Mg Of Amitriptyline Research Articles

Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer

The effectiveness of amitriptyline in relieving neuropathic pain following treatment of breast cancer was studied in 15 patients in a randomised, double-blind placebo-controlled crossover study. The dose was escalated from 25 mg to 100 mg per day in 4 weeks. The placebo and amitriptyline phases were separated by a 2-week wash-out period. Visual analogue and verbal rating scales were used for the assessment of pain intensity and pain relief. Other measures included the number of daily activities disturbed by the pain, the Finnish McGill Pain Questionnaire, adverse effects, anxiety, depression, pressure threshold and grip strength. Amitriptyline significantly relieved neuropathic pain both in the arm and around the breast scar. Eight out of 15 patients had a more than 50% decrease in the pain intensity (‘good responders’) with a median dose of 50 mg of amitriptyline. The 7 patients who had a less than 50% effect had drug concentrations equaling those of the good responders. The ‘poor responders’ reported significantly more adverse effects with amitriptyline and placebo than the good responders. It is concluded that amitriptyline effectively reduced neuropathic pain following treatment of breast cancer. However, the adverse effects of amitriptyline put most of the patients off from using the drug regularly.

The Effect of Amitriptyline, Doxepin, Fluvoxamine, and Paroxetine Treatment on Heart Rate Variability

A total of 32 unmedicated patients with episodes of major depression (DSM-III-R) and 32 normal control subjects matched for age and sex were tested for heart rate variability (R-R variation) while resting and during deep breathing. Compared with the group of healthy subjects, the depressed patients showed no abnormalities before therapy. The patients were randomly allocated for treatment with 150 mg of amitriptyline per day (N = 8), 150 mg of doxepin per day (N = 8), 150 mg of fluvoxamine per day (N = 8), and 20 mg of paroxetine per day (N = 8). During treatment with either amitriptyline or doxepin, the coefficients of variation at rest and during deep breathing, which are largely independent of heart rate, had significantly decreased after 14 days (p = 0.012), whereas patients treated with fluvoxamine or paroxetine showed no significant changes of heart rate variability parameters after 14 days. The implications of these findings are discussed.

Drug and Ethanol Effects on the Clinical Test for Drunkenness: Single Doses of Ethanol, Hypnotic Drugs and Antidepressant Drugs

The clinical test for drunkenness has been used in Finland to detect alcohol-induced impairment of driving fitness. Since the data about the effects of psychotropic drugs on the clinical test for drunkenness are limited, this test was administered in two randomized double-blind cross-over trials with 12 subjects in each. The clinical tests were done at 2 hr and 5 hr after drug intake. For comparison, the representative laboratory tests used were digit symbol substitution, simulated driving (tracking+reaction time) and "global psychomotor performance". In Trial I, 15 mg of diazepam, 50 mg of amitriptyline and 15 mg of mirtazepine, each drug administered alone, had minor effects on the clinical tests. Compared to the placebo, mirtazepine, and diazepam, diazepam+mirtazepine impaired performance on the motor subtests at 2 hr. The tracking error percentage was increased by amitriptyline, diazepam+amitriptyline, and diazepam+mirtazepine up to 4.5 hr. In Trial II with 7.5 mg of zopiclone, 0.25 mg of triazolam and 0.8 g/kg of ethanol, ethanol alone and hypnotic-ethanol combinations impaired performance on the motor and vestibular subtests, whereas single drug intake had minor effects. Tracking was more sensitive to drugs than to ethanol. In conclusion, the clinical test for drunkenness detected impaired performance following single doses of ethanol or drug-ethanol combinations better than it detected impaired performance following moderate doses of drugs or drug-drug combinations, respectively.

Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution

An experimental rat model was used to study postmortem redistribution of amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of amitriptyline, the rats ( n = 40) were anaesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO 2 and left at room temperature for either 0.1, 1, 2, 5, 24, 48, or 96 h. Postmortem blood samples from the heart and the inferior vena cava, and tissue samples from the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal vena cava and brain were analyzed by high performance liquid chromatography. A significant increase was observed within 2 h postmortem in heart blood and later also in blood from the inferior vena cava. At 96 h postmortem the concentration increase was 4.4 ± 0.5-fold ( P < 0.01) and 3.0 ± 1.1-fold ( P < 0.05) as compared to the antemortem values observed in heart blood and blood from the inferior vena cava, respectively (mean ± SEM). In the lungs there was a fall in the concentration of AMI from 148 ± 16.7 μmol/kg at 0.1 h to 49.1 ± 7.8 μmol/kg at 96 h postmortem ( P < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concentration, while in heart muscle and liver an increase in drug concentration was observed. In animals where the lungs were removed agonally ( n = 7), the drug concentration in heart blood had increased significantly less at 2 h postmortem. Accordingly, this animal model demonstrates that postmortem drug release from the lungs play an important role in the phenomenon of postmortem drug redistribution.

Screening, detection and management of depression in elderly primary care attenders. II: Detection and fitness for treatment: a case record study.

Case note data were obtained for 186 elderly primary care attenders who also completed the 15 item Geriatric Depression Scale (GDS15). The presence or absence in the case notes of a current or past diagnosis of depression, of current treatment of depression, and of a number of clinical features of depression were noted. Case notes were also rated for the presence or absence of contraindications to the use of tricyclic antidepressants (TCAs) and to serotonin-specific reuptake inhibitors (SSRIs). Whereas 65 (35%) patients were rated as 'cases' of depression on the GDS15, only 28 (15%) had a current case note diagnosis of depression and 37 (20%) had one or more current symptoms of depression recorded in the case notes. Patients rated by their GP as having one or more current symptoms of depression scored higher on the GDS15 (P < 0.05) and were more likely to be categorized as a GDS case (P = 0.05). There was no significant relationship between GDS caseness and a current case note diagnosis of depression. Seventy-three patients (39%) had a past history of depression and 53 (28.5%) patients had previously been treated with antidepressants. The former was significantly associated with GDS caseness (P < 0.05). Twenty-four patients (13%) were currently on antidepressants, 19 of them receiving adequate doses (equivalent to at least 75 mg of amitriptyline). Current antidepressant treatment was not associated with GDS 'caseness'.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary Observations of the Effects of Amitriptyline in Decomposing Tissues on the Development of Parasarcophaga ruficornis (Diptera: Sarcophagidae) and Implications of This Effect to Estimation of Postmortem Interval

Abstract Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of amitriptyline to study the effects of this drug on the development of this insect species. The rabbits were given 300, 600, and 1000 mg of amitriptyline via ear vein infusion. No significant differences in rates of larval growth were observed among the colonies. Durations of the larval stage were significantly longer for larvae fed on tissues from rabbits receiving amitriptyline. Larval mortality was observed to be 5.5% for the control colony, but ranged from 40.5 to 57.5% for the test colonies. Durations of the puparial stage were significantly longer for the colonies fed on tissues from the rabbits receiving the 600 and 1000 mg dosages of amitriptyline than for the control and colony fed on tissues from the rabbit receiving the 300 mg dosage. Observed differences in the durations of the larval and pupal stages from the test colonies were sufficient to alter a postmortem interval estimate by up to 77 h, if based on normal developmental patterns for this species at 26°C. Presence of amitriptyline and nortriptyline could be detected in larvae from all colonies fed on tissues from the rabbits receiving amitriptyline using high-performance liquid chromatography (HPLC).

Low-dose amitriptyline as an adjunct to opioids for postoperative orthopedic pain: A placebo-controlled trial

Tricyclic antidepressants (TCAs) have been found to be useful in the management of a variety of chronic pain conditions, although there is little published regarding the potential efficacy of this class of drug as an adjunct for the control of acute postoperative pain and related symptoms. Twenty-eight patients undergoing total hip or knee arthroplasty completed a randomized, placebo-controlled, double-blinded trial of 50 mg of amitriptyline p.O. HS on postoperative days 1, 2 and 3 while using patient-controlled morphine or meperidine analgesia (PCA). Visual analog (VAS) and numerical verbal (NVS) pain ratings, sedation scores, sleep quantity/quality scores, and sense of well-being scores were assessed twice daily on each of the days succeeding amitriptyline/placebo use. Hourly opioid use was recorded and transcribed from the memory of the PCA devices in use. Mean scores in the amitriptyline group for pain NVS were greater ( P < 0.05) (higher score = greater pain) on day 1 and greater on day 2 for the pain VAS. Mean scores for sense of well-being were greater ( P < 0.05) (higher score = better sense of well-being) for the placebo group on days 1 and 2. On days 2 and 3, sleep scale variable mean scores were worse in the placebo group ( P < 0.025). There were no other statistically significant differences between the control and active drug groups for any of the outcome variables measured. We conclude that amitriptyline at the dose prescribed is no different than placebo in altering the majority of postoperative symptom variables studied in the sample study population but caused no significant adverse effects. There does not appear to be an opioid-sparing effect nor an improvement in general well-being. Although this specific drug (or other TCAs) may be indicated for symptom management in selected postoperative patients, the results of this study do not support general use as a co-analgesic.

An Animal Model of Postmortem Amitriptyline Redistribution

An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 +/- 0.8 (mean +/- sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 +/- 0.3 (n = 5), and at 96 h 55.1 +/- 23.8 (n = 4). For the main metabolite nortriptyline (NOR), the concentration changes followed the same pattern, but to a lesser extent. Among the tissues, the liver lobes had high, but variable drug concentrations; lobes lying closest to the stomach had the highest drug concentrations. The drug concentration in the lungs declined significantly. This animal model demonstrates postmortem drug concentration changes similar to those described in humans. Probable mechanisms include drug diffusion from the stomach and GI tract to the surrounding tissues and blood; and postmortem drug release from the lungs and possibly other drug-rich tissues into the blood.

Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers.

To determine whether commonly used psychoactive drugs increase the risk of involvement in motor vehicle crashes for drivers > or = 65 years of age, the authors conducted a retrospective cohort study. Data were obtained from computerized files from the Tennessee Medicaid program, driver's license files, and police reports of injurious crashes. Cohort members were Medicaid enrollees 65-84 years of age who had a valid driver's license during the study period 1984-1988 and who met other criteria designed to exclude persons unlikely to be drivers and to ensure availability of necessary study data. There were 16,262 persons in the study cohort with 38,701 person-years of follow-up and involvement in 495 injurious crashes. For four groups of psychoactive drugs (benzodiazepines, cyclic antidepressants, oral opioid analgesics, and antihistamines), the risk of crash involvement was calculated with Poisson regression models that controlled for demographic characteristics and use of medical care as an indicator of health status. The relative risk of injurious crash involvement for current users of any psychoactive drug was 1.5 (95% confidence interval (CI) 1.2-1.9). This increased risk was confined to benzodiazepines (relative risk = 1.5; 95% CI 1.2-1.9) and cyclic antidepressants (relative risk = 2.2; 95% CI 1.3-3.5). For these drugs, the relative risk increased with dose and was substantial for high doses: 2.4 (95% CI 1.3-4.4) for > or = 20 mg of diazepam and 5.5 (95% CI 2.6-11.6) for > or = 125 mg of amitriptyline. Analysis of data for the crash-involved drivers suggested that these findings were not due to confounding by alcohol use or driving frequency.

Diffusion as a mechanism of postmortem drug redistribution: an experimental study in rats.

In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion from these reservoirs could contribute to the phenomenon of postmortem drug redistribution. Overnight fasted rats were sacrificed by CO2 and 75 mg of amitriptyline (AMI) was administered by a gastric tube. In the first series (n = 19), the tubes were removed after AMI administration. In the second series (n = 17), the trachea was ligated and cut prior to drug administration to prevent airways contamination. The rats were left at room temperature on their back for a period of 5, 10, 24, 48, 96 up to 192 h and samples of heart blood, blood from the inferior vena cava, tissue samples from heart, lungs, different liver lobes, kidney and psoas muscle were taken. In both series of rats we observed that as early as 5 h postmortem increasing concentrations of amitriptyline were found in the liver lobes lying closest to the stomach. In rats where the trachea was not ligated, drug contamination of the lungs also resulted in an increase in drug concentration within 5 h in heart blood and heart muscle. In rats where the trachea had been ligated, amitriptyline was found in the lungs after 96 h postmortem. The main metabolite nortriptyline was also detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Extremely Long Plasma Half-Life of Amitriptyline in a Woman with the Cytochrome P450IID6 29/29-Kilobase Wild-Type Allele—A Slowly Reversible Interaction with Fluoxetine

A 61-year-old woman, a nonsmoker, was admitted to the hospital because of endogenous depression. No concomitant disease, especially kidney or liver dysfunction, was diagnosed. After 9 days of treatment with 125 mg of amitriptyline (AMI) daily, she developed signs of a severe anticholinergic syndrome. Plasma concentrations of AMI (510 ng/ml) and nortriptyline (NOR; 320 ng/ml) were very high and the half-life of AMI was about 120 h. The debrisoquine metabolic ratio was 0.55 and 0.79 on two occasions, which shows that she had no deficiency of cytochrome P450IID6. This result was confirmed with a dextromethorphan test, analysis of restriction fragment length polymorphisms (29/29-kb fragments), and genotyping with allele-specific polymerase chain reaction (homozygous 29 kb wild-type alleles). Patients with high plasma levels of tricyclic antidepressants are usually poor metabolizers of debrisoquine. Before the administration of AMI, our patient was pretreated with fluoxetine. A slowly reversible interaction with fluoxetine or an extremely long-lasting metabolite may be responsible for the long plasma half-life of AMI.

A Double-Blind Study of Minaprine versus Amitriptyline in Major Depression

This study was designed to compare the antidepressant effects of minaprine and amitriptyline in a group of 60 outpatients suffering from a major depressive episode as defined by the DSM III. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible daily doses of 200-300 mg of minaprine and 50-75 mg of amitriptyline. Both drugs showed significant global antidepressant efficacy with no significant difference between the two treatment groups. The Hamilton item 'psychomotor retardation' improved earlier with minaprine than amitriptyline. The incidence of anticholinergic adverse effects was significantly higher in the amitriptyline treatment group.

Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study

This study was designed to compare the antidepressant effects of alprazolam and amitriptyline in a group of 30 inpatients suffering from a severe major endogenous depression, diagnosed by Research Diagnostic Criteria and the Newcastle Rating scale, and to examine the effects of alprazolam and amitriptyline on two biological markers of depression, the dexamethasone suppression test and sleep EEG parameters. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible doses of 4–9 mg of alprazolam and 100–225 mg of amitriptyline. After 4 weeks of treatment the antidepressant effects of amitriptyline significantly exceeded those of alprazolam, as measured on the Hamilton Rating Scale for Depression. There was a high drop-out rate in the alprazolam group because of ineffectiveness of treatment. Alprazolam showed similar effects on sleep parameters as amitriptyline: lengthening of the REM latency and a tendency to shorten stages 3 and 4 and stage REM. These negative clinical results should be interpreted with caution, because of the severity of our selection criteria, and should not be extended to all depressive disorders.

Cyclobenzaprine overdose: The importance of a clinical history in analytical toxicology

AbstractClinicians have become increasingly dependent on advanced analytical technology to supplement their diagnostic impression of comatose patients. We report a comatose patient who had ingested cyclobenzaprine, penatazocine, and ethchlorvinyl. The cyclobenzaprine was mistakenly identified as amitriptyline. Structurally these two agents are very similar with the exception of one double bond at the central aromatic group. The techniques of conventional thin‐layer chromatography, high‐efficiency thin‐layer chromatography, Toxi‐Lab thin‐layer chromatography, gas chromatography, high‐performance liquid chromatography, EMIT enzyme immunoassay, and gas chromatography‐mass spectrometry could not distinguish between the two compounds. An additional investigation of urine specimens from four volunteers who took (1) 50 mg of amitriptyline, (2) 20 mg of cyclobenzaprine, and (3) both 50 mg of amitriptyline and 20 mg of cyclobenzaprine was unable to distinguish the two agents. These results serve to reinforce the necessity of a clinical history taken in conjunction with analytical techniques before identifying potential agents present in various biological material.

Two tricyclic antidepressant poisoinings: Levels of amitriptyline, nortriptyline and desipramine in postmortem biological samples

Two deaths due to amitriptyline and desipramine overdoses are reported. The first case deals with a 20-year-old Caucasian male who was found dead at his residence. Toxicological analysis of the blood, urine, liver and kidney revealed the presence of amitriptyline (1.7 mg/l, 0.13 mg/l, 36.0 mg/kg and 98.0 mg/kg) and nortriptyline (0.66 mg/l,0.74 mg/l, 12.0 mg/kg and 37.0 mg/kg). The gastric content contained only 220 mg of amitriptyline. The urine also contained norverapamil, which was consistent with previous verapamil therapy. The second case involved a 19-year-old Caucasian male who attempted suicide earlier and was on desipramine medication. The blood, urine, liver and gastric content disclosed the presence of desipramine in the concentrations of 14.2 mg/l, 33.7 mg/l, 112.5 mg/kg and 180 mg, respectively. The levels of these tricyclics analyzed by high pressure liquid chromatography were in agreement with the levels reported in the literature. Though with the amitriptyline poisoning no significant anatomic changes were noted, the desipramine-caused death was further supported by the multisystem vascular congestion and ischemic changes consistent with cardiopulmonary failure.

Subacute Painful Myopathy From Chronic Propoxyphene Napsylate Abuse

To the Editor.— A number of drugs may produce an acute or subacute rapidly evolving myopathic syndrome of muscle pain, tenderness, and muscle weakness that is usually reversible if use of the responsible drug is withdrawn early at the onset. 1 To the list of the drugs previously reported, 1 I want to report another commonly used analgesic that, if abused, can cause severe myopathic symptoms and raise diagnostic dilemmas. Report of a Case.— A 42-year-old woman was being treated for at least three years with a steady dose of 600 mg of propoxyphene napsylate (Darvon-N) daily in divided doses for chronic low back pain, and with 75 mg of amitriptyline at bedtime for a chronic depressive neurosis. During the last six months she began to complain of extreme fatigue, low endurance, loss of energy, severe muscle pains, and weakness in her legs and arms, and she had difficulty climbing

Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction.

Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyline free plasma concentrations were increased by a logarithmic mean of 204%, 186% and 127% at 1.5, 2, and 2.5 h, respectively, and amitriptyline free AUC0-8h was increased by 48% +/- 13% (means +/- SEM) (t = 5.21, p less than 0.01). Nortriptyline total AUC0-8h was increased by 26.6% +/- 12% (means +/- SEM) (t = 2.21, p less than 0.09). At the time of peak amitriptyline plasma concentrations, mean postural sway was increased over baseline by 92% with, and 2% without ethanol; likewise, mean short term memory (word recall) was decreased over baseline by 71% with, and 37% without ethanol. Ethanol increases free amitriptyline plasma concentrations most dramatically during the period of drug absorption; this is due to a decrease in amitriptyline hepatic clearance, resulting in decreased first-pass extraction. Together with the pharmacodynamic interaction, the kinetic changes provide a rationale for the toxicity of this combination and its deleterious effects on psychomotor skills.

Serum Prolactin Level Increase in Normal Subjects Following Administration of Perphenazine Oral Dosage Forms: Possible Application to Bioavailability Testing

Two pilot studies were performed to determine if oral phenothiazine products could generate a significant increase in serum levels of the hormone prolactin. The two studies employed three and four healthy normal male subjects, respectively. In the first study the subjects received a screening dose, a placebo, one 8-mg perphenazine tablet, and two 8-mg perphenazine tablets. In the second study, the subjects were dosed with two 10-mg amitriptyline tablets, one 10-mg amitriptyline tablet with one combination tablet containing 10 mg of amitriptyline and 4 mg of perphenazine, and two combination tablets, each containing 10 mg of amitriptyline and 4 mg of perphenazine. In both cases the drug treatments produced a significant rise in the serum prolactin levels versus a placebo or control. This increase was defined as a prolactin response. The possible utility of this response in bioavailability testing is discussed.

Electroencephalographic sleep in unipolar depressive subtypes: support for a biological and familial classification.

A tripartite classification of unipolar disease based on family history has been proposed by Winokur. In this study, we sought to investigate whether the familial pure depressive disorder (FPDD) and the sporadic depressive disorder (SDD) populations could be differentiated on the basis of baseline EEG sleep as effected by a tricyclic pharmacological probe. A subject group consisting of 26 females and 10 males yielding 18 FPDD/SDD pairs matched for age was selected. Both groups of patients demonstrated a considerable amount of sleep continuity disturbance with an overall sleep efficiency of 80.5 per cent in the pure depressive (FPDD) group and 83 per cent in the sporadic (SDD) group. Examination of the rapid eye movement (REM) sleep variables revealed the usual shortened REM latency as well as increased REM activity and REM density changes. However, the only significant difference between the two groups on baseline was the presence of more stage 3 and 4 sleep in the sporadic group, but stage 3 and 4 sleep was found in less than 40 per cent of the total sample. In contrast, analysis of the first two nights of EEG sleep on 50 mg of amitriptyline demonstrated several significant findings between the two groups. While considerable REM sleep suppression occurred in both groups, REM activity, REM intensity, and the number of REM periods were significantly more suppressed in the pure group than the sporadic group. Application of these variables led to a successful discrimination of 75 per cent of all the cases. These findings suggest a hyper-reactivity of sleep in patients with FPDD to a pharmacological probe.

Beeinflussung schizophrener Erkrankungen durch eine neuroleptische Intensivbehandlung und der weitere Verlauf nach Absetzen jeder neuroleptischen Medikation

Since 1976 a group of 229 patients with schizophrenic or other paranoid illnesses (9 patients) were treated for about 14 weeks with intramuscular or intravenous injections of fluphenazinedecanoate. During the first 2 weeks, three injections of 250 mg were given after which time the injections were given at three weekly intervals with slowly decreasing dosage. The patients also received tablets of procyclidine and 100–150 mg of amitriptyline &lt;i&gt;per os&lt;/i&gt;. After the initial intensive phase the patients received an average of 145 mg i.m. every 3 weeks. A total of 209 patients could be followed up. Of those, 127 had for various reasons not continued with oral medication. The course of their illnesses was compared with that of the patients who had complied. The present report which represents a 3-year follow-up study confirms the findings of an earlier paper which showed the rapid onset and stability of remission, the absence of relapses among the patients who were under continued treatment, and the relative freedom from relapses among the patients who did not continue to have further neuroleptic medication. The anticipation that the initial high-dosage medication would have deleterious effects on the personality, producing robots or zombies, was shown to be groundless.