• To be able to do a risk assessment of a tricylic antidepressant poisoning
• Understand the mechanism of toxicity, in particular the effects of sodium channel blockade
• Understand treatment of tricylic antidepressants, in particular the theory behind manipulation of pH.

1. Cyclic antidepressants
2. Dawson AH : Cyclic antidepressant drugs. Detailed Monograph from Hypertox App
3. McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med 1998; 32(3 Pt 1):329-333.
4. Bradberry S etal . Management of the cardiovascular complications of tricyclic antidepressant poisoning. Role of sodium bicarbonate . Toxicol reviews 2005 ;24(3) : 195-204
5. Segar D A critical reconsideration of the clinical effects and treatment recommendations for sodium channel blocking drug cardiotoxicity.Toxicol Rev. 2006; 25(4):283-96.
6. Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity. Annals of Emergency Medicine 2007; 49(2): 178-185
7. Blackman K, Brown SGA, Wilkes GJ. Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emergency Medicine 2001;13:204-210.

A 20-year-old man, weight 80 kg, presents 40 minutes after ingestion of 3 grams of amitriptyline. He is agitated but appears fully conscious. Pulse 110, BP 140/80, ECG normal conduction.

1. Would you decontaminate him?
2. What method would you use?

A 24-year-old man, weight 70 kg, presents some time after ingestion an unknown amount of amitriptyline, the packets suggest an ingested dose between 1 and 3 grams. GCS 5. Pulse 130, BP 110/60, ECG QRS 115.

1. Would you decontaminate him?
2. What method would you use?
   • The patient has a generalised seizure lasting 20 seconds.
3. Discuss how this influences your risk assessment and management

A 70 kg man presents on 3 occasions following a TCA overdose.

Admission 1: Unconscious, Seizure, BP 60 Systolic
Admission 2: Unconscious, QRS 110, Pulse 120 BP 130/80
Admission 3: Chronic ingestion. Conscious following a seizure, QRS 130 msec

Discuss your use of bicarbonate in each situation; speculate on the likely doses required.

A 65 kg woman of 24 years has been resuscitated after presenting with a TCA overdose. She is intubated, has been hyperventilated to a serum pH of 7.5, and received 210mEq of sodium bicarbonate during her resuscitation. Her serum sodium is currently 148 mmol/L, and her QRS is 130msec on and ECG that has just been repeated.

1. Her pulse rate remains at 130 with a blood pressure of 75/40. Outline your approach to haemodynamic support.
2. She subsequently has a sustained run of pulse less VT. Outline your approach to her arrhythmia management.

• To be able to do a risk assessments of SSRI, venlafaxine and MAOI poisonings
• Understand the syndrome of serotonin toxicity, in particular the risk factors for developing serotonin toxicity with significant morbidity

1. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for serotonin toxicity. Q J Med 2003;96:635-642 fulltext
2. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Q J Med 2003;96:369-374 fulltext
3. Kelly CA, Dhaun N, Laing WJ, et al. Comparative Toxicity of Citalopram and the Newer Antidepressants After Overdose Clinical Toxicology 2004 42: 67-71
4. Boyer EW, Shannon M. The serotonin syndrome.N Engl J Med. 2005 Mar 17;352(11):1112-20. http://content.nejm.org/cgi/reprint/352/11/1112.pdf
5. Isbister GK, Hackett LP, Dawson AH, Whyte IM, Smith AJ. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. British Journal of Clinical Pharmacology 2003;56:441-450 fulltext
6. Isbister GK, Bowe S, Dawson AH, Whyte IM. Relative Toxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Overdose. Clinical Toxicology 2004;42(3):277-285
7. Isbister GK. Electrocardiogram changes and arrhythmias in Venlafaxine overdose. Br J Clin Pharmacol 2009;67(5):572-576 fulltext

WikiTox: SSRI monograph
and Serotonin syndrome
WikiTox: Venlafaxine monograph
WikiTox: Monoamine oxidase monograph

A 17-year-old female presents following an overdose of venlafaxine and moclobemide.

She presents 3 hours after ingesting 20 x 37.5 mg venlafaxine (Efexor) and 10 x 300 mg of moclobemide (Aurorix). She has previously taken an overdose of fluoxetine, but has no other medical history.

She is very anxious and agitated with an obvious fine tremor. She is diaphoretic with the following observations: HR 125; BP 140/90; Temp 37.3. Neurological examination reveals mid-range reactive pupils with rapid, alternating eye movements without any slow component (ocular clonus). She has generally increased muscle tone with sustained ankle clonus and hyperreflexia.

1. What does the electrocardiograph shown demonstrate?
2. What is the diagnosis, and what clinical features are most useful in recognising the condition?
3. What are the current treatment options for this condition?
4. W hat are the best indicators in severe cases of progressing toxicity?

See ECG.bmp [1.5MB]

A 21 year old male with a background of depression managed on Venlafaxine XR 150mg presents feeling “stressed out” at 9am after a night “clubbing”. He appears oddly euphoric and mildly agitated, with a resting tremor, mildly increased tone in the lower limbs and associated inducible clonus. His temperature is normal, his pulse 120 and his BP 135/75.

1. How might his symptoms and signs be explained?
2. Would biochemical evaluation be expected to contribute to his care?
3. Outline the management options available.

• To understand the differences in these agents pharmacologically.
• To outline the spectrum of illness seen in overdose.
• Predict those patients likely to suffer more severe poisoning.
• Understand when specific interventions are required.

• Venlafaxine Monograph
• Bupropion Monograph
• Mirtazapine Monograph
• Mianserin Monograph
• Monoamine Oxidase Inhibitors Monograph
• Whyte IM, Dawson AH. Relative toxicity of venlafaxine and serotonin specific reuptake inhibitors in overdose. J Toxicol Clin Toxicol 2001; 39(3):255.
• Kumar VV, Oscarsson S, Friberg LE, Isbister GK, Hackett LP, Duffull SB.
The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose.
• Clin Pharmacol Ther. 2009 Oct;86(4):403-10. Epub 2009 Jul 15.
• Isbister GK. Electrocardiogram changes and arrhythmias in venlafaxine overdose. Br J Clin Pharmacol. 2009 May;67(5):572-6. Epub 2009 Feb 2.

• Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Isbister GK, Hackett LP, Dawson AH, Whyte IM, Smith AJ. Br J Clin Pharmacol. 2003 Oct;56(4):441-50
• Bupropion overdose: QTc prolongation and its clinical significance. Isbister GK, Balit CR. Ann Pharmacother. 2003 Jul-Aug;37(7-8):999-1002.
• Bupropion poisoning: a case series. Balit CR, Lynch CN, Isbister GK. Med J Aust. 2003 Jan 20;178(2):61-3
• Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data.Buckley NA, McManus PR. BMJ. 2002 Dec 7;325(7376):1332-3.

A 48 year old male (75 kg) presents to hospital very agitated, confused and diaphoretic. He has a Glasgow Coma scale of 11. He has not been seen for 24 hours and there are lots of empty packets of Venlafaxine 150 mg slow release preparation lying around his house .

His vital signs are :

HR 120 bpm, BP 150/102 mmHg, GCS 10, Respiratory rate 22 breaths per minute

1. Does venlafaxine ingestion explain this clinical picture, if so why ?
2. What is the role of decontamination in Venlafaxine poisoning and in this case ?
3. Outline your further management of this patient and what particular clinical features you would be looking out for ?

A 26 year old woman (65 kg) presents to hospital 2 hours after ingesting the following medications:

• Paracetamol 16, 500 mg tablets
• Amoxycillin 30, 250 mg tablets
• Venlafaxine 40, 125 mg tablets

She is currently awake and alert with normal vital signs. She now regrets taking the overdose.

1. What is your risk assessment?
2. Is decontamination indicated, if so, how?
3. How long should she be observed for?
4. What potential complication could be anticipated and what are the indicators that these may be more likely to occur?

A 54 year old man takes an overdose of his own medication one hour ago:

• Reboxetine 60, 4 mg tablets
• Fluvoxamine 30, 100 mg tablets

1. What is your risk assessment?
2. Is decontamination indicated, if so, how? What would you do if he refuses?
3. What potential complication could be anticipated?
4. How long should he be observed for?

• To understand the differences in these agents pharmacologically.
• To outline the spectrum of illness seen in overdose.
• Understand the clinical characteristics of neuroleptic malignant syndrome
• Understand the treatment options for neuroleptic malignant syndrome

1. Whyte IM, Carter G. Neuroleptic Malignant Syndrome in WikiTox 2004.
2. Balit CR, Isbister GK, Hackett LP, Whyte IM. Quetiapine poisoning: a case study. Annals of Emergency Medicine 2003;42(6):751-758.
3. Burns MJ. The pharmacology and toxicology of atypical antipsychotic agents. Clinical Toxicology 2001;39(1):2001.
4. Buckley NA, Whyte IM, Dawson AH. Cardiotoxicity more common in thioridazine overdose than with other neuroleptics. Clinical Toxicology 1995;33(3):199-204.
5. WikiTox: Neuroleptics

A 56 year old man is referred to hospital from a psychiatric facility. He was witnessed, 30 minutes ago, to ingest an unknown amount of medication saying he had been “saving them up for a special occasion”. Staff admit they had not directly observed him take his regular medications which are:A ying he had been “saving them up for a special occasion”. Staff admit they had not directly observed him take his regular medications which are:

• Thioridazine 200 mg tds
• Benztropine 2 mg nocte
• Zolpiderm 10 mg nocte
• Thiamine 100 mg nocte

He has been an inpatient for 2 weeks after an exacerbation of his schizophrenia.
1. What is your risk assessment?
2. Is decontamination indicated, if so, how?
3. How long should he be observed for?
4. What potential complication could be anticipated and what are the indicators that these may be more likely to occur?

A 25 year old man is referred to hospital from a psychiatric facility. He was admitted 1 week ago for the first time with a provisional diagnosis of schizophrenia and commenced on olanzapine in increasing doses; currently he is on 10 mg bd and has been having haloperidol 20 mg IM; usually 2 –3 times a day.

He was noted to be febrile overnight and, after some investigations ordered in the morning, he was referred to hospital.

The following are noted:

• HR 70/min
• BP 130/70
• RR 16/min
• Temp 38.5oC

He is not sweating. He quietly mumbles to himself and will not answer direct questions. On neurological exam he is not very compliant but no gross abnormality is evident.

The results included in his referral are:

• WCC 17.5
• CK 2100

1. Does this patient have Neuroleptic Malignant Syndrome? Can any of his features be attributable to his medications?
2. What investigations are required?
3. In the absence of any obvious source of infection on a septic screen, including LP (cultures are pending) how would you treat him and where?

What is the evidence for the efficacy of bromocriptine or dantrolene in the management of Neuroleptic Malignant Syndrome?

1. Fritschy JM, Brünig I. Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications. Pharmacology & Therapeutics 2003;98:299-323PMID12782242
2. Whyte IM. Chapter 140: Miscellaneous anxiolytics, sedatives, and hypnotics. Detailed monograph in WikiTox
3. Gueye PN, Lofaso F, Borron SW, Mellerio F, Vicaut E, Harf A, Baud FJ. Mechanism of respiratory insufficiency in pure or mixed drug-induced coma involving benzodiazepines. Clinical Toxicology 2002;40(1):35-47 PMID11990203

It is known that patients will often wake with benzodiazepine blood levels that are as high as or higher than when they became unconscious. What are the possible mechanisms for this?
Flumazenil is GABA antagonist. Given the above information what impact do you think it should have on the duration of stay in patients with benzodiazepine overdose?

WikiTox: Tricyclic Antidepressants
WikiTox: Salicylate monograph
WikiTox: SSRI monograph
and Serotonin syndrome
WikiTox: Venlafaxine monograph
WikiTox: Monoamine oxidase monograph
WikiTox: Neuroleptics
and Neuroleptic Malignant Sydnrome
WikiTox: Benzodiazepines
WikiTox: Anxiolytics, sedatives, hypnotics