Psychiatric Medication Overdose

1. Psychiatric Medication Overdose Rama B. Rao, MD Bellevue/New York University Medical Center

2. Tricyclic Antidepressants • A patient takes 30 tablets of nortriptylline in a suicide attempt, she calls her family member who summons an ambulance. • On arrival, the paramedics note she is unresponsive, tachycardic, and hypotensive. • She seizes.

4. TCA Toxicity • Anticholinergic/Antihistaminergic • Somnolence, Tachycardia •  Adrenergic blockade • Hypotension • GABA Cl- Channel Antagonist • Seizures • Sodium Channel Blockade • Myocardial Depression, dysrhythmias

5. Myocardial Cell: Depolarization Ca2+ Na+ 1 2 0 3 SR 4 Ca2+

6. TCA Ca2+ Na+ TCA 1 2 pH 0 3 SR 4 Ca2+

7. TCA 1 Ca2+ Na+ 2 TCA 0 3 pH 4 SR Ca2+

8. Wide QRS 1 2 • > 100 msec predictive of seizures • > 160 msec predictive of dysrythmias 3 0 4 Boehnert M, Lovejoy FH Jr. New Engl J Med 1985;313:474-479

9. L aVR I Myocardium

10. L aVR I With TCA: QRS widening from sodium channel blockade

11. TCA: Terminal Rightward Axis L aVR I R in aVR S in I,L QRS > 100 msec

12. TCA Toxicity • S in I, L • R in aVR • QRS >100 msec • Drowsy/obtunded patient •  HR,  BP aVR Boehnert M, Lovejoy FH Jr. New Engl J Med 1985;313:474-479

13. Sodium bicarbonate* 1 2 • Place patient on monitor • Run strip • Administer bolus of 1 mEq/kg • Observe for QRS narrowing • Keep pH 7.5-7.55 • Intubate/hyperventilate if sodium contraindicated 0 3 4 NaHCO3 * Useful for TCA, Cocaine, Type Ia antidysrhythmics

15. After NaHCO3

16. TCA Toxicity: General Management • 2 Large bore intravenous lines • Continuous ECG monitoring • Assessment for QRS widening, terminal RAD, and response to sodium bicarbonate • Aggressive decontamination • Benzodiazepines for seizure management* *Fingerstick blood glucose

17. St John’s Wort

18. MECHANISM OF ACTION: TCA, SSRI, MAO-I Pre-synaptic Post-synaptic DA NE Neuronal Tissue

19. Pre-synaptic Post-synaptic DA NE 5HT Neuronal Tissue

20. Pre-synaptic Post-synaptic Propagation DA NE 5HT Neuronal Tissue

21. Post-synaptic Pre-synaptic Propagation DA NE 5HT MAO C-O-MT

22. Pre-synaptic Post-synaptic Propagation DA NE 5HT TCA, SSRI

23. Pre-synaptic Post-synaptic Propagation DA NE 5HT MAO-I

24. Pre-synaptic Post-synaptic Propagation DA NE 5HT MAO-I TCA, SSRI

25. Serotonin Syndrome • Excessive serotonergic tone 5HT1A, 5HT2 • Continuum of neuropsychiatric manifestations Serotonin

26. Serotonin Syndrome: Major Criteria* • Confusion • Elevated mood • Coma • Fever • Diaphoresis • Chills • Rigidity • Hyperreflexia • Myclonus • Tremor 4 major, or 3 major and 2 minor Birmes P CMAJ 2003;168:1439-1442

27. Minor Criteria: Serotonin Syndrome • Agitation • Nervousness • Insomnia • Tachypnea • Dyspnea • Tachycardia • High or low BP • Akathisia • Incoordination • Mydriasis • Diarrhea 4 major, or 3 major and 2 minor Birmes P CMAJ 2003;168:1439-1442

28. Fatal Serotonin Syndrome • Abrupt onset • Autonomic instability • Hyperthermia, diaphoresis • Neuromuscular rigidity, movement disorder • Altered mental status • Absence of a neuroleptic or other cause

29. Serotonin Syndrome • Most often iatrogenic • Resolution in 48-96 hours • Death from uncontrolled hyperthermia

30. Serotonin Syndrome: Therapeutic Goals • Rapid identification of Hyperthermia • Continuous core temperature monitoring, aggressive cooling, benzodiazepines for sedation • Rule out other potential etiologies

31. Serotonin Syndrome • Identification of serotonergic factors, particularly the presence of monoamine oxidase inhibitors • ?Role of serotonin antagonists: cyproheptadine 4 mg po in mild cases

32. Drugs Implicated in Serotonin Syndrome • MAO-Inhibitors • SSRIs • Clomipramine • Venlafaxine • Lithium • MDMA* • L-Tryptophan* • Meperidine* • Dextromethorphan* • Cocaine*

33. Pre-synaptic Post-synaptic Propagation DA NE 5HT MAO-I

35. Monoamine Oxidase Inhibitors • Isolated overdose • Can be fatal…HTN followed by hypotension and catecholamine depletion • Aggressive decontamination • Tyramine Crisis • Dietary interaction • HTN, headache, flushing, vomiting • Supportive, alpha antagonists, self-limited

36. What is the finding on this ECG?

38. Citalopram • SSRI with toxic metabolite • In overdose can prolong QRS, QTc, • Seizures • Delay in onset Catalano G. Clin Neuropharmacol 2001;24:158-62

39. Citalopram Overdose • Immediate cardiac monitoring for QTc, IV lines • Assess and correct electrolytes, especially K+, Ca2+, Mg2+ • Decontamination • Use of Mg2+ for torsade • Admission of minimum 24 hours of cardiac monitoring

40. Venlafaxine SSRI and NE Uptake inhibition HTN,HR Reboxitine Selective NE uptake inhibition HTN Bupropion DA,NE, 5HT re-uptake inhib SZ, HTN Mirtazipine SSRI, 2 adrenergic blockade QT, ↓BP, HR Trazadone SSRI, 2 adrenergic blockade ↓BP, HR Atypical Antidepressants

41. Antipsychotics • CYP2D6 metabolism • Dystonia • Akithisia • NMS • Overdose: • QT, hypotension, tachycardia, small pupils • Depressed mental status • Anticholinergic

42. Lithium • Treated by body like sodium • Serial levels • Hyperreflexia, clonus, nystagmus • Not bound by AC • Aggressive decontamination with WBI • Aggressive saline hydration • Hemodialysis esp for acute on chronic cases

43. Valproic Acid • Mood stabilizer • In toxicity • Hypoglycemia • Hyperammonemia • Depressed mental status • Supportive therapy • Carnitine

44. Summary Poisoning with Psychiatric Medications: • Rapid screening for conduction abnormalities • Rapid evaluation and intervention for hyperthermic patients • Aggressive fluid management for agents with  blockade, or lithium toxicity • Glucose evaluation