The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward.

The clinical features and toxicokinetics of amitriptyline were studied in nine patients with severe amitriptyline poisoning. Amitriptyline and amitriptyline metabolites were studied in plasma, red blood cells, and cerebral spinal fluid. Eight patients were intubated and six required assisted ventilation. Two patients had ventricular arrhythmias, three patients convulsions and two were hypotensive. All complications developed within four hours of admission. Early in the course of the intoxication the QRS duration correlated with plasma, unbound and red blood cell nortriptyline concentration. The QRS duration also correlated with unbound but not the plasma amitriptyline concentration. The level of consciousness correlated with the plasma and unbound amitriptyline both in alpha and beta phase and with red blood cell amitriptyline in alpha phase. There was no correlation between nortriptyline concentration and level of consciousness. No correlation between coma grade or QRS duration and cerebral spinal fluid concentration of amitriptyline was found. There was no correlation between any hydroxymetabolite in blood or cerebral spinal fluid and QRS duration or coma grade. The beta half-life for amitriptyline was shorter for two patients with high concentrations of hydroxymetabolites. Although intubated, neither patient required assisted ventilation or developed complications. Because of the wide range of concentrations of amitriptyline and amitriptyline metabolites observed between individuals, it is not possible to predict outcome based on a single tricyclic antidepressant concentration.

Tricyclic antidepressants (TCA) bind to activated charcoal both in vitro and in vivo in healthy volunteers after a therapeutic dose of TCA. These findings provide a basis for the routine use of activated charcoal in TCA poisoning. The object of this study was to examine the effect of a single dose of 20 g of activated charcoal in overdose patients. Ninety-one patients from four centres with suspected TCA overdose were entered into a randomized study. Gastric lavage was performed on all patients. Thirty-four received 20 g of activated charcoal and 43 served as controls. Fourteen patients were excluded. Plasma drug concentrations were taken on admission and at 1, 2, 4, 8 and 24 h. The incidence of toxic symptoms was registered during 24 h. There was no significant difference in the area under the plasma drug concentration versus time curve, the peak plasma concentrations or plasma half-lives between the two groups. Toxic symptoms were more frequent in the non-treated groups although this difference was not statistically significant. In patients with TCA overdose initially treated with gastric lavage, a single dose of 20 g of activated charcoal had no effect on the systemic absorption or elimination of TCA.

Self‐poisoning with antidepressant drugs was studied retrospectively in 225 patients admitted to an intensive care unit. Amitriptyline accounted for the overwhelming majority of cases (70%); 106 patients (47%) had taken two or more drugs, in 81 patients (36%) ethanol was found in the blood. Four patients (2%) died. On admission, 111 patients (49%) were unconscious (grade III). A further 30 patients (13%) were in grade IV coma, and of these 27 had taken amitriptyline. Twenty‐four hours after admission, 22 patients (10%) remained in coma. Thirty‐six patients (16%) required assisted ventilation. Nineteen patients (8%) had convulsions and 6 (3%) aspired stomach contents. Sixty‐one patients (27%) had a widened QRS interval exceeding 100 msec, 18 (30%) of them required assisted ventilation, 21 (34%) were in stage IV coma and 15 (25%) had convulsions. This relationship between a widened QRS interval and the severity of intoxication should be considered in the initial assessment of patients with tricyclic antidepressant poisoning.

Intoxication with tricyclic antidepressants (TCA) is a common cause of admission to an intensive care unit and a major cause of death due to drug overdose. It is difficult to identify at an early stage those patients for whom toxic events are likely. There is a poor correlation between the plasma concentration of TCAs and the risk of developing toxic symptoms. A better predictor of complications following tricyclic overdose is the level of consciousness on admission to hospital. It has been claimed that "newer" antidepressant agents are less toxic then the classic antidepressants when taken in overdoses. In Sweden, two of these "newer" antidepressants, maprotiline and lofepramine, have been marketed. Of these, only lofepramine is less toxic than the classic TCAs. Maprotiline has the same cardiotoxicity as the TCAs, convulsions are seen more often and a longer plasma half-life leads to longer time spent on a ventilator and longer time in an ICU when it is taken in overdose.