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A controlled comparison of flupenthixol and amitriptyline in depressed outpatients.

Sixty depressed outpatients were allocated to treatment with either amitriptyline (75-225 mg/day) or flupenthixol (1-5-4-5 mg/day) in flexible dosage for six weeks under double-blind procedures. Various objective and subjective assessments were carried out before and after one, three, and six weeks of treatment. Twenty-three patients completed the course of amitriptyline and 28 the course of flupenthixol. Almost all variables improved significantly over time, irrespective of drug. On most ratings there were no significant differences between the two drugs, but the trends favoured flupenthixol. In particular, flupenthixol lessened anxiety scores more than amitriptyline. Unwanted effects were few and not troublesome except in two patients receiving amitriptyline. Flupenthixol, in low dosage, is a useful alternative antidepressant for depressed outpatients.

Adult↗

Evaluation of the prophylactic efficacy of amitriptyline and citalopram, alone or in combination, in patients with comorbidity of depression, migraine, and tension-type headache.

Antidepressants are used to treat chronic daily headache disorders such as migraine and chronic tension-type headache (TTH), which are often associated with depression and anxiety. Here, we studied the efficacy and tolerability of amitriptyline and citalopram, given alone or in combination, in patients with 'triple' comorbidity of depression, TTH, and migraine. Eighty-eight patients were enrolled in the study and randomly divided into two groups. The first group received amitriptyline and the second citalopram for 16 weeks. Patients were assessed at weeks 0, 4, 8, and 16. The two drugs were equally efficacious in relieving depressive symptoms, although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks. Patients who did not respond to monotherapy (<30% of improvement in the clinical scores) were treated with a combination of the two drugs for 16 additional weeks. In these selected patients, the combined treatment produced a substantial improvement in depression, migraine and TTH without producing major side effects such as those commonly related to the 'serotonergic' syndrome. The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH, migraine and comorbid depression that do not respond to monotherapy.

Adult↗

Pharmacokinetic interaction between amitriptyline and neuroleptics.

The influence of amitriptyline on the plasma level of various neuroleptics was studied in 25 chronic schizophrenic patients. The study lasted 20 weeks. Patients were kept first 4 weeks on their former neuroleptic medication, with amitriptyline added for 12 subsequent weeks, and withdrawn during the last 4 weeks when only the neuroleptic medication was continued unchanged. The plasma level of neuroleptics was assayed by gas-liquid chromatography, once weekly throughout the study. The amitriptyline plasma level was also evaluated once weekly during the 12 weeks of its administration. The mean neuroleptic plasma values for each 4-week period were pooled together in three groups: aliphatic, piperdine and piperazine phenothiazine derivatives. Amitriptyline provoked some increase of the plasma level of all phenothiazine derivatives. This augmentation was significant only transitorily, however. The putative mechanisms of this neuroleptic tricyclic antidepressant interaction are discussed.

Adult↗

Mianserin versus amitriptyline for depression: a double-blind 6-week trial.

34 patients who met the research diagnostic criteria for major depressive disorder as defined by Spitzer et al. [Archs gen. Psychiat. 35: 773-782, 1978] completed a double-blind 6-week trial of mianserin versus amitriptyline following 1 week of single-blind placebo washout. After 2 weeks of dose build-up, patients took 150 mg/day of mianserin or 300 mg/day of amitriptyline throughout the next 4 weeks. At week 6, 63% of mianserin patients and 73% of amitriptyline patients were rated as responders; this difference is not statistically significant. No clinically meaningful differences between drugs were observed with respect to number or severity of side effects as reported by either patient or physician. Overall, mianserin was found to be equivalent to amitriptyline in terms of efficacy, patient tolerance and ease of administration.

Adolescent↗

Double-blind comparative study of paroxetine and amitriptyline in depressed patients of a university psychiatric outpatient clinic (pilot study).

21 depressed patients of the Basle University Psychiatric Outpatient Clinic were treated in a double-blind study with paroxetine and amitriptyline. 11 of these patients did not continue the trial until the end of the 7th week. There was a significant difference in the number of dropouts between the two groups: 80% of the amitriptyline group did not continue until the end, while in the paroxetine group we found only 30% dropouts. The patients of both groups showed a gradual decrease of the median total scores on the Hamilton and the Montgomery and Asberg Depression Rating Scales. Although the number of patients who stayed in the trial for at least 4 weeks (8 with paroxetine, 6 with amitriptyline) is quite small, we see from the results of the clinical global impression that the members of the paroxetine group improved most of all in the somatic symptoms, while considering their moods we found no differences between the groups. Patients of both groups complained about side effects, most of all about dry mouth and tiredness. From the high rate of dropouts under amitriptyline we found that the side effects under this drug were more severe and therefore led to the dropouts.

Adolescent↗

Biotransformation of amitriptyline in man: interaction with phenothiazines.

The biotransformation modification of amitriptyline by phenothiazines has been studied in 65 depressive inpatients. Thirty-four of them were treated with oral amitriptyline and 31 with a combination of amitriptyline and phenothiazine. Urinary and plasmatic results showed a decrease in hydroxylated metabolites of amitriptyline (OHAMTc and OHAMT) in patients with added phenothiazine.

Adult↗

Weight changes in antidepressants: a comparison of amitriptyline and trazodone.

Weight data taken from a 6-week randomized double-blind study comparing amitriptyline, trazodone and placebo were analyzed to determine differential weight changes between the two drugs. In 272 depressed outpatients doses were increased over a period of 4 days to reach a maximum level of 200 mg amitriptyline or 400 mg trazodone. After grouping the subjects according to initial weights (ideal, overweight, 20% above, and underweight, 20% below) mean changes were determined for each treatment. The results indicate that amitriptyline, which differed from placebo and trazodone, produced significantly higher weight gains in the ideal and overweight groups. Trazodone on the other hand produced a slight weight loss in the overweight group. Due to a low number of patients in the underweight group, the results were not significantly statistically. The antidepressant effects of both trazodone and amitriptyline were the same and no correlations between Hamilton scores and weight change were found.

Adolescent↗

Evaluation of possible interactions between ethanol and trazodone or amitriptyline.

The pharmacodynamic effects of single doses of trazodone (100 mg), amitriptyline (50 mg) or placebo either alone or with ethanol (0.5 ml/kg) were investigated in 6 healthy volunteers in a double-blind crossover study. Plasma concentrations of the drugs and ethanol were also measured. Pharmacodynamic tests were critical flicker fusion frequency threshold (CFF), choice reaction time (CRT), manual dexterity, a digit span test and visual analogue scales. Blood ethanol concentrations were not influenced by the co-administration of either antidepressant. tmax for trazodone was prolonged by ethanol but the other pharmacokinetic parameters for trazodone and amitriptyline were not influenced by ethanol. Trazodone and amitriptyline caused the expected profound depressant effects on CFF, CRT, manual dexterity and on the rating scales for drowsiness, 'clearheadedness', aggression and disinhibition. Ethanol alone impaired manual dexterity, increased drowsiness, reduced 'clearheadedness' and also tended to reduce feelings of aggression. In combination with either trazodone or amitriptyline, ethanol caused little additional effect except in the case of manual dexterity, which was further impaired. This result may reflect the profound effects of the antidepressants alone and does not suggest that it is safe for patients receiving antidepressant medication to take ethanolic drinks.

Adult↗

Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients.

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.

Adult↗

Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptyline.

265 adult outpatients with dysthymic disorder (DSM-III) associated with clinically manifest anxiety (according to FDA criteria) were included in a multicenter, randomized double-blind study. The trial consisted of three phases: placebo pretreatment phase and inclusion in the trial, treatment phase, placebo posttreatment phase. Patients were treated in monotherapy for 42 days with a mean dosage of 3 tablets per day corresponding to 37.5 mg/day of tianeptine or 75 mg/day of amitriptyline respectively. The following assessment instruments were used: the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS), and the Check-List for the Evaluation of Somatic Symptoms of J.D. Guelfi and C.B. Pull (CHESS 82). Analysis of MADRS total scores showed an important and rapid improvement in tianeptine and amitriptyline groups, reaching statistical significance as soon as D7. At the end of the 6-week treatment period the tianeptine group reached a decrease of 64% in the initial MADRS total score versus 69% in the amitriptyline group. 78% of patients treated with tianeptine and 83% of patients treated with amitriptyline were considered as treatment responders. There was no difference in drop-out rates between the two groups. HARS scores showed a decrease in psychic as well as somatic anxiety in both groups. The action of tianeptine on anxious-depressive symptomatology was confirmed by the concomitant improvement of global clinical rating and patients' self-rating (HSCL). Statistical comparison of all clinical rating-scale scores in patients having completed the trial failed to show any significant group differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A double-blind study of minaprine versus amitriptyline in major depression.

This study was designed to compare the antidepressant effects of minaprine and amitriptyline in a group of 60 outpatients suffering from a major depressive episode as defined by the DSM III. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible daily doses of 200-300 mg of minaprine and 50-75 mg of amitriptyline. Both drugs showed significant global antidepressant efficacy with no significant difference between the two treatment groups. The Hamilton item 'psychomotor retardation' improved earlier with minaprine than amitriptyline. The incidence of anticholinergic adverse effects was significantly higher in the amitriptyline treatment group.

Adult↗

Radioimmunoassay of amitriptyline and nortriptyline in body fluids.

A radioimmunoassay for the measurement of amitriptyline and nortriptyline in serum, saliva, and urine is described. The sensitivity of the assay is such that 0.5 ng/ml of drug can be measured, although the assay does not distinguish between amitriptyline and nortriptyline. Other tricyclic compounds cross-react with the antiserum to varying degrees, but the metabolites of amitriptyline did not significantly cross-react. Total tricyclic compounds were detected in serum and saliva after single oral doses of amitriptyline, although the absorption was slow.

Amitriptyline↗

Once-daily treatment for mixed anxiety/depressive states: a comparison of slow release amitriptyline and fluphenazine with nortriptyline.

Patients suffering from mixed anxiety/depressive states referred to a psychiatric out-patient clinic completed a four course of either a once-daily table of 30 mg nortriptyline with 1-5 mag fluphenazine, or a sustained release capsule of 50 mg amitriptyline once daily, on a double-blind basis. Depression improved satisfactorily on either treatment, but there was a greater reduction of anxiety on fluphenazine/nortriptyline, Drowsiness, however, occurred more frequently among the patients on amitriptyline, suggesting the sedative properties of this drug did not substitute adequately for a specific anxiolytic effect. Dry mouth was also noticeably more frequent with amitriptyline. As might be expected on pharmacokinetic and phsyological grounds, the results suggest that the sustained release characteristics of the amitriptyline preparation lead to a maximization of side-effects during the day without conferring any therapeutic advantage.

Adolescent↗

A double-blind comparison of zimelidine and amitriptyline in depressive out-patients.

A double-blind, randomized clinical study was conducted in thirty-four out-patients suffering from major depressive disorders comparing zimelidine with amitriptyline. The dosage was flexible, maintenance doses varying between 50-150 mg in the amitriptyline group and 50-300 mg in the zimelidine group. After a wash-out period of at least a week the mean score in Hamilton Rating Scale for depression (HRS) was 22.2 for zimelidine and 21.9 for amitriptyline. During the treatment period of 6 weeks, zimelidine and amitriptyline appeared to be equally effective as antidepressants in HRS and Global Ratings. The zimelidine group showed significantly less somnolence and dry mouth. No clinically important changes were seen in the laboratory parameters during the study.

Adult↗

Determination of amitriptyline in the hair of psychiatric patients.

A study was conducted on 60 psychiatric patients to evaluate the reliability of a drug-exposure screening test based on gas chromatography/mass spectrometry analysis of hair samples for amitriptyline, and the possibility of using the hair concentrations of amitriptyline to monitor patients' therapeutic compliance. The qualitative test was found to be very reliable (sensitivity 93.3%; specificity 100%; positive and negative predictive values 100 and 93.8%) in assessing the consumer status of patients over a period of 2 months before analysis. Hair levels of amitriptyline ranged from 0 to 17.21 ng mg-1. A significant relationship (r = 0.563; P < 0.002) was found between the hair concentrations and the cumulative intake of amitriptyline over the studied period, but was not judged close enough to estimate one individual's therapeutic compliance. The results are discussed in the light of existing literature.

Adolescent↗

Continuation therapy with amitriptyline in depression.

Thirty-two patients who had responded to amitriptyline (150 mg daily) when suffering from a depressive illness were allocated either to receive placebo or to remain on the same medication for one year. Plasma concentrations of the drug were regularly estimated. There was no correlation between plasma concentration and subsequent residual affective morbidity. In spite of considerable encouragement, three of the patients did not take the prescribed amitriptyline and they all relapsed. Five out of sixteen patients who received placebo relapsed. None of the patients who continued to take amitriptyline relapsed. It is emphasized that the patients studied were selected, inasmuch as they were apparent responders to amitriptyline. It is concluded that this group of patients should continue to be treated with antidepressant medication for eight months after apparent recovery, and care should be taken to ensure the patients' compliance.

Adult↗

Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system.

The effects of the tricyclic antidepressant amitriptyline on the rat hypothalamic-pituitary-adrenocortical (HPA) system were studied. The time-course experiments showed that amitriptyline, given via the drinking water (4.5 mg/kg.day), produces significant decreases (P < 0.05) in adrenal weight after 5 (-20%) and 7 weeks (-21%) of treatment. Hippocampal mineralocorticoid receptor (MR) levels were down-regulated at days 3 (-27%) and 7 (-20%), and transiently up-regulated at 2 (+40%), 5 (+74%), and 7 (+18%) weeks of treatment. Hippocampal glucocorticoid receptor (GR) levels were slightly down-regulated at days 3 (-8%) and 7 (-17%), transiently up-regulated by 26% at 5 weeks, and indistinguishable from controls after 7 weeks of treatment. MR levels were unchanged in the hypothalamus and neocortex, whereas hypothalamic GR concentrations were elevated and neocortical receptor levels were not altered. Dose-response experiments showed significant decreases in adrenal weight when rats were treated with 4.5 (-14%), 8.8 (-16%) and 14.5 (-13%) mg/kg.day antidepressant, but this applied only for the 4.5- (-14%) and 8.8- (-12%) mg/kg.day doses when the ratio of adrenal weight to body weight was considered. The dose-response relationship regarding hippocampal GR content displayed an inverted U-shaped curve, whereas this was less marked for MR levels. A dose of 4.5 mg/kg.day appeared to be optimal for the rise in MR as well as GR. Concerning the neuroendocrine implications of chronic antidepressant treatment, amitriptyline (5 weeks, 4.5 mg/kg.day) produced significant decreases in basal (ACTH, -47%; corticosterone, -31%) as well as stress (30 min novel environment)-induced plasma ACTH (-38%) and corticosterone (-57%) levels. Previous experiments have forwarded a role of limbic MR in the tonic control of basal HPA activity. Based on the present data, we hypothesize that during amitriptyline treatment a rise in limbic MR may be the initial phenomenon in a successively adjusting HPA system, as evidenced by the decreasing plasma hormone concentrations, declining adrenal size, and up-regulation of GR in particular brain regions.

Adrenal Cortex↗

Amitriptyline, but not lorazepam, relieves postherpetic neuralgia.

In a double-blind, randomized, crossover study, 58 patients with postherpetic neuralgia received 6-week courses of amitriptyline, 12.5 to 150 mg/d; lorazepam, 0.5 to 6 mg/d; or lactose placebo. Doses were titrated to the maximum level tolerated. Patients rated pain in a diary, using lists of verbal descriptors. Forty-seven percent of patients reported moderate or greater relief with amitriptyline, 16% with placebo, and 15% with lorazepam. Mean amitriptyline dose was 65 mg/d. Greater relief was associated with higher amitriptyline doses, up to the maximum dose of 150 mg/d, and with higher serum tricyclic levels. Lorazepam did not relieve pain and was associated with severe depressive reactions in four patients.

Adult↗