Tricyclic antidepressant overdose
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Overview
Tricyclic antidepressant overdose is caused by excessive use or overdose of a tricyclic antidepressant drug. It is a significant cause of fatal drug poisoning. The severe morbidity and mortality associated with these drugs is well documented due to their cardiovascular and neurological toxicity. Additionally, it is a serious problem in the pediatric population due to their potential toxicity[1] and the availability of these in the home when prescribed for bed wetting and depression.
References
- ↑ Rosenbaum T, Kou M (2005). “Are one or two dangerous? Tricyclic antidepressant exposure in toddlers”. J Emerg Med. 28 (2): 169–74. doi:10.1016/j.jemermed.2004.08.018. PMID 15707813.
Historical Perspective
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References
Pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Overview
Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have anticholinergic effects, cause excessive blockade of norepinephrine reuptake at the preganglionic synapse, direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having quinidine like effects on the myocardium.[1]
Pathophysiology
Toxicity
Tricyclics have a narrow therapeutic index, i.e., the therapeutic dose is close to the toxic dose.[2] In the medical literature the lowest reported toxic dose is 6.7 mg per kg body weight. Although there are differences in toxicity with the drug class, ingestions of 10 to 20 mg per kilogram of body weight are a risk for moderate to severe poisoning, however, doses ranging from 1.5 to 5 mg/kg may even present a risk. Most poison control centers refer any case of TCA poisoning (especially in children) to a hospital for monitoring.[3] Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs.[4] However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.[5] TCA levels >1000 ng/ml were associated with QT and QRS prolongation and convulsions.
References
- ↑ Kerr G, McGuffie A, Wilkie S (2001). “Tricyclic antidepressant overdose: a review”. Emerg Med J. 18 (4): 236–41. doi:10.1136/emj.18.4.236. PMC 1725608. PMID 11435353.
- ↑ 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 (2007). “Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management”. Clin Toxicol (Phila). 45 (3): 203–33. doi:10.1080/15563650701226192. PMID 17453872.
- ↑ McFee R, Mofenson H, Caraccio T (2000). “A nationwide survey of the management of unintentional-low dose tricyclic antidepressant ingestions involving asymptomatic children: implications for the development of an evidence-based clinical guideline”. J Toxicol Clin Toxicol. 38 (1): 15–9. doi:10.1081/CLT-100100910. PMID 10696919.
- ↑ Preskorn S, Irwin H (1982). “Toxicity of tricyclic antidepressants–kinetics, mechanism, intervention: a review”. J Clin Psychiatry. 43 (4): 151–6. PMID 7068546.
- ↑ Boehnert M, Lovejoy F (1985). “Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants”. N Engl J Med. 313 (8): 474–9. doi:10.1056/NEJM198508223130804. PMID 4022081.
Causes
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References
Differentiating Tricyclic Antidepressant Overdose from other Diseases
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References
Epidemiology and Demographics
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Epidemiology and Demographics
Studies in the 1990s in Australia and the United Kingdom showed that between 8 and 12% of drug overdoses were following TCA ingestion. TCAs may be involved in up to 33% of all fatal poisonings, second only to analgesics.[1][2] Another study reported 95% of deaths from antidepressants in England and Wales between 1993 and 1997 were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. It was determined there were 5.3 deaths per 100,000 prescriptions.[3] Sodium channel blockers such as Dilantin should not be used in the treatment of TCA overdose as the Na+ blockade will increase the QTI.
References
- ↑ Thomas S, Bevan L, Bhattacharyya S, Bramble M, Chew K, Connolly J, Dorani B, Han K, Horner J, Rodgers A, Sen B, Tesfayohannes B, Wynne H, Bateman D (1996). “Presentation of poisoned patients to accident and emergency departments in the north of England”. Hum Exp Toxicol. 15 (6): 466–70. doi:10.1177/096032719601500602. PMID 8793528.
- ↑ Buckley N, Whyte I, Dawson A, McManus P, Ferguson N (1995). “Self-poisoning in Newcastle, 1987-1992”. Med J Aust. 162 (4): 190–3. PMID 7877540.
- ↑ Shah R, Uren Z, Baker A, Majeed A (2001). “Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database”. Psychol Med. 31 (7): 1203–10. PMID 11681546. Unknown parameter
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Risk Factors
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References
Natural History, Complications and Prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Complications
More severe complications include
- Hypotension
- Cardiac rhythm disturbances
- Hallucinations
- Seizures
- Apnea
References
Diagnosis
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | CT | MRI | Other Imaging Findings | Other Diagnostic Studies
Treatment
Treatment
Medical Therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
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