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Toxic levels of tricyclic drugs in accidental overdose

Three Part Question

In [patients who have accidentally taken a tricyclic overdose] what is the [minimum toxic dose] that [requires assessment in the Emergency Department]

Clinical Scenario

A 7 year old boy presents to the emergency department after swallowing two of his mother's 75mg tablets of amitriptyline. This seems to be a genuine mistake, he is asymptomatic, and there are no concerns about his home situation. Can you send him home with reassurance or does he require further assessment?

Search Strategy

MEDLINE 1950 - November 2007 Ovid interface
[(antidepressant.mp. or exp Antidepressive Agents/) or (Antidepressive Agents, Tricyclic/ or tricyclic antidepressant.mp.) or (tricyc$.af.) or (amitriptyline.mp. or exp Amitriptyline/) or (nortriptyline.mp. or exp Nortriptyline/) or (imipramine.mp. or exp Imipramine/) or (desipramine.mp. or exp Desipramine/) or ( protriptyline.mp. or exp Protriptyline/) or (clomipramine.mp. or exp Clomipramine/ ) or (doxepin.mp. or exp Doxepin/) or (dothiepin.mp. or exp Dothiepin/) or (lofepramine.mp. or exp Lofepramine/) or (trimipramine.mp. or exp Trimipramine/) or (prothiaden.mp.) or (dosulepin.mp.) or (melipramine.mp.)] AND [(toxic dose.mp.) or (toxicity.mp. or exp Drug Toxicity/) or (LD50.mp. or exp Lethal Dose 50/) or (minimum toxic dose.mp.)] AND [(overdose.mp. or exp Overdose/) or (poisoning.mp. or exp Poisoning/)]
Limits: humans, english

Search Outcome

578 papers. Of these one was an evidence-based guideline published in 2007.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Woolf AD et al
2007
USA
Consensus guideline for pre-hospital triage of patients with reported overdose of tricyclic agentsReview/guidelineAmitriptyline>5 mg/kgThe following drugs were not included because they are not used in the US: dothiepin, dibenzipine, melipramine, prothiaden (dosulepin). Amoxapine, loxapine, and maprotiline were not considered as they are heterocyclic compounds and have different adverse effect profiles.
Clomipramine>5 mg/kg
Desipramine>2.5 mg/kg
Doxepin>5 mg/kg
Doxepin cream (if ingested)>5 mg/kg
Imipramine>5 mg/kg
Nortriptyline>2.5 mg/kg
Protriptyline>1 mg/kg
Trimipramine>2.5 mg/kg

Comment(s)

This guideline was constructed by a group in the USA based on evidence and consensus. The authors reviewed trials, case reports, and guidance from Poison Centers up to 2003. Published case reports were divided into those of patients under the age of 6, and those aged 6 years or over. As there was little difference between the two groups the authors chose to provide guidance suitable for all age groups. The guidance is suitable for patients who have taken an accidental overdose, are asymptomatic, and have no significant cardiovascular or neurological disease, or taking a cardiodepressant drug or monoamine oxidase inhibitor. This is the best evidence on the subject, but it does not include some drugs still used in the UK, such as dothiepin. We were unable to find evidence to alter these conclusions.

Clinical Bottom Line

The minimum overdose of tricyclic agent that should be investigated further is generally 5 mg/kg or over. Except in the cases of desipramine (>2.5mg/kg), nortriptyline(>2.5mg/kg), trimipramine(>2.5mg/kg), and protriptyline(>1mg/kg).

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

  1. Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, Wax PM, Manoguerra AS, Scharman EJ, Olson KR, Chyka PA, Christianson G, Troutman WG. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology (2007) 45:3, 203233