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Annals of the Academy of Medicine,... Apr 2020Amitriptyline (AMT) is a tricyclic antidepressant. In this review, we evaluate the clinical and epidemiological profile, pathological mechanisms and management of... (Review)
Review
INTRODUCTION
Amitriptyline (AMT) is a tricyclic antidepressant. In this review, we evaluate the clinical and epidemiological profile, pathological mechanisms and management of AMT-associated movement disorders.
MATERIALS AND METHODS
A search for relevant reports in 6 databases was performed. Studies that reported patients developed only ataxia or tremor after AMT use were excluded.
RESULTS
A total of 48 reports on 200 cases were found. AMT-associated movement disorders included myoclonus (n = 26), dyskinesia (n = 11), dystonia (n = 8), stutter (n = 5), akathisia (n = 3) and restless legs syndrome (n = 1). For less well-defined cases, 99 patients had dyskinesia, 19 had psychomotor disturbances, 3 had myoclonus, 11 had dystonia, 12 had Parkinsonism and 1 each had akathisia and extrapyramidal symptoms. Mean and standard deviation (SD) and median ages were 45.40 years (SD 16.78) and 40 years (range 3.7-82 years), respectively. Over half were women (58.13%) and the most common indication was depression. Mean and median AMT doses were 126 mg (SD 128.76) and 75 mg (range 15-800 mg), respectively. In 68% of patients, onset of movement disorders was <1 month; time from AMT withdrawal to complete recovery was <1 month in 70% of cases. A weak negative linear correlation (r = -0.0904) was found between onset of movement disorders and AMT dose. AMT withdrawal was the most common treatment.
CONCLUSION
Amitriptyline is associated with various movement disorders, particularly myoclonus, dystonia and dyskinesias. Stutters and restless legs syndrome are some of the less common associations.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Humans; Movement Disorders
PubMed: 32419008
DOI: No ID Found -
Medicina Aug 2023There is a wealth of information on early pharmacological supportive treatment for early rehabilitation following acute ischemic stroke. This review aims to provide... (Review)
Review
There is a wealth of information on early pharmacological supportive treatment for early rehabilitation following acute ischemic stroke. This review aims to provide healthcare professionals involved in rehabilitating patients with a summary of the available evidence to assist with decision-making in their daily clinical practice. A search for randomized clinical trials and observational studies published between 1/1/2000 and 28/8/2022 was performed using PubMed, Cochrane and Epistemonikos as search engines with language restriction to english and spanish. The selected studies included patients older than 18 with acute ischemic stroke undergoing early rehabilitation. The outcomes considered for efficacy were: motor function, language, and central pain. The selected pharmacological interventions were: cerebrolysin, levodopa, selegiline, amphetamines, fluoxetine, citalopram, escitalopram, antipsychotics, memantine, pregabalin, amitriptyline and lamotrigine. Evidence synthesis and evaluation were performed using the GRADE methodology. This review provided a summary of the evidence on pharmacological supportive care in early rehabilitation of post-acute ischemic stroke patients. This will make it possible to improve current recommendations with the aim of collaborating with health decision-making for this population.
Topics: Humans; Ischemic Stroke; Medicine; Amitriptyline; Antipsychotic Agents; Citalopram
PubMed: 37624681
DOI: No ID Found -
Drug Delivery and Translational Research Apr 2022Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical...
Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical properties of the molecule, amitriptyline is also a promising candidate for delivery as a topical analgesic. Here we report the dermal delivery of amitriptyline from a range of simple formulations. The first stage of the work required the conversion of amitriptyline hydrochloride to the free base form as confirmed by nuclear magnetic resonance (NMR). Distribution coefficient values were measured at pH 6, 6.5, 7, and 7.4. Solubility and stability of amitriptyline were assessed prior to conducting in vitro permeation and mass balance studies. The compound demonstrated instability in phosphate-buffered saline (PBS) dependent on pH. Volatile formulations comprising of isopropyl alcohol (IPA) and isopropyl myristate (IPM) or propylene glycol (PG) were evaluated in porcine skin under finite dose conditions. Compared with neat IPM, the IPM:IPA vehicles promoted 8-fold and 5-fold increases in the amount of amitriptyline that permeated at 24 h. Formulations containing PG also appear to be promising vehicles for dermal delivery of amitriptyline, typically delivering higher amounts of amitriptyline than the IPM:IPA vehicles. The results reported here suggest that further optimization of topical amitriptyline formulations should be pursued towards development of a product for clinical investigational studies.
Topics: Administration, Cutaneous; Amitriptyline; Analgesia; Analgesics; Animals; Excipients; Propylene Glycol; Skin; Skin Absorption; Swine
PubMed: 33886076
DOI: 10.1007/s13346-021-00982-x -
European Review For Medical and... May 2024Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN.
PATIENTS AND METHODS
We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria.
RESULTS
No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively).
CONCLUSIONS
No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed.
Topics: Pregabalin; Amitriptyline; Humans; Diabetic Neuropathies; Analgesics; Quality of Life
PubMed: 38856135
DOI: 10.26355/eurrev_202405_36296 -
Advances in Rheumatology (London,... Jul 2020Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more... (Review)
Review
BACKGROUND
Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more effective and safer. This study aimed to compare evidence of the efficacy and safety of duloxetine compared with amitriptyline in the treatment of adult patients with fibromyalgia. This work contributes to guiding clinicians on the use of duloxetine or amitriptyline for the treatment of fibromyalgia and provides information for public health decision-makers.
METHODS
Overview of systematic reviews of clinical trials comparing duloxetine and amitriptyline in the treatment of fibromyalgia. The reviews were screened in Cochrane, PubMed, EMBASE, and SRDR with no restrictions on language and year of publication, considering that the research was conducted in July 2018 and updated until May 2020. The selection was based on the following criteria: adult patients with a diagnosis of fibromyalgia treated with duloxetine or amitriptyline, comparing the efficacy and safety in pain, fatigue, sleep, and mood disorder symptoms and quality of life, in addition to the acceptability of these antidepressants. The methodological quality and strength of evidence were assessed using the AMSTAR and GRADE instruments.
RESULTS
Eight systematic reviews were selected. Amitriptyline had low evidence for pain, moderate evidence for sleep and fatigue, and high evidence for quality of life. Duloxetine had high quality of evidence in patients with mood disorders. With low evidence, duloxetine has higher acceptability, but is safer in older patients, while amitriptyline is safer for non-elderly individuals.
CONCLUSION
Both antidepressants are effective in the treatment of fibromyalgia, differing according to the patient's symptoms and profile.
REGISTRATION
PROSPERO: CRD42019116101.
Topics: Amitriptyline; Antidepressive Agents; Duloxetine Hydrochloride; Fibromyalgia; Humans; Syndrome; Systematic Reviews as Topic
PubMed: 32641165
DOI: 10.1186/s42358-020-00137-5 -
European Journal of Clinical... Sep 2023We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of...
Synergistic combination of carvedilol, amlodipine, amitriptyline, and antibiotics as an alternative treatment approach for the susceptible and multidrug-resistant A. baumannii infections via drug repurposing.
We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of Acinetobacter baumannii infections caused by susceptible and multidrug-resistant strains. A. baumannii is a multidrug-resistant Gram-negative bacteria causing nosocomial infections, especially in intensive care units. It has been identified in the WHO critical pathogen list and this emphasises urgent need for new treatment options. As the development of new therapeutics is expensive and time consuming, finding new uses of existing drugs via drug repositioning has been favoured. Antimicrobial susceptibility tests were conducted on all 13 drugs according to CLSI. Drugs with MIC values below 128 μg/mL and control antibiotics were further subjected to synergetic effect and bacterial time-kill analysis. Carvedilol-gentamicin (FICI 0.2813) and carvedilol-amlodipine (FICI 0.5625) were determined to have synergetic and additive effect, respectively, on the susceptible A. baumannii strain, and amlodipine-tetracycline (FICI 0.75) and amitriptyline-tetracycline (FICI 0.75) to have additive effect on the multidrug-resistant A. baumannii strain. Most remarkably, both amlodipine and amitriptyline reduced the MIC of multidrug-resistant, including some carbapenems, A. baumannii reference antibiotic tetracycline from 2 to 0.5 μg/mL, for 4-folds. All these results were further supported by bacterial time-kill assay and all combinations showed bactericidal activity, at certain hours, at 4XMIC. Combinations proposed in this study may provide treatment options for both susceptible and multidrug-resistant A. baumannii infections but requires further pharmacokinetics and pharmacodynamics analyses and in vivo re-evaluations using appropriate models.
Topics: Humans; Anti-Bacterial Agents; Drug Repositioning; Amitriptyline; Carvedilol; Amlodipine; Drug Synergism; Microbial Sensitivity Tests; Acinetobacter Infections; Drug Resistance, Multiple, Bacterial; Tetracyclines; Acinetobacter baumannii
PubMed: 37428238
DOI: 10.1007/s10096-023-04634-5 -
Neurochemistry International Nov 2021The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering...
The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering other long-term neuroprotective mechanisms of these drugs, we hypothesized that this combination might exert some synergistic effects on neuropathic pain linked with its possible ability to prevent Wallerian degeneration (WD). The effects of individual and fixed-ratio of 1:1 combinations of orally administered amitriptyline and paracetamol were assayed in the two phases of the formalin test and in the chronic constriction injury (CCI) model in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Amitriptyline, paracetamol, and fixed-ratio amitriptyline-paracetamol combinations produced dose-dependent antinociceptive effects mainly on the inflammatory tonic phase. Repeated doses of individual drugs and their combination decreased CCI-induced mechanical allodynia in a dose-dependent manner. ED (formalin) and ED (CCI) values were estimated for the individual drugs, and isobolograms were constructed. Theoretical ED values for the combination estimated from the isobolograms were 16.5 ± 3.9 mg/kg and 26.0 ± 7.2 mg/kg for the single and repeated doses in persistent and neuropathic pain models, respectively. These values were significantly higher than the actually observed ED values, which were 0.39 ± 0.1 mg/kg and 8.2 ± 0.8 mg/kg in each model, respectively, indicating a synergistic interaction. Remarkably, CCI-induced sciatic nerve WD-related histopathological changes were prevented by this combination compared to either drug administered alone.
Topics: Acetaminophen; Administration, Oral; Amitriptyline; Analgesics, Non-Narcotic; Animals; Dose-Response Relationship, Drug; Drug Synergism; Male; Neuralgia; Pain Measurement; Rats; Rats, Sprague-Dawley
PubMed: 34411687
DOI: 10.1016/j.neuint.2021.105160 -
Gastroenterology Feb 2016
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Citalopram; Dyspepsia; Female; Humans; Male; Quality of Life; Selective Serotonin Reuptake Inhibitors
PubMed: 26718175
DOI: 10.1053/j.gastro.2015.12.029 -
The Cochrane Database of Systematic... Jul 2015This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.
OBJECTIVES
To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies.
SELECTION CRITERIA
We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions.
DATA COLLECTION AND ANALYSIS
We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.
MAIN RESULTS
We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence).
AUTHORS' CONCLUSIONS
Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.
Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Antidepressive Agents, Tricyclic; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 26146793
DOI: 10.1002/14651858.CD008242.pub3 -
Agri : Agri (Algoloji) Dernegi'nin... Oct 2023Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and...
OBJECTIVES
Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use.
METHODS
Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed.
RESULTS
In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance.
CONCLUSION
PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.
Topics: Rats; Humans; Animals; Anti-Anxiety Agents; Pregabalin; Rats, Wistar; Antidepressive Agents; Fluoxetine; Amitriptyline; Ketamine; Epilepsy
PubMed: 37886867
DOI: 10.14744/agri.2022.98474