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PubMed1990

Treatment of posttraumatic stress disorder with amitriptyline and placebo.

Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder.

Ambulatory Care↗

PubMed1999

Chronopharmacokinetics of amitriptyline in rats.

The circadian changes in absorption, tissue distribution and elimination of amitriptyline after single intravenous (i.v.) and intragastric (i.g.) administration, as well as the differences in pharmacokinetic profile after multiple i.g. administration (at 10:00 and 22:00 h) during a 12 h dosing interval, were investigated. The circadian changes of pharmacokinetic parameters of amitriptyline such as AUC (serum and tissues), clearance (i.v. and i.g.), volume of distribution, biological half-life and bioavailability were estimated. Acrophases for clearance appeared between 19:00 and 21:00 h; the bioavailability was highest during the dark phase at around 04:00 h. Higher values of AUC in serum were observed at the beginning of the light phase. A circadian rhythm of tissue distribution (AUC, K(D)) of amitriptyline with acrophase in the dark phase was observed for brain (12 h period), lung and liver (24 h), but not for heart or kidney. After single (i.v. and i.g.) amitriptyline administration, concentrations of its major metabolite, nortriptyline, were negligible; however, after ten doses, nortriptyline serum and tissue levels were similar to the concentrations of the parent drug with higher values during the day (light phase).

Absorption↗

PubMed1988

Genotoxicity evaluation of the tricyclic antidepressants amitriptyline and imipramine using human lymphocyte cultures.

Two tricyclic antidepressants, amitriptyline and imipramine, were evaluated for their in vitro cytogenetic effects in human lymphocyte cultures. Peripheral blood cultures from three normal healthy donors were set up for 72 hr for each of the drugs. The drugs were added at the start (72-hr exposure), 24 hr (48-hr exposure), and 48 hr (24-hr exposure) after initiation of the cultures. The concentrations evaluated at each exposure time were 50, 250, 1,000, and 10,000 ng/ml for amitriptyline and 25, 500, and 5,000 ng/ml for imipramine. The first two concentrations correspond to the plasma levels of the respective drugs after therapeutic doses. All treatments for a donor were given at the same time. Untreated cultures served as controls for the baseline frequency of the parameters assayed. The parameters assayed were chromosome aberrations, mitotic index, and sister chromatid exchanges (SCEs). Amitriptyline was found to be nongenotoxic at plasma levels by all the parameters assayed. However, frequencies of chromosome aberrations and SCEs were significantly increased at concentrations 4 and 40 times the plasma level (1,000 and 10,000 ng/ml) although the actual increases was small. The mitotic index was not affected at any concentration. Through imipramine showed a significant increase in chromosome damage at the upper plasma level and at concentrations higher than that, SCE frequency was significantly increased only at concentration higher than the plasma level (5,000 ng/ml), the actual increase being small for both these parameters. The mitotic index was not affected at any concentration. These results suggest that amitriptyline may be a slightly safer drug than imipramine from a genetic point of view.

Amitriptyline↗

PubMed2006

Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson's disease and depression: effect on quality of life.

We assessed the effect of 3-month treatment of sertraline (50 mg) or low-dose amitriptyline (25 mg) on depression and quality of life in 31 patients with Parkinson's disease in a prospective single-blind randomized study. Both drugs significantly reduced the Hamilton Depression Rating Scale (HDRS-17) score. Completion rate was 75% for sertraline (12 of 16) and 73% for amitriptyline (11 of 15). Responder rate (HDRS-17 score reduction >/= 50%) was 83.3% for sertraline and 72.7% for amitriptyline. Sertraline but not amitriptyline treatment determined a significant benefit on quality of life (PDQ-39 scale). We found no change in Unified Parkinson's Disease Rating Scale scores. However, the improvement in specific PDQ-39 subscores (mobility, activities of daily living, and stigma) suggests that depression affects patient self-perception of motor function and further emphasizes the need for its treatment.

Amitriptyline↗

PubMed1991

In-patient major depression: is rolipram as effective as amitriptyline?

The antidepressant efficacy and adverse-effects of rolipram (a dialkoxyphenyl-2-pyrrolidone) were compared to those of amitriptyline in the treatment of depressive illness requiring hospital admission in a double-blind study. Fifty patients meeting DSM-III criteria for Major Depression whose scores on the Hamilton Rating Scale for Depression (HRSD) remained above 17 after 5 to 7 days on placebo were randomly allocated to either treatment. The rate of recovery in those patients treated by amitriptyline was substantially greater than in those patients treated by rolipram. Twice as many patients dropped out of treatment by rolipram because of lack of efficacy or adverse-effects compared with patients treated by amitriptyline. Rolipram produced fewer adverse-effects attributable to cholinergic blockade, but more nausea. We conclude that amitriptyline is more effective than rolipram in the treatment of depressed hospital in-patients.

Adolescent↗

PubMed1993

A comparison of the effects of single doses of amoxapine and amitriptyline on autonomic functions in healthy volunteers.

We have studied the effects of single oral doses of amoxapine (100 mg and 200 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced double-blind crossover design. Amitriptyline significantly reduced salivation and it significantly attenuated both miosis evoked by locally applied pilocarpine and sweat secretion evoked by locally applied carbachol. Amoxapine did not significantly alter any of these measures. Neither treatment significantly altered the pupillary light reflex (latency, amplitude, or 75% recovery time). Resting pupil diameter was significantly reduced by the higher dose of amoxapine but was not affected by the other treatments. The higher dose of amoxapine significantly increased supine systolic blood pressure, but did not affect heart rate or diastolic blood pressure; amitriptyline had no effect on any of these cardiovascular measures. These results confirm the antimuscarinic effects of amitriptyline in man, but provide no evidence for antimuscarinic effects of amoxapine.

Adolescent↗

PubMed1976

Effects of amitriptyline and isocarboxazid on 5-hydroxytryptophan induced head twitches in mice.

Effects of amitriptyline and isocarboxazid on brain 5-HT and 5-HIAA were examined in relation to their action on 5-HTP induced head twitches. Amitriptyline reduced 5-HTP induced head twitches but isocarboxazid increased them. Both amitriptyline and isocarboxazid caused a significant increase of brain 5-HT concentration in 5-HTP treated mice. Amitriptyline also caused a significant increase of 5-HIAA concentration, while isocarboxazid reduced 5-HIAA concentration in the brains of 5-HTP treated mice. Probenecid, which significantly increased 5-HIAA concentration without affecting brain 5-HT concentration in 5-HTP treated mice, reduced 5-HTP induced heat twitches. These results suggest that 5-HTP induced head twitches might be induced by an increase of 5-HT concentration, and reduced by an increase of 5-HIAA or a decrease of 5-HT concentration in the brains of mice.

5-Hydroxytryptophan↗

PubMed1983

A randomized double blind group comparative study of sulpiride and amitriptyline in affective disorder.

A randomized double blind group comparison study of sulpiride and amitriptyline was carried out in 36 patients suffering from major depressive disorder (DSM III criteria). Sulpiride showed equivalent antidepressant activity to amitriptyline at 4, 6 and 12 weeks, using the Hamilton Rating Scale (HRS) and the Wakefield Self-Rating Scale for depression (WRS). However, at 24 weeks the antidepressant activity of amitriptyline was just statistically significantly better than that of sulpiride. Timing of onset of action was comparable in both drugs. The anxiolytic activity of sulpiride was equivalent to that of amitriptyline at 4, 6, 12 and 24 weeks using the Salkind Manifest Anxiety Inventory as a measure. There were no significant differences between the two groups, of variables measured by the Crown-Crisp Experiential Index, a life events scale and Paykel's Social Adjustment Scale.

Adult↗

PubMed1984

The effect of amitriptyline treatment on the growth hormone response to apomorphine.

The growth hormone response to subcutaneous administration of the dopamine agonist apomorphine (0.005 mg/kg) was assessed in six normal male subjects before and at the end of a course of amitriptyline. Amitriptyline treatment significantly reduced the growth hormone response to apomorphine, confirming the findings of an earlier study in depressed patients. The way in which amitriptyline attenuates the effect of apomorphine is not clear. Direct blockade of dopamine receptors in the hypothalamus is a possibility, but long-term amitriptyline treatment could result in adaptive changes in the monoamine pathways which control GH release.

Adult↗

PubMed1982

Amitriptyline and nortriptyline excretion in human breast milk.

Simultaneous blood and milk samples were obtained from a 30-year-old woman who was on sustained release amitriptyline, and the concentrations of amitriptyline and the active metabolite, nortriptyline, were estimated by GLC. Serum and milk concentrations were similar with a slight tendency for the amitriptyline concentrations to be higher in milk. Calculation of the transfer of drug from the mother to the baby showed that the baby received an amitriptyline dose which was about one hundredth the dose given to the mother. No active drug could be estimated in the baby's serum and the baby showed no clinical signs which could be drug related.

Adult↗

PubMed1982

Blood noradrenaline and 5-HT levels in depressed women during amitriptyline or lithium treatment.

Noradrenaline levels and platelet and free serotonin concentrations were studied in depressed women in-patients (n=78) before and during amitriptyline (n=41) or lithium treatment (n=37). Pronounced monthly differences in platelet serotonin level have been shown in these subjects before treatment. In all clinical subgroups (neurotic, involutional, manic-depressive patients) a significant fall in platelet serotonin level was observed with amitriptyline medication while an increase was noted with lithium. No significant correlations between serotonin concentrations and clinical outcome were found. Amitriptyline treatment also produced a decrease in peripheral noradrenaline concentration in all subgroups, while an increase was observed with lithium. Some correlations between noradrenaline level and degree of depression were noted in patients treated with amitriptyline or lithium. A more extended analysis of blood amine levels could supply meaningful information on the peripheral action of antidepressive drugs on noradrenaline and serotonin concentrations in depression.

Adult↗

PubMed1984

Effects of zimeldine, mianserin and amitriptyline on psychomotor skills and their interaction with ethanol a placebo controlled cross-over study.

13 healthy volunteers participated in a double-blind, four-period, cross-over study. In each period, the trial drugs (placebo, zimeldine, amitriptyline and mianserin) were given in fixed dosages for 8 days; amitriptyline 10-50 mg twice daily, mianserin 10-30 mg twice daily and zimeldine 200 mg once daily. Ethanol 1 g/kg bodyweight was drunk 2 hours after drug intake on Days 1 and 8 of each period, the latter being separated by a 2 week wash-out period. Ratings of subjective feelings and side effects, and performance tests were done on Days 1 and 8 of each period before, 1.5, 3 and 4.5 h after drug intake, i.e. 2 of the tests were performed under the influence of ethanol. Mianserin decreased critical flicker frequency, slowed reactions under discriminative stimulation and tended to cause nystagmus, but only on Day 1 (after the first 10 mg dose). Amitriptyline impaired coordination on Days 1 (after the initial 10 mg dose) and 8, and lowered the flicker threshold on Day 8 at "steady state" (after the 50 mg morning dose). Both these antidepressants were felt to be sedative, especially in the initial phase of the treatment, and they interacted additively with ethanol. No impairment of psychomotor skills was associated with zimeldine, only a subjective sedative effect of the 200 mg dose was seen on Day 1. Zimeldine did not enhance the effects of ethanol; it even showed some antagonism of ethanol-induced body sway in the standing steadiness test. In contrast to amitriptyline and mianserin, zimeldine was regarded as not harming psychomotor skills, and as not having any observable interaction with ethanol.

Adult↗

PubMed1987

A double-blind comparison of the pharmacodynamic effects of single doses of lofepramine, amitriptyline and placebo in elderly subjects.

In a double-blind five-way cross-over study, six drug free healthy elderly subjects received single oral doses of lofepramine (70 mg, 105 mg and 140 mg), amitriptyline (50 mg) and matched placebo tablets. A dose related increase in plasma drug levels and pharmacological effects of lofepramine was observed. Lofepramine (140 mg) improved psychomotor performance (choice reaction time and letter cancellation), but no such change was seen with lower dose regimes or placebo. No significant differences between lofepramine and placebo were observed in other parameters measured. Amitriptyline, as expected, reduced salivary volume, produced drowsiness and impaired psychomotor performance. These changes correlated with plasma amitriptyline levels. The incidence of subjective side-effects with amitriptyline was also higher than that of lofepramine or placebo. In the dosage used, lofepramine exhibited no deleterious effect on the peripheral cholinergic system or psychomotor performance. This drug therefore is likely to be a relatively safe antidepressant for the elderly, but further investigations during long-term medication are required to verify these observations.

Aged↗

PubMed1979

Inhibition of platelet uptake of serotonin in plasma from patients treated with clomipramine and amitriptyline.

The inhibition of serotonin uptake by platelets has been measured in blood from 20 patients on amitriptyline (50--225 mg daily), 14 patients on clomipramine (25--200 mg daily), and in an untreated group of 21 depressed patients. A complete kinetic analysis was carried out in each patient. Using the increase in the kinetic parameter Km as a measure of uptake inhibition, there was high correlation between the daily dose and inhibition within each drug group, clomipramine being about 10 times more potent than amitriptyline. The inhibition did not vary with age, sex, duration of treatment (up to 3 years), or concomitant use of moderate doses of benzodiazepines, neuroleptics or lithium. In the amitriptyline group the inhibition was significantly smaller in smokers than in non-smokers. The kinetic parameter Vmax was essentially unchanged in the amitriptyline group, and was markedly reduced in the clomipramine group, but without any correlation with dose. The mixed competitive-noncompetitive effect of clomipramine confirms previous in vitro findings.

Adult↗

PubMed1977

Comparative bioavailability of a sustained release preparation of amitriptyline and conventional tablets.

A sustained release preparation of amitriptyline has been compared with conventional tablets in eight healthy human volunteers. The tablet produced a distinct peak in serum concentration shortly after administration, whereas the sustained release preparation caused a slow rise to a plateau. The maximum serum concentration and the time of its occurrence differed significantly between the two preparations. The differences between the serum concentration curves of the two preparations can be explained on the basis of a two compartment model of amitriptyline pharmacokinetics and from a difference in the absorption rate. The similar clinical effect obtained with a lower daily dose of the sustained release preparation than of the tablet cannot be accounted for in terms of pharmacokinetics. It is possible that a single evening dose of sustained release amitriptyline gives a more appropriate serum concentration profile of amitriptyline and its active metabolite nortriptyline than a conventional tablet taken three times a day.

Adult↗

PubMed1985

Cimetidine interaction with amitriptyline.

The interaction of cimetidine with amitriptyline was assessed by means of amitriptyline and nortriptyline plasma concentration measurements, standing blood pressure and pulse rate, digit symbol substitution, and visual analogue scales. Cimetidine increased plasma amitriptyline concentrations and decreased plasma nortriptyline concentrations, apparently by inhibiting presystemic metabolism. The changes in blood pressure, pulse rate and digit symbol substitution correlated with changes in concentrations of amitriptyline in plasma and expected changes based on a dose ranging preliminary experiment. Changes in subjective ratings of effects correlated with changes in nortriptyline concentrations in plasma.

Adult↗

PubMed1976

Alterations in the vigilance performance of children receiving amitriptyline and methylphenidate pharmacotherapy.

The effects of amitriptyline (Elavil) and methylphenidate (Ritalin) on the vigilance of 20 hyperactive/aggressive children was investigated using an auditory version of the Continuous Performance Test (CPT). Over the course of this letter-detection task, correct detections tended to return to pretreatment levels under placebo, but were maintained at significantly improved levels under amitriptyline and methylphenidate. The relatively steep performance decrement which occurred in the placebo condition was found to be associated with a progressive increase in responses to the letter which immediately followed a target letter. Treating these 'late' responses as slow but 'correct' detections failed to eliminate the treatment effects obtained with amitriptyline and methylphenidate. It was concluded that in addition to keeping detection response latencies from increasing, the medications produced a heightened level of vigilance which resulted in an absolute increase in the number of correct detections. The facilitation of vigilance performance by amitriptyline was in apparent contradiction to reports by parents and teachers that children appeared 'drowsy' while receiving this medication. Findings of the study suggested that children's ability to process information was unaffected by the reported side effect.

Amitriptyline↗

PubMed1978

Effect of intravenous infusion of amitriptyline on total blood serotonin content.

18 female patients with primary depression received a slow intravenous infusion of amitriptyline and a good therapeutic response was observed in 15 patients as early as after 6 days. A highly significant correlation was found between improvement scores following the first and last infusions, which suggests that intravenous infusion of amitriptyline may serve as a prognostic test for prediction of drug efficacy. Total blood serotonin content prior to treatment was significantly lower than in normal controls. Amitriptyline infusion caused variable changes in blood serotonin and the changes were inversely correlated with pretreatment levels. A series of six infusions caused a gradual increase in baseline levels, together with a rapid decrease in the magnitude of the amitriptyline-induced changes in serotonin content.

Adult↗