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PubMed1992

Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline.

This retrospective study was designed to assess the effects of acyclovir treatment of acute herpes zoster on subsequent postherpetic neuralgia, and to examine the effects of amitriptyline in the treatment of postherpetic neuralgia. Eighty seven patients with postherpetic neuralgia of three or more months' duration were studied: 24 of them had had their herpes zoster treated with oral acyclovir. At first presentation, only 25% of the 24 patients who had had their herpes zoster treated with acyclovir selected the word group containing burning on the McGill pain questionnaire compared with 76% of the 63 patients who had not received acyclovir. A higher proportion of patients who had had acyclovir than had not selected the word group which contains the word aching (63% versus 49%). Acyclovir thus appears to change the nature of postherpetic neuralgia. Postherpetic neuralgia was treated with amitriptyline, alone or in combination with distigmine and/or sodium valproate. There was a strong correlation between pain relief and the interval between the occurrence of herpes zoster and the initiation of treatment with amitriptyline--early treatment is almost twice as likely to be successful as late. Since conventional analgesics and sympatholytic drugs are of no benefit in the treatment of established postherpetic neuralgia, the sequelae of herpes zoster must, therefore, be recognized and treated with amitriptyline as soon as possible.

Acute Disease↗

PubMedDate not supplied

The effect of some microsomal enzyme inducers on amitriptyline distribution in rats.

The influence of different types of enzyme inducers: phenobarbital, Aroclor 1254 and benzo(a)pyrene, on distribution of amitriptyline and its metabolite nortriptyline in rats was investigated. The level of amitriptyline and nortriptyline in serum, brain, heart and liver was determined by gas chromatography. The maximum concentration values of amitriptyline and nortriptyline as well as areas under concentration-time curves (AUC0-6) in serum and organs were statistically compared using Student t test and AUCCOMP computer program. The results suggest that studied xenobiotics significantly influence the distribution of amitriptyline and nortriptyline in rats. The changes of these drugs concentration in target organs may be very important from the toxicological point of view.

Amitriptyline↗

PubMedDate not supplied

[Monitoring of the treatment of endogenous depression with imipramine and amitriptyline (preliminary report)].

Monitored treatment of a depressed phase of unipolar affective disorder was conducted in 11 female patients receiving imipramine and in 12 females taking amitriptyline. Patients were randomly assigned to one of the drug and in 6 patients the drugs were switched because of the lack of response to the first used compound. In the imipramine treated group a satisfactory response after 4 weeks of management (less than 6 points on Hamilton's depression scale) was observed in 6 patients and in amitriptyline treated group in 5 patients. Patients displaying a satisfactory response to amitryptyline had significantly higher--as compared to remaining patients in the group--plasma levels of the drug after two and four weeks of treatment. Such an association was not observed in patients treated wtih imipramine. Severity of depression and motor retardation before the treatment was similar both in patients with satisfactory and with poor response to imipramine as well as to amitriptyline. However the intensity of anxiety symptoms was higher in patients exhibiting poor response to treatment with amitriptyline and imipramine as well.

Adult↗

PubMed1991

[A control study of clomipramine and amitriptyline for treating obsessive-compulsive disorder].

This paper reported a comparative study of clomipramine (n = 21) and amitriptyline (n = 18) for treatment OCD. The improvement rate of clomipramine and amitriptyline was 95.2% and 55.6%, respectively (P less than 0.01). The decreased scores of obsessive-compulsive and depressive factors of SCL-90 of clomipramine were higher than amitriptyline. The results showed that clomipramine has better therapeutic effects and less side-effects than amitriptyline.

Adolescent↗

PubMed1991

A comparison of three computer models for prediction of dose in acute amitriptyline overdose.

The pharmacokinetics of amitriptyline in overdose have been reported not to fit conventional compartmental models. In this study, the dose-concentration-time relationships of amitriptyline in overdose were modeled with discriminant analysis, with an evolutionary heuristic search program, and with a decision-tree model based on the entropy of uncertainty of classification. The computer models all used the same data from dogs administered treatment (80 mg/kg), toxic (250 mg/kg), or fatal (500 mg/kg) doses directly into the surgically isolated duodenum. All the models achieved a high degree of success (77 to 93%) in assigning records to the high-, low-, or middle-dose groups. Two of the models gave a probability of the assignment. Results of this analysis suggest that blood amitriptyline and nortriptyline concentrations are most useful in estimating dose in acute amitriptyline overdose.

Amitriptyline↗

PubMed1989

Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial.

Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline.

Aged↗

PubMed1989

Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects.

Amitriptyline (up to 75 mg/day), fluoxetine (up to 40 mg/day) and placebo were administered to 12 normal, healthy subjects for a period of 7 days. Subjects received each drug in random order and a minimum of 28 days was left between drug treatments. A battery of physiological, psychomotor and subjective tests was administered before drugs (day 1) and on days 4 and 8. On day 8 a measured dose of alcohol was given and the tests repeated at 1 and 3 h after alcohol. Tests before alcohol showed little effect on physiological or psychomotor activity either between drugs or between drugs and placebo. Subjective ratings did show some differences between drugs and in general amitriptyline was tolerated less well than fluoxetine. There were few differences between drugs after alcohol but with some measures the interaction with amitriptyline was subjective rather than additive or potentiating. This reflected the already substantial effects of amitriptyline alone.

Amitriptyline↗

PubMedDate not supplied

[Effect of amitriptyline on analgesia induced by acupuncture and inescapable painful electrodermal stimulation in the rat].

The effect of amitriptyline (1.5 and 3 mg/kg intraperitoneally once a day for 1, 3, 5 days) on the latencies (L) of hot plate (HP) and tail flick (TF) at rest, after acupuncture (A) of bilateral Ho-ku and after inescapable foot-shock (IFS--1.0 mA, 50 Hz, 5 min) was studied in experiments on rats. It was shown that amitriptyline in the above doses, used in different periods of time, failed to effect L of HP and TF at rest. However, after A an increase of the analgesic effect was observed in the rats treated with 3 mg/kg of amitriptyline for 3 days. In the experiment with IFS an increase of the effect was pronounced in TF test 24 hours following administration of 1.5 and 3.0 mg/kg of amitriptyline.

Acupuncture Analgesia↗

PubMed1986

Comparison of some effects of paroxetine with amitriptyline on the cardiovascular system in animals.

The effects of intravenous infusions of paroxetine, a novel inhibitor of 5-hydroxytryptamine (5HT) uptake, and of the tricyclic antidepressant, amitriptyline, on the cardiovascular system have been compared in the conscious rabbit and in the anaesthetised cat. As judged by the dose required to produce changes in ECG waveform (including PR and QTc intervals) and disorders of heart rhythm, paroxetine was less cardiotoxic than amitriptyline in both species. Thus, paroxetine has the advantage over amitriptyline of being less toxic to the cardiovascular system which could constitute a considerable advantage in clinical use particularly as other work has shown it to be more potent than amitriptyline in tests for antidepressant activity.

Amitriptyline↗

PubMed1977

Psychomotor skills during acute and two-week treatment with mianserin (ORG GB 94) and amitriptyline, and their combined effects with alcohol.

Twenty paid healthy volunteers took a placebo, 10 mg of mianserin and 25 mg of amitriptyline, t.i.d. for two weeks each, in a double-blind cross-over manner. There was one week's "wash-out" between the treatments. Several psychomotor tests were done on the first, 7th and 14th days of each period with either alcohol (0.5 g/kg) or a placebo drink. Co-ordinative and reactive skills and critical flicker frequency were affected by all the drug-drink combinations while attention was slightly impaired only after amitriptyline alone or mianserin together with alcohol. Drug actions and drug-alcohol interactions were most obvious on the first day but declined towards the end of the drug periods. After mianserin the skills were impaired on the first day only, but after amitriptyline up to the 7th day in most of the tests. Both drugs seemed to interact additively with alcohol. Impairment of flicker fusion by amitriptyline + alcohol remained constant over the whole 2-week period. Psychomotor effects of antidepressants have practical importance in the acute phase of treatment. Their concurrent use with alcohol must increase accident risk in traffic.

Adult↗

PubMed1977

Which tricyclic for depressed outpatients, imipramine pamoate or amitriptyline?

Fifty-seven neurotically depressed outpatients with sleep disturbance were randomly assigned to treatment with either imipramine pamoate or amitriptyline given in a single dose at bedtime in a double-blind study for four weeks. The results indicate that both imipramine pamoate and amitriptyline are equally effective in treating neurotic depression. The clinical lore that imipramine is more effective for retarded depression and amitriptyline for anxious, agitated depression was not supported by this study. Of special interest is the fact that the imipramine pamoate group had significantly earlier rising times, and a trend toward better quality of sleep. The side effect profiles of the two drugs were also remarkably similar in this population though more patients complained of side effects on amitriptyline than on imipramine.

Adjustment Disorders↗

PubMed1987

Long-term versus short-term amitriptyline side effects as measured by a postmarketing surveillance system.

As part of a large-scale postmarketing surveillance study, the adverse clinical events (ACEs) reported by 85 outpatients taking amitriptyline were investigated. Two discrete groups of patients were identified based on their duration of amitriptyline treatment: 45 had started the drug within 2 weeks of their interview (mean = 10.1 days, SD = 1.6 days), while 40 were much longer term tricyclic antidepressant patients (mean = 227.2 days, SD = 135 days). Our analysis of amitriptyline side effects reported by each of these two discrete groups challenges the common clinical impression that tricyclic side effects, in general, abate with continued treatment. Shorter term patients were much better able to correctly attribute their adverse clinical events to their drug therapy. Anticholinergic side effects were reported as new symptoms by the long-term patients just as frequently with similar ratings of subjective severity. These reports of adverse drug reactions of recent onset by long-term amitriptyline users may reflect the fact that such symptoms fluctuate in their occurrence and may not be recognized as potentially drug-induced until some threshold for patient tolerance is exceeded.

Adult↗

PubMed1979

Epileptic phenomena induced in the cat by the antidepressants maprotiline, imipramine, clomipramine, and amitriptyline.

The epileptogenic properties of four tricyclic antidepressant drugs: maprotiline, imipramine, clomipramine, amitriptyline, were investigated in locally anesthetized cats immobilized with gallamine and supplied with neocortical, hippocampal, and reticular recording electrodes. The drugs were infused intravenously at a constant rate (0.5 or, in some cases, 0.25 mg/kg per min) up to a final dose of 45 mg/kg. Already in small doses (1 to 5 mg/kg) all four antidepressants produced local signs of epileptiform pathology. Generalized sustained discharges occurred, on the average, at between 20 and 25 mg/kg with all four drugs. Imipramine and amitriptyline, after the first or first few generalized discharges, led to a pattern of repeated short generalized seizures alternating with silent periods. Maprotiline invariably produced this later alternating pattern only after a 10- to 30-min period of a seminormal high amplitude pattern. Clomipramine assumed a position between maprotiline on the one hand and imipramine and amitriptyline on the other. Starting at doses of 2-4 mg/kg, imipramine, clomipramine and amitriptyline, all three being norepinephrine and serotonin uptake inhibitors, induced a high amplitude "sleep" pattern. Maprotiline, a norepinephrine uptake inhibitor, which is thought devoid of serotonin-uptake inhibiting properties, led to high amplitude slow waves only with doses of at least 12.5 to 15 mg/kg.

Amitriptyline↗

PubMed1978

Comparative single-dose kinetics of amitriptyline and its N-oxide in a volunteer.

Plasma drug levels and urinary metabolites were measured in a volunteer for 28 h after ingestion of amitriptyline hydrochloride or amitriptyline N-oxide (amitriptylinoxide) equivalent to 100 mg of amitriptyline base. The N-oxide initially produced high plasma levels and 15% of the dose was excreted unchanged within 14 h. From comparison of the metabolite excretions, it can be concluded that about 70% of the dose was reduced at the N-oxide group, while comparison of the areas under the plasma group, while comparison of the areas under the plasma level-time curves for amitriptyline pointed to a 55% reduction to the amine. Less drowsiness was experienced after ingesting the N-oxide, and there was no depressive mood.

Adult↗

PubMed1983

A double-blind comparison of bupropion and amitriptyline in depressed inpatients.

Bupropion and amitriptyline were compared in a double-blind study of depressed inpatients. Treatment ranged from 2 to 4 weeks: early responders (Hamilton Depression Scale scores less than 10) were often removed from treatment after 2 or 3 weeks. Twenty-two patients completed treatment with bupropion and 18 with amitriptyline. Doses ranged from 450 to 750 mg/day for bupropion and 75 to 225 mg/day for amitriptyline. Overall, bupropion and amitriptyline were equally effective, as measured by the Hamilton Depression and Anxiety scales, Clinical Global Impressions, Zung Depression scale, and the SCL-90. Differences in the side effect profile and in weight change are described.

Adult↗

PubMed1978

A radioimmunoassay for the determination of combined amitriptyline and nortriptyline concentrations in microliter samples of plasma.

A sensitive radioimmunoassay for amitriptyline and nortriptyline in blood has been developed. The antibodies used in the radioimmunoassay were raised in a sheep against a conjugate of nortriptyline and bovine serum albumin. Using tritiated amitriptyline as the label, the assay is capable of detecting concentrations as low as 2.0 ng/ml in a 50 microliter sample of plasma. Cross-reactivity studies have demonstrated the specificity of the radioimmunoassay for both amitriptyline and nortriptyline, and comparison with gas-liquid chromatography assay has indicated the applicability of the assay to a routine situation. The radioimmunoassay has been used to study the plasma drug levels after single oral administration of amitriptyline to four volunteers. A wide variation in maximum drug concentrations, ranging from 18 to 62 ng/ml, was seen, with the time taken to reach the maxima ranging between 1.5 and 3 hours. A second concentration peak was seen in three of the volunteers, at 4 to 5 hours after ingestion of the drug.

Amitriptyline↗

PubMed1984

[Inhibition of monoamine oxidase A and B in the heart and brain of the rat with amitriptyline, pargyline and pirlindol].

The inhibition of monoamine oxidase (MAO) A and B by amitriptyline, pargyline and pirlindole was measured in heart and brain homogenates of rats with tryptamine and beta-phenylethylamine as substrates. The tricyclic antidepressant amitriptyline inhibited MAO B stronger in the brain (Ki = 8.41 X 10(-6) mol/l) as well as in the heart (Ki = 7.03 X 10(-5) mol/l) compared to the A-form (1.51 X 10(-4) and 1.03 X 10(-4) mol/l, respectively). Pargyline diminished the activity of both enzyme forms of the heart in the same range (4.29 and 1.60 X 10(-6) mol/l), whereas in the brain the B-form was blocked in a more pronounced manner, too (5.80 X 10(-8) and 4.01 X 10(-6) mol/l, respectively). In contrast to amitriptyline and pargyline pirlindole inhibited the MAO with tryptamine as a substrate in the brain 100 times (2.49 X 10(-7) mol/l) and in the heart nearly 1000 times (3.42 X 10(-8) mol/l) more than with phenylethylamine as a substrate (5.21 and 5.99 X 10(-5) mol/l, respectively). These results show that amitriptyline and pargyline are relatively selective inhibitors of MAO B, whereas pirlindole blocks the A-form of MAO much stronger than MAO B.

Amitriptyline↗

PubMed1978

A comparison of the onset of action and therapeutic efficacy of amoxapine and amitriptyline.

A total of 61 moderately to severely depressed outpatients were treated for four weeks with either amoxapine (a dibenzoxapine tricyclic) or amitriptyline. This double blind study showed that amoxapine was as effective as amitriptyline and had an earlier onset of action. Maximum doses used were 300 mg of amoxapine and 150 mg of amitriptyline. Side effects were similar for the two drugs, except for impotence or loss of libido in eight male amoxapine, as against three amitriptyline patients. Laboratory, EKG, and vital signs findings showed no pathological trends.

Adolescent↗