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Cephalalgia : An International Journal... Apr 2024Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and amitriptyline in pediatric migraine prophylaxis.
METHODS
In a randomized, double-blind trial, patients aged 4-17 years with migraine who were eligible for prophylaxis enrolled. The primary outcome was a reduction response rate of ≥50% with < 0.005 with respect to headache characteristics. The secondary outcome was migraine disability assessment. We evaluated patients every four weeks for three months: T1: week 4, T2: week 8 and T3: week 12. The safety profile was also assessed.
RESULTS
Thirty patients were randomly assigned to each group. However, 43 patients completed the trial. Headache frequency decreased in amitriptyline group more effectively in T1 ( = 0.004). Amitriptyline was more successful in reducing the headache duration in all three periods ( < 0.005). There was no significant difference in severity improvement and reducing disability score between the two groups ( > 0.005). No serious adverse events were observed.
CONCLUSIONS
Both medications are effective in ameliorating migraine headaches and related disabilities. However, amitriptyline appears be a preferable option over cinnarizine, given its faster onset of action, efficacy in reducing headache duration and longer-lasting effects. The study was registered with the Iranian Registry of Clinical Trials (IRCT) under the code IRCT-20191112045413N1.
Topics: Humans; Child; Cinnarizine; Amitriptyline; Iran; Treatment Outcome; Migraine Disorders; Headache; Analgesics; Double-Blind Method
PubMed: 38641932
DOI: 10.1177/03331024241230963 -
American Family Physician Feb 2016
Review
Topics: Amitriptyline; Humans; Low Back Pain; Muscle Relaxants, Central
PubMed: 26926618
DOI: No ID Found -
British Journal of Clinical Pharmacology 19771. Double-blind controlled comparisons of nomifensine with placebo, imipramine, desipramine, viloxazine, nortriptyline, a combination of amitriptyline and... (Clinical Trial)
Clinical Trial Comparative Study Review
1. Double-blind controlled comparisons of nomifensine with placebo, imipramine, desipramine, viloxazine, nortriptyline, a combination of amitriptyline and chlordiazepoxide, and diazepam have been carried out in various parts of the world. 2. Dosage ranged from 50-225 mg daily, and treatment lasted from 2-26 weeks. 3. Nomifensine was shown to possess useful antidepressive activity, to counteract inhibition, to restore drive and to relieve anxiety. 4. Adverse reactions were uncommon, particularly anticholinergic effects, and nomifensine was not shown to cause sedation or to interact with alcohol. No withdrawal phenomena were observed after 6 months' treatment. 5. Nomifensine is not suitable for severely agitated patients.
Topics: Adult; Aged; Amitriptyline; Clinical Trials as Topic; Depression; Double-Blind Method; Doxepin; Drug Evaluation; Humans; Imipramine; Isoquinolines; Nomifensine; Placebos; Viloxazine
PubMed: 334230
DOI: 10.1111/j.1365-2125.1977.tb05759.x -
Systematic Reviews Mar 2020Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades...
BACKGROUND
Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals.
METHODS
A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using meta-regression (for indication, outcome, and time points) and I statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment.
DISCUSSION
We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations.
SYSTEMATIC REVIEW REGISTRATION
Submitted to PROSPERO; assignment is in progress.
Topics: Adult; Amitriptyline; Drug-Related Side Effects and Adverse Reactions; Humans; Meta-Analysis as Topic; Systematic Reviews as Topic; United States
PubMed: 32183872
DOI: 10.1186/s13643-020-01296-8 -
Pain Physician 2014Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor...
BACKGROUND
Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects.
OBJECTIVE
The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats.
STUDY DESIGN
Controlled animal study.
METHODS
Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied.
RESULTS
The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05).
LIMITATIONS
Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings.
CONCLUSION
The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Analgesics, Opioid; Analysis of Variance; Animals; Dexmedetomidine; Disease Models, Animal; Drug Therapy, Combination; Hyperalgesia; Male; Pain; Pain Measurement; Pain Threshold; Posture; Psychomotor Performance; Rats; Rats, Wistar; Sciatic Neuropathy; Time Factors; Tramadol
PubMed: 24658480
DOI: No ID Found -
Journal of Pain and Symptom Management Aug 1995Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this...
Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia. One patient experienced an extrapyramidal reaction temporally related to the administration of IV amitriptyline, which was successfully managed with diphenhydramine. Further prospective, controlled studies are needed to further assess the safety, efficacy and tolerability of this novel use of amitriptyline.
Topics: Adolescent; Adult; Amitriptyline; Analgesics; Child; Child, Preschool; Female; Humans; Infusions, Intravenous; Male; Pediatrics; Retrospective Studies
PubMed: 7561230
DOI: 10.1016/0885-3924(95)00062-4 -
Veterinary Medicine and Science May 2021There are limited studies on the utilization of analgesics in testudines. Management of pain in reptiles is by use of analgesics generally used in other vertebrate...
BACKGROUND
There are limited studies on the utilization of analgesics in testudines. Management of pain in reptiles is by use of analgesics generally used in other vertebrate species. Evidently, some analgesics considered to be generally effective in reptiles are not effective in certain reptile species.
OBJECTIVE
The purpose of this study was to examine the effect of amitriptyline hydrochloride on nociceptive behaviour in Speke's hinge-back tortoise.
METHODS
Twenty-four adult Speke-hinged tortoises weighing 500-700 g were used. The effects of amitriptyline hydrochloride on nociception were evaluated using the formalin, capsaicin and hot plate nociceptive tests. Amitriptyline was administered intracoelomically at doses of 0.5, 1.0 and 3.0 mg/kg.
RESULTS
The higher doses of amitriptyline hydrochloride caused an increase in nociceptive behaviour (time spent in hindlimb withdrawal) on the formalin and capsaicin nociceptive tests, suggesting a potentiating effect. However, the doses used had no significant change in nociceptive behaviour on withdrawal response in the hot plate test.
CONCLUSIONS
The study showed that amitriptyline hydrochloride which is widely used in management of neuropathic pain potentiates nociceptive effects in the formalin and capsaicin nociceptive tests in the Speke's hinge-back tortoise. The hot plate test, which previously has not been reported in these animals, gave results not in line with the other tests and therefore more testing and validation of the test is required. Amitriptyline modulates chemical and thermal pain differently.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Animals; Female; Male; Nociception; Turtles
PubMed: 33559977
DOI: 10.1002/vms3.444 -
British Journal of Clinical Pharmacology Aug 1996Reboxetine is a novel antidepressant that has been shown to be effective in the treatment of major depressive disorders. The present experiment was designed to assess... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Reboxetine is a novel antidepressant that has been shown to be effective in the treatment of major depressive disorders. The present experiment was designed to assess whether it affects the cognitive and psychomotor skills necessary for optimum function in everyday life. Ten healthy male volunteers received reboxetine 0.5 mg, 1 mg or 4 mg, amitriptyline 25 mg, or matched placebo with and without alcohol (0.6 mg kg-1) in a double-blind 10-way crossover study. A psychometric test battery was administered at baseline and at 1, 2.25, 3.5, 6 and 9 h post-dose. The results showed that reboxetine had little or no effect on performance at any dose, compared with placebo. Amitriptyline, however, with and without alcohol, lowered critical flicker fusion threshold compared with placebo and/or reboxetine at all test points (e.g. at 3.5 h: 28.51 vs 30.33 Hz; P < 0.05); increased reaction time (e.g. 619 vs 540 ms; P < 0.05); increased tracking error (e.g. 16.34 vs 8.54 RMS units; P < 0.05); and slowed short-term memory scanning (e.g. 742 vs 590 ms; P < 0.05). It is concluded that reboxetine at doses of 4 mg and below is free from disruptive effects on cognitive function and psychomotor performance, and that it does not act synergistically with alcohol, in contrast to amitriptyline.
Topics: Adolescent; Adult; Amitriptyline; Antidepressive Agents; Central Nervous System Depressants; Cognition; Drug Interactions; Ethanol; Humans; Male; Morpholines; Psychomotor Performance; Reboxetine
PubMed: 8864325
DOI: 10.1046/j.1365-2125.1996.39016.x -
Canadian Family Physician Medecin de... Sep 2018
Topics: Amitriptyline; Canada; Consensus; Humans; Neuralgia; Nortriptyline
PubMed: 30209089
DOI: No ID Found -
Headache May 2013Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant... (Randomized Controlled Trial)
Randomized Controlled Trial
Childhood and Adolescent Migraine Prevention (CHAMP) study: a double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in the prevention of childhood and adolescent migraine.
BACKGROUND
Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents.
METHODS
CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28-day baseline and the final 28 days of treatment (weeks 20-24).
CONCLUSIONS
The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes.
Topics: Adolescent; Amitriptyline; Analgesics; Child; Comparative Effectiveness Research; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Research Design; Topiramate
PubMed: 23594025
DOI: 10.1111/head.12105