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PubMed1998

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

Adrenergic Uptake Inhibitors↗
PubMed2006

Influence of hypothyroidism induced by thiamazole on the toxicity of amitriptyline in chick embryos.

The effect of hypothyroidism induced by thiamazole on the toxicity of amitriptyline was studied in chick embryos. Fertilized eggs of White Leghorns were incubated and investigated. 1.2 mg/0.2 ml/egg of thiamazole was injected into the albumen of fertilized eggs on the 9th day of incubation. The control group was given 0.2 ml/egg of physiological saline in the same manner. Amitriptyline at 1 mg/egg was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the injection. After the injection of amitriptyline into the thiamazole-treated eggs, the heart rate was significantly decreased compared with the untreated eggs. These findings indicate that hypothyroidism induced by thiamazole has a marked influence on the toxicity of amitriptyline in chick embryos.

Amitriptyline↗
PubMed1991

A case of a chemically dependent patient with a thalamic pain syndrome treated with amitriptyline.

A fifty year old white male with a right sided thalamic pain syndrome became alcohol and benzodiazepine dependent in an attempt to alleviate the pain. He entered an inpatient alcohol and drug treatment facility where, in an attempt to treat this pain, he was placed on low dose amitriptyline. Comparison of results on a symptoms checklist (SCL-90-R) completed at amitriptyline dosages of 30 mg. and 50 mg. showed a statistically significant difference in the somatization scale (p = .029). The low dose of amitriptyline used, its low blood level, and the early onset of effect make it unlikely that its antidepressant action was a significant factor in this patient's pain relief. This is, perhaps, the first described case where low dose amitriptyline has been shown to relieve the thalamic pain syndrome in a chemically dependent person.

Alcoholism↗
PubMed1999

Use of transdermal amitriptyline gel in a patient with chronic pain and depression.

A man with severe inflammatory bowel disease suffered from chronic abdominal pain and depression. A transdermal amitriptyline gel preparation was compounded since he was unable to take drugs orally Serum concentrations of amitriptyline and its active metabolite nortriptyline were measured over 24 hours. Symptoms of depression were monitored before starting transdermal therapy and at the end of 6 weeks. Pain symptoms and amitriptyline adverse drug events were monitored daily Steady-state serum concentrations of drug and metabolite were within the therapeutic range over 24 hours. The patient reported that his mood was improved but his abdominal pain remained unchanged. Transdermal amitriptyline gel was well tolerated and is an alternative delivery system in patients unable to take drugs orally.

Administration, Cutaneous↗
PubMed1993

Acute amitriptyline withdrawal and hyponatraemia. A case report.

The tricyclic antidepressants (TCAs) are commonly used in the treatment of depression and, perhaps due to the nature of the condition being treated, figure prominently in cases of deliberate overdosage, where the toxicity of amitriptyline has been well established. However, the abrupt cessation of TCA administration can also be detrimental to the patient, triggering withdrawal phenomena often characterised by an exacerbation of the symptoms for which the patient was originally treated. We present a biochemically proven case of amitriptyline withdrawal where the clinical features at presentation made it difficult to distinguish from acute toxicity. The patient's neurological signs and distended bladder suggested amitriptyline toxicity, whereas the history and signs of cholinergic hyperactivity were consistent with acute withdrawal. The diagnosis was confirmed at a later date when further history and a biochemical analysis of plasma TCA concentrations became available. Hyponatraemia may have exacerbated the condition of the patient, whether or not it was caused by amitriptyline.

Acute Disease↗
PubMed1990

A double blind trial of moclobemide versus amitriptyline in the treatment of depressive disorders.

The antidepressant efficacy and side-effect profile of amitriptyline were compared to those of moclobemide, a reversible monoamine oxidase inhibitor with selectivity for the type A isozyme. Forty nine patients with DSM-III major depression were randomly assigned to receive either amitriptyline or moclobemide. Thirty seven patients (amitriptyline n = 16, moclobemide n = 21) completed the six week protocol, which was conducted under double blind conditions. The results indicated a comparable antidepressant time course and efficacy for the two treatments. Amitriptyline produced significantly more sedation and antimuscarinic side-effects. Moclobemide appears to be a well tolerated antidepressant without the liability to produce significant postural hypotension and without the need for a tyramine-poor diet.

Adult↗
PubMed1993

A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness.

The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.

Adult↗
PubMed1979

Clomipramine and amitriptyline in the treatment of severe pain.

Clomipramine is the most potent 5-HT reuptake blockade agent among the antidepressants. A comparison between the effect of clomipramine and a less powerful 5-HT reuptake blockade agent (amitriptyline) could test the hypothesis that brain 5-HT is a mediator of pain sensation. Groups of patients of either sex, with pain indication of trigeminal neuralgia, tension headache or postherpatic neuralgia, received doses of clomipramine or amitriptyline in a single blind clinical experiment. The results after three months of treatment showed that clomipramine: (1) was better than amitriptyline in treating trigeminal neuralgia; (2) tended to be better in the treatment of tension headache; and (3) amitriptyline is better in treating postherpatic neuralgia. Clomipramine was better tolerated. The results support the hypothesis that in certain pain situations, clomipramine exerts a beneficial effect, not only because of its effect on the depression and anxiety level of the patient, but also via its effects on the 5-HT brain system.

Adult↗
PubMed1993

Effects of epinephrine and norepinephrine on hemodynamic parameters and arrhythmias during a continuous infusion of amitriptyline in rats.

Epinephrine and norepinephrine were evaluated in treatment of hemodynamic compromise in amitriptyline intoxication. One hundred and one male Wistar rats were monitored hemodynamically during amitriptyline intoxication and given one of three infusion rates (0.1, 0.5 or 5.0 mg/kg/min) of either epinephrine or norepinephrine. Sixteen rats served as controls and received only glucose after intoxication. Amitriptyline intoxication lowered mean arterial pressure, heart rate, left ventricular max dP/dt, and increased left ventricular end-diastolic pressure. All doses of norepinephrine and the two higher doses of epinephrine increased mean arterial blood pressure and left ventricular max dP/dt. Heart rate increased with both drugs, more with epinephrine, but not beyond pre-intoxicated levels at any dose. Left ventricular end-diastolic pressure was unaltered by both drugs. Malignant arrhythmias appeared in 7% of all animals, whereas a progressive decline of cardiac contractility caused cardiac arrest in 36% of all animals. This suggests that myocardial depression is the aspect most likely to cause death. At intermediate doses epinephrine resulted in significantly fewer arrhythmias and lower mortality compared to norepinephrine. We conclude that epinephrine and norepinephrine each appeared effective in reversing amitriptyline-induced hemodynamic alterations. Epinephrine had fewer arrhythmogenic properties than norepinephrine and may be preferable to norepinephrine.

Amitriptyline↗
PubMed2001

Acute eosinophilic pneumonia associated with amitriptyline in a hemodialysis patient.

Drugs are well known causes of eosinophilic lung disease. In many patients, drug-induced eosinophilic lung disease presents with transient eosinophilic infiltrates that disappear after discontinuation of the drug. Some patients, however, experience a fulminant, acute eosinophilia-like disease. Recently, we experienced a case of amitriptyline-associated acute eosinophilic pneumonia with respiratory failure in a diabetic hemodialysis patient. Eight days after treatment with amitriptyline, sudden fever, chill, dry cough and dyspnea developed. Subsequently, multiple patch consolidations appeared on the chest radiographs. Bronchoalveolar lavage (BAL), established a diagnosis of acute eosinophilic pneumonia. After immediate discontinuation of amitriptyline, a rapid clinical and radiological improvement was observed. The present case indicates that the possibility of acute eosinophilic pneumonia should be fully considered in dialysis patients developing unexplained respiratory symptoms while on amitriptyline therapy.

Acute Disease↗
PubMedDate not supplied

Efficacy of amitriptyline as a pharmacological adjunct to behavioral modification in the management of aggressive behaviors in dogs.

The efficacy of amitriptyline as a pharmacological adjunct to behavioral modification in the clinical management of aggressive behaviors in dogs was evaluated in two phases. Twelve dogs presenting for aggressive behaviors were treated sequentially with amitriptyline (2 mg/kg body weight, per os [PO] bid) and a placebo for 4 weeks in a prospective, randomized, double-blind, placebo-controlled trial. Standardized protocols for behavior modification were implemented throughout the trial. Owners maintained behavioral records and reported on the number of aggressive incidents as well as the dog's overall improvement at the end of each 4-week period. In the second phase, 27 cases of dogs presenting for aggressive behaviors and treated with amitriptyline were reviewed, and clients were contacted to record each dog's response to treatment. Reports were compared to those for dogs receiving behavior modification alone (i.e., placebo phase of prospective study). No significant difference was observed in the patients' responses to adjunctive amitriptyline versus behavior modification alone.

Aggression↗
PubMed1976

[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine].

The literature was surveyed concerning the frequency and conditions for confusional states and deliria following Amitriptyline and Clozapine treatment, and certain discrepancies were noted. As a result a retrospective comparative investigation was carried out as to the frequency and the conditions for such events in a group of patients treated along the same lines. While our experience with Amitriptyline is not different from that reported by others, this does not seem to be the case with Clozapine. Confusional states and deliria are four times as frequent as the average reported in the literature; it is clear that they depend on conditions different from those of confusional states and deliria due to Amitriptyline; there is a slightly significant (p less than 0.05) correlation between the appearance of confusion and a temperature of over 37.5 degrees C. The anticholinergic properties of Amitriptyline and of Clozapine cannot explain the difference in frequency, nor the differing conditions for the appearance, of pharmacogenic confusional states and deliria with those two substances.

Adult↗
PubMed2000

Microsomal binding of amitriptyline: effect on estimation of enzyme kinetic parameters in vitro.

The effect of binding of amitriptyline to human liver microsomes and to microsomes from human B-lymphoblastoid cells on the estimation of enzyme kinetic parameters describing N-demethylation to nortriptyline was investigated using a combination of microsomal binding and in vitro enzyme kinetic studies. Quantitative binding in both matrices increased with higher microsomal protein concentrations (free fractions 0.88-0.32 at 100-500 microg protein/ml in human liver microsomes and 0.82-0.26 at 250-1000 microg protein/ml in microsomes from B-lymphoblastoid cells) and was independent of amitriptyline concentration over a concentration range of 0.2 to 200 microM. Addition of heat-inactivated microsomal protein (50-450 microg/ml) to native human liver microsomes (50 microg/ml) reduced the amitriptyline N-demethylation rate in a protein concentration dependent manner. This effect was greater at lower substrate concentrations and was overcome by saturating concentrations of substrate, thereby decreasing the apparent affinities of the high- and low-affinity components of the N-demethylation process, with minimal effect on the net V(max). Addition of metabolically inactive microsomes from untransfected human lymphoblastoid cells (750 microg/ml) to CYP2C19 (250 microg/ml protein) increased the apparent K(m) value for amitriptyline N-demethylation by 3.5-fold and increased the uncompetitive substrate inhibition constant (K(s)) by 2.2-fold, making substrate inhibition essentially undetectable. A similar effect was seen with CYP3A4, with a 1.8-fold increase in the S(50) (substrate concentration at which half-maximal velocity of a Hill enzyme is achieved). Microsomal binding did not alter the V(max) of either CYP isoform to any appreciable extent. These findings emphasize the importance of incorporating microsomal binding in the estimation of enzyme kinetic parameters in vitro and making appropriate corrections for unbound drug concentrations.

Algorithms↗
PubMed2000

[A comparative efficiency of amitriptyline, fluoxetine and maprotiline in prevention of migraine in attack-free period].

To reduce frequency and severity of the attacks, migraine was treated preventively between the attacks. The most effective drugs were beta-blockers and antidepressants. In a single-blind study we estimated comparative efficiency of amitriptiline (inhibitor of noradrenaline and serotonin reuptake and 5-HT2-receptor antagonist) 12.5-25 mg/daily, fluoxetine (a selective serotonin reuptake inhibitor) 10-20 mg/daily, and maprotiline (a selective noradrenaline reuptake inhibitor) 10-25 mg/daily. The duration of the therapy of migraine between the attacks was 12 weeks. Each group included 20 patients. 46 patients completed the whole course of therapy: 14 patients received amitriptyline, 16 patients--fluoxetine, and 16 patients--maprotiline. Positive results of the treatment (a reduction of the frequency of the migraine attacks during a treatment by 50% as compared with the baseline period) were observed in 71% of the patients treated with amitriptyline, in 56% of the patients treated with fluoxetine, and in 38% of the patients treated with maprotiline. All the drugs were able to reduce both intensity and duration of a headache. Index of the Quality of Life in the patients with migraine was increased in the groups treated with either amitriptyline or fluoxetine, but not in a group treated with maprotiline. The results obtained agree with the notion about high efficiency of antidepressants given between migraine attacks. Amitriptyline and fluoxetine were more efficient in preventive therapy than maprotiline. These findings suggested indirectly, that the efficiency of antidepressants in treatment of migraine is explained by inhibition of serotonin reuptake and by 5-HT2-receptor antagonism, while influence on the inhibition of noradrenaline reuptake was not so significant.

Acute Disease↗
PubMedDate not supplied

[A comparison between low doses of amitriptyline and low doses of fluoxetin used in the control of depression in patients suffering from Parkinson's disease].

INTRODUCTION: On average 40% of all patients suffering from Parkinson s disease (PD) undergo bouts of depression. It is thought that this is due to a dysfunction in the orbitofrontal and dorsolateral circuits, together with hypometabolism in the orbital, caudate nucleus and frontal dorsolateral tract regions. AIMS: The aim of this study is to compare the effectiveness of low doses of fluoxetin with that of low doses of amitriptyline in controlling depression in patients with PD. PATIENTS AND METHODS: The study examined a total of 77 patients (34 females and 43 males), with an average age of 68.2 years, who had been suffering from PD (according to the diagnostic criteria of Calne et al, in stage II of Hoehn and Yahr) for an average of 6.9 years. They were divided randomly into two groups which received fluoxetin (37 patients, dosage: 20 40 mg/day) or amitriptyline (40 patients, dosage: between 25 and 75 mg/day). A basal evaluation and four others (at 3, 6, 9 and 12 months of treatment) were performed, including the STMS (Short test of mental status), the Hamilton scale, and extent of functional disability using the UPDRS. A statistical analysis was performed by comparing the variance of the above mentioned parameters and the c2 test with Yates correction or the Fisher exact two tailed test, to evaluate the reasons for dropping out. In both cases a value of p< 0.05 was accepted as significant. RESULTS: 58 patients finished the study. Drop out because of side effects only took place in the group that received amitriptyline (p< 0.02), which was better than fluoxetin at controlling the depression (p< 0.009, 0.001, 0.002 and 0.00006) at 3, 6, 9 and 12 months, respectively. CONCLUSIONS: At an average dosage of 35.2 mg/day, amitriptyline is effective in controlling the depression presented by patients with PD. However, despite the low dosage, the side effects it caused forced 15% of the patients abandon the treatment.

Aged↗
PubMed1976

Gas-chromatographic analysis for therapeutic concentrations of amitriptyline and nortriptyline in plasma, with use of a nitrogen detector.

We describe a gas-chromatographic procedure for the simultaneous determination of amitriptyline and its active metabolite, nortriptyline, in therapeutic concentrations in human plasma, with use of a nitrogen detector. Both drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, back-extracted into dilute HCl, and re-extracted into hexane/isoamyl alcohol after alkalinization of the HCl. The solvent is evaporated and the residue gas-chromatographed. Protriptyline is used as the internal standard. As little as 5 mug of amitriptyline or nortriptyline can be detected per liter of plasma. The coefficients of variation, for a concentration of 200 mug/liter, are 4.6% and 4.3% within-day and 8.6% and 3.4% day-to-day for amitriptyline and nortriptyline, respectively. The procedure was applied to patients receiving therapeutic doses of both drugs and also to patients who had taken overdoses of amitriptyline.

Amitriptyline↗
PubMedDate not supplied

[Treatment of chronic tension type headache with mirtazapine and amitriptyline].

INTRODUCTION: The mechanisms at play in the production of tension type headaches (TTH) are partially unknown. Some of the aspects that have been discussed in connection with this issue include genetic, vascular and biochemical factors and even a predisposition of certain personalities to suffer from this kind of pain. Yet, the relation between neurotransmitters like noradrenalin (NAd) and serotonin (5 HT) and chronic TTH (CTTH) seems to be quite clear and hence the use of antidepressants that act on these substances in the pharmacological treatment of CTTH. In this study, the qualitative and quantitative efficiency of amitriptyline is compared with that of mirtazapine (two antidepressants that act on NAd and 5 HT) in the prophylaxis of CTTH. PATIENTS AND METHODS: A sample of 60 patients with CTTH criteria was divided into two groups, and subjects were administered one of the drugs at 50% random for six months. Group I was administered 25 mg of amitriptyline and group II received 30 mg of mirtazapine, both given in a single night time oral dose. Later, the two groups were compared before and after treatment, taking into account the following aspects: objective and subjective improvements, depression criteria according to the Hamilton 17 coefficient, reduction in the amount of pain killers taken, and the side effects produced by the two drugs. RESULTS: Both groups of patients presented depression criteria, which improved after taking the drugs, without any objective differences between the two forms of therapy, although the subjective feeling of improvement was greater with mirtazapine. In both groups there was a significant reduction in the usual consumption of analgesics after the prophylaxis. Side effects with both antidepressants were relatively frequent, but well tolerated, and the most common were a dry mouth and drowsiness. There were significantly fewer in the group of patients treated with mirtazapine than in those who received amitriptyline. CONCLUSIONS: First, depression and CTTH clearly coexist and that there is a certain dysphoric component associated to suffering chronic headache. Second, mirtazapine has proved to be as efficient in the treatment of CTTH as amitriptyline, but has significantly fewer side effects, probably because it acts more selectively on the brain receptors. It could, therefore, be a drug worth considering for use in the prophylaxis of chronic TTH.

Adult↗
PubMed1977

Controlled comparison of bromazepam, amitriptyline, and placebo in anxiety-depressive neurosis.

Seventy-two private practice patients with moderate or severe anxiety-depressive neurosis received mean daily oral doses of 23.8 mg bromazepam, 94 mg amitriptyline, or 4.6 capsules of placebo in a double-blind four-week study. The patient's condition was assessed initially and at weekly intervals by using the Brief Psychiatric Rating Scale and the Hamilton Psychiatric Rating Scale for Depression. From the first through the fourth week evaluations, a larger proportion of patients improved on bromazepam than on amitriptyline. Bromazepam was also superior to amitriptyline and placebo in the degree of improvement made Statistical significance (p less than 0.05) of the changes noted after one week was even greater after four weeks, particularly in BPRS items of somatic concern, depressive mood, anxiety and tension and in nearly all representative psychic and somatic symptoms on the depression scale, confirmed by global evaluation. Compared to bromazepam patients, amitriptyline patients had significantly severer adverse reactions which were the major cause of the group's higher dropout rate (66% vs 33%). The prompt clinical response to bromazepam contributed to its superior safety and patient progress in that it was possible to carefully titrate dosage and thus help to control adverse reactions and allow patients to maintain alertness and productivity under therapy.

Adjustment Disorders↗