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Buspirone vs amitriptyline in the treatment of chronic tension-type headache.

OBJECTIVES: The aim of this study was to explore the efficacy of buspirone (BSR), in comparison with amitriptyline (AML) in the prophylactic treatment of chronic tension-type headache (CTH), in an open and randomized clinical trial. MATERIAL AND METHODS: Twenty-six CTH patients (10 men and 16 women) were treated with BSR (30 mg daily) for 12 weeks. A parallel group of 32 CTH patients (12 men and 20 women) was treated with AML (50 mg daily). The major clinical parameters evaluated were the headache index (days with headache per month), the frequency of drug use for the acute management of headaches, the patients' opinion for the treatment and the Hamilton anxiety and depression rating scales. RESULTS: During the study 9 patients dropped out (4 from the BSR group and 5 from the AML group). Twelve (54.4%) patients from the BSR group responded to treatment (> 50% reduction in the headache index), compared to 17 (60.7%) from the AML group. In the BSR group, 14 (53.8%) patients reported various mild side effects (nausea most frequently), vs 21 (65.5%) of the AML group (mouth dryness more frequently). Patients treated with AML had better opinion and used less drugs for the acute treatment of headaches than the BSR treated patients. CONCLUSION: These results suggest that BSR may be effective in the prophylactic treatment of CTH, and that further investigation in a placebo controlled study is needed.

Adult↗

A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients.

The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle.

Adult↗

A double-blind comparison of nomifensine and amitriptyline in the treatment of depression.

A double-blind study was carried out to compare the efficacy and tolerability of nomifensine and amitriptyline in 17 Malaysian patients with moderate to severe depression. The two drugs did not differ with regard to antidepressant effect but nomifensine-treated subjects report fewer side-effects with no complaints of palpitations. Nomifensine also increases capacity for work and activity.

Adult↗

Clinical investigations into antidepressive mechanisms. II. Dexamethasone suppression test predicts response to nomifensine or amitriptyline.

This prospective study investigates the possibility of a central noradrenergic-cholinergic imbalance in subgroups of depressed inpatients using the dexamethasone suppression test (DST) as one peripheral indicator. The DST was performed in 43 depressed inpatients. Subsequently, a group (n = 20) of DST suppressors (DST-) and a group (n = 23) of DST nonsuppressors (DST+) were treated under double blind conditions with either nomifensine (NOM) a noradrenaline potentiating drug, or amitriptyline (AMI) a noradrenaline potentiating and strong anticholinergic compound. DST+ depressives responded favorably to AMI, but not to NOM. Conversely, DST- depressives responded favorably to NOM but less well to AMI. Together with other biochemical findings this data suggests: 1) a hypofunction of the noradrenergic system in DST- patients who may, from a clinical point of view, usually show minor or 'neurotic' depressions; 2) a hypofunction of the noradrenergic and a hyperfunction of the cholinergic system in DST+ patients who may present a more severe or 'endogenous' depression. These data suggest a biochemical heterogeneity of depression and offer an aid for a more specific antidepressive drug therapy.

Adult↗

Failure to correlate urinary MHPG with clinical response to amitriptyline.

On the basis of studies carried out in a group of 44 patients with endogenous depressive illness, the authors conclude that MHPG in urine is not a good predictor of response to amitriptyline treatment. There are no correlations between MHPG level and clinical improvement after 2 weeks' treatment and with final results of the therapy.

Amitriptyline↗

Sedative effects of maprotiline and amitriptyline.

By means of critical flicker fusion measurements and subjective estimation of drowsiness, experiments with 12 healthy subjects over periods of 8 h showed that maprotiline caused less than half the amount of sedation compared to amitriptyline, both drugs given in single doses of 50 mg. The experiments were blind, randomized and placebo controlled. Implications for clinical use are discussed.

Amitriptyline↗

Treatment resistance of depression after head injury: a preliminary study of amitriptyline response.

Thirteen patients with depression following minor head injury were matched with 13 functional depressives. Both groups were indistinguishable psychopathologically. Five of the functional group had a family history of affective disorder and none of the head-injury group had such a history. Both groups were treated with amitriptyline, beginning with 100 mg daily, increasing to a maximum of 250 mg/d. There were significant differences in response between the 2 groups, with only 4 of the head-injury patients improving. Our preliminary results suggest that this condition is relatively resistant to tricyclic therapy.

Adult↗

Psychomotor performance of patients with rheumatoid arthritis: cross-over comparison of dextropropoxyphene, dextropropoxyphene plus amitriptyline, indomethacin, and placebo.

Actions on performance of dextropropoxyphene (DXP) alone and in combination with amitriptyline (AMI), indomethacin (IN), and placebo were compared in 15 patients with rheumatoid arthritis. The patients were on their prescribed maintenance regimen excluding analgesics. In four randomized test sessions at two-week intervals, they received double blind and crossover single oral doses of DXP 130 mg, IN 50 mg, DXP 65 mg + AMI 25 mg or placebo, each after two days' pretreatment with the same drug. Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration. DXP impaired critical flicker discrimination, symbol copying and body balance without modifying tracking, choice reactions or attention. It rendered the subjects elated, muzzy, mentally slow and calm. Actions of AMI + DXP were about the same. IN impaired body balance and critical flicker recognition. Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low. We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills. Small doses of AMI may not enhance the mild psychomotor effects of DXP. Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance.

Adult↗

Glucuronidation of amitriptyline in man in vivo.

The urinary excretion of amitriptyline (AT) as N-glucuronide was studied in healthy volunteers after single oral doses of AT and in patients on continuous treatment with AT. In the volunteers, 8 +/- 3% of a 25 mg dose of AT was recovered in urine as glucuronide during 108 hr. No difference between slow and rapid debrisoquine hydroxylators with respect to the excretion of AT glucuronide was seen. 0.08 to 1.68% of the given AT dose was recovered in urine in unchanged form. The excretion of unchanged AT correlated with the debrisoquine metabolic ratio (rs = 0.61; p less than 0.01). In 5 patients on continuous treatment with AT (125-150 mg/day), 8 +/- 5% of the daily dose was recovered in 24-hr urine as AT glucuronide. The present study shows that direct glucuronidation is a minor metabolic pathway of AT in man in vivo both after single low doses and during continuous treatment with therapeutic doses.

Administration, Oral↗

Actions and interactions of psychotropic drugs on human performance and mood: single doses of ORG 3770, amitriptyline, and diazepam.

Actions and interactions of two antidepressants and diazepam on human skilled performance and mood were studied in a randomized double-blind cross-over trial with single oral doses of 50 mg amitriptyline (AMI), 15 mg Org 3770 (ORG) and placebo, given alone and in combination with 15 mg diazepam (DZ) to 12 young healthy subjects at one-week intervals. Objective tests (digit substitution, tapping, flicker fusion, Maddox wing, tracking, choice reactions, body sway, memory) and subjective assessments (visual analogue scale) were performed at baseline and 1.5, 3, 4.5 and 6 hours after drug administration. Side-effects were reported, blood pressure and heart rate measured and blood samples taken after each testing run. Placebo was nearly inert on performance and mood. DZ impaired some objective skills and showed sedative effects in the subjective tests. AMI produced sedation and impaired coordination as well as cognitive performance (digit substitution), most clearly at 3 to 4.5 hr. ORG resembled AMI in impairing objective and subjective performance, however, not necessarily in the same tests. Their combined effects with DZ were additive in objective tests but less additive in subjective tests. The drug combinations, but not any single drug, impaired learning acquisition. Plasma concentrations of the drugs given alone were about as expected, without important interactions. We conclude that the combinations of benzodiazepines with the antidepressants used impair skilled performance but may not cause major hazards.

Adult↗

Acute myocardial infarction associated with amitriptyline overdose.

Tricyclic antidepressant overdose is known to cause cardiopulmonary and central nervous system complications. As with other cardiovascular complications, amitriptyline toxicity may cause acute myocardial infarction. This paper reports the case of a young female with acute myocardial infarction as a novel consequence of tricyclic antidepressant overdose.

Adult↗

Amitriptyline and femoxetine, but not clomipramine or citalopram, antagonize hyperthermia induced by directly acting 5-hydroxytryptamine-like drugs in heat adapted rats.

5-HT uptake inhibitors and pirenperone (a 5-HT2 receptor antagonist), which in previous experiments antagonized fenfluramine (5-HT releaser)-induced hyperthermia in heat adapted rats, were tested against hyperthermia induced by the directly acting 5-HT agonist--m-CPP and quipazine. Pirenperone and --to a lesser degree--amitriptyline and femoxetine antagonized the hyperthermia. Citalopram and clomipramine were inactive. It is concluded that hyperthermia induced by 5-HT-like drugs in rats is due to the stimulation of the 5-HT2 receptor and that the antagonistic effect of citalopram and clomipramine against fenfluramine-induced hyperthermia might be connected with their effect on the uptake of 5-HT.

Adaptation, Physiological↗

Repeated treatment with imipramine or amitriptyline increases the locomotor response of rats to (+)-amphetamine given into the nucleus accumbens.

Effects of bilateral injections of (+)-amphetamine (5 micrograms/0.5 microliter) into the nucleus accumbens were investigated in rats treated repeatedly with imipramine or amitriptyline. Repeated but not acute administration of either drug enhanced the locomotor hyperactivity induced by (+)-amphetamine given 2 or 72 h after the last dose of antidepressant. The results indicate that the increased responsiveness of the mesolimbic dopaminergic system may be involved in the action of antidepressant drugs.

Amitriptyline↗

Lethal cardiomyopathy in epidermolysis bullosa associated with amitriptyline.

There are previous reports of dilated cardiomyopathy (DCM) in recessive dystrophic epidermolysis bullosa (RDEB), a debilitating blistering skin disorder. The pathogenesis of DCM in RDEB remains uncertain, although dietary deficiency of selenium and carnitine have been implicated. A 6 year old girl with RDEB who died of DCM is reported; attention is drawn to the possible role of two potentially cardiotoxic drugs, amitriptyline and cisapride.

Amitriptyline↗

Amitriptyline and imipramine poisoning in children.

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.

Amitriptyline↗

Electrocardiographic changes in amitriptyline poisoning.

In imipramine and amitriptyline poisoning the electrocardiographic abnormalities comprise arrhythmias, widening of the QRS complex, and marked changes in die S-T segment. These features were found to be of value in the differential diagnosis of unknown poisoning. The unusual configuration of qR with raised S-T segment in V1, simulating myocardial infarction, was seen in one of our patients and has been noted in four cases reported by other workers.

Adolescent↗

Myocardial infarction: a complication of amitriptyline overdose.

A 22 year old woman was admitted with amitriptyline overdose. Twenty six hours later she developed acute myocardial infarction. Cardiotoxic effects of tricyclic antidepressants are discussed and the importance of considering myocardial infarction as a complication of tricyclic antidepressant overdose is emphasized.

Adult↗