morphine).
RESULTS
It was found that treatment with ceftriaxone or amitriptyline attenuated the development of tolerance to the antinociceptive effect of morphine and also reduced naloxone-precipitated withdrawal jumping and standing on feet. Furthermore, coadministration of ceftriaxone and amitriptyline at low doses (50 mg/kg, i.p. and 5 mg/kg, i.p., respectively) prior to morphine injection also decreased both morphine-induced tolerance and dependence.
CONCLUSION
Results indicate that the treatment with ceftriaxone and amitriptyline, alone or in combination, could attenuate the development of morphine-induced tolerance and dependence.
Topics: Amitriptyline; Animals; Ceftriaxone; Drug Tolerance; Male; Mice; Morphine; Morphine Dependence
PubMed: 25557842
DOI: 10.1016/j.aat.2014.11.001 -
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 -
The New England Journal of Medicine Jan 2017Which medication, if any, to use to prevent the headache of pediatric migraine has not been established. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Which medication, if any, to use to prevent the headache of pediatric migraine has not been established.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment.
RESULTS
A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt.
CONCLUSIONS
There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281 ).
Topics: Adolescent; Amitriptyline; Anticonvulsants; Child; Double-Blind Method; Fatigue; Female; Fructose; Humans; Linear Models; Male; Migraine Disorders; Paresthesia; Placebos; Topiramate; Treatment Failure; Xerostomia
PubMed: 27788026
DOI: 10.1056/NEJMoa1610384 -
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 -
Revista de Neurologia Apr 2022Neuropathic pain (NP) is difficult to treat due to the heterogeneity of causes, symptoms and underlying mechanisms. It constitutes a great medical need that is not... (Review)
Review
INTRODUCTION
Neuropathic pain (NP) is difficult to treat due to the heterogeneity of causes, symptoms and underlying mechanisms. It constitutes a great medical need that is not covered, and has a high number of therapeutic failures in recent randomized clinical trials.
DEVELOPMENT
This narrative review presents an update on the pharmacological treatment of NP with emphasis on the new published clinical guidelines, new drugs in development, and the new challenges that arise in the therapeutic management of this entity.
CONCLUSIONS
First-line drugs proposed include tricyclic antidepressants (particularly amitriptyline), serotonin and norepinephrine reuptake inhibitors (particularly duloxetine), pregabalin, and gabapentin. However, the latest recommendations are still relevant and the most recent clinical studies even question the role of pregabalin as a first-line treatment. Therefore, we consider that periodic updates of the clinical guidelines in NP are necessary to better guide our daily clinical practice and rationalize the use of all available therapeutic options. Furthermore, the expansion of knowledge in NP has generated a series of challenges, such as the development of new drugs based on pathophysiological mechanisms investigated in animals, and the development of optimal therapeutic approaches in clinical trials, based more on personalized than etiological approaches.
Topics: Amitriptyline; Analgesics; Animals; Antidepressive Agents, Tricyclic; Gabapentin; Humans; Neuralgia; Pregabalin
PubMed: 35383875
DOI: 10.33588/rn.7408.2021381 -
Canadian Family Physician Medecin de... Dec 2015
Review
Topics: Acute Disease; Adult; Aged; Amitriptyline; Back Pain; Humans; Middle Aged; Muscle Relaxants, Central; Pain Management
PubMed: 26668287
DOI: No ID Found -
Comparative Biochemistry and... Nov 2023Many studies have demonstrated that microplastics (MPs) can combine with various coexisting chemical pollutants, increasing their bioavailability and changing the...
Many studies have demonstrated that microplastics (MPs) can combine with various coexisting chemical pollutants, increasing their bioavailability and changing the combined toxicity to organisms. However, information on the combined effects of MPs and amitriptyline (AMI, a widely used tricyclic antidepressant) on aquatic species is still limited. In this study, we exposed zebrafish to MPs (2-μm polystyrene beads, 0.44 mg/L), AMI (2.5 μg/L), and their mixture for 7 days and investigated the alternation in their behaviors and ocular oxidative stress. As a result, combined exposure to MPs and AMI could significantly elevate locomotor activity, increase the frequency and duration of shoaling behavior in zebrafish, and alter their post-stimulation behaviors. Although combined exposure to MPs and AMI exhibited stronger behavioral toxicity than individual exposure, no significant interactive effects on the behavioral traits were detected, suggesting that the combined behavioral toxicity appeared to be an additive effect. However, their combined exposure to MPs or AMI significantly decreased the ocular levels of SOD, CAT, and GSH in zebrafish, with significant interaction effects on the CAT activity and GSH content. Significant correlations between some post-stimulation behavioral traits and ocular levels of SOD, CAT, and GSH in zebrafish were detected, suggesting that ocular oxidative stress induced by combined exposure to MPs and AMI may play an important role in their behavioral toxicity.
Topics: Animals; Microplastics; Amitriptyline; Zebrafish; Plastics; Water Pollutants, Chemical; Oxidative Stress; Superoxide Dismutase
PubMed: 37586580
DOI: 10.1016/j.cbpc.2023.109717 -
The Cochrane Database of Systematic... Oct 2014Sleep bruxism is an oral activity characterized by involuntary teeth grinding or clenching during sleep. Several forms of treatment have been proposed for this disorder,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sleep bruxism is an oral activity characterized by involuntary teeth grinding or clenching during sleep. Several forms of treatment have been proposed for this disorder, including behavioural, dental and pharmacological strategies.
OBJECTIVES
To evaluate the effectiveness and safety of pharmacological therapy for the treatment of sleep bruxism compared with other drugs, no treatment or placebo.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2014), MEDLINE (1966 to August 2014), EMBASE (1980 to August 2013) and LILACS (1982 to August 2014). We identified additional reports from the reference lists of retrieved reports and from reviews on treatment of sleep bruxism. We applied no language restrictions.
SELECTION CRITERIA
We selected randomized controlled trials (RCTs) or quasi-RCTs that compared drugs with other drugs, no treatment or placebo in people with sleep bruxism.
DATA COLLECTION AND ANALYSIS
Review authors carried out data extraction and quality assessment of the included trials independently and in duplicate. We discussed discrepancies until we reached consensus. We consulted a third review author in cases of persistent disagreement. We contacted authors of primary studies when necessary.
MAIN RESULTS
We identified 18 potentially relevant RCTs, but only seven met the inclusion criteria. All studies had a small number of participants, ranging from seven to 16 people per study and had a cross-over design. Three studies were of low risk of bias, while four were of uncertain risk. Amitriptyline (three studies), bromocriptine (one study), clonidine (one study), propranolol (one study), levodopa (Prolopa®) (one study) and tryptophan (one study) were compared with placebo. Studies evaluating bromocriptine, clonidine, propranolol and levodopa reported our primary outcome of indices of bruxism motor activity.Results were imprecise and consistent with benefit, no difference or harm. These were the specific findings for each of the drugs according to specific outcomes: 1. Amitriptyline versus placebo for masseteric electromyography (EMG) activity per minute: standardized mean difference (SMD) -0.28 (95% confidence interval (CI) -0.91 to 0.34; P value = 0.37), 2. bromocriptine versus placebo for bruxism episodes per hour: mean difference (MD) 0.60 (95% CI -2.93 to 4.13), bruxism bursts per hour: MD -2.00 (95% CI -53.47 to 49.47), bruxism bursts per episode: MD 0.50 (95% CI -1.85 to 2.85) or number of episodes with grinding noise: MD 2.40 (95% CI -24.00 to 28.80), 3. clonidine versus placebo for number of bruxism episodes per hour: MD -2.41 (95% CI -4.84 to 0.02), 4. propranolol versus placebo for the number of bruxism episodes per hour: MD 1.16 (95% CI -1.89 to 4.21), 5. L-tryptophan versus placebo for masseteric EMG activity per second: SMD 0.08 (95% CI -0.90 to 1.06) and 6. levodopa versus placebo for bruxism episodes per hour of sleep: MD -1.47 (95% CI -3.64 to 0.70), for bruxism bursts per episode: MD 0.06 (95% CI -2.47 to 2.59).We combined several secondary outcomes (sleep duration, masseteric EMG activity per minute and pain intensity) in a meta-analysis for comparison of amitriptyline with placebo. The results for most comparisons were uncertain because of statistical imprecision. One study reported that clonidine reduced rapid eye movement (REM) sleep stage and increased the second stage of sleep. However, results for other sleep-related outcomes with clonidine were uncertain. Adverse effects were frequent in people who took amitriptyline (5/10 had drowsiness, difficulty awakening in the morning, insomnia or xerostomia compared with 0/10 in the placebo group), as well as in people who received propranolol (7/16 had moderate-to-severe xerostomia compare with 2/16 in the placebo group). Clonidine was associated with prolonged morning hypotension in three of 16 participants. The use of preventive medication avoided any adverse effects in people treated with levodopa and bromocriptine.
AUTHORS' CONCLUSIONS
There was insufficient evidence on the effectiveness of pharmacotherapy for the treatment of sleep bruxism. This systematic review points to the need for more, well-designed, RCTs with larger sample sizes and adequate methods of allocation, outcome assessment and duration of follow-up. Ideally, parallel RCTs should be used in future studies to avoid the bias associated with cross-over studies. There is a need to standardize the outcomes of RCTs on treatments for sleep bruxism.
Topics: Amitriptyline; Bromocriptine; Clonidine; Humans; Levodopa; Propranolol; Randomized Controlled Trials as Topic; Sleep Bruxism; Tryptophan
PubMed: 25338726
DOI: 10.1002/14651858.CD005578.pub2 -
Veterinary Anaesthesia and Analgesia Nov 2015To evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs.
STUDY DESIGN
Prospective randomized experiment.
ANIMALS
Five healthy Greyhound dogs (three males and two females) aged 2-4 years and weighing 32.5-39.7 kg.
METHODS
After jugular vein catheterization, dogs were administered a single oral or IV dose of amitriptyline (4 mg kg(-1)). Blood samples were collected at predetermined time points from baseline (0 hours) to 32 hours after administration and plasma concentrations of amitriptyline and nortriptyline were measured by liquid chromatography triple quadrupole mass spectrometry. Non-compartmental pharmacokinetic analyses were performed.
RESULTS
Orally administered amitriptyline was well tolerated, but adverse effects were noted after IV administration. The mean maximum plasma concentration (CMAX) of amitriptyline was 27.4 ng mL(-1) at 1 hour and its mean terminal half-life was 4.33 hours following oral amitriptyline. Bioavailability of oral amitriptyline was 6%. The mean CMAX of nortriptyline was 14.4 ng mL(-1) at 2.05 hours and its mean terminal half-life was 6.20 hours following oral amitriptyline.
CONCLUSIONS AND CLINICAL RELEVANCE
Amitriptyline at 4 mg kg(-1) administered orally produced low amitriptyline and nortriptyline plasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1-4 mg kg(-1)) is appropriate in dogs.
Topics: Administration, Oral; Amitriptyline; Analgesics; Animals; Biological Availability; Dogs; Female; Half-Life; Injections, Intravenous; Male; Nortriptyline
PubMed: 25683584
DOI: 10.1111/vaa.12248