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PubMed1992

Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients.

The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles.

Adult↗
PubMed1994

The efficacy and safety of tianeptine in the treatment of depressive disorder: results of a controlled double-blind multicentre study vs. amitriptyline.

Three hundred in- and outpatients suffering from depressive disorder, as diagnosed using DSM-III criteria were treated for 6 weeks under double-blind conditions in a multicenter controlled study of tianeptine vs. amitriptyline. Both groups presented steady improvement of depressive syndrome from day 7 up to the end of the treatment, as shown by all evaluation scales: HDRS, SAD, CGI. Furthermore, anxiety linked to the depressive syndrome decreased equally in both groups, as shown by the HARS measurements. In addition to the improvement of mood, the tianeptine-treated patients presented less somatic complaints and side effects when compared to the reference antidepressant. These results confirm previous findings that tianeptine is an effective antidepressant with a lower side effect profile than amitriptyline.

Adolescent↗
PubMed1994

Variation in the affinity of amitriptyline for muscarine receptor subtypes.

The affinity of amitriptyline for muscarine M1 receptors was studied in the rat cerebral cortex and rabbit vas deferens utilizing binding studies as well as inhibition of carbachol-induced phosphoinositide hydrolysis in the cerebral cortex and blockade of the muscarinic prejunctional inhibition of sympathetic nerve stimulation in the rabbit vas deferens. The inhibition constants (KI) or dissociation constants (KB) obtained were approximately 6- to 20-fold lower than those obtained at muscarine M2 receptors in rat atria (binding and negative inotropic response) indicating that amitriptyline exhibits a degree of muscarine M1 receptor selectivity.

Amitriptyline↗
PubMed1975

Double-bind comparison of maprotiline with amitriptyline in the treatment of depressive illness.

Thirty patients closely matched for age, sex and duration of illness were treated with either amitriptyline or maprotiline in a double-blind, between-patient trial. Within limits of the small number of patients in the trial, maprotiline produced a significantly quicker improvement during the first 2 weeks as judged by the scores on the Hamilton Rating Scale. Maprotiline showed better tolerability than amitriptyline overall, especially as far as trial drop-out rates were concerned.

Adult↗
PubMedDate not supplied

Responses of isolated canine basilar artery and human platelet to chlorpromazine and amitriptyline.

Sustained contraction of isolated canine basilar artery was induced by addition of prostaglandin F2 alpha, prostaglandin E2, hemoglobin-containing solution, or serum. Human platelet aggregation was induced by 1.0 microM adenosine diphosphate. The sustained contraction of basilar artery and the aggregation of platelet, particularly its secondary aggregation, were inhibited in a dose-dependent manner by addition of chlorpromazine or amitriptyline; calmodulin antagonist. The molar concentrations at 50% inhibition by chlorpromazine or amitriptyline were 5.9 to 7.7 microM or 28 to 39 microM for the contraction of basilar artery and 57 microM or 111 microM for the secondary aggregation of platelet. The results were discussed mainly on the basis of interaction of psychotropic drugs and Ca2+, calmodulin-dependent enzymes, particularly myosin light chain phosphorylation.

Adenosine Diphosphate↗
PubMed1981

Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline.

Prompted by recognition of the similar structures of riboflavin (vitamin B(2)), phenothiazine drugs, and tricyclic antidepressants, our studies sought to determine effects of drugs of these two types upon the conversion of riboflavin into its active coenzyme derivative, flavin adenine dinucleotide (FAD) in rat tissues. Chlorpromazine, a phenothiazine derivative, and imipramine and amitriptyline, both tricyclic antidepressants, each inhibited the incorporation of [(14)C]riboflavin into [(14)C]FAD in liver, cerebrum, cerebellum, and heart. A variety of psychoactive drugs structurally unrelated to riboflavin were ineffective. Chlorpromazine, imipramine, and amitriptyline in vitro inhibited hepatic flavokinase, the first of two enzymes in the conversion of riboflavin to FAD. Evidence was obtained that chlorpromazine administration for a 3- or 7-wk period at doses comparable on a weight basis to those used clinically has significant effects upon riboflavin metabolism in the animal as a whole: (a) the activity coefficient of erythrocyte glutathione reductase, an FAD-containing enzyme used as an index of riboflavin status physiologically, was elevated, a finding compatible with a deficiency state, (b) the urinary excretion of riboflavin was more than twice that of age- and sex-matched pair-fed control rats, and (c) after administration of chlorpromazine for a 7-wk period, tissue levels of flavin mononucleotide and FAD were significantly lower than those of pair-fed littermates, despite consumption of a diet estimated to contain 30 times the recommended dietary allowance. The present study suggests that certain psychotropic drugs interfere with riboflavin metabolism at least in part by inhibiting the conversion of riboflavin to its coenzyme derivatives, and that as a consequence of such inhibition, the overall utilization of the vitamin is impaired.

Amitriptyline↗
PubMed1977

Thyroid function and growth hormone secretion in amitriptyline-treated depression.

The authors studied changes in indices of thyroid function prospectively in a group of 11 patients given amitriptyline to treat depression. The drug caused no significant alteration in these indices, but scores on the Hamilton Depression Rating Scale improved significantly. In another group of subjects with depression, the stimulation of growth hormone secretion by L-dopa was unaffected by amitriptyline therapy.

Adult↗
PubMed1981

Behavioral predictors of amitriptyline response in depression.

In this study of 18 female depressed patients and 18 age- and sex-matched control subjects, the authors examined the relationship between nonverbal behavior and treatment outcome with amitriptyline. A behavioral analysis indicated that amitriptyline responders could be differentiated from nonresponders before drug treatment on the basis of discrete nonverbal behaviors. Nonresponders showed a high frequency of body-focused self-adaptors, posture shifts, and pauses and a low frequency of smiles, while responders displayed long speech pauses and long durations of head aversion.

Adolescent↗
PubMed1984

Prediction of relapse with the TRH test and prophylactic amitriptyline in 39 patients with endogenous depression.

The authors conducted a double-blind prospective study of 39 patients with unipolar endogenous depression who recovered after ECT. Thyrotropin (TSH)-releasing hormone (TRH) tests were performed before and after ECT. Patients were divided into three groups on the basis of their altered TSH response: Persistent remission was predicted for patients in group 1 (N = 15) and relapse was predicted for groups 2A (N = 13) and 2B (N = 11). Patients in groups 1 and 2A received placebo and those in group 2B received amitriptyline for 6 months. Fewer relapses occurred in groups 1 and 2B than in group 2A (p less than .05), showing that relapse can be predicted by the TRH test and prevented by amitriptyline.

Adult↗
PubMed1990

Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression.

In a double-blind study lasting for 4 weeks, the authors compared the effectiveness of amoxapine, an antidepressant with potential antipsychotic properties, with a combination of amitriptyline plus perphenazine in the treatment of 38 patients who had the diagnosis of major depression with psychotic features (psychotic or delusional depression). Patients in each group showed similar improvement in depression and psychosis. There was a tendency for the patients treated with amitriptyline plus perphenazine to have higher global response rates. However, the patients given amoxapine had significantly fewer extrapyramidal side effects.

Adult↗
PubMed1993

Predicting response to amitriptyline in posttraumatic stress disorder.

OBJECTIVE: This study evaluated the relation between baseline clinical phenomena and response to amitriptyline in patients with posttraumatic stress disorder (PTSD). METHOD: Data were obtained from an 8-week placebo-controlled, double-blind study of combat veterans. Bivariate and multivariate statistics were used to evaluate the relations between the following variables and outcome: age, depression, anxiety, severity of PTSD symptoms, personality, psychiatric comorbidity, level of exposure to trauma, and individual symptoms of depression, anxiety, and traumatic stress. Outcome measures were scores on the Clinical Global Impression scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Impact of Event Scale. RESULTS: Drug response was related to lower baseline levels of depression, neuroticism, combat intensity, anxious mood, impaired concentration, somatic symptoms, feelings of guilt, and one intrusion and four avoidance symptoms of PTSD. CONCLUSIONS: The results demonstrate that response to amitriptyline is related to measures of depression, anxiety, PTSD, personality, and intensity of combat trauma. Similar relationships were not observed in the placebo group, suggesting a specific relationship to the drug.

Amitriptyline↗
PubMed1976

A comparison of amitriptyline and a fluphenazine/nortriptyline preparation in anxiety-depressive states.

Patients suffering from mixed anxiety/depressive reactions, referred to the out-patient department of a large psychiatric hospital, were treated with either amitriptyline tablets or fluphenazine with nortriptyline (f/n) tablets for a period of four weeks. The study utilized a double-blind, completely randomised design, and patients' progress was assessed by means of the Wing Present State Examination, the Wakefield Self-Assessment Depression Inventory, and a side effects inventory. Both the symptom rating scales showed that purely depressive symptomatology improved significantly in each treatment group, but the patients' self-ratings showed that only f/n produced a significant alleviation of anxiety symptoms and panic attacks. The patients receiving f/n rated themselves as significantly (p less than 0.05) less irritable, as well as less anxious, after 4 weeks treatment, than those receiving amitriptyline. The PSE schedule did not differentiate between the 2 treatment groups, but self-rating, which is a more sensitive method of eliciting drug effectiveness in patients suffering from mild psychiatric disorders, did demonstrate patient preference for f/n. This should have important implications for compliance with treatment.

Adolescent↗
PubMed1978

A comparison of the effects of single doses of mianserin and amitriptyline on psychomotor tests in normal volunteers.

Eight healthy volunteers received single doses of either mianserin 10 mg, mianserin 20 mg, amitriptyline 25 mg or placebo. Critical flicker frequency, reaction time, digit substitution and addition times were tested up to six hours afterwards. Mianserin 20 mg and amitriptyline 25 mg significantly prolonged reaction time and mianserin 10 mg and 20 mg significantly reduced critical flicker frequency. No other significant effects were found. Patients should be warned of possible sedation when first starting treatment with mianserin.

Amitriptyline↗
PubMed1985

Comparison of limbitrol (chlordiazepoxide/amitriptyline) and amitriptyline alone as a single night-time dose for the treatment of depression with anxiety.

Four hundred and thirty-four patients suffering from mild to moderate depression were recruited into a double-blind multicentre general practice study and randomly received either Limbitrol (25 mg amitriptyline and 10 mg chlordiazepoxide) or amitriptyline 25 mg in matching white capsules given as a single night-time dose. The dose was titrated to a maximum of four capsules per night. Patients were assessed on entry and at 7-day intervals for depressive state (Hamilton Rating Scale for Depression), cardiovascular effect and side-effects for 28 days. Self-assessments of depression and anxiety using the Leeds Scale were made in the form of a patient questionnaire. Both groups showed significant improvement at each visit and significantly more patients improved after 7 days in the Limbitrol group. There was no significant difference in treatment over all between groups, in the incidence of side-effects, or in the effects on the heart.

Adult↗
PubMed1980

A double-blind controlled trial of mianserin and amitriptyline in depression.

A double-blind trial was carried out in 47 patients with depression to compare the effectiveness of 30 mg mianserin, 60 mg mianserin and 50 mg sustained-release amitriptyline, each given as a single dose at night over a period of 4 weeks. Hamilton Rating Scale scores showed significant, progressive improvement from Week 1 with all three regimens. Although the differences between the groups were not significant, the greatest improvement occurred after 60 mg mianserin daily and the order of effectiveness was consistent for various Hamilton Rating Scale items. Patient self-assessment, using visual analogue scales, gave similar results to the Hamilton Rating Scale with significant, progressive improvement in all groups. Once again, a consistent order of effectiveness was evident with most of the items, the greatest improvement being noted with 60 mg mianserin daily and the least with 30 mg mianserin daily. There was a considerable reduction in the number of reports of symptoms recorded before the trial during treatment in all groups. The only increase in symptoms possible drug-related was of blurred vision in patients receiving amitriptyline.

Adolescent↗
PubMed1989

Primary care treatment of depression in the elderly: a double-blind, multi-centre study of flupenthixol ('Fluanxol') and sustained-release amitriptyline.

A multi-centre general practice study was carried out to compare flupenthixol and a sustained-release preparation of amitriptyline in the primary care treatment of depression in the elderly. Fifty-one clinically depressed patients, aged 65 years or over, were allocated at random to one of the two treatment groups in this 4-week double-blind, double-dummy study. On entry, patients received either a 0.5 mg flupenthixol tablet in the morning and a placebo capsule at night (25 patients) or a 25 mg sustained-release amitriptyline capsule at night and a placebo tablet in the morning (26 patients), but at the end of the first or second weeks the dosage could be doubled according to the assessed clinical need. Fourteen patients in each treatment group had their dosages doubled. Patient assessment was undertaken on study entry and after 1, 2 and 4 weeks of treatment using a 0 to 3 scale global assessment and the Montgomery Asberg Depression Rating Scale; side-effects were recorded on the UKU Scale. After 4-weeks' treatment, over 80% of patients in each group had improved and in the flupenthixol group there was additionally a noticeable and highly significant reduction in symptom severity after only 1 week of treatment. Patients treated with flupenthixol had fewer and milder side-effects.

Administration, Oral↗
PubMed2005

Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazine.

Drugs and alcohol often occur together in fatal poisonings, complicating the process of determining the cause of death. Especially when found in concentrations generally regarded as toxic but not lethal, the question arises whether the combination of sublethal amounts was the likely cause of death. In this study, we examined poisoning deaths involving amitriptyline, propoxyphene and promazine, which are, after benzodiazepines, the most frequently occurring drugs in Finnish alcohol-related poisonings. From the forensic toxicology database, covering the years 1995-2002, we extracted 332 fatal poisonings, calculated median blood alcohol and drug concentrations, constructed concentration-concentration and concentration-response curves and evaluated the significance of the presence of therapeutic amounts of benzodiazepines. Median amitriptyline and propoxyphene concentrations were lower in alcohol-related cases than in clean drug poisonings. Correspondingly, the median blood alcohol concentrations in all drug-related poisonings were 1.5-2.2 mg/g lower than that found in clean alcohol poisonings. Alcohol concentration proved to be a more sensitive indicator of alcohol-drug interaction than drug concentration. This result suggests that when alcohol is present, relatively small overdoses of the studied drugs may result in fatal poisoning. In this context, fatal drug and alcohol concentrations and the issue of determining the most important agent in fatal drug-alcohol intoxications are discussed.

Amitriptyline↗
PubMed1982

Phenelzine and amitriptyline: effects on symptoms of neurotic depression.

A double-blind controlled trial of phenelzine, amitriptyline and placebo was carried out in out-patients suffering from depression or mixed anxiety and depression. After six weeks treatment both active drugs were clearly superior to placebo and of similar efficacy; therapeutic effects started to appear at two weeks. Comparisons on symptom ratings showed that both drugs acted as true antidepressants, producing their greatest effects on ratings of depressive mood and thought content. There were additional weak differences, phenelzine producing more improvement on anxiety ratings, while amitriptyline gave greater effects on depressive impairment of work and interests and anergia. Analyses showed little evidence of clinical subgroups responding preferentially to either drug. The findings indicate that MAO inhibitors and tricyclic antidepressants have more closely similar clinical effects than has been thought and that either may be a useful treatment for these patients who are often considered to respond poorly to antidepressant drug treatment.

Adult↗