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PubMed1978

Abuse of amitriptyline.

Amitriptyline hydrocholride (Elavil) is frequently used in treating mild to moderate depressive states. A survey of 346 persons enrolled in a methadone maintenance program showed that 86 (25%) had admitted taking amitriptyline with the purpose of achieving euphoria. Thin-layer chromatography of random urine specimens over five months showed that 34% of the patients had a positive result for amitriptyline at least once during this time. These results suggest that misuse of amitriptyline is not uncommon and should be carefully considered prior to prescribing this agent to narcotic dependent persons.

Amitriptyline↗
PubMed1982

A controlled comparison of trimipramine and amitriptyline.

Depressed patients seen in a private psychiatric practice (N = 41) were randomly assigned to receive trimipramine or amitriptyline over a study period of at least 4 weeks. Patients in both groups showed significant improvement over time on measures of mood and depression, and on psychological scales. Only one variable, the global improvement rating, showed a significant overall between-groups difference, which favored amitriptyline treatment. This difference may reflect the presence of significantly less baseline symptomatology in the amitriptyline group. Trimipramine patients were more seriously ill on initial diagnosis and showed significantly more improvement at week 2 than amitriptyline patients and a trend toward fewer side effects. Thus, trimipramine may be useful for patients particularly sensitive to side effects in whom evidence of early response is important.

Adult↗
PubMed1982

Cardiovascular effects of phenelzine and amitriptyline in depressed outpatients.

Blood pressure and ECG changes were monitored in depressed outpatients treated for 6 weeks with amitriptyline, 150 mg/day, or phenelzine, 60 mg/day, as part of an ongoing double-blind study. Phenelzine produced significant decreases in blood pressure and a significant increase in orthostatic fall in pressure. Amitriptyline produced little overall change in blood pressure. The degree of MAO inhibition in phenelzine-treated patients was significantly correlated with blood pressure. Tricyclic plasma concentrations were also related to some blood pressure measures. Reported dizziness/faintness did not correlate with blood pressure changes in either group. Amitriptyline significantly increased heart rate, while phenelzine produced slowing. Amitriptyline was associated with significant prolongation of QRS and QTc but not PR intervals. Phenelzine produced significant shortening of the QTc interval.

Adult↗
PubMed1980

Plasma levels and clinical improvement--a comparative study of clomipramine and amitriptyline in depression.

To see if the clinical efficacy of amitriptyline and clomipramine is related to plasma level of the active drug or its main metabolite, or to the balance between them, plasma levels and clinical progress have been studied in 48 patients taking standard dosage. Dose for dose, plasma levels of clomipramine and desmethylclomipramine are usually higher than those of amitriptyline and its main metabolite nortriptyline, but no significant relationship between plasma levels and clinical improvement was found following clomipramine administration. By contrast, optimum responses to amitriptyline therapy were obtained at plasma levels of 50--100 micrograms/l for amitryiptyline itself and 25--75 micrograms/l for nortriptyline, but when their ratio exceeded 0--7 improvement declined. Steady states were reached after two to three weeks but a crude measure could be obtained from the plasma level after four days' treatment. Clomipramine and amitriptyline appeared to be equally effective, with clomipramine taking slightly longer to relieve depression.

Amitriptyline↗
PubMed1980

Prediction of steady-state plasma levels of amitriptyline and nortriptyline from a single dose 24 hr. level in depressed patients.

Amitriptyline and nortriptyline plasma levels were measured in depressed outpatients 24 hours after a single dose of amitriptyline and following chronic dosing to steady state. Plasma levels of amitriptyline and nortriptyline measured after the single dose correlated highly with steady state plasma levels. Full use as a test to rapidly place patients on a "therapeutic" dosage of drug will need to await a clear delineation of the relationship between blood levels and clinical response for amitriptyline.

Amitriptyline↗
PubMed1980

Drug interactions of amitriptyline and nortriptyline with warfarin in the rat.

Treatment of rats with amitriptyline or nortriptyline for 6 days at 6, 15 and 30 mg/kg produced no increases in the activities of aniline hydroxylase and aminopyrine N-demethylase or the content of microsomal protein and cytochrome P-450. Significant decreases in aminopyrine N-demethylase activity and cytochrome P-450 content were observed at 30 mg/kg. This inhibition of activity appeared to be at the level of cytochrome P-450 and not a cytotoxic effect in liver cells. Concomitant administration of amitriptyline or nortriptyline (6, 15 and 30 mg/kg)with warfarin to rats produced a dose dependent increase in the prothrombin time. At high doses of the tricyclic antidepressants, these increases in prothrombin time correlated with increases observed in the plasma half-life of warfarin. In vitro studies suggested that amitriptyline and nortriptyline inhibited the metabolism of warfarin. A double-reciprocal plot (Lineweaver-Burk method) showed this inhibition to be competitive. Nortriptyline produced greater inhibition of warfarin metabolism than amitriptyline and correspondingly greater enhancement of the anticoagulant effect.

Amitriptyline↗
PubMed1994

[Amitriptyline in therapy of chronic tension headache].

In a double-blind, placebo-controlled trial, the effect of 75 mg of a slow-release formulation of amitriptyline on the clinical severity of chronic tension-type headache and on headache-associated neurophysiological parameters (EMG activity, exteroceptive suppression of temporal muscle activity, contingent negative variation (CNV) and experimental pain sensitivity) was investigated. All of the patients treated had a history of headaches of many years standing, and numerous failed attempts at treatment. In the amitriptyline group, a significant reduction in daily headache duration was already found in the third week of treatment, while in the placebo group no significant changes in headache duration were to be seen. In week 6 the amitriptyline group had a significantly shorter daily duration of headache than the placebo group. Treatment did not result in any significant effects on EMG recording of pericranial muscle activity either during relaxation or contraction, on exteroceptive suppression of the temporal muscle and on CNV. The sensitivity to suprathreshold experimental pain, however, was significantly reduced. The data show a statistically relevant reduction of daily headache duration in chronic tension-type headache. However, they also show that amitriptyline can only partly alleviate chronic headaches but cannot cure them.

Adolescent↗
PubMed1993

[Comparative study of the pharmacokinetics of amitriptyline oxide and trimipramine after single administration in healthy male probands and patients with renal failure].

The pharmacokinetics of the antidepressants amitriptyline oxide and trimipramine and their major metabolites amitriptyline, nor-triptyline and desmethyltrimipramine, were studied in twelve healthy male subjects (aged from 22 to 62 years) and twelve patients (aged from 25 to 73 years) with severe renal impairment (glomerular filtration rate < 10 ml/min). Oral single doses of 60 mg amitriptyline oxide and 50 mg trimipramine, separated by a washout period, were administered to all study participants. Blood and urine samples were collected up to 120 hours after administration. For trimipramine and desmethyltrimipramine, a new HPLC method was developed. The "Fischer Somatic and Undesired Effects Check List" was used for the assessment of adverse events. The mean plasma half-life and AUC of amitriptyline oxide and its metabolites were significantly higher in patients than in healthy adults. For trimipramine the AUC was significantly higher in patients. The plasma half-life of trimipramine was longer in patients, but statistically not significant. The maximum plasma concentrations for both drugs and metabolites were at an average distinctly higher in patients. Clearance rate of amitroptylinoxide and trimipramine also differed between the two groups. Correlating with these results a high incidence and a longer persistence (in most cases > 12 hours) and more pronounced adverse effects were noted in the patient group, whereas in volunteers adverse events were only observed up to approximately eight hours.

Adult↗
PubMed1996

[Exploratory study of amitriptyline resistance in depressed patients: results of WHO French collaborating center on depressions resistant to treatments].

A multicountry, multicentre double-blind study in a group of depressives, coordinated by the Mental Health Division of the World Health Association (WHO) has been done. The goal of the study is to determine whether the therapeutic effects of amitriptyline can be enhanced and potentiated by combining it with an antioxydant (gingko biloba). An exploratory study has preceded the main study which had the objective to estimate the proportion of non-response patient to amitriptyline. We report the results concerning the French center. 23 inpatients meet the ICD-10 criteria for depression (F32 and F33) and were treated during 6 weeks by amitriptyline with the initial daily dose of 50 mg until the maximum dose of 200 mg. The proportion of non-responsive patient to amitriptyline was 34.78 (95% confidence interval : 15.32 to 54.24%), all clinically deteriorated.

Adult↗
PubMed1997

Biphasic kinetics of quaternary ammonium glucuronide formation from amitriptyline and diphenhydramine in human liver microsomes.

The tricyclic antidepressant amitriptyline and the H1-receptor antagonist diphenhydramine are conjugated in human liver microsomes fortified with UDP-glucuronic acid at their tertiary amino groups with the formation of quaternary ammonium glucuronides. The kinetics of the reactions were found to be biphasic with apparent KM1 and KM2 values of 1.4 microM and 311 microM for amitriptyline and 2.6 microM and 1180 microM for diphenhydramine in four liver samples. Vmax1 values varied between 2 and 17 pmol-mg protein-1.min-1 for the two substrates and Vmax2 values between 80 and 740 pmol-mg protein-1.min-1. A close correlation existed between amitriptyline and diphenhydramine glucuronidation rates in microsomes from seven livers at concentrations corresponding to 10-40% of KM2. At low concentrations, diphenhydramine competitively inhibited the glucuronidation of amitriptyline. Vmax/K(M) values of the high-affinity UDP-glucuronosyltransferase(s) (UGTs) exceed those of the low-affinity enzyme(s) severalfold, such that the former should make the major contribution to N-glucuronidation of the drugs at therapeutic concentrations in vivo.

Amitriptyline↗
PubMedDate not supplied

Phenytoin hypersensitivity syndrome with positive patch test. A possible cross-reactivity with amitriptyline.

A 34-year-old woman, after 2 weeks of treatment with phenytoin and amitriptyline, developed fever and cutaneous lesions consisting of a generalized maculopapular rash and eosinophilia. Her biochemical data showed abnormal liver functions with increased levels of SGOT, SGPT, LDH, gamma-glutamyl transpeptidase and alkaline phosphatase. The skin biopsy pattern was compatible with phenytoin drug eruption of the erythemamultiforme-like type (lymphocytic exocytosis, isolated dyskeratotic cells, vacuolation of basal cells and incontinence of pigment). The patch tests were positive with phenytoin (patch test biopsy showed a typical eczematous pattern). The patch test with amitriptyline was negative. An oral challenge with amitriptyline showed an erythematous maculopapular rash. The challenge with phenytoin was not carried out because the previously abnormal liver function tests contraindicated the challenge. Although there are a few cases reported, the patch tests could be useful for diagnosing phenytoin allergy. Cross-reactivity between phenytoin and amitriptyline is possible.

Administration, Oral↗
PubMed1998

Amitriptyline treatment for severe recurrent idiopathic cystitis in cats.

OBJECTIVE: To evaluate the safety and efficacy of amitriptyline hydrochloride in the treatment of severe recurrent idiopathic cystitis (IC) in cats. DESIGN: Prospective study. ANIMALS: 15 cats with IC that failed to respond to other treatments. PROCEDURE: Each cat received 10 mg of amitriptyline, PO, every 24 hours in the evening for 12 months or until signs recurred. Urinalysis, CBC, serum biochemical analysis, urine bacteriologic culture, and cystoscopy were performed initially, and after 6 and 12 months in responders. Severity scores of owner-observed signs of lower urinary tract (bladder and urethra) disease were recorded. RESULTS: During the first 6 months of treatment, 11 of the 15 cats had no owner-observed signs of lower urinary tract disease. During the next 6 months, 9 of 15 cats remained free of signs of cystitis. Despite clinical improvement, cystoscopic abnormalities persisted in all cats at the 6- and 12-month evaluations. Hematuria and proteinuria were decreased at the 12-month evaluation compared with the initial evaluation. Two of 15 cats initially appeared somnolent after amitriptyline treatment. Of 9 cats completing the study, 7 had increased body weight and 8 had decreased coat quality compared with the initial evaluations. Four cats developed small cystic calculi during the first 6 months of the study. Serum biochemical or hematologic abnormalities were not detected during the study. CLINICAL IMPLICATIONS: Amitriptyline treatment successfully decreased clinical signs of severe recurrent IC in 9 of 15 cats treated. Somnolence, weight gain, decreased grooming, and transient cystic calculi were observed during treatment in some cats.

Adrenergic Uptake Inhibitors↗
PubMed1998

[The bioequivalence of a new amitriptyline tablet formulation in comparison with a reference preparation].

An investigation of the bioequivalence of a new tablet formulation (amitriptylin 25 von ct) with 28.3 mg amitriptyline hydrochloride (CAS 549-18-8) was performed in a two-way cross-over study with 18 subjects. The relative bioavailability with respect to a reference preparation for AUC related to amitriptyline (CAS 50-48-6) was 99.3% and for Cmax 100.4%. A positive decision for bioequivalence derived from the usual confidence intervals for both parameters related to amitriptyline and the metabolite nortriptyline (CAS 72-69-5), respectively tmax showed no difference. The new formulation was bioequivalent to the reference.

Adult↗
PubMed1975

Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Clinical response to imipramine or amitriptyline.

The urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in unipolar depressed patients before and during the fourth week of treatment with either imipramine hydrocloride or amitriptyline hydroxhloride. On the basis of strict rating criteria, 24 patients were selected as either unequivocal responders or nonresponders. In the imipramine group the mean pretreatment MHPG was significantly lower in the nine responders in the seven nonresponders; the converse was found with the amitriptyline patients. Of particular interest is that there was no overlap in individual values between the responders and nonresponders to either drug. Treatment with eigher imipramine or amitriptyline was associated with a significant decrease in MHPG excretion, which was independent of clinical response.

Adult↗
PubMed1978

A comparison of electroconvulsive therapy and combined phenelzine-amitriptyline in refractory depression.

Combined monoamine oxidase (MAO) inhibitor-tricyclic antidepressant therapy and electroconvulsive therapy (ECT) were compared in a population of refractory depressive patients. Seventeen patients were randomly assigned to either of the treatment groups, and an independent observer was used to rate overall progress. Between four and ten ECTs or a combination of phenelzine and amitriptyline were administered. Assays for MAO activity and plasma levels of amitriptyline and nortriptyline were performed. In both psychotic and neurotic depression, ECT was superior. When depression was accompanied by character disorder, the response was generally poor. Adequate levels of MAO inhibition were obtained, but tricyclic antidepressant levels were low. Electroconvulsive therapy is still considered to be the treatment of choice for severe depression, whereas the combination of low doses of phenelzine and amitriptyline are ineffective. This treatment modality needs further investigation.

Adjustment Disorders↗
PubMed1980

Phenelzine and amitriptyline in the treatment of depression. A comparison of present and past studies.

We present the results of a direct comparison of pheneizine sulfate and amitriptyline hydrochloride therapy in 105 depressed patients. We believe this is the first definitive double-blind controlled clinical trial of a monoamine oxidase inhibitor and a tricyclic antidepressant in the outpatient setting. The results show both antidepressants to be effective, with the similarities between the two exceeding the differences. Both drugs had marked antidepressant and antianziety effects. Phenelzine tended to exert a stronger antianxiety action; amitriptyline was more effective in reversing weight loss and improving sleep. The incidence of two side effects, sedation and orthostatic hypotension, was almost identical. Dry mouth was more prevalent with amitriptyline. We discuss the indications for the differential clinical use of both drugs in depressed outpatients.

Adult↗
PubMed1983

The safety and efficacy of combined amitriptyline and tranylcypromine antidepressant treatment. A controlled trial.

Sixty patients meeting DSM-III criteria for major depression were assigned randomly to double-blind treatment for four weeks according to fixed-dosage steps with (1) amitriptyline hydrochloride alone, up to a maximum dosage of 300 mg/day; (2) tranylcypromine alone, up to 40 mg/day; or (3) the combination of amitriptyline hydrochloride, up to 150 mg/day, and tranylcypromine, up to 20 mg/day. The conditions of patients in all three treatment groups improved equally. The combined treatment did not produce a higher frequency of side effects, and no side effects, such as hypertensive or hyperthermic crises, occurred in any patient. Both amitriptyline alone and combined treatment produced substantially more anticholinergic side effects than did tranylcypromine. These results support the safety and efficacy of the combined treatment, although claims for superior efficacy over single-antidepressant treatments in this heterogenous population were not supported.

Adult↗
PubMed1985

Alprazolam vs amitriptyline in depressions with reduced REM latencies.

This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this six-week trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency.

Adolescent↗