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PubMed1996

Double-blind comparative study of the antidepressant, unwanted and cardiac effects of minaprine and amitriptyline.

1. A double-blind, multicentre study comparing the efficacy and safety of minaprine and amitriptyline in patients with major depression was carried out. Five hundred and thirty-one patients were randomly assigned to treatment with either minaprine 100 mg, 200 mg or 300 mg day-1 or with amitriptyline 150 mg day-1 (75 mg during the first week). The medication was administered for 6 weeks. 2. Efficacy was assessed using the Hamilton rating scale for depression (HDRS), the Montgomery-Asberg depression rating scale (MADRS) and visual analogue assessments of depression carried out by both the investigators and patients. Unwanted effects were assessed by a questionnaire and spontaneous reporting. In a subgroup of patients cardiovascular effects were investigated by high speed ECG and systolic time intervals. 3. Patients in each treatment group showed a significant clinical improvement (P < 0.01) from baseline. The mean HDRS and MADRS scores adjusted for baseline differences, showed significantly less improvement in the minaprine 100 mg once daily (P < 0.01) and the minaprine 300 mg daily (P < 0.01) groups than in the amitriptyline group at both week 4 and week 6. The MADRS score at week 4 suggested that 200 mg day-1 minaprine was less effective than amitriptyline (P < 0.05), but there was no difference between the two groups at week 6 on either the HDRS or the MADRS. 4. Both drugs were well tolerated and there were no significant differences between treatment groups in any of the safety and tolerance assessments. In the ECG, amitriptyline produced a significant increase in the heart rate and PR interval while minaprine had no effect on electrocardiographic measurements. Neither drug produced changes in the systolic time intervals.

Adolescent↗
PubMed1999

A double-blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice.

OBJECTIVE: This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice. METHODS: In this double-blind, multicentre study conducted in the general practice, patients with depression (Montgomery Asberg Depression Rating Scale [MADRS] score > or = 20) who were regarded as requiring antidepressant therapy were randomly assigned to receive paroxetine (20 mg, n = 184) or amitriptyline (50-100 mg, n = 191) once daily for 9 weeks. RESULTS: More patients completed treatment with paroxetine than with amitriptyline (71.1% vs 56.1%, p = 0.009). Depression rating scores (MADRS and Clinical Global Impression [CGI]) were improved with both agents, but at week 9, paroxetine achieved more favourable scores compared with amitriptyline on MADRS (p=0.019), CGI severity of depression (p=0.044), and CGI efficacy index (p = 0.038). CONCLUSIONS: Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline.

Adult↗
PubMed1998

Amitriptyline is effective in chronic but not in episodic tension-type headache: pathogenetic implications.

The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.

Adrenergic Uptake Inhibitors↗
PubMedDate not supplied

Effectiveness of amitriptyline in the prophylactic management of childhood headaches.

OBJECTIVE: To study the effectiveness of a standardized dose of amitriptyline, 1 mg/kg, for childhood headaches. BACKGROUND: Amitriptyline has been shown to be effective for the prophylaxis of migraine in adults. Studies in children, however, have been quite limited. In adults, the suggested effective dose range is 10 to 150 mg. In children, a standardized dosage is often not used, resulting in a dosage range in clinical practice that often varies from a very low dose to a dose equivalent to that used in adults. METHODS: Children with more than three headaches per month were treated with amitriptyline, slowly increasing the dose to 1 mg/kg per day. The frequency, severity, and duration of their headaches were initially evaluated and subsequently measured at each follow-up evaluation. Two hundred seventy-nine children had headaches occurring frequently enough to indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with amitriptyline. The average age at presentation was 12.0 (+/- 3.0) years. The ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1 (+/- 10.1) days per month. The average severity was 6.84 (+/- 1.67) on a 10-point pain scale. The average duration was 11.5 (+/- 15.0) hours. The most frequent diagnoses using International Headache Society criteria were migraine (60.6%), migraine with aura (7.9%), and tension-type headache (10.4%). Of these children, 146 have been seen for at least one follow-up examination, occurring on average 67.3 (+/- 32.3) days after beginning prophylactic treatment. RESULTS: A total of 84.2% of the children reported an overall perception of being better, while 11.6% reported being the same. The frequency of headaches improved to 9.2 (+/- 10.0) days per month. The average severity was reduced to 5.1 (+/- 2.1), and the average duration was reduced to 6.3 (+/- 11.1) hours. If daily or continuous headaches were excluded, the improvements were more marked. Minimal side effects were reported from these children and their families. Long-term evaluation (156 to 415 days) showed continued sustained improvement. CONCLUSIONS: Amitriptyline is an effective prophylactic medication for children with frequent headaches. A standardized dosing regimen results in a significant number of children responding with minimal side effects. The children are able to tolerate this dosing scheme and demonstrate good adherence to a dosing schedule of once a day.

Amitriptyline↗
PubMed2001

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study.

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.

Adult↗
PubMed1994

Blood levels of mianserin and amitriptyline and clinical response in aged depressed patients.

Steady-state plasma levels of mianserin, amitriptyline, and nortriptyline were determined by HPLC in two groups of elderly depressed patients who underwent a 5-week treatment with mianserin (60 mg/day in three oral doses) or amitriptyline (75 mg/day in three oral doses). Both treatments proved to be effective in reducing depressive symptoms. In the mianserin group, responder patients had steady-state plasma concentrations of mianserin higher than nonresponders. No relationship was found between amitriptyline, nortriptyline, or amitriptyline+nortriptyline plasma levels and clinical response in amitriptyline treated patients.

Aged↗
PubMed1985

Cardiovascular effects of single doses of the antidepressants amitriptyline and lofepramine in healthy subjects.

In a placebo-controlled double blind study, single oral doses of lofepramine (140 mg and 210 mg) and amitriptyline (100 mg and 150 mg) were given to 5 healthy volunteers. Heart rate, blood pressure, systolic time intervals, and electrical impedance cardiogram were recorded in supine and upright position for 8 hours after drug administration. In addition, plasma drug concentrations were measured simultaneously. Amitriptyline caused a more pronounced increase in heart rate, especially under orthostatic stress, than did lofepramine. Both drugs reduced total peripheral resistance; amitriptyline's effect was greater. A rise in blood pressure (supine position) and shortening of the electromechanical systole under lofepramine indicated an improvement of cardiac performance. In contrast amitriptyline, particularly, in the upright position, lowered blood pressure and lengthened electromechanical systole. Since both drugs have a comparable antidepressant activity, lofepramine is suggested to induce fewer untoward cardiovascular reactions than amitriptyline.

Adult↗
PubMed1985

Treatment of pathologic laughing and weeping with amitriptyline.

Patients with bilateral forebrain disease may commonly manifest the syndrome of pathologic laughing and weeping. We investigated the efficacy of low-dose amitriptyline in 12 patients in whom this syndrome was a consequence of multiple sclerosis. In a double-blind crossover study comparing amitriptyline with placebo, eight patients experienced dramatic and significant improvement with amitriptyline (P = 0.02). The mean dose of amitriptyline was 57.8 mg per day and did not exceed 75 mg per day in any patient. Concurrent measurements of depression showed no change during the study. We conclude that amitriptyline is effective in the treatment of this disturbance of affective expression, and that this effect is distinct from the antidepressant effect of the medication.

Adult↗
PubMed1976

Cardiac effects of amitriptyline in rats.

The effect of intravenous amitriptyline (0.5-2 mg/kg) on heart rate, blood pressure, ECG, and electrolytes in plasma and heart muscle was studied in rats. In addition, the effect on monophasic action potentials was studied in rats with open chest. Amitriptyline caused a significant decrease in blood pressure and heart rate and a significant prolongation of QRS and PQ duration. At the time of maximal QRS prolongation (mean +94%) the duration of monophasic action potentials was virtually unchanged. Beta-adrenergic blockade by means of pretreatment with 0.1 mg propranolol did not influence the amitriptyline-induced prolongation of QRS duration. Amitriptyline administration causing obvious QRS prolongation induced no detectable changes in plasma and heart muscle electrolytes. The results contradict adrenergic dominance or marked imbalance between intra- and extra-cellular electrolytes as a cause of the ECG changes. The present data indicate that the amitriptyline effect is compatible with a direct quinidine-like action on the heart, resulting mainly in a slowing of impulse propagation in the intracardiac conduction system.

Action Potentials↗
PubMedDate not supplied

Application of expert systems analysis to interpretation of fatal cases involving amitriptyline.

Part I. Expert 4: The object of this study was to investigate the applicability of commercially available expert system shells to interpretation in forensic toxicology. Amitriptyline toxicology was selected as a pilot trial. Blood and tissue concentrations of amitriptyline and nortriptyline in fatal and nonfatal amitriptyline cases from the literature and from the Registry of Human Toxicology databank were entered into the expert system shell Expert 4 (Rivers, Elsevier). The statistical evaluation routines of the shell were used to search for patterns in the data. Successive changes in the data base were made to test for the influence of the data base on the conclusions. Finally the data base was refined, based on the evaluations, to strengthen the probabilities of the conclusions. The refined database was coupled with the Expert 4 inference engine to infer unknown parameters in the cases. The results of the expert system analysis were compared to known values and published expert opinions. The ratio of amitriptyline/nortriptyline and tissue levels of nortriptyline were found to be the most significant measures for interpretation of effect and time since ingestion. Part II. Computer Induction of Rules: Blood and tissue concentrations of amitriptyline and nortriptyline in fatal and nonfatal amitriptyline cases from the literature and from the Registry of Human Toxicology databank were entered into the expert system shell BEAGLE, (Forsyth, Machine Learning Research, Ltd.). The automatic rule induction routines of the shell were used to search for patterns in the data. The program expressed these patterns as numerical predictions or Boolean logic rules. The results were compared to those obtained with the Expert 4 (Rivers, Elsevier) using the same case knowledge base.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗
PubMed2005

Postamputation pain and sensory changes in treatment-naive patients: characteristics and responses to treatment with tramadol, amitriptyline, and placebo.

BACKGROUND: Pain after amputation is common but difficult to treat, and few controlled treatment studies exist. METHODS: In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment. RESULTS: After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol. CONCLUSIONS: In treatment-naive patients, both amitriptyline and tramadol provided excellent and stable phantom limb and stump pain control with no major adverse events. Both drugs demonstrated consistent and large antinociceptive effects on both the stump and the intact limbs.

Adolescent↗
PubMed2006

Mitigation of direct neurotoxic effects of lidocaine and amitriptyline by inhibition of p38 mitogen-activated protein kinase in vitro and in vivo.

BACKGROUND: Local anesthetic-induced direct neurotoxicity (paresthesia, failure to regain normal sensory and motor function) is a potentially devastating complication of regional anesthesia. Local anesthetics activate the p38 mitogen-activated protein kinase (MAPK) system, which is involved in apoptotic cell death. The authors therefore investigated in vitro (cultured primary sensory neurons) and in vivo (sciatic nerve block model) the potential neuroprotective effect of the p38 MAPK inhibitor SB203580 administered together with a clinical (lidocaine) or investigational (amitriptyline) local anesthetic. METHODS: Cell survival and mitochondrial depolarization as marker of apoptotic cell death was assessed in rat dorsal root ganglia incubated with lidocaine or amitriptyline either with or without the addition of SB203580. Similarly, in a sciatic nerve block model, the authors assessed wallerian degeneration by light microscopy to detect a potential mitigating effect of MAPK inhibition. RESULTS: Lidocaine at 40 mm/approximately 1% and amitriptyline at 100 microm reduce neuron count, but coincubation with the p38 MAPK inhibitor SB203580 at 10 mum significantly reduces cytotoxicity and the number of neurons exhibiting mitochondrial depolarization. Also, wallerian degeneration and demyelination induced by lidocaine (600 mm/approximately 15%) and amitriptyline (10 mm/approximately 0.3%) seem to be mitigated by SB203580. CONCLUSIONS: The cytotoxic effect of lidocaine and amitriptyline in cultured dorsal root ganglia cells and the nerve degeneration in the rat sciatic nerve model seem, at least in part, to be mediated by apoptosis but seem efficiently blocked by an inhibitor of p38 MAPK, making it conceivable that coinjection might be useful in preventing local anesthetic-induced neurotoxicity.

Amitriptyline↗
PubMed1988

Amitriptyline for post-traumatic agitation.

Agitated behavior is exhibited in up to 30% of patients recovering from a traumatic brain injury. Past treatment protocols have included proactive behavioral management and major tranquilizers. We now report the use of amitriptyline for control of agitation. For a period of over 2 years, 43 male and 15 female patients with a "recent" severe brain injury were admitted for inpatient rehabilitation and subjected to traditional structured programming for treatment of post-traumatic amnesia (PTA). In 20 patients, 18 men and 2 women, where agitation persisted sufficiently to impede rehabilitation despite initiation of structure, amitriptyline was instituted. These patients were of a comparable age (29.4 years for the agitated group versus 25.6 years for the nonagitated group), but the agitated patients had a lower median Rancho Los Amigos Hospital Level of Cognitive Functioning in a comparison to nonagitated patients (V versus VI). All patients were monitored for cognitive performance by the Orientation Group Monitoring System, and a daily account of frequency, severity and type of agitation was recorded. Within 7 days of initiation of therapy, 12 of 17 patients within PTA had dramatic decrease in agitation (5/5 patients at Rancho IV; 4/8 at Rancho V; 3/4 at Rancho VI). Two of the three patients at Rancho VII had agitation that was unresponsive to amitriptyline. The amitriptyline-responsive patients were maintained on the drug through PTA, and the Orientation Group Monitoring System scale demonstrated no impedance in cognitive recovery. Thus, amitriptyline appears most useful as an adjunct for treatment of nondirected agitation; it also has a role in reducing the severity of the directed agitation that is seen during but not after PTA.

Adolescent↗
PubMed1992

Lack of effect of amitriptyline in murine myotonia.

Amitriptyline, a tricyclic antidepressant, has been reported to diminish signs of human myotonic muscular dystrophy, but has not been examined in other myotonias. Normal and myotonic (ADRmto) mice were injected acutely with either amitriptyline, phenytoin, procainamide or 0.9% saline. In addition, two groups of myotonic mice were injected chronically with either 0.9% saline or amitriptyline for 28 days. Behavior, assessed before injection using a "drop test," was re-evaluated at 30-min intervals for up to 180 min postinjection, as well as at the end of the 28-day chronic trial. If improvement in behavior was noted, the mice were then evaluated with insertional needle electromyography (EMG) and in vitro contractility (maximal tetanic tension and relaxation time) studies. Neither acute nor chronic amitriptyline administration had any beneficial effect on behavior, EMG or contractile parameters in myotonic mice. Phenytoin abolished abnormal EMG activity and improved behavior. Procainamide improved behavior and contractility parameters but had no effect on EMG. These results confirm that the myotonic mouse is responsive to classic antimyotonic agents, but not to amitriptyline.

Amitriptyline↗
PubMed2000

Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case. METHODS: In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale. RESULTS: A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline. CONCLUSION: These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine.

Aged↗
PubMed1985

Amitriptyline and hydroxylated metabolite plasma levels in depressed outpatients.

As part of a double-blind clinical trial comparing phenelzine and amitriptyline in outpatients with predominantly major depressive disorder, plasma tricyclic antidepressant drug concentrations were measured in 83 amitriptyline-treated patients. In 29 of these patients, hydroxymetabolites were also assayed. Patients were treated for 6 weeks at a fixed dose of 150 mg/day of amitriptyline after the first 5 days. Therapeutic outcome was assessed with a structured depression interview schedule, the Symptom Checklist-90, a side effects checklist, and a global improvement scale. Steady state plasma levels of 10-hydroxynortriptyline were in the same range as amitriptyline or nortriptyline concentrations. Clinical response did not relate significantly to plasma levels of either the parent drug, its metabolites, or the sum of all four pharmacologically active substances. Minimum threshold tricyclic antidepressant levels for therapeutic effect were not found. Assay of its active hydroxymetabolites does not appear to improve the clinical utility of routine amitriptyline level monitoring in patients with major depression in an outpatient setting.

Adult↗
PubMed1990

Pooling two controlled comparisons of milnacipran (F2207) and amitriptyline in endogenous inpatients. A new approach in dose ranging studies.

Milnacipran is a new potential antidepressant selected for its equipotent inhibition of noradrenaline and serotonin uptake and its lack of effect at any postsynaptic receptor. We recently compared milnacipran 100 and 50 mg/d and amitriptyline 150 mg/d in three parallel randomized groups of major depressive inpatients and found a statistically significant superiority of milnacipran 100 mg/d and amitriptyline over milnacipran 50 mg/d after 4 weeks of treatment. Later on we found similar improvement with milnacipran 200 mg and amitriptyline 150 mg but better tolerance with milnacipran. In order to compare the therapeutic activity of the three doses of milnacipran (50 mg/d, 100 mg/d, and 200 mg/d) we used the responses to amitriptyline as a reference against which to compare the 3 doses of the new drug using analysis of variance on the adjusted data. This approach reveals milnacipran 200 mg is more effective than milnacipran 50 and 100 mg and is the only dose which shows efficacy at least equivalent to that of amitriptyline 150 mg. The dose/efficacy relationship was linear.

Amitriptyline↗
PubMed1994

Alprazolam and amitriptyline in the treatment of moderate depression.

Forty-three out-patients with depression of a moderate degree were enrolled in a randomized, double-blind parallel group study comparing amitriptyline and alprazolam for 6 weeks of treatment. Patients were evaluated at the end of placebo washout and at Weeks 1, 2, 3 and 6 of drug therapy using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) and Clinical Global Impression (CGI). Drug dosage was determined in a fixed-flexible design resulting in mean final doses of alprazolam 3.2 mg/day and of amitriptyline 115 mg/day. Although both drug groups improved there were statistically significant differences in favour of amitriptyline at the end of the study on the HAM-D, BDI and HAM-A scales. Patients on amitriptyline reported more side effects overall than patients taking alprazolam with significantly more reports of dry mouth in the amitriptyline group.

Adolescent↗