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ACS Chemical Neuroscience Feb 2021Amitriptyline was the second tricyclic antidepressant to appear on the market for major depressive disorder under the brand name Elavil in 1961. Since its emergence,... (Review)
Review
Amitriptyline was the second tricyclic antidepressant to appear on the market for major depressive disorder under the brand name Elavil in 1961. Since its emergence, amitriptyline has been an effective therapeutic in various disease states and disorders but has also been a concerning source of cardiotoxicity. Amitriptyline inhibits serotonin and norepinephrine reuptake as well as produces off-target activity at histaminergic, muscarinic, and various other receptors. Its role as a modulator of monoamines helped further establish the monoamine theory to understand various mood disorders, paving the way for the now more common selective serotonin/norepinephrine reuptake inhibitors. In this review, we will discuss amitriptyline's synthesis, manufacturing information, drug metabolism, pharmacology, adverse effects, and its history and importance in therapy to present amitriptyline as a true classic in chemical neuroscience.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Humans; Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 33438398
DOI: 10.1021/acschemneuro.0c00467 -
Expert Review of Neurotherapeutics Oct 2015Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend... (Review)
Review
Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10-75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Fibromyalgia; Humans; Randomized Controlled Trials as Topic
PubMed: 26395929
DOI: 10.1586/14737175.2015.1091726 -
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 -
Therapeutique (La Semaine Des Hopitaux) Mar 1969
Topics: Amitriptyline; Animals; Depression; Humans
PubMed: 5386060
DOI: No ID Found -
The Urologic Clinics of North America Feb 1994Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may... (Review)
Review
Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may be an effective treatment modality in nonulcerative interstitial cystitis. Both the ease of administration and the relatively rapid onset of relief make these types of drugs appropriate to consider for first-line therapy after bladder distention has failed.
Topics: Amitriptyline; Animals; Clinical Trials as Topic; Cystitis; Humans
PubMed: 8284851
DOI: No ID Found -
Gastroenterology Jan 1988We report the case of a patient in whom amitriptyline administration for 5 wk was followed by prolonged cholestasis. Jaundice and pruritus lasted 19 and 20 mo,...
We report the case of a patient in whom amitriptyline administration for 5 wk was followed by prolonged cholestasis. Jaundice and pruritus lasted 19 and 20 mo, respectively. Three liver biopsies were performed at different stages of the disease showing the course of liver lesions. Cholestasis initially located in the region of the hepatic venule came to be associated with the progressive development of portal tract lesions consisting of inflammatory infiltration, fibrosis, and disappearance of interlobular bile ducts. Amitriptyline hydroxylation and dextromethorphan O-demethylation are deficient in subjects with the poor metabolizer phenotype of debrisoquine. Drug oxidation phenotyping with dextromethorphan showed that this patient had the extensive metabolizer phenotype. This observation demonstrates that amitriptyline can induce prolonged cholestasis and suggests that the susceptibility to develop liver injury while taking this drug may not be related to a genetic deficiency of its hydroxylation.
Topics: Adult; Amitriptyline; Biopsy; Cholestasis; Depression; Humans; Liver; Male; Time Factors
PubMed: 3335290
DOI: 10.1016/0016-5085(88)90631-2 -
Clinical Pharmacokinetics 1985In this article, studies on the disposition of amitriptyline after administration of a single dose, as well as following long term administration are reviewed. While... (Review)
Review
In this article, studies on the disposition of amitriptyline after administration of a single dose, as well as following long term administration are reviewed. While long term studies showed bias towards a higher mean apparent oral clearance, studies in normal subjects nevertheless indicated a higher apparent oral clearance than that calculated from steady-state concentrations in depressed patients. Methodological issues could account for some of the discrepancies in mean values of the pharmacokinetic parameters of amitriptyline. Broad individual variability in the elimination rate of amitriptyline has been confirmed but could not be attributed to the clinical characteristics of the subjects.
Topics: Amitriptyline; Depressive Disorder; Half-Life; Humans; Kinetics; Models, Biological; Nortriptyline
PubMed: 3893842
DOI: 10.2165/00003088-198510030-00005 -
The New Zealand Medical Journal Jul 1980
Topics: Akathisia, Drug-Induced; Amitriptyline; Female; Humans; Middle Aged; Tinnitus
PubMed: 6933335
DOI: No ID Found -
Lancet (London, England) Jan 1979
Topics: Amitriptyline; Biological Availability; Dose-Response Relationship, Drug; Humans; Methylation; Nortriptyline
PubMed: 83498
DOI: 10.1016/s0140-6736(79)90493-8 -
Nursing Times
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Drug Interactions; Humans; Nortriptyline; Nursing
PubMed: 15633843
DOI: No ID Found