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PubMed2006

Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy.

OBJECTIVE: The objective of this prospective, randomized, controlled study (N = 28) was to evaluate the effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. METHODS: Patients were selected based on a clinical history consistent with postviral vagal neuropathy and a history of an antecedent upper respiratory tract infection. All patients had been tried on antireflux medication (proton pump inhibitors) and had a negative chest x-ray before presentation. All were nonsmokers without a history of asthma. Patients on angiotensin-converting enzyme inhibitors were excluded from the study. All patients completed a pretreatment, validated cough-specific quality-of-life (QOL) survey. Patients were randomized by chart numbers to either 10 mg amitriptyline at bedtime or 10 to 100 mg/5 mL, 10 mL codeine/guaifenesin every 6 hours standing dose while awake. Both groups were instructed to complete 10 days of therapy and then asked to subjectively rate the reduction in the frequency and severity of their cough by 100%, 75%, 50%, 25%, or 0% as well as completing the posttreatment cough QOL questionnaire. Those patients experiencing a 75% to 100% reduction were recorded as having a complete response, 25% to 50% a partial response, and 0% as having no response. Final results and the cough QOL survey were recorded and used for statistical analysis. RESULTS: A majority of patients in the amitriptyline group achieved a complete response on the initial dose of 10 mg. None of the codeine/guaifenesin group achieved a complete response. The data were analyzed using a logistic regression model, and amitriptyline was found to be a highly significant predictor of a greater than 50% response when compared with codeine/guaifenesin (P = .0007). The same data were analyzed using a proportional odds model and similar results were noted. CONCLUSIONS: Chronic cough can have a profound impact on the psychosocial function of patients. The most common causes of a persisting cough in the absence of infection or chronic smoking are laryngopharyngeal reflux, asthma, particularly the cough variant, allergy, rhinosinusitis, bronchitis, and medications, in particular angiotensin-converting enzyme inhibitors. Currently, there are few effective treatments for cough with an acceptable therapeutic ratio and more selective drugs with a more favorable side effect profile are needed. This is this first prospective, randomized, controlled study comparing the effectiveness of amitriptyline versus codeine/guaifenesin for select cases of chronic cough resulting from suspected postviral vagal neuropathy.

Amitriptyline↗
PubMed2005

Amitriptyline abuse and misuse.

Deaths related to amitriptyline toxicity are relatively common and are typically related to suicidal overdose. A less well-recognized situation of amitriptyline intoxication occurs when the drug is abused for its euphorigenic effects. An amitriptyline-related death due to a mixed drug intoxication is presented. Death investigation revealed that the death was accidental rather than suicidal. The case serves to remind forensic investigators that not all amitriptyline overdose deaths represent suicides. A segment of the population is known to abuse amitriptyline.

Adult↗
PubMed2004

Differential effects of two types of antidepressants, amitriptyline and fluoxetine, on anorectal motility and visceral perception.

BACKGROUND: Although antidepressants are used for functional gastrointestinal disorders, the mechanisms of their effects on gut are incompletely understood. AIM: To assess the effects of two types of antidepressants (tricyclic, serotoninergic) on anorectal motility and visceral perception. METHODS: A placebo-controlled, randomized, double-blind, crossover study was performed in 12 healthy male volunteers who received a single oral dose of amitriptyline (80 mg), fluoxetine (40 mg) or placebo. Drug effects were assessed using phasic isobaric distensions of the rectum with an electronic barostat (11 levels from 1 to 51 mmHg) 4 h after drug intake. Maximal rectal volume and pressure, mean and residual pressures at upper anal canal, mean pressure at lower anal canal, defecation sensation (5-level scale) and visceral perception (visual analogue scale) were recorded at each level of distending pressure. RESULTS: Ten subjects completed the study. Compared with placebo, neither amitriptyline nor fluoxetine modified rectal compliance or visceral perception. Compared with placebo, antidepressants significantly reduced mean and residual pressures at upper anal canal (-18%, P = 0.0019, and -27%, P = 0.0002, respectively, for amitriptyline; -26%, P = 0.0001, and -33%, P = 0.0001, respectively, for fluoxetine) whereas only amitriptyline significantly reduced mean pressure at lower anal canal (-16%, P = 0.0008). CONCLUSION: Both antidepressants similarly relaxed the internal anal sphincter, probably through a non-specific mechanism, without modifying visceral perception. Only amitriptyline relaxed the external anal sphincter.

Adolescent↗
PubMed1992

Low dose amitriptyline in the treatment of chronic pain.

The analgesic efficacy of amitriptyline 25 mg was compared with placebo in 41 patients with chronic (more than 3 months) nonmalignant pain, using a double-blind randomised multiple-dose 3-week treatment period crossover design. Amitriptyline 25 mg provided significantly greater efficacy than placebo, with significant differences evident within the first week. There was no significant difference on mood scores between amitriptyline and placebo. The results suggest that surprisingly low doses of amitriptyline may be effective without substantial adverse effects, that the effect is evident early, and that the effect is distinguishable from any effect of the amitriptyline on mood.

Adult↗
PubMed1993

Dose-response for analgesic effect of amitriptyline in chronic pain.

A randomised, double-blind, multiple dose, crossover study with three 3-week treatment periods was set up to compare the analgesic efficacy and adverse effects of amitriptyline in oral doses of 25, 50 or 75 mg. Patients used diaries to assess their pain, and clinic assessments were made at the end of each treatment period. It was found that in 29 patients with chronic (more than 2 months) pain, amitriptyline 75 mg provided significantly greater efficacy than amitriptyline 25 or 50 mg. There was no significant difference in mood scores between the different doses of amitriptyline, but sleep was judged significantly better with 75 mg compared with 25 mg. The incidence of adverse effects was significantly higher with the 75 mg dose, and the principal adverse effects were dry mouth and drowsiness. In the context of chronic pain, the analgesic effect of amitriptyline was shown to have a dose-response unrelated to mood elevation, but there was a dose-response for the incidence of adverse effects.

Adult↗
PubMed1980

A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects.

1 Six healthy male volunteers participated in a double-blind placebo crossover comparison of the pharmacodynamic profiles of single oral doses of 75 mg nomifensine and 50 mg amitriptyline. 2 Nomifensine treatment did not influence salivary flow and did not significantly affect psychomotor performance (critical flicker fusion, pursuit rotor and reaction time): in addition nomifensine had no significant effect on subjective measurements of sedation and concentration. 3 By contrast, amitriptyline treatment significantly reduced salivary flow and was associated with significant sedation and reduced concentration: significant changes in psychomotor performance were also noted. 4 Plasma concentrations of amitriptyline and nomifensine were measured at 2 h. The respective median concentration values were 55.0 ng/ml and 52.0 ng/ml. 5 Ex vivo platelet amine uptake of dopamine (DA) and 5-hydroxytryptamine (5HT) was measured 2 h after each treatment. Both nomifensine and amitriptyline treatment significantly inhibited DA uptake to a similar extent. Amitriptyline treatment additionally inhibited 5-HT uptake.

Amitriptyline↗
PubMed1983

A double-blind comparative trial with mianserin and amitriptyline in outpatients with major depressive disorders.

1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Emergent Symptom Scale (TESS). 3 Mianserin and amitriptyline were comparable with respect to efficacy. 4 More adverse experiences were reported by amitriptyline patients. The predominant amitriptyline adverse experiences were of the anticholinergic type; the predominant mianserin adverse experience was drowsiness/fatigue. 5 The Efficacy Index (EI), a scale combining efficacy and adverse experiences, clearly demonstrated the superiority of mianserin over amitriptyline.

Amitriptyline↗
PubMed1988

Comparative effects of fluoxetine and amitriptyline on cardiac function.

1. The effects of fluoxetine and amitriptyline on the electrocardiogram (ECG) and systolic time intervals (STIs) were measured during a double-blind parallel-group study in depressed patients. 2. ECGs and STIs were measured after a 1 week placebo run-in, following 1 week's treatment with fluoxetine 40 mg daily or amitriptyline 100 mg daily, and then after 3 weeks' treatment with fluoxetine 60-80 mg daily or amitriptyline 150-200 mg daily. 3. Fluoxetine had no effect on the ECG or STIs at any dose. Amitriptyline 150-200 mg daily shortened the sinus cycle length by a mean of 12%, prolonged the PR interval by 8% and the QRS duration by 10%. Amitriptyline did not significantly alter the STIs.

Adult↗
PubMed1977

A comparison in rabbit isolated hearts of the dysrhythmogenic potential of amitriptyline, maprotiline and mianserin in relation to their ability to block noradrenaline uptake.

1. In isolated hearts of rabbits, perfusion with (-)-noradrenaline (0.0059 to 5.9 micronM) resulted in chronotropic and inotropic responses and a shortening of the interval between peak atrial and peak ventricular tensions (the A-V contraction interval). No dysrhythmias developed but at higher concentrations (590 micronM) 2 out of 7 hearts developed dysrhythmias (extrasystoles). 2. Perfusion with the antidepressants amitriptyline or maprotiline (4.8 micronM) or mianserin (28.8 micronM) reduced ventricular force, did not change heart rate and only amitriptyline reduced atrial force and lengthened the A-V contraction interval. At 4.8 micronM mianserin produced only a marginal shortening of the A-V contraction interval. 3. At these concentrations no dysrhythmias developed but at higher concentrations (amitriptyline 8 micronM, maprotiline 8 micronM, mianserin 60 micronM) all the agents produced dysrhythmias involving an interference with atrio-ventricular synchronization. 4. In the presence of mianserin (4.8 micronM) perfusion with noradrenaline (0.0059 to 5.9 micronM) shortened the A-V contraction interval and did not produce dysrhythmias. In the presence of amitriptyline or maprotiline (4.8 micronM) or mianserin (28.8 micronM) the A-V contraction interval generally lengthened and most hearts developed dysrhythmias (usually involving interference with atrio-ventricular synchronization). 5. [3H]-(-)-Noradrenaline uptake in perfused rabbit hearts and in mouse isolated atria or vasa deferentia was inhibited by the antidepressants to a similar extent, amitriptyline being marginally most potent (molar potency taken as 1.0), maprotiline being less potent (1.5) and mianserin least potent (2.0)). 6. It is concluded that of these three antidepressants, mianserin is least cardiotoxic in this preparation and that the ability of these antidepressants to predispose to noradrenaline-induced dysrhythmias is not related to blockade of noradrenaline uptake.

Amitriptyline↗
PubMed2001

The effect of amitriptyline on pain intensity and perception of stress in bruxers.

PURPOSE: The purpose of this clinical pilot study was to evaluate the effect of a tricyclic antidepressant, amitriptyline, on pain-intensity level and level of stress in bruxers. MATERIALS AND METHODS: In a randomized, double-blind, crossover experimental design, 10 subjects received active (amitriptyline 25 mg/night) and inactive (placebo 25 mg/night) medication, over a period of 4 weeks. RESULTS: The administration of amitriptyline for 4 weeks did not significantly (p >.05) reduce pain intensity. However, it significantly (p <.05) reduced the level of stress perception. CONCLUSION: The results of this limited study do not support the administration of small doses of amitriptyline over a period of 4 weeks for the management of pain resulting from sleep bruxism. However, the results support the administration of small doses of amitriptyline for the management of the perception of stress levels associated with sleep bruxism.

Amitriptyline↗
PubMed1981

Cardiovascular, sedative and anticholinergic effects of amitriptyline and zimelidine in young and elderly volunteers.

Single doses of amitriptyline (50 mg) and zimelidine (100 mg) were administered orally to 4 young and 4 elderly healthy volunteers (aged 21--26 and 68--75 respectively) in a comparative study of the two drugs. Systolic time intervals, supine and standing blood pressure, salivary flow and indices of sedation were measured at regular intervals up to 6 hours post dose. No conclusive changes in the QS2 interval, left ventricular ejection time (LVETc) LVET index, pre-ejection period (PEPc), resting heart rate, or blood pressures were observed with either drug. Salivary flow was reduced by about 40% at 3.5 hours and 50% at 5.5 hours after ingestion of amitriptyline. No change in salivary flow was observed after zimelidine (significant difference between treatments; P less than 0.01 at 3.5 and 5.5 hours). Subjective drowsiness as measured by visual analogue ratings was significantly greater for amitriptyline at 3.5 hours (P less than 0.01). Postural sway was also increased by amitriptyline but not zimelidine (difference between treatments significant at 3.5 and 5.5 hours; P less than 0.01 and 0.05 respectively). Auditory reaction time increased with amitriptyline, the difference between treatments achieving significance at 5.5 hours. No differences in response to either drug between young and elderly volunteers were demonstrable in these small groups, although variability was greater in the older group. Possible implications of these findings for the treatment of depression in the elderly are discussed.

Adult↗
PubMed1987

Alprazolam compared to amitriptyline in the treatment of major depression.

In a double-blind randomized study the therapeutic effect and safety of alprazolam was compared with amitriptyline in 81 outpatients suffering from major depression. Variable dosages of both drugs were used, the mean final dose of alprazolam being 3.05 and that of amitriptyline 130 mg. Both treatment groups improved steadily, assessed weekly with the use of the Hamilton Rating Scale for Depression, and no significant differences were found between the groups, either on comparison between single items or total scores. On several of the criteria used for assessment of treatment response, however, more patients responded to amitriptyline than to alprazolam. In an analysis of specific subgroups, patients whose depression was accompanied by retardation, those in whom there were no precipitating factors and those with low levels of anxiety, responded better to amitriptyline. Considerably fewer side effects were reported by patients receiving alprazolam. In particular, there was a significantly lower incidence of dry mouth, light-headedness, tremor and tachycardia in patients receiving alprazolam compared with amitriptyline.

Adolescent↗
PubMed1998

Differential effects of amitriptyline on perception of somatic and visceral stimulation in healthy humans.

Tricyclic antidepressants treat chronic pain both in patients with somatic illness and with functional bowel disorders. We compared the effects of amitriptyline on perception of cutaneous and gastrointestinal stimulation to assess differential analgesic effects of tricyclics on somatic and visceral pain. Cutaneous electrical stimulation and rectal and esophageal distension were performed before and after 21 days of double-blind 50 mg amitriptyline vs. placebo in healthy volunteers. Amitriptyline increased currents that elicited cutaneous threshold, moderate discomfort, and moderate pain compared with basal (P < 0.05), whereas placebo had no effect. Amitriptyline had no effect on perception of rectal and esophageal distension and did not alter luminal compliance; thus the lack of effect on perception is not due to altered visceral elastic wall properties. In conclusion, amitriptyline reduces perception of cutaneous stimulation but does not alter visceral perception or compliance. This investigation demonstrates differential effects of tricyclics on somatic and visceral afferent function in healthy humans and provides insight into mechanisms of action in chronic pain both from somatic disease and from functional bowel disorders.

Adult↗
PubMed1983

A double-blind controlled multicenter trial comparing butriptyline with amitriptyline.

77 primary depressive in-patients aged 18-70 years (mean = 46/47 years) were assigned randomly to experimental and control groups and treated in double-blind conditions in ten centers. Butriptyline and amitriptyline were both administered with an identical increasing schedule, up to 150 mg daily in the first week and a flexible schedule for the last 3 weeks of trial. Mean daily doses were 145 mg butriptyline and 142 mg amitriptyline after 2 weeks, and 77.5 mg amitriptyline and butriptyline after 4 weeks. Nitrazepam (5-10 mg) and haldol (5 mg) were also allowed, only if necessary. Symptomatology and antidepressant efficacy were assessed using the rating scales of Hamilton, Overall, BPRS, CGI and a side effect checklist. After initial comparison of the two treatment groups, the results showed that the antidepressant effects were significantly better with butriptyline on the number of dropouts, on the total score and on the following factors of the Overall Depression Scale: depression, guilt, anxiety, somatization and somatic complaints. Frequency of haldol prescription was significantly lower with butriptyline than with amitriptyline. The overall frequency of side effects and of autonomic symptoms did not differ in the two groups. The effects on other parameters (hematological and biochemical variables, ECG and EEG) were similar for both drugs. In conclusion, butriptyline has the same indications as amitriptyline but shows a better antidepressant efficacy at the same dosage.

Adolescent↗
PubMed1979

A double-blind trial with amitriptyline and lofepramine in the treatment of endogenous depression.

A double-blind trial was undertaken to compare the antidepressant efficacy and the side effects of Lofepramine with those of Amitriptyline in the treatment of endogenous depression. The study involves 22 acutely ill endogenously depressive patients. 11 patients were treated with Lofepramine and the remaining 11 with Amitriptyline. The results demonstrate that both substances are effective in the treatment of depression. However, the therapeutical efficacy of Lofepramine is significantly greater than that of Amitriptyline. Furthermore, the tolerance of Lofepramine is better than that of Amitriptyline, and the side effects of Amitriptyline, especially in blood pressure dysregulation, are greater than those of Lofepramine.

Adult↗
PubMed2000

Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia.

The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.

Adolescent↗
PubMed2006

Acute and subchronic effects of amitriptyline 25mg on actual driving in chronic neuropathic pain patients.

The acute and subchronic effects of low doses nocturnally administered amitriptyline were compared to placebo in a double-blind crossover randomized study on driving ability and driving-related skills involving seven chronic neuropathic pain patients. Performance testing occurred at the first and last day of each 15-day drug administration period, which was preceded by a 6-day washout phase. A standardized method of measuring driving ability, the on-the-road driving test, was performed on all visits. Patients were instructed to drive with a steady lateral position while maintaining a constant speed of 95 km/h. The primary outcome of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), which is an index of weaving of the car. At the first treatment day, driving performance was significantly impaired in patients after nocturnal administration of 25 mg amitriptyline compared to placebo. The increase in SDLP of 3 cm was higher than the increment generally observed with a blood alcohol concentration of 0.5 mg/ml or higher, the legal limit for driving in many countries. Also, reaction times on a memory test were significantly increased, indicating worse performance after acute treatment of amitriptyline compared to placebo. In contrast, after 2 weeks of treatment, no significant differences were found between amitriptyline and placebo, suggesting that tolerance had developed to the impairing effects of amitriptyline.

Adult↗
PubMed1988

A double blind comparison of alprazolam and amitriptyline hydrochloride in the treatment of nonpsychotic depression.

In a six week, double-blind, parallel study of alprazolam and amitriptyline hydrochloride in 130 outpatients suffering from moderate to severe nonpsychotic depression, alprazolam was as effective as amitriptyline hydrochloride in relieving depressive symptoms and significantly more effective in relieving symptoms of anxiety and somatization. Alprazolam showed an earlier onset of activity in most measurements of efficacy and produced fewer side effects than amitriptyline hydrochloride. Anticholinergic side effects were reported more frequently by patients taking amitriptyline hydrochloride, while drowsiness was reported more frequently by patients taking alprazolam. At the end of the study, the average daily doses were 2.4 mg alprazolam and 135 mg amitriptyline hydrochloride. The Hamilton Psychiatric Rating Scale for Depression, Hamilton Anxiety Rating Scale, Physician's Global Impressions, Patients' Global Impressions, Hopkins Self-Rating Symptom Scale, and Symptom and Side Effects Checklist were evaluated at the end of weeks 1, 2, 3 and 6 to determine and compare the efficacy and safety of the two study drugs.

Adult↗