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PubMed1982

A comparison of the safety and efficacy of bupropion HCL and amitriptyline hcl in depressed outpatients.

1. Thirty adult outpatients diagnosed with depressive illness were treated with either bupropion HCL or amitriptyline HCL. 2. Weekly ratings of efficacy and safety were undertaken using the Hamilton Depression, Hamilton Anxiety, Clinical Global Improvement, and Treatment Emergent Symptom Scales. Periodic physical investigations were also performed. 3. After 4 weeks of active treatment patients in both drug groups showed significant improvement on all rating scales. 4. The side effect profile of each drug was clinically different from one another with a notable absence of anticholinergic side effects characteristic of the bupropion group. 5. No significant laboratory or physical changes were found although slight changes in weight were noted with bupropion patients having a slight weight loss and amitriptyline patients a slight weight gain. There were no withdrawal effects from discontinuing either drug.

Adult↗
PubMed2003

High platelet-serotonin uptake activity is associated with a rapid response in depressed patients treated with amitriptyline.

Based on the assumption that there is a biological basis behind the individual differences in the speed with which an antidepressant produces its therapeutic effects, we compared initial serotonin (5HT) uptake characteristics in platelets of rapid (2 weeks), slow (4 weeks) and non-responders in a group of 47 depressed patients who were treated with amitriptyline for at least 4 weeks. A response was defined as a reduction in the Hamilton Depression Rating Scale score of > or =50% from baseline. In 16 rapid responders, a significantly higher mean 5HT uptake efficiency (Vmax/Km) corresponded with a significantly higher 5HT uptake activity at a low, physiological substrate concentration in comparison with the 15 non-responders or the 16 slow responders (33.1+/-7.8 versus 25.5+/-7.7 versus 24.1+/-5.8 pMol [3H]-5HT/10(9) plat. x 5 min, respectively). The findings indicate that pre-treatment 5HT uptake activity contributes to the individual variability in response time to amitriptyline treatment.

Adult↗
PubMed1999

Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat.

A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected, respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in the majority of the animals within 10 days following streptozocin. In contrast, dynamic allodynia took almost twice as long to develop and was only present in approximately 60% of rats. Morphine (1-3 mg/kg, s.c.) and amitriptyline (0.25-2.0 mg/kg, p.o.) dose-dependently blocked static allodynia. However, neither of the compounds was effective against dynamic allodynia. In contrast, gabapentin (10-100 mg/kg, p.o.) and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked both types of allodynia. However, the corresponding R-enantiomer (10-100 mg/kg, p.o.) of pregabalin, was found to be inactive. The intrathecal administration of gabapentin dose-dependently (1-100 microg/animal) blocked both static and dynamic allodynia. In contrast, administration of similar doses of gabapentin into the hind paw failed to block these responses. It is suggested that in this model of neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static type involves small diameter nociceptive fibres. These data suggest that gabapentin and pregabalin possess a superior antiallodynic profile than morphine and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain.

Acetates↗
PubMed1982

Simultaneous determination of amitriptyline, nortriptyline and their respective isomeric 10-hydroxy metabolites in plasma by liquid chromatography.

An ion-pair reversed-phase liquid chromatographic method for the determination of the tricyclic antidepressant amitriptyline, the demethylated metabolite nortriptyline, and their respective cis- and trans-hydroxylated metabolites in plasma is presented. After extraction from 1 ml of plasma, the reconstituted residue was chromatographed on a trimethylsilyl packed column using a mobile phase of acetonitrile and acetate buffer with sodium heptane-sulfonate and triethylamine. Recovery of the drugs and its metabolites from plasma ranged from 56 to 99%. The method is suitable for determining plasma concentrations as low as 5 ng/ml (C.V. less than 9%) for all six compounds. Plasma concentrations of amitriptyline and its metabolites from eleven different patients are presented.

Amitriptyline↗
PubMed1996

Quantitative analysis of amitriptyline and nortriptyline in human plasma and liver microsomal preparations by high-performance liquid chromatography.

A simple, rapid, highly selective and sensitive method for the analysis of amitriptyline and nortriptyline in plasma and human liver microsomes is described. It is suitable for the routine analysis of large numbers of samples using readily available instrumentation and low cost consumables. The detection limit was 2 ng/ml for both compounds and calibration curves were linear over a wide range of concentrations and passed through the origin. The within-batch and between-batch coefficients of variation for amitriptyline and nortriptyline were less than 7.4% and 12.8%, respectively. A series of compounds, including inhibitors used for probing cytochrome P450 activity in vitro, were tested for interference in the assay. Only ketoconazole caused interference and the assay was modified to allow samples containing ketoconazole to be analysed.

Administration, Oral↗
PubMed1997

Death attributed to the toxic interaction of triazolam, amitriptyline and other psychotropic drugs.

A 71-year-old man was found dead in a car into which exhaust fumes had been introduced. His wife who was in the same car recovered consciousness following hospitalization. She claimed that they had both attempted suicide by taking a large number of sleeping pills. Autopsy revealed no significant external injuries or medical disorders that would have led to the husband's death. The concentrations of alcohol and carbon-monoxide hemoglobin in his whole blood were 0.26 mg/ml and < 10%, respectively. Therefore, poisoning by carbon monoxide from the exhaust fumes was ruled out, and further toxicological examinations were undertaken. Triazolam, pentobarbital, amitriptyline and bromazepam were all detected in the tissues of the victim; whole blood concentrations were 45.60, 386.4, 521.2 and 166.7 ng/g, respectively. Triazolam (7.350 ng/g) and pentobarbital (288.2 ng/g) were also detected in the whole blood of the wife, collected 17 h after admission to hospital. When evaluating these results in the light of existing literature, we concluded that the victim and his wife had indeed attempted suicide by taking triazolam and pentobarbital. However, only the man had died of triazolam poisoning due to its apparently lethal combination with amitriptyline and other psychotropic drugs which had been prescribed to treat his depression.

Aged↗
PubMed2002

Simultaneous dissolution profiles of two drugs, sulfadiazine-trimethoprim and amitriptyline-perphenazine, in solid oral dosage forms by a FIA manifold provided with a single spectrophotometric detector.

The simultaneous determination of two dissolution profiles wih the aid of a flow injection analysis assembly has been applied to: (a) sulfadiazine-trimethoprim in tablets and (b) amitriptyline-perphenazine in sugar coated pills. The selected combinations are drugs which have overlapping UV-vis spectra. The officially proposed procedure from the pharmacopoeias has been adapted for the FIA methodology and derivative spectrophotometry and zero crossing. Preliminary experiments on the suitability of the simultaneous determination of both drugs were performed. The empirical profiles were adjusted by regression analysis using different approaches. The 3-parameter plot method was finally selected as the most suitable for the sulfadiazine-trimethoprim and the 4-parameter equation plot for amitriptyline-perphenazine.

Administration, Oral↗
PubMed1996

Voltammetric determination of imipramine hydrochloride and amitriptyline hydrochloride using a polymer-modified carbon paste electrode.

In this paper the voltammetric behaviors of imipramine.HCl and amitriptyline. HCl, which are both tricyclic antidepressants, were investigated using a carbon paste electrode, modified by the addition of poly(N-vinylimidazole), in various solutions of different pHs. It was shown that the current density for imipramine increased with modification of the carbon paste electrode and amitriptyline, which was electroinactive with the normal carbon paste electrode, became electroactive on the modified electrode. The optimum conditions for the quantitive determination of imipramine.HCl and amitriptyline.HCl were determined and statistical analysis of the linear relationship between current and concentration is given. The method was applied for the determination of these substances in the pharmaceutical dosage forms.

Amitriptyline↗
PubMed1975

Effects of maintenance amitriptyline and psychotherapy on symptoms of depression.

Depressives responding to initial treatment were maintained on amitriptyline for eight months, withdrawn double-blind to placebo after two months, or withdrawn overtly onto no medication. In each group half the patients received weekly psychotherapy and half were seen once monthly. Effects on symptom ratings were examined. Maintenance amitriptyline gave a significant advantage over early withdrawal in preventing symptom recrudescence. There were no differences between double-blind or overt withdrawal. There were no interactions between drug withdrawal and psychotherapy. Psychotherapy produced no significant advantages over low contact on symptoms, although it did improve social adjustment ratings reported elsewhere.

Adjustment Disorders↗
PubMed1979

Classification of depression and response to amitriptyline therapy.

Fifty-four patients suffering from primary depressive illness were rated on the Newcastle diagnostic scale while taking part in a pharmacokinetic study of amitriptyline therapy, and their clinical response was assessed by the Hamilton Rating Scale for depression. Patients with a Newcastle score of 4-8 showed the best response to amitriptyline. Patients with low Newcastle scores, representing the non-endogenous or neurotic group, responded poorly. Patients with high scores on the Newcastle scale, representing those with marked endogenous features, also responded poorly.

Amitriptyline↗
PubMed1982

Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment.

Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.

Amitriptyline↗
PubMed2001

Effects of amitriptyline on diurnal variations of oxidation-reduction enzyme activities in rat lymphocytes during experimental desynchronosis.

We studied the effects of amitriptyline on diurnal variations of oxidative-reduction enzyme activities (succinate dehydrogenase, lactate dehydrogenase, and NADPH diaphorase) in rat peripheral blood lymphocytes during experimental desynchronosis. Desynchronosis was induced by constant light exposure for 14 days and manifested in a morning shift of maximum lactate dehydrogenase activity and elevated morning NADPH diaphorase activity. Amitriptyline normalized morning lactate dehydrogenase activity and diurnal variations in NADPH diaphorase activity.

Amitriptyline↗
PubMed2003

Antidepressant properties of Proproten and amitriptyline: comparative experimental study.

Antidepressant properties of Proproten (antibodies to S100 protein in ultralow doses) were studied on outbred albino rats. The animals were subjected to the Porsolt's test of behavioral helplessness and Nomura's test of forced swimming in a reservoir with freely rotating wheels. Proproten in a dose of 2.5 ml/kg produced a strong antidepressant effect. It was observed after single and repeated (5 days) peroral treatment with the preparation. Proproten decreased the immobility time (Porsolt's test) and increased the number of wheel turns (Nomura's test). The activity of Proproten compared well with the standard preparation amitriptyline. As differentiated from amitriptyline, Proproten did not produce the sedative effect.

Amitriptyline↗
PubMed1984

Differential effects of amitriptyline and of zimelidine on the sleep electroencephalogram of depressed patients.

The effects of amitriptyline (n = 14) or zimelidine (n = 13) on the sleep electroencephalogram of hospitalized depressed patients were assessed in a double-blind protocol involving 28 days of active dosing. Zimelidine induced no immediate improvement in sleep continuity, and even after 3 wk on zimelidine subjects tended to have longer sleep latency, more awakenings, and lighter non-rapid eye movement (REM) sleep than before taking the drug. Zimelidine did, however, induce a rapid and persistent alteration of sleep architecture and selected REM measures. REM sleep, which was suppressed over the first two nights on zimelidine, was maximally suppressed after 1 wk, but by 3 wk there was some tolerance for selected REM measures. While zimelidine induced none of the sedative effects of amitriptyline, both were equivalent in their REM-suppressant effects. These findings are discussed in terms of the differences in uptake blockade and anticholinergic potency in these two drugs.

Adult↗
PubMed1985

Reliability of amitriptyline dose prediction based on single-dose plasma levels.

To assess prospectively the predictability of therapeutic dosage based on tricyclic antidepressant (TCA) concentrations after a single dose, 30 subjects were given amitriptyline. In the first 11 subjects maintained on a fixed amitriptyline dose regimen, predictive capacities of 18- and 24-hr single-dose levels were assessed and confirmed in relation to steady-state levels. For the other 19 subjects, the dose that would achieve a therapeutic steady-state concentration of 200 ng/ml was predicted from the 18-hr single-dose level and was rapidly instituted. Subjects achieved a mean steady-state TCA level of 204 ng/ml, with approximately 90% of the levels falling within the therapeutic range. There was clinical improvement within 2 wk in 84% of the subjects. Our results suggest that dose prediction based on TCA levels after a single dose is reliable and useful.

Adult↗
PubMed1992

Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes.

In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S-form of which is hydroxylated by a P450IIC isozyme, was carried out before amitriptyline therapy. Metabolites were determined in 24-hour urine samples collected on treatment day 8, and the contributions of individual compounds, including the four isomers of 10-hydroxyamitriptyline and 10-hydroxynortriptyline to total excretion were calculated. Formation of (-)-E-10-hydroxyamitriptyline and (-)-E-10-hydroxynortriptyline apparently depends on the activity of cytochrome P450IID6 because negative correlations existed between the log metabolic ratio of dextromethorphan and the relative quantities of these enantiomers. In contrast, correlations were positive for nortriptyline, (+)-E-10-hydroxynortriptyline, (-)-Z-10-hydroxynortriptyline, and (+)-Z-10-hydroxynortriptyline. The mephenytoin hydroxylase seems to participate in side-chain demethylation to the secondary and primary amines, because the log metabolic ratio of mephenytoin correlated negatively with the relative quantity of E-10-hydroxydidesmethylamitriptyline and positively with that of amitriptyline and its N-glucuronide.

Adult↗
PubMed2000

Amitriptyline treatment of chronic pain in patients with temporomandibular disorders.

Randomized clinical trials of amitriptyline will require data from pilot studies to be used for sample size estimates, but such data are lacking. This study investigated the 6-week and 1-year effectiveness of low dose amitriptyline (10-30 mg) for the treatment of patients with chronic temporomandibular disorder (TMD) pain. Based on clinical examination, patients were divided into two groups: myofascial and mixed (myofascial and temporomandibular joint disorders). Baseline pain was assessed by a Visual Analogue Scale (VAS) for pain intensity and by the McGill Pain Questionnaire (MPQ). Depression was assessed by the Beck Depression Inventory (BDI) short form. Patient assessment of global treatment effectiveness was obtained after 6 weeks and 1 year of treatment by using a five-point ordinal scale: (1) worse, (2) unchanged, (3) minimally improved, (4) moderately improved, (5) markedly improved. The results showed a significant reduction for all pain scores after 6 weeks and 1 year post-treatment. The depression scores changed in depressed but not in non-depressed patients. Global treatment effectiveness showed significant improvement 6 weeks and 1 year post-treatment. However, pain and global treatment effectiveness were less improved at 1 year than at 6 weeks.

Adult↗