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A method for the quantitative analysis of tricyclic antidepressants in the serum of psychiatric patients is described. The method can be used for determining amitriptyline, nortriptyline, imipramine, demethyllimipramine, clomipramine, demethylclomipramine, trimipramine and protriptyline. The method consists in a series of extraction steps followed by gas chromatography with flame-ionization detector. The drugs are determined in their native state. The internal standard method is used for the quantitation.
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Objective We assessed the availability of essential medicines for mental healthcare (MH) across levels of the public healthcare system to aid in future systems planning. Design Non-expired MH medications were assessed in 24 public health facilities and 13 district warehouses across Sofala Province, Mozambique, from July to August 2014. Medication categories included: antipsychotics, antidepressants, benzodiazepines, antiepileptics and mood stabilizers, and anticholinergics and antihistamines. Results Only 7 of 12 (58.3%) district warehouses, 11 of 24 (45.8%) of all health facilities, and 10 of 12 (83.3%) of facilities with trained MH staff had availability of at least one medication of each category. Thioridazine was the most commonly available antipsychotic across all facilities (9 of 24, 37.5%), while chlorpromazine and thioridazine were most common at facilities providing MH care (8 of 12, 66.7%). The atypical antipsychotic risperidone was not available at any facility or district warehouse. Amitriptyline was the most commonly available antidepressant (10 of 12 districts; 12 of 24 overall facilities; 9 or 12 MH facilities). Despite being on the national essential drug list, fluoxetine was only available at one quaternary-level facility and no district warehouses. Conclusions Essential psychotropic medicines are routinely unavailable at public health facilities. Current essential drug lists include six typical but no atypical antipsychotics, which is concerning given the side-effect profiles of typical antipsychotics. Ensuring consistent availability of at least one selective serotonin reuptake inhibitor should also be a priority, as they are essential for the treatment of individuals with underlying cardiovascular disease and/or suicidal ideation. Similar to successful task-sharing approaches used for HIV/AIDS, mid-level providers could be retrained and certified to prescribe and monitor first-line psychotropic regimens.
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Mathematical formulation of the relationship between the costs of a quality improvement program and the degree of underuse and overuse.
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Amitriptyline is a tricyclic antidepressant that is historically indicated and used to manage depression. More recently, due to clinical evidence demonstrating efficacy, it is often prescribed in the management of painful neuropathic disorders (PNDs). However, the amitriptyline label contains numerous preclusions (contraindications, warnings/precautions, drug interactions). Our objective was to measure the frequency of amitriptyline prescriptions in PND patients using the U.K. General Practice Research Database and assess whether any prescriptions were given to patients with preclusions listed in the product label. We identified a total of 13,546 patients (mean age 59 +/- 16.2 years; 66.7% female) who had a diagnosis of a PND and received > or =1 prescription for amitriptyline between July 1998 and June 2001. Nearly half (46.7%) of PND patients prescribed amitriptyline had > or =1 preclusion for its use; 3.5% had > or =1 contraindication; 22% had > or =1 warning/precaution; and 33% received > or =1 medication with a potential for drug interactions with amitriptyline. Preclusions were more likely in women than in men (48.3% vs. 43.4%, P < 0.0001); their incidence increased with age (42.8%, 50.4%, 55.1%, and 52.3% among those ages <65, 65-74, 75-84, and 85+ years, P < 0.0001), and the number of patients with preclusions was the highest in the phantom limb pain group (67.4%) and lowest in the atypical facial pain group (42.9%), P < 0.001. The average daily amitriptyline doses (starting: 33.6 +/- 32.4 mg; maintenance: 42.1 +/- 39.9 mg) were low compared to those used for the treatment of depression. Results indicate that, in a significant number of cases, the existence of preclusions did not prevent the prescribing of amitriptyline. Our findings raise a potential concern about the way this medication is being used. However, the clinical significance of these data is, as yet, unclear. Although, in theory, adverse outcomes may have been associated with this practice, we could not confirm this with this database analysis.
In vitro studies suggest that [3H]yohimbine binds to alpha 2-adrenoceptors while [3H]idazoxan binds preferentially at a non-adrenergic site. In order to compare in vitro with in vivo effects male New Zealand White rabbits received the following treatments: 5 days idazoxan 1.1 mg/kg per h, 10 days noradrenaline 46 micrograms/kg per h (intravenous infusion), 21 days amitriptyline 30 mg/kg per day (intraperitoneally) or vehicle. The effect of these treatments on the number of [3H]yohimbine and [3H]idazoxan binding sites was examined. Ten days noradrenaline infusion and 21 days amitripytyline treatment significantly reduced [3H]yohimbine binding in kidney and hindbrain membranes respectively, but had no significant effect on [3H]idazoxan binding. Five days idazoxan infusion significantly increased [3H]yohimbine binding in the forebrain, while a significant reduction in [3H]idazoxan binding sites in the kidney was observed. Thus differential regulation of the two binding sites was observed in vivo. These alterations in binding site number are consistent with the differing affinities of noradrenaline and idazoxan for the [3H]yohimbine and [3H]idazoxan binding sites previously observed in vitro and support the hypothesis that in the rabbit idazoxan binds preferentially at non-adrenergic sites while yohimbine binds to an alpha 2-adrenergic site. The idazoxan site may be an imidazoline type of receptor but further work, including functional studies, is required to substantiate this.
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Two identically designed, randomized, double-blind, placebo- and active-controlled, parallel-group studies in patients aged 18-75 years with muscle spasm associated with neck or back pain. Patients received CER 15 or 30 mg once daily, cyclobenzaprine immediate release (CIR) 10 mg three times daily, or placebo for 14 days. Primary efficacy measures were patient's rating of medication helpfulness and physician's clinical global assessment of response to therapy at day 4. Secondary measures were patient's rating of medication helpfulness and physician's clinical global assessment of response (days 8 and 14), relief from local pain, global impression of change, restriction in activities of daily living, restriction of movement, daytime drowsiness, quality of nighttime sleep (days 4, 8, and 14), and quality of life (days 8 and 14).
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Information on patients, interventions, outcomes and results was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Hypericum with placebo and standard antidepressants was the responder rate ratio (responder rate in treatment group/responder rate in control group). The main outcome measure for side effects was the number of patients reporting side effects.
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Amitriptyline and gabapentin are the primary treatments for painful diabetic neuropathy (PDN), and it is clear that they produce beneficial effects, but there are questions about these treatments that have not been adequately addressed. For example, although there is a growing consensus that the therapeutic effects of amitriptyline in pain patients are independent of its effects on mood, it is not clear that amitriptyline has specific and direct effects on pain. There is also a fairly broad consensus that gabapentin is safe and well tolerated, but the side-effect profile of gabapentin has not been adequately assessed in pain populations. The rat streptozotocin (STZ) model of PDN was used (a) to assess the effects of amitriptyline on objective, quantitative measures of tactile allodynia, a common type of pain in PDN patients, and (b) to assess the side effects of gabapentin using measures of motor/ambulatory and cognitive function. Amitriptyline did not attenuate STZ-induced mechanical allodynia, even after chronic administration of high doses. Gabapentin produced robust anti-allodynic effects but also produced deficits in tests of motor/ambulatory and cognitive functions. The present experiments suggest that the beneficial effects of amitriptyline in PDN may not be a result of anti-allodynic efficacy and that gabapentin produces robust anti-allodynic effects but may also produce significant motor and cognitive deficits even at or near the lowest effective doses. These findings challenge the consensus opinions about these primary treatments for PDN and suggest that their therapeutic and adverse effects should be explored further in pain patients.
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To outline how the inclusion of pharmacogenetic data lends additional information in the overall decision making relative to drug therapy in the elderly patient.
In a double-blind, placebo-controlled study the analgesic efficacy of the combination of a tricyclic antidepressant and morphine was investigated. One of two tricyclic antidepressants (either amitriptyline, a relatively selective serotonin uptake inhibitor or desipramine, a relatively selective noradrenaline uptake inhibitor) or a placebo, was given for 1 week prior to surgery, followed by a single postoperative dose of morphine. Desipramine, but not amitriptyline, both increased and prolonged morphine analgesia. Neither tricyclic antidepressant reduced dental postoperative pain in the absence of morphine. We propose that desipramine enhances opiate analgesia by enhancing a noradrenergic component that contributes to endogenous opioid-mediated analgesia systems.
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Current controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014.
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Pharmacokinetics of 3 doses (70 mg, 105 mg and 140 mg) of lofepramine were compared with amitriptyline (50 mg) in 6 healthy drug free elderly subjects aged between 65 and 72 years. Pharmacokinetics of lofepramine in the elderly appear to be similar to young adults as published before. Peak plasma lofepramine and amitriptyline concentrations were achieved at about 1 h and 3 h of dosing respectively. Elimination half-life of lofepramine was 2.5 h and that of amitriptyline was 31 h. A 24-fold inter-individual variation in peak plasma lofepramine concentrations was observed, but amitriptyline levels in plasma showed less variation. Pharmacokinetic parameters of amitriptyline were comparable to other published studies involving elderly people. Compared to placebo and lofepramine, amitriptyline produced drowsiness and dry mouth, reduced salivary volume and increased movement reaction time. These effects correlated with the plasma amitriptyline levels.
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The pharmacodynamic effects of single doses of trazodone (100 mg), amitriptyline (50 mg) or placebo either alone or with ethanol (0.5 ml/kg) were investigated in 6 healthy volunteers in a double-blind crossover study. Plasma concentrations of the drugs and ethanol were also measured. Pharmacodynamic tests were critical flicker fusion frequency threshold (CFF), choice reaction time (CRT), manual dexterity, a digit span test and visual analogue scales. Blood ethanol concentrations were not influenced by the co-administration of either antidepressant. tmax for trazodone was prolonged by ethanol but the other pharmacokinetic parameters for trazodone and amitriptyline were not influenced by ethanol. Trazodone and amitriptyline caused the expected profound depressant effects on CFF, CRT, manual dexterity and on the rating scales for drowsiness, 'clearheadedness', aggression and disinhibition. Ethanol alone impaired manual dexterity, increased drowsiness, reduced 'clearheadedness' and also tended to reduce feelings of aggression. In combination with either trazodone or amitriptyline, ethanol caused little additional effect except in the case of manual dexterity, which was further impaired. This result may reflect the profound effects of the antidepressants alone and does not suggest that it is safe for patients receiving antidepressant medication to take ethanolic drinks.
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There has been much attention on appropriate prescribing in older adults in recent years. Recent guidelines favor the use of newer antidepressants over older agents based on their safety profile in this population. This study aimed to examine whether there has been a decline in older antidepressants and an increase in newer antidepressants used by older adults.
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129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.
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Our objective was to better understand UK-wide practice in managing sialorrhoea in motor neuron disease among specialist clinicians. We used a survey of neurologists in the UK with a special interest in motor neuron disease designed to establish clinicians' attitudes towards treatment options and resources for sialorrhoea management. Twenty-three clinicians replied, representing 21 centres. Sixteen centres were specialist MND Care Centres. Clinicians estimated seeing a total of 1391 newly diagnosed patients with MND in 2011. One hundred and ninety-three patients were described. Forty-two percent of patients reviewed in clinicians' last clinic had sialorrhoea and 46% of those with sialorrhoea had uncontrolled symptoms. Clinicians' preferred drugs were hyoscine patches, amitriptyline, carbocisteine and botulinum toxin. Botulinum toxin was used in 14 centres. Risk of dysphagia and staff skills were identified as the main barriers to botulinum toxin use. This survey suggests that there may be as many as 1700 patients with MND in the UK who have symptoms of sialorrhoea and that symptoms may be poorly controlled in nearly half. Treatment strategies varied, reflecting the lack of evidence based guidelines. The use of specialist treatments was influenced by local infrastructure. This study highlights the need for further work to develop evidence based guidance.
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The antidepressant-induced reduction in immobility time in the forced swimming test may depend on memory impairment due to the drug's anticholinergic efficacy. Therefore, the present study evaluated learning and memory of the immobility response in rats after the pretest and test administrations of antidepressants having potent, comparatively lower, and no anticholinergic activities. Immobility was measured in the test session performed 24 h after the pretest session. Scopolamine and MK-801, which are agents that have memory impairing effects, were used as reference drugs for a better evaluation of the memory processes in the test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased immobility time suggesting impaired "learning to be immobile" in the animals. The test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg), moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg) decreased immobility time, which suggested that the drugs exerted antidepressant activity or the animals did not recall that attempting to escape was futile. The test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg) produced no effect on immobility time. Even though the false-negative and positive responses made it somewhat difficult to interpret the findings, this study demonstrated that when given before the pretest antidepressants with or without anticholinergic activity seemed to be devoid of impairing the learning process in the test.
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A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline.
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The use of a fully parametric Bayesian method for analysing single patient trials based on the notion of treatment 'preference' is described. This Bayesian hierarchical modelling approach allows for full parameter uncertainty, use of prior information and the modelling of individual and patient sub-group structures. It provides updated probabilistic results for individual patients, and groups of patients with the same medical condition, as they are sequentially enrolled into individualized trials using the same medication alternatives. Two clinically interpretable criteria for determining a patient's response are detailed and illustrated using data from a previously published paper under two different prior information scenarios.
Fifty-five cases (36 males, 19 females; mean, 4.8 years; range, 2 hours to 17 years) were identified. This corresponded to 3.3% (55/1669) of all postmortems. Ten cases were group 1, 42 cases were group 2, and 3 cases were group 3. The results in group 1 were methadone (n = 2); methadone, alcohol, and dothiepin (n = 1); diazepam (n = 1); dothiepin (n = 1); carbon monoxide (n = 2); tramadol (n = 1); codeine and paracetamol (n = 1); and dihydrocodeine, citalopram, amitriptyline, and paracetamol (n = 1). The types of death were considered accidental (n = 2), suicide (n = 2), and undetermined (n = 6).
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To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN).
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To examine general practitioners' (GPs') diagnosis of a case vignette presenting both anxiety and depression symptoms, and to understand their treatment preferences for the case.
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A retrospective chart review of 42 patients seen by one clinician that met established CVS diagnostic criteria revealed 30 cases with available outcome data. Participants were treated on a loose protocol consisting of fasting avoidance, co-enzyme Q10 and L-carnitine, with the addition of amitriptyline (or cyproheptadine in those < 5 years) in refractory cases. Blood level monitoring of the therapeutic agents featured prominently in management.
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The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. This guideline is focused on patients with episodic migraine (headache on ≤ 14 days a month).
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Paroxetine therapy is more efficacious than empirical high-dose antisecretory treatment, or even the low-dose amitriptyline therapy in alleviating globus symptoms, and producing global improvements for refractory globus patients.
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General practices in the United Kingdom that used VAMP computers to maintain their patient records from January 1988 to February 1993.
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A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.
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The spontaneous activities of afferent fibers in naïve rats had high frequency (35.23 +/- 6.63 Hz) and pattern discharge based on their instantaneous frequencies and interspike interval distributions. In rats that had received SNL, afferent fibers exhibited spontaneous discharge (mean of 11.05 +/- 3.66 Hz) with an irregular discharge pattern or short bursting activity in some cases. Only 5/13 (38%) afferent fibers from naïve rats showed reduced spontaneous activities after amitriptyline (2 mg/kg, IV), whereas amitriptyline significantly inhibited ectopic discharge in 13/18 (72%) afferent fibers from SNL rats (ID(50) = 1.66 +/- 0.17 mg/kg). Furthermore, the greatest inhibitory effect of amitriptyline was consistently observed on those afferent fibers exhibiting low frequency (<20 Hz) and/or bursting discharge.
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After our institutional ethics committee approved, a retrospective cross sectional drug utilization study of 600 prescriptions was undertaken. Preparation of the protocol and conduct of the study was as per the WHO - DUS and the STROBE guidelines.
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Sleepwalking in adolescents and adults may lead to serious injuries and require treatment. Anecdotal treatment recommendations include benzodiazepines (which also work in focal seizures of the frontal lobe that are an important differential diagnosis), imipramine and amitriptyline.
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A retrospective, cross-sectional study was conducted, involving older adults (aged 65 years and older), using 2009-2010 Medical Expenditure Panel Survey (MEPS) data. The 2012 AGS Beers Criteria were used to define potentially inappropriate anticholinergic medications on the basis of the list of medications to avoid using in older adults irrespective of the diagnosis. Descriptive analyses were used to examine the nature and extent of potentially inappropriate anticholinergic medication use. Multivariable logistic regression within the conceptual framework of the Andersen Behavioral Model was used to identify the factors associated with potentially inappropriate anticholinergic use in older adults.
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PubMed, CINAHL, Medline, Science Direct and Ovid databases were used to search keywords. The literature search identified 59 potentially relevant studies; after removing duplicates and reviewing titles a total of 26 articles were examined. In the end, a total of 18 studies met the inclusion criteria.