Clin Chem. 1994 Jun;40(6):929-33.
Monitoring tricyclic antidepressant concentrations in serum by fluorescence polarization immunoassay compared with gas chromatography and HPLC.

Rao ML, Staberock U, Baumann P, Hiemke C, Deister A, Cuendet C, Amey M, Hartter S, Kraemer M.

Psychiatrische Klinik und Poliklinik, Rheinischen Friedrich-Wilhelms- Universitat, Bonn, Germany.

The fluorescence polarization immunoassay (FPIA) developed by Abbott to diagnose intoxication with tricyclic antidepressants was adapted for therapeutic drug monitoring and validated with chromatograpic methods to investigate its potential for this use. We compared serum concentrations of tricyclic antidepressants in vivo and in vitro obtained by FPIA with those by gas chromatography and HPLC. For amitriptyline, imipramine, clomipramine, and doxepin, the detection limit of the FPIA was 72, 71, 64, and 72 nmol/L (approximately 20 micrograms/L), respectively; that by gas chromatography was 18, 18, and 16 nmol/L (approximately 5 micrograms/L) for amitriptyline, imipramine and clomipramine, respectively; with HPLC the lower limit of detection for doxepin was 36 nmol/L (10 micrograms/L). The intra- and interassay CVs ranged from 3% to 6%. In patients being treated with amitriptyline, imipramine, clomipramine, and doxepin, at steady-state the correlation coefficients between FPIA and GC/HPLC results for split samples were 0.95, 0.92, 0.90 and 0.70, respectively. However, the slopes were close to unity only for amitriptyline and doxepin, being 0.6 for imipramine and 1.9 for clomipramine.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8087988&dopt=Abstract Elavil amitriptyline




Crit Care Med. 1994 Mar;22(3):494-8.
Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat.

Knudsen K, Abrahamsson J.

Department of Anesthesia and Intensive Care, University of Goteborg, Sweden.

OBJECTIVES: Amitriptyline poisoning is associated with ventricular arrhythmias. Standard treatment is sodium bicarbonate but further intervention may be necessary. The present study compared the actions of lidocaine and magnesium sulfate on ventricular tachycardia induced by amitriptyline. DESIGN: Nonrandomized, controlled, intervention trial. SETTING: University laboratory. SUBJECTS: Thirty male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: After pretreatment with norepinephrine, the animals were subjected to a continuous infusion of amitriptyline. After the appearance of ventricular tachycardia, they were treated with magnesium sulfate (45 mg/kg + 15 mg/kg/min) or lidocaine (1 mg/kg + 0.5 mg/kg/min) or glucose infusion as a control. MEASUREMENTS AND MAIN RESULTS: In the group treated with magnesium sulfate, electrocardiogram tracings demonstrated that nine of ten animals converted from ventricular tachycardia to sinus rhythm compared with one of ten in both the lidocaine- and glucose-treated groups (p < .001). The animals treated with magnesium sulfate also had a significantly longer total time in sinus rhythm (10.0 +/- 1.6 mins) than those rats treated with lidocaine (1.7 +/- 1.5 mins) or glucose (1.5 +/- 1.5 mins). Magnesium sulfate significantly decreased blood pressure and heart rate, but no severe hemodynamic side effects were observed. CONCLUSIONS: Magnesium sulfate is effective in converting ventricular tachycardia in hyperadrenergic amitriptyline poisoning. In contrast, lidocaine had no effect on arrhythmias.

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Ann Emerg Med. 1994 Mar;23(3):480-6.
Experimental amitriptyline poisoning: treatment of severe cardiovascular toxicity with cardiopulmonary bypass.

Larkin GL, Graeber GM, Hollingsed MJ.

Department of Surgery, West Virginia University, Morgantown.

STUDY OBJECTIVE: To compare cardiopulmonary bypass (CPB) with more conventional therapy in the treatment of severe amitriptyline poisoning. DESIGN: Prospective, randomized, controlled, laboratory investigation. INTERVENTIONS: Profound cardiovascular toxicity was induced in 20 anesthetized Yorkshire swine (72 +/- 8.3 kg) by amitriptyline infusion at 0.5 mg/kg/min. Ventilation was adjusted to keep arterial pH at 7.50 +/- 0.05 and the PCO2 at 35 mm Hg. The swine were randomized in a 1:1 ratio to one of two groups, CPB or control. Both groups received amitriptyline infusion until they experienced near-lethal toxicity, defined as a systolic blood pressure below 30 mm Hg for one minute. The control group was then given supportive treatment, including IV fluids, sodium bicarbonate, vasopressors, and standard pharmacologic (advanced cardiac life support) interventions. Control animals failing to respond to supportive measures after five minutes were given open-chest cardiac massage for 30 minutes or until the return of spontaneous circulation. The CPB group received only mechanical support by CPB for 90 to 120 minutes. No sodium bicarbonate, antiarrhythmics, or cardiotonic agents were provided to the CPB group during this resuscitation. RESULTS: All 20 animals experienced cardiac conduction delays, dysrhythmias, and progressive hypotension within 30 minutes of receiving IV amitriptyline at 0.5 mg/kg/min. The ten swine receiving CPB as treatment for cardiovascular toxicity were able to completely correct the dysrhythmias, cardiac conduction abnormalities, and hypotension produced by the amitriptyline; however, only one of ten control animals could be resuscitated (P = .0001). Nine of ten swine treated with CPB were easily weaned off bypass without any pharmacologic intervention; however, one required norepinephrine to be weaned. All 11 resuscitated swine were able to be salvaged. CONCLUSION: CPB improved survival in our swine model of severe amitriptyline poisoning.

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J Pharm Sci. 1994 Jan;83(1):100-3.
Tranylcypromine does not enhance the effects of amitriptyline on 5-HT2 receptors in rat cerebral cortex.

Goodnough DB, Baker GB.

Department of Psychiatry, University of Alberta, Edmonton, Canada.

The combination of amitriptyline (a tricyclic antidepressant) and tranylcypromine (a monoamine oxidase inhibitor) has been reported to be effective for treatment of refractory depressed patients. In the study reported here, this drug combination was compared with amitriptyline administered alone on the number and affinity of 5-HT2 receptors in rat brain. Male Sprague-Dawley rats were given vehicle (distilled water), amitriptyline (3.5 mg/kg/day), or tranylcypromine and amitriptyline (0.5 and 3.5 mg/kg/day, respectively) in combination subcutaneously via osmotic minipumps for 4, 10, or 28 days. A membrane fraction prepared from whole cortex was employed for studying binding to 5-HT2 receptors ([3H]ketanserin as the radioligand). The combination of amitriptyline and tranylcypromine produced a small but significantly greater down-regulation (decrease in number) of 5-HT2 sites than did amitriptyline alone after 10 days of administration; at 4 and 28 days, both amitriptyline and the drug combination had produced down-regulation, but there was not a significant difference between the two treatments. These data suggest that the antidepressant efficacy observed with this combination is not likely due to an enhanced effect on 5-HT2 receptors.

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Psychiatr Pol. 1994 Jan-Feb;28(1):27-38.
[Psychotropic profile of essential antidepressants (amitriptyline, imipramine, desipramine, chlorimipramine): comparative study]

[Article in Polish]

Koszewska I, Beresewicz M, Puzynski S, Kalinowski A.

II Kliniki Psychiatrycznej Instytutu Psychiatrii i Neurologii w Warszawie.

Comparative studies of the therapeutic activity of amitriptyline, imipramine, desipramine and chlorimipramine were studied in a group of 185 patients with endogenous depression. After standard 28-day treatment, the best results were obtained while using amitriptyline (improvement rate 67%, the greatest reduction in the Hamilton Depression Scale scored on 28-day of the treatment). The profile and characteristics of antidepressive action of all the drugs taken into consideration are comparable (including slightly more expressed sedative and deliberative effects of amitriptyline). Desinhibitive influence of desipramine and imipramine was not proved. Neither was tachythymoleptic activity of desipramine found. The study does not support the relation between the antidepressive action profile of tricyclic antidepressants and their influence on reuptake of monoamines (norepinephrine and serotonine).

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Hum Exp Toxicol. 1994 Jan;13(1):29-31.
A five year review of fatal self-ingested overdoses involving amitriptyline in Edinburgh 1983-'87.

Bolster M, Curran J, Busuttil A.

Department of Pathology, Cork Regional Hospital, Wilton, Ireland.

One hundred and twelve cases of fatal self-ingested overdoses were investigated in the Forensic Medicine Unit of the Department of Pathology of the University of Edinburgh in the period 1983-'87 (inclusive). Of these, 24 cases involved amitriptyline as either the sole agent or in combination with another drug, the most common of which was ethanol. The mean age of the latter group was 43 years with a marked female preponderance. The social history was documented with six out of the 24 cases living alone and five out of the 24 cases divorced. The number previously referred for psychiatric treatment and the number of cases where over 100 tablets of the drug had been prescribed at any one time (where known) was recorded: eight out of 24 cases. The fact that amitriptyline was by far the commonest of the tricyclic antidepressants to be encountered in a fatal overdose situation raises the important question of the prescribing of amitriptyline as a first line therapy in mental depression.

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Psychopharmacology (Berl). 1976 Jul 9;48(1):101-4.
Effects of amitriptyline and isocarboxazid on 5-hydroxytryptophan induced head twitches in mice.

Nakamura M, Fukushima H, Kitagawa S.

Effects of amitriptyline and isocarboxazid on brain 5-HT and 5-HIAA were examined in relation to their action on 5-HTP induced head twitches. Amitriptyline reduced 5-HTP induced head twitches but isocarboxazid increased them. Both amitriptyline and isocarboxazid caused a significant increase of brain 5-HT concentration in 5-HTP treated mice. Amitriptyline also caused a significant increase of 5-HIAA concentration, while isocarboxazid reduced 5-HIAA concentration in the brains of 5-HTP treated mice. Probenecid, which significantly increased 5-HIAA concentration without affecting brain 5-HT concentration in 5-HTP treated mice, reduced 5-HTP induced heat twitches. These results suggest that 5-HTP induced head twitches might be induced by an increase of 5-HT concentration, and reduced by an increase of 5-HIAA or a decrease of 5-HT concentration in the brains of mice.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=823564&dopt=Abstract Elavil amitriptyline