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Texas Heart Institute Journal 2003A 66-year-old woman presented with new-onset complete left bundle branch block and congestive heart failure. She had had chronic paranoid schizophrenia for 35 years and...
A 66-year-old woman presented with new-onset complete left bundle branch block and congestive heart failure. She had had chronic paranoid schizophrenia for 35 years and had been taking medications to control her psychiatric disorder for the past 10 years. A 2-dimensional echocardiogram performed at the onset of congestive heart failure showed dilated cardiomyopathy with global impairment of left ventricular function (ejection fraction <0.25). Despite withdrawal of the medications most likely responsible for the heart problems (perphenazine, 2 mg; and amitriptyline, 25 mg), the patient died of refractory congestive heart failure 2 years later. Histologic examination at autopsy showed evidence of persistent toxic myocarditis with fibrosis of the heart and persistent chronic hepatitis. These autopsy findings were considered to be drug related.
Topics: Adrenergic Uptake Inhibitors; Aged; Amitriptyline; Antipsychotic Agents; Female; Heart Failure; Humans; Myocarditis; Perphenazine; Schizophrenia, Paranoid
PubMed: 12638679
DOI: No ID Found -
British Journal of Clinical Pharmacology Jul 1999To characterize the pharmacokinetics of amitriptyline and its metabolite nortriptyline following OROS and IR treatments, and to correlate them with anticholinergic... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
AIMS
To characterize the pharmacokinetics of amitriptyline and its metabolite nortriptyline following OROS and IR treatments, and to correlate them with anticholinergic side-effects.
METHODS
The pharmacokinetics and safety of amitriptyline following administration of an osmotic controlled release tablet (OROS and an immediate release (IR) tablet were evaluated in 14 healthy subjects. In this randomized, open label, three-way crossover feasibility study, the subjects received a single 75 mg OROS tablet, three 25 mg IR tablets administered every 8 h, or 3x25 mg IR tablets administered at nighttime. In each treatment arm serial blood samples were collected for a period of 84 h after dosing. The plasma samples were analysed by gas chromatography for amitriptyline and its metabolite nortriptyline. Anticholinergic effects such as saliva output, visual acuity, and subject-rated drowsiness and dry mouth were measured on a continuous scale during each treatment period.
RESULTS
Following dosing with OROS (amitriptyline hydrochloride), the mean maximal plasma amitriptyline concentration Cmax (15.3 ng ml-1 ) was lower and the mean tmax (25.7 h) was longer than that associated with the equivalent IR dose administered at nighttime (26.8 ng ml-1 and 6.3 h, respectively). The bioavailability of amitriptyline following OROS dosing was 95% relative to IR every 8 h dosing, and 89% relative to IR nighttime dosing. The metabolite-to-drug ratios after the three treatment periods were similar, suggesting no change in metabolism between treatments. The relationships between plasma amitriptyline concentration and anticholinergic effects (e.g. reduced saliva weight, dry mouth, and drowsiness) were similar with all three treatments. Of the anticholinergic effects, only decreased saliva weight and dry mouth correlated well with plasma amitriptyline concentrations; drowsiness did not. There was no apparent correlation between anticholinergic effects and the plasma nortriptyline concentration.
CONCLUSIONS
The bioavailability of OROS (amitriptyline hydrochloride) was similar to that of the IR treatments and the pharmacokinetics of amitriptyline after OROS dosing may decrease the incidence of anticholinergic effects compared with that seen with nighttime dosing of the IR formulation. Therefore, this controlled-release formulation of amitriptyline may be appropriate for single daily administration.
Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Chemistry, Pharmaceutical; Cholinergic Antagonists; Cross-Over Studies; Dose-Response Relationship, Drug; Feasibility Studies; Humans; Male
PubMed: 10383563
DOI: 10.1046/j.1365-2125.1999.00973.x -
The Cochrane Database of Systematic... Jun 2016This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms.
OBJECTIVES
To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults.
SEARCH METHODS
We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors.
SELECTION CRITERIA
We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults.
DATA COLLECTION AND ANALYSIS
We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence 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 drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included a total of four studies with 296 participants.Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety).Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low quality evidence). There was no statistically significant difference between quetiapine and placebo in the proportion of participants withdrawing due to adverse events (tolerability) (very low quality evidence), in the frequency of serious adverse events (safety) (very low quality evidence) and in the proportion of participants reporting dizziness and somnolence as an adverse event (very low quality evidence). In more participants in the quetiapine group a substantial weight gain was noted (RD 0.08, 95% CI 0.02 to 0.15; number needed to treat for an additional harm (NNTH) 12, 95% CI 6 to 50) (very low quality evidence). We downgraded the quality of evidence by three levels to a very low quality rating because of limitations of study design, indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed).One parallel design study with 90 participants compared quetiapine (50 to 300 mg/day flexible at bedtime) to amitriptyline (10 to 75 mg/day flexible at bedtime). The study had three major risks of bias and we judged it to be at moderate risk of bias overall. We downgraded the quality of evidence by two levels to a low quality rating because of indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). Third tier evidence indicated no statistically significant differences between the two drugs. Both drugs did not statistically significantly differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life and in the proportion of participants reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared to amitriptyline, more participants left the study due to adverse events (low quality evidence). No serious adverse events were reported (low quality evidence).We found no relevant study with other antipsychotics than quetiapine in fibromyalgia.
AUTHORS' CONCLUSIONS
Very low quality evidence suggests that quetiapine may be considered for a time-limited trial (4 to 12 weeks) to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits in shared decision making with the patient.
Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Antipsychotic Agents; Fibromyalgia; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Sleep Wake Disorders
PubMed: 27251337
DOI: 10.1002/14651858.CD011804.pub2 -
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 -
Indian Journal of Pharmacology 2020To evaluate and compare efficacy and tolerability of Vilazodone with Escitalopram and Amitriptyline in patients of major depressive disorder(MDD). (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparative evaluation of efficacy and tolerability of vilazodone, escitalopram, and amitriptyline in patients of major depressive disorder: A randomized, parallel, open-label clinical study.
OBJECTIVES
To evaluate and compare efficacy and tolerability of Vilazodone with Escitalopram and Amitriptyline in patients of major depressive disorder(MDD).
METHODS
This was a randomized, prospective, parallel-group, open label clinical study in which newly diagnosed patients of MDD were randomized to receive Tab Vilazodone 20 mg daily or Tab Escitalopram 20mg daily or Tab Amitriptyline 75mg daily for 12 weeks. Antidepressant activity was assessed by change in score from baseline to week 12 on HAMD-17 and MADRS scales while change in score on HAM-A scale was used to assess antianxiety effect. Change in scores on the three scales was also compared between the three treatment groups. Severity and causality of adverse events were assessed by the modified Hartwig & Siegel scale and Naranjo scale respectively. Data was analyzed in accordance with per protocol analysis.
RESULTS
Reduction in HAMD-17 and MADRS scores was significantly more in vilazodone group compared to the other two drugs indicating that vilazodone is more efficacious antidepressant. Number of remitters were also significantly more in the vilazodone group (=11) compared to escitalopram (=4) (<0.05) and amitriptyline (=0) (<0.001) at 12 weeks. Similar results were also obtained with HAM-A score. Number of patients showing MADRS sustained response at 12 weeks was statistically significantly more in vilazodone (=12) and escitalopram (=12) groups compared to amitriptyline (=01) (<0.001). Reported adverse events were constipation and sedation(amitriptyline group); nausea and headache(escitalopram and vilazodone groups). These adverse events were of mild severity. Most adverse events belonged to probable category.
CONCLUSION
Vilazodone is more efficacious and well tolerated antidepressant compared to escitalopram and amitriptyline.
Topics: Adult; Affect; Amitriptyline; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Female; Humans; India; Male; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome; Vilazodone Hydrochloride; Young Adult
PubMed: 32565594
DOI: 10.4103/ijp.IJP_441_18 -
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 -
Naunyn-Schmiedeberg's Archives of... Jun 2021We have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic...
We have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (HR-TG) mice that overexpress the human H histamine receptor (HR) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on HRs. Here, we wanted to determine whether the histamine effects in HR-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from HR-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM-10 μM) to higher concentrations (rightward shift) in left atrial preparations from HR-TG. Similarly, in isolated perfused hearts from HR-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the HR-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from HR-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at HRs in HR-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline.
Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Dose-Response Relationship, Drug; Heart Atria; Histamine; Histamine H2 Antagonists; Humans; Mice; Mice, Transgenic; Myocardial Contraction; Receptors, Histamine H2; Species Specificity
PubMed: 33625558
DOI: 10.1007/s00210-021-02065-7 -
British Medical Journal May 1971
Topics: Amides; Amitriptyline; Benzoates; Catheterization; Chlorpromazine; Digestive System; Hiccup; Humans; Orphenadrine; Pharynx; Respiratory System
PubMed: 5572375
DOI: No ID Found -
Environmental Science and Pollution... Mar 2024The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study....
The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study. Cress (Lepidium sativum L.) and pea (Pisum sativum L.) were employed as model plants. These plants were grown in tap water containing the selected pharmaceuticals at concentrations ranging from 0.010 to 10 mg L, whereby the latter concentration was employed for the (tentative) identification of drug-related metabolites formed within the plant. Thereby, mainly phase I metabolites were detected. Time-resolved uptake studies, with sampling after 1, 2, 4, 8, and 16 days, revealed that all four pharmaceuticals were taken up by the roots and further relocated to plant stem and leaves. Also in these studies, the corresponding phase I metabolites could be detected, and their translocation from root to stem (pea only) and finally leaves could be investigated.
Topics: Amitriptyline; Pisum sativum; Brassicaceae; Orphenadrine; Tramadol; Lidocaine; Plants; Vegetables; Pharmaceutical Preparations; Plant Roots
PubMed: 38363510
DOI: 10.1007/s11356-024-32379-x