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PubMed1992

An Australian multicentre study of moclobemide versus amitriptyline in the treatment of depression.

This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods.

Adult↗
PubMed1990

Quaternary N-glucuronides of 10-hydroxylated amitriptyline metabolites in human urine.

1. Conjugated metabolites were isolated from the urine of patients receiving amitriptyline treatment using a combination of solid-phase extraction, h.p.l.c. and t.l.c. 2. By n.m.r. and mass spectrometry, N-glucuronides of E- and Z-10-hydroxyamitriptyline and of trans-10,11-dihydroxyamitriptyline were identified in addition to the previously described O-glucuronides of E- and Z-10-hydroxyamitriptyline and -nortriptyline and amitriptyline-N-glucuronide. 3. The quaternary ammonium glucuronides proved to be resistant to acid hydrolysis, but could be cleaved enzymatically. 4. In urine samples from three patients, 35-60% of conjugated 10-hydroxyamitriptyline was found in the form of N-glucuronides. 5. A volunteer given an i.v. infusion of amitriptyline-N-glucuronide excreted E- and Z-10-hydroxyamitriptyline-N-glucuronide; following ingestion of E-10-hydroxyamitriptyline its N-glucuronide could be measured in urine.

Adult↗
PubMed1982

Protective effects of clonidine and verapamil in experimental amitriptyline poisoning in rabbits.

The effects of various agents on acute amitriptyline-induced cardiotoxicity were investigated in conscious rabbits. Amitriptyline (50 mg/kg, IP) regularly produced consistent and reproducible electrocardiographic changes such as lengthening of Q-T intervals, widening of the QRS complex, arrhythmias of various types, convulsion, and severe hypotension. Prevention of these toxic manifestations by the use of various agents alone or in combination was explored. Clonidine (50 micrograms/kg, IV) and verapamil (0.25 mg/kg, IV) alone or in combination at lower doses (25 micrograms/kg plus 0.125 mg/kg, respectively) significantly reduced the lengthening of the QRS and Q-T intervals, restored sinus rhythm, maintained blood pressure at a constant level, and protected against a lethal dose of amitriptyline (75 mg/kg). These results suggest that verapamil, clonidine, and their combination appear to be promising antidotal agents in restoring cardiac function under these conditions.

Amitriptyline↗
PubMed1985

Arterio-venous plasma concentration differences in amitriptyline overdose.

The aim of this study was to determine whether femoral arterio-venous plasma concentration differences (AVD) of amitriptyline exist during acute intoxication in man. All patients studied were comatose and were divided into a control group who had two successive blood samples drawn from the same vessel and a study group who had samples drawn from the femoral artery and vein simultaneously. Serial plasma concentrations of amitriptyline were measured by gas liquid chromatography. In each group the differences were assessed by means of the Wilcoxon matched pairs test. In the control group (n = 13) there were no differences (T = 31, n = 12). In the study group (n = 24) the AVD were significantly different (T = 52, n = 23). For amitriptyline, the arterial or venous origin of blood samples for toxicological studies must be stated.

Adolescent↗
PubMed2000

[A double-blind comparative study of the effectiveness and tolerance of paroxetine and amitriptyline in treatment of breast cancer patients with clinically assessed depression].

OBJECTIVE: In this double-blind, non-placebo controlled study [corrected], 179 patients with treated breast cancer who fulfilled the ICD-10 criteria for an acute depressive episode underwent an 8-week course of antidepressant treatment with either the tricyclic amitriptyline (75-150 mg, n = 87) or the serotonin-reuptake inhibitor paroxetine (20-40 mg, n = 88). METHODS: The change in clinical status relative to baseline was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI), the Functional Living Index-Cancer (FLIC) and the Patient Global Evaluation. RESULTS: Both treatment groups showed significant improvement in all parameters at weeks 3, 5 and 8. At no time was there a significant difference in the efficacy of the antidepressants used. Adverse events, most of which were transitory, were reported by 53% of the patients in the paroxetine group and 60% in the amitriptyline group. The 8-week treatment was completed by 81% of the paroxetine and 76% of the amitriptyline patients. CONCLUSIONS: The results of this study show that depression in breast-cancer patients can be correctly diagnosed and adequately treated by non-psychiatrists. The treatment with both medications was carried out in dose ranges which correspond to that employed in physically well patients.

Adaptation, Psychological↗
PubMed2000

Costs and outcomes of use of amitriptyline, citalopram and fluoxetine in major depression: exploratory study.

BACKGROUND: The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants. The aim of the study was to compare the costs and outcomes of using amitriptyline, citalopram and fluoxetine in the treatment of major depression. METHODS: Ninety patients (69 women) with a mean age of 44.5 years (S.D. = 14.3) suffering from major depression were treated with amitriptyline (N = 31), citalopram (N = 29) and fluoxetine (N = 30). Direct medical costs and effectiveness (indicated by the number of hospitalization-free days) were assessed in a prospective, open, intent-to-treat study. RESULTS: Neither cost nor effectiveness were significantly different among the treatment groups. CONCLUSION: Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies. There is no advantage in restricting patients from treatment with SSRIs, which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants.

Adolescent↗
PubMed1975

[Effect of amitriptyline and nortriptyline on the intracular pressure and aqueous humor dynamics in rabbits (author's transl)].

Both amitriptyline and nortriptyline applied conjunctivally produced pupil size enlargement, intraocular pressure decrease and a fall in aqueous humor formation. Phenoxybenzamine and superior cervical sympathetic ganglionectomy prevented the amitriptyline or nortriptyline inducing intraocular pressure changes. Either systemic administered or conjunctivally applied amitriptyline or nortriptyline, potentiated the effects on the pupil and intraocular pressure of exogenously norepinephrine.

Amitriptyline↗
PubMed1975

Cardiovascular effects of amitriptyline, nortriptyline, protriptyline, and doxepin in conscious rabbits after subacute pretreatment with protriptyline.

Conscious rabbits which had been permanently catheterized into their aortas and posterior caval veins, were injected daily with 10 mg/kg of protriptyline subcutaneously, divided in 3 doses. The blockade of the membrane pump in sympathetic nerve terminals by protriptyline was checked by pressor tests with noradrenaline (NA) and tyramine. In the presence of the membrane pump blockade 2.5 mg/kg of amitriptyline, nortriptyline, or protriptyline, or 3.0 mg/kg of doxepin was injected i.v. The antidepressants lowered blood pressure transiently and increased the heart rate, doxepin and amitriptyline being more effective than nortriptyline and protriptyline. Amitriptyline and doxepin provoked more severe cardiac arrhythmias on ECG than nortriptyline, and protriptyline caused no arrhythmias. Intravenous infusion of NA (11 mug/min) raised the blood pressure and lowered the heart rate. Injection of antidepressants during NA infusion resulted in more pronounced depressor and tachycardic effects than occurred without NA infusion. Major ECG changes were only slightly more apparent than without NA infusion. The rank order of toxicity of the antidepressants was the same. It is concluded that the NA potentiation by tricyclic antidepressants is not the main reason for their cardiotoxic effects.

Amitriptyline↗
PubMed1975

Influence of some antidepressant drugs on the circulatory system: II. Action of amitriptyline and nortriptyline on basic circulatory parameters.

Amitriptyline and nortriptyline in doses higher than 0.5 mg/kg exert a hypotensive action, and doses of less than 0-5 mg/kg have no characteristic effect on blood pressure. Both drugs diminished amplitude of cardiac contractions in situ in experimental animals. Low doses increased frequency and amplitude of respirations, and higher doses paralyzed respiratory function. Animals died as a result of paralysis of the respiratory center. In decapitated animals both drugs exhibited activity similar to that in animals with intact central nervous system, but their hypotensive effect was less pronounced. Blockade of the sympathetic and parasympathetic systems and of vegetative ganglia had no influence on the action of amitriptyline and nortriptyline on blood pressure. In low doses both amitriptyline and nortriptyline potentiated, and in high doses weakened the hypertensive effect of noradrenaline.

Amitriptyline↗
PubMedDate not supplied

[Salivation test in patients with affective disorders treated with amitriptyline, mianserin and electroconvulsive therapy].

The aim of this work was assessment of the peripheral anticholinergic effects by use of a salivary test in patients with depression on the background of affective disease, treated over four weeks in a psychiatric department by one of three methods: amitriptyline, mianserin or nondominant unilateral electroconvulsive therapy (NDULECT). There were 22 patients treated with amitriptyline, 26 mianserin and 20 by NDULECT. The degree of depression was assessed by Hamilton's scale of depression and was similar in the groups of patients compared. Also the amount of saliva excreted was similar in the material examined before treatment. Among the methods of treatment the most severe inhibition of salivation was noted in the group treated with amitriptyline, the least--after NDULECT. Mianserin reduced salivation to a small degree--taking up a middle position in the comparison of methods of treatment. Practically speaking there is a conclusion: in patients whose somatic condition contraindicates, during treatment of endogenous depression, unwanted symptoms occurring after inhibition of the cholinergic receptor, the most acceptable of the three methods would be the use of mianserin or NDULECT.

Adult↗
PubMedDate not supplied

Circadian changes in the elimination of amitriptyline in rats.

The circadian changes in elimination and absorption of amitriptyline after its intravenous and intragastric administration in rats were investigated. The values of such parameters as: AUC, MRT, t1/2, Cl, Vd, k(a) for amitriptyline change in the circadian rhythm. The fastest elimination of amitriptyline was observed in the dark phase (the acrophases for clearance were ca. 11 p.m. for iv administration and ca. 10 p.m. for po administration). The maximal value of clearance corresponds to the minimal values of MRT and t1/2. The acrophase for the constant absorption rate (po) falls at 7 p.m. Cyclic changes were not observed as far as the bioavailability is concerned.

Absorption↗
PubMed1992

[Serum concentrations of amitriptyline and its metabolites and clinical effect in depressive patients].

The serum concentrations of amitriptyline and its 3 metabolites--nortriptyline, 10-hydroxy-amitriptyline and 10-hydroxy-nortriptyline were determined in 18 depressive patients treated with amitriptyline for 6 weeks. The relationships between the serum concentrations and the clinical effects were statistically analyzed and showed significant correlations. The authors suggest that the total TAD serum concentration (280 ng/ml) can be used as the index for clinical efficacy, so far as the above data are concerned.

Adult↗
PubMedDate not supplied

Analytical application of the reactions of amitriptyline with eriochrome cyanine R and pyrocatechol violet.

Eriochrome cyanine R (ECR) and pyrocatechol violet (PCV) have been tested as reagent for the determination of amitriptyline (AMT). They react in aqueous media with AMT forming coloured compounds sparingly soluble in walter. Optimal conditions for the reaction have been established and new extractive-spectrophotometric methods have been developed for the determination of amitriptyline. It can be assayed in the concentration range 8.0-80.0 microg/ml for the ECR method and in the range 1.5-15.0 microg/ml in the case of PCV. The methods were applied to the determination of amitriptyline in albumin and pharmaceutical preparations. The UV-VIS studies of the reagents and the formed compounds were performed.

Amitriptyline↗
PubMedDate not supplied

Urinary metabolites of amitriptyline in the dog.

Dogs excreted approximately 45% of an oral dose of 14C-amitriptyline (30 mg/kg) in the urine in 24 hr. Two new urinary metabolites of the drug were identified as dihydrodiol derivatives of amitriptyline and nortriptyline, respectively. The major metabolite in dog urine was 10-hydroxyamitriptyline, excreted mainly in conjugated form. Other metabolites were characterized as 10-hydroxynortriptyline, amitriptyline N-oxide, and nortriptyline. Together, these metabolites accounted for approximately 47% of the urinary radioactivity.

Amitriptyline↗
PubMedDate not supplied

Long-term follow-up of patients with atypical facial pain treated with amitriptyline.

OBJECTIVE: The aim of this study was to assess the efficacy of low-dose amitriptyline in patients with atypical facial pain for one-year follow-ups. PATIENTS AND METHODS: Sixteen patients, ten females and six males, ranging in age from 15 to 77 years (mean 46.6 +/- 15.95 years), participated in the study. The onset, duration and temporal pattern of pain, events related to pain, drugs used before treatment and side effects of amitriptyline were recorded. The severity of pain was evaluated by using the visual analogue scale (VAS). Patients were followed for up to 12 months. RESULTS: The results showed that the onset of pain was related to dental pain in half of patients; and 10 patients had continuous pain. The mean VAS scores for pretreatment, post treatment, and 1, 3, 6, and 12 months were 9.6, 4.8, 2, 0.8, 0.3 respectively. In 12 patients, pain was reduced at the first month (p<0.05). All patients, except one, were pain-free at 12 months. It was statistically significant in achieving pain relief for 12 months (p<0.05). The common side effects of the drug were dry mouth and drowsiness. CONCLUSION: Data obtained from this study suggested that amitriptyline may be preferred in patients with atypical facial pain for rapid, satisfying analgesic effects. Long-term follow-up should be conducted to determine the analgesic effects and to prevent recurrence, even if the analgesic effect occurs in a short time.

Adolescent↗
PubMedDate not supplied

[Cardiac arrhythmia in amitriptyline poisoning in children].

UNLABELLED: Amitriptyline (Antideprin) determines severe intoxications, especially because of its cardiac side effects. METHOD: We studied 8 children (2-14 years old) admitted with signs of amitriptyline intoxication. RESULTS: The clinical picture revealed altered general status, generalized hypertonia, arterial hypotension up to collapse, mydriasis, coma and cardiac arrhythmia. ECG monitoring showed ventricular premature beats, isolated, couplets and triplets, ventricular tachycardia and torsade des points, severe ventricular repolarisation disturbances with diffuse subendocardial ischemia. The treatment consisted in: gastric lavage with activated charcoal, alkalinisation with sodium bicarbonate, antiarrhythmic drugs and sustained vital functions. All cases recovered in 4-6 days. CONCLUSION: The severity of amitriptyline intoxication requires continue clinical and ECG monitoring, for early detection of some life threatening cardiovascular events. Thus, the treatment will be started early and will alleviate the severe prognosis of this intoxication.

Adolescent↗
PubMed2006

[Comparison of efficacy of gabapentin and amitriptyline in the management of peripheral neuropathic pain].

In this single center, double blind and randomized trial gabapentin as a new anticonvulsant was compared in efficacy and safety with amitriptyline which is a classic agent in neuropathic pain treatment. Fourty six patients with neuropathic pain which was burning, stabbing and shooting in quality were allocated to take gabapentin (group GBP) and amitriptyline (group AMI) monotherapy. The assesment variables were burning, stabbing, shooting pain on visual analog scale (VAS; 0: no pain, 10: worst pain imaginable), allodynia as present or not by lightly touching the skin with cotton. Primary efficacy variable was the degree of burning, stabbing and shooting pain improvement that was accepted as the difference of beginning and 4th week's VAS of all pain qualities. The secondary efficacy variable was the patient satisfaction scale determined as whether possible side effects of study drugs affect the patients' daily life. The degree of pain improvement was only seen in shooting pain and was statistically significantly high in group GBP. The patient satisfaction scale was also high in group GBP. Both gabapentin and amitriptyline provided effective pain control in peripheral neuropathic pain. Additionally gabapentin was more effective especially in paroxysmal shooting pain than other pain qualities. And also gabapentin was tolerated well.

Amines↗
PubMedDate not supplied

Comparison of the cardiovascular effects of amineptine with those of amitriptyline and imipramine in anaesthetized rats.

In this study, two tricyclic antidepressant drugs and amineptine, administered to anaesthetized rats by intravenous bolus injection, were compared with regard to their in vivo cardiovascular effects. Amitriptyline and imipramine decreased mean arterial blood pressure and heart rate and caused conduction and rhythm changes in ECG. Amineptine, on the other hand, increased mean arterial blood pressure and caused a transient reduction of heart rate only at doses higher than those of amitriptyline and imipramine, while producing no noticeable ECG effects, even at doses 8 times higher than for the two tricyclic antidepressant drugs. The results of this study imply that amineptine, which structurally resembles tricyclic antidepressant drugs in having three rings and a side chain, has, nevertheless, a pattern of cardiovascular effects differing from that of amitriptyline and imipramine.

Amitriptyline↗