Summary
Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (>500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
Similar content being viewed by others
References
Bailey DN, van Dyke C, Langou A, Jatlow PI (1978) Tricyclic antidepressant plasma levels and clinical findings in overdose. Am J Psychiatry 135: 1325–1328
Biggs JT, Spiker DG, Petit JM, Ziegler VE (1977) Tricyclic antidepressant overdose. Incidence and symptoms. J Am Med Assoc 237: 135–138
Bjerre M, Gram LF, Kragh-Sørensen P, Kristensen CB, Pedersen OL, Møller M, Thayssen P (1981) Dose dependent kinetics of imipramine in elderly patients. Psychopharmacology 75: 354–357
Burch JE, Hullin RH (1981) Amitriptyline pharmacokinetics. A cross over study with single doses of amitriptyline and nortriptyline. Psychopharmacology 74: 35–42
Burrows GD, Norman T, Hughes I (1981) Cardiovascular effects of antidepressants. In: Usdin E, Dahl S, Gram LF, Lingjaerde O (eds) Clinical pharmacology in psychiatry: Neuroleptic and antidepressant research. McMillan, London, pp 321–341
Callahan M (1979) Tricyclic antidepressant overdose. J Am Coll Emerg Phys 8: 413–435
Collis MG, Shephard JT (1981) Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein. J Pharmacol Exp Ther 213: 616–622
Gram LF (1982) Antidepressants: Receptors, pharmacokinetics and clinical effects. In: Burrows GD, Norman T, Davis B (eds) Drugs and psychiatry. Vol. I: Antidepressants. Elsevier/North-Holland Biomedical Press, Amsterdam
Hall H, Ögren S-O (1981) Effects of antidepressant drugs on different receptors in the brain. Eur J Pharmacol 70: 393–407
Jefferson JW (1975) A review of the cardiovascular effects and toxicity of tricyclic antidepressants. Psychosom Med 37: 160–79
Klitgaard NA (1977) Determination of therapeutic concentrations of doxepin and desmethyldoxepin in human serum by high-pressure liquid chromatography. Arch Pharm Chem Sci Ed 5: 61–66
Kragh-Sørensen P, Larsen N-E (1980) Factors influencing nortriptyline steady-state kinetics: plasma and saliva levels. Clin Pharmacol Ther 28: 796–803
Langou RA, van Dyke C, Tahan SR, Cohen LS (1980) Cardiovascular manifestations of tricyclic antidepressant overdose. Am Heart J 100: 458–464
Lewis RP, Rittgers SE, Forester WF, Boudoulas H ((1977) A critical review of systolic time intervals. Circulation 56: 146–158
Manoguerra AS, Weaver LC (1977) Poisoning with tricyclic antidepressant drugs. Clin Toxicol 10: 149–158
Mellström B, Bahr C von (1981) Demethylation and hydroxylation of amitriptyline and its oxidized metabolites in human liver microsomes. Drug Metab Dispos 9: 565–568
Nagy A, Treiber L (1973) Quantitative determination of imipramine and desipramine in human blood plasma by direct densitometry of thinlayer chromatograms. J Pharm Pharmacol 25: 599–603
Noble S, Matthew H (1969) Acute poisoning by tricyclic antidepressants, clinical features and management of 100 patients. Clin Toxicol 2: 403–421
Overgaard J, Hvid-Hansen O, Land A-M, Pedersen KK, Christensen S, Haase J, Hein O, Tweed WA (1973) Prognosis after head injurys based on early clinical examination. Lancet 2: 631–635
Petit JM, Spiker DG, R Ruwitch JF, Ziegler VE, Weiss AN, Biggs JT (1977) Tricyclic antidepressant plasma levels and adverse effects after overdose. Clin Pharmacol Ther 21: 47–51
Rollins DE, Alvan G, Bertilsson L, Gillette JR, Mellström B, Sjöqvist F, Träskman L (1980) Interindividual differences in amitriptyline demethylation. Clin Pharmacol Ther 28: 121–129
Spiker DG, Weiss AN, Chang SS, Ruwitch JF, Biggs JT (1975) Tricyclic antidepressant overdose: clinical presentation and plasma levels. Clin Pharmacol Ther 18: 539–546
Spiker DG, Biggs JT (1976) Tricyclic antidepressants: Prolonged plasma levels after overdose. J Am Med Assoc 236: 1711–1712
Spiker DG (1978) The toxicity of tricyclic antidepressants. Commun Psychopharmacol 2: 419–427
Starkey IR, Lawson AAH (1980) Poisoning with tricyclic and related antidepressants — A ten-year review. Q J Med 49: 33–49
Taylor JE, Braithwaite RA (1978) Cardiac effects of tricyclic antidepressant medication. Br Heart J 40: 1005–1009
Thayssen P, Bjerre M, Kragh-Sørensen P, Møller M, Pedersen OL, Kristensen CB, Gram LF (1981) Cardiovascular effects of imipramine and nortriptyline in elderly patients. Psychopharmacology 74: 360–364
Thorstrand C (1974) Cardiovascular effects of poisoning with tricyclic antidepressants. Acta Med Scand 195: 505–514
Thorstrand C (1976) Clinical features in poisoning by tricyclic antidepressant drugs with special reference to the ECG. Acta Med Scand 199: 337–344
Weissler AM, Harris WS, Schoenfeld CD (1968) Systolic time intervals in heart failure in man. Circulation 37: 149–159
Weissler AM, Harris WS, Schoenfeld CD (1969) Bedside technics for the evaluation of ventricular function in man. Am J Cardiol 23: 577–583
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pedersen, O.L., Gram, L.F., Kristensen, C.B. et al. Overdosage of antidepressants: Clinical and pharmacokinetic aspects. Eur J Clin Pharmacol 23, 513–521 (1982). https://doi.org/10.1007/BF00637499
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00637499