dothiepin-hydrochloride and Poisoning

Antidepressants are used frequently in non-fatal self-poisoning. There are national guidelines for prescribing antidepressants. There have been few investigations of how non-fatal self-poisoning with antidepressants varies in relation to prescribing and to patient characteristics.. A comparative study of the use of specific antidepressants (amitriptyline and dosulepin (tricyclics), citalopram, fluoxetine, paroxetine and sertraline (selective serotonin reuptake inhibitors) and venlafaxine (serotonin norepinephrine reuptake inhibitor)) for non-fatal self-poisoning (episode-based), relative to prescribing, in three centres in England, 2004 to 2006.. There was marked variation between centres in the ratio of rates of self-poisoning to prescribing for specific antidepressants. Higher rates of self-poisoning relative to prescribing for all antidepressants combined, and for venlafaxine, were found in the centre with greater proportions of patients with a history of self-harm and/or previous psychiatric treatment. Within each centre, higher rates of self-poisoning relative to prescribing were found for citalopram and fluoxetine than amitriptyline. However, rates of self-poisoning relative to prescribing for either amitriptyline or dosulepin were also similar to sertraline, which is of concern given the known toxicity of tricyclics.. An ecological study, where prescriptions were for all indications and not specifically for the patients who self-poisoned.. Marked differences found in ratios of self-poisoning with antidepressants to levels of prescribing, in three centres in England, are likely to reflect differences in both prescribing practices (despite clear national guidance) and patient characteristics. Risk of overdose and toxicity should be considered when local prescribing policy and clinical practice relating to antidepressants are under review.

Topics: Amitriptyline; Antidepressive Agents; Cross-Sectional Studies; Cyclohexanols; Dothiepin; England; Guideline Adherence; Humans; Odds Ratio; Poisoning; Practice Patterns, Physicians'; Recurrence; Risk Factors; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

High pressure liquid chromatography coupled to photodiode array detector and capillary gas chromatography coupled to mass spectrometry were employed to quantify dothiepin in biological fluids, tissues and hair in a death attributed to oral dothiepin (Prothiaden) ingestion. The blood concentration of dothiepin was 5.75 mg/l. Hair analysis clearly indicated a chronic antidepressant exposure, with a dothiepin concentration of 1.89 ng/mg hair. Results are discussed in the light of the existing literature.

Topics: Adult; Antidepressive Agents, Tricyclic; Chromatography, High Pressure Liquid; Dothiepin; Fatal Outcome; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Hair; Humans; Male; Poisoning

Epidemiological studies have implicated dothiepin in a greater number of self-poisoning deaths than would be expected from its use. We have prospectively assessed the clinical toxicity of dothiepin and other tricyclic antidepressants (TCAs) in overdose. We followed-up consecutively admitted patients with TCA poisoning managed by our department between January, 1987, and August, 1992. 75 patients had taken dothiepin, 101 amitriptyline, 83 doxepin, and 61 other TCAs. Death after TCA poisoning is rare nowadays, so we used intermediate outcome measures--general seizures, tachyarrhythmias, sedation, and QRS width on the electrocardiogram. 15 patients had seizures and 7 tachyarrhythmias. When we excluded patients who had taken more than one TCA, general seizures were more likely after dothiepin than after other TCAs (9/67 vs 5/220) as were arrhythmias (4/67 vs 3/220). Rates of other complications were similar. The dothiepin group had ingested a larger dose, attributable to the larger average tablet strength, than patients who took other TCAs. The odds ratio for seizures with dothiepin versus other TCAs was 6.7 (95% Cl 2.2-20.7) unadjusted and 7.1 (2.2-23.2) after adjustment for sex, age, and ingested dose. The corresponding odds ratios for arrhythmias were 4.6 (1.0-21.1) and 3.4 (0.7-16.3). Dothiepin in overdose seems to be proconvulsant. Patients with only minor sedation and normal limb-lead QRS width may still have major complications. Consideration should be given to the use of other antidepressants in patients at risk of seizures or suicide. Regulatory authorities should review the need for a 75 mg strength tablet of any TCA.

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Dothiepin; Drug Overdose; Female; Humans; Male; Poisoning; Seizures

Topics: Arrhythmias, Cardiac; Bias; Dothiepin; Drug Overdose; Humans; Poisoning; Seizures

Topics: Child, Preschool; Dothiepin; Humans; Infant; Intestines; Poisoning; Therapeutic Irrigation

Although the tricyclic antidepressant dothiepin is often encountered in deliberate self-poisonings, there are no published studies of its disposition in overdose. In the present study, we have documented the plasma disposition of dothiepin and its major metabolites in eight overdose patients. All had high initial levels of dothiepin (819-3,851 micrograms/L), dothiepin-S-oxide (655-2,162 micrograms/L), nordothiepin (88-422 micrograms/L), and nordothiepin-S-oxide (176-530 micrograms/L) that were considerably above steady-state therapeutic concentrations. In three patients who received treatment with repeated-dose activated charcoal, dothiepin half-lives were 10.6, 12.5, and 13.1 h compared with the literature range of 18.5-24 h. All patients survived and none experienced any significant cardiovascular event despite exhibiting clinical signs of tricyclic antidepressant overdose. We suggest that repeated-dose activated charcoal treatment may decrease the dothiepin half-life after overdose.

Topics: Adult; Charcoal; Dothiepin; Female; Humans; Infant; Male; Middle Aged; Poisoning; Tissue Distribution

Topics: Accidents, Home; Age Factors; Child, Preschool; Dibenzothiepins; Diuresis; Dothiepin; Humans; Male; Poisoning