Psychiatric drug poisoning

Last updated: September 27, 2023

Summarytoggle arrow icon

Poisoning from the ingestion of psychiatric drugs (e.g., antidepressants, antipsychotics, or mood stabilizers) may occur as a result of an accidental or intentional overdose, changes in metabolism or excretion, or interactions with other drugs or food. Clinical features vary depending on the medication, amount ingested, and duration of therapy. Diagnosis is primarily clinical, with supportive studies including toxicological studies (e.g., serum drug levels) for certain substances, ECG, and laboratory studies. Management is primarily supportive with early involvement of the local Poison Control Center. Symptomatic patients generally require admission for further monitoring and treatment.

See also “Benzodiazepine overdose” and “Stimulant intoxication and withdrawal” for prescription stimulants.

Antidepressant overdosetoggle arrow icon

Overview [1]

Approach to antidepressant overdose [1][4]


Initial management

GI decontamination

Substance-specific management

Consults and disposition [1][4]

Guidance for disposition is limited. Disposition should be determined based on individual risk in consultation with Poison Control.

  • Consult psychiatry for all intentional overdoses.
  • Admit symptomatic patients for continuous monitoring.
  • Admit to the ICU if hemodynamic stabilization, mechanical ventilation, or dialysis is required.
  • Consider discharge after ≥ 6 hours of observation for asymptomatic patients with a normal ECG.

Tricyclic antidepressant overdosetoggle arrow icon

Mechanism of action [7]

Clinical features [1][7][8]

Diagnostics [1][4]

Tricyclic antidepressant (TCA) overdose is a clinical diagnosis, but studies may be performed to support the diagnosis and determine severity.

Serial ECGs should be performed to detect dynamic changes. [1]

The three Cs of tricyclic poisoning: Convulsions, Coma, and Cardiac conduction abnormalities (prolonged QTc interval).

Management [1][4]

Initial management

Symptom-specific management

In patients with TCA overdose, sodium bicarbonate can help overcome sodium channel blockade and prevent ventricular dysrhythmias, reduce conduction delays, and increase blood pressure. [1]

Class IA antiarrhythmics, class IC antiarrhythmics, and class III antiarrhythmics are contraindicated in TCA overdose. [1]

Physostigmine is contraindicated in patients with suspected TCA overdose because it can precipitate cardiac arrest. [4]

Disposition [1][4]

SSRI overdosetoggle arrow icon

Clinical features [1][4]

Selective serotonin reuptake inhibitors (SSRIs) have a high therapeutic index and thus overdoses are well-tolerated and rarely fatal. [4]

Diagnostics [1][4]

SSRI overdose is a clinical diagnosis.

Management [1][4]

SNRI overdosetoggle arrow icon

Clinical features [4]

Diagnostics [4]

Selective serotonin norepinephrine reuptake inhibitor (SNRI) overdose is a clinical diagnosis.

Management [4]

MAOI poisoningtoggle arrow icon

Clinical features [1]

MAOI poisoning can be due to overdose, food-drug interactions, or drug-drug interactions. The symptoms of MAOI overdose are distinct from those of MAOI poisoning caused by food-drug or drug-drug interactions.

MAOI overdose

Hyperadrenergic crisis

Tyramine is found in red wine, aged cheese, liver, smoked meat, and yeast extract. [1]

Hyperadrenergic crisis due to eating tyramine-containing foods can occur up to 3 weeks after discontinuation of MAOIs. [4]

Serotonin syndrome

Diagnostics [4]

MAOI poisoning is a clinical diagnosis.

Patients taking selegiline will test positive for methamphetamine on drug screening, as methamphetamine is a metabolite of selegiline. [4]

Management [1][4]

Avoid indirectly acting vasopressors (e.g., dopamine) in patients with hypotension, as their effectiveness is likely to be reduced as a result of catecholamine depletion. [4]

Disposition [1][4]

  • Asymptomatic patients with a suspected food-drug interaction may be discharged after ≥ 6 hours of observation.
  • Admit patients with MAOI overdose for further monitoring, preferably to the ICU.
  • Admit patients with autonomic instability or refractory hyperthermia to the ICU.

Bupropion overdosetoggle arrow icon

Clinical features [13]

Extended-release bupropion overdose is associated with delayed-onset seizures. [4]

Diagnostics [4]

Management [1][4]

Antipsychotic overdosetoggle arrow icon

Clinical features [1][9]

Symptoms of antipsychotic overdose develop within hours of ingestion and vary based on the drug's affinity for dopamine, muscarinic, and/or adrenergic receptors.

Diagnostics [1][4][14]

Antipsychotic overdose is mainly a clinical diagnosis based on a toxicological history and physical examination. Perform a toxicological risk assessment and obtain routine diagnostic studies.

Management [1][4][15]

Initial management

Symptom-specific management

Disposition [4]

Lithium poisoningtoggle arrow icon

Definitions [1][4]

Etiology [1][4]

Clinical features [1][4][17]

Lithium slowly redistributes from the serum into the CNS. Therefore, in acute poisoning, GI symptoms predominate early, while in chronic poisoning, neurological symptoms predominate. [4]

Diagnostics [1][4]

Lithium poisoning is diagnosed based on history, clinical features, and serum lithium levels.

Management [1][4]

Initial management

GI decontamination

Indications for hemodialysis [20]

Monitoring and disposition

  • Obtain serial serum lithium levels every 2–4 hours until two consecutive declining levels are observed. [4]
  • Symptomatic patients should be admitted for further monitoring and treatment.
  • Admit patients with indications for hemodialysis to the ICU.
  • Consider discharging asymptomatic patients with lithium levels within the therapeutic range after 6 hours (immediate-release) or 12 hours (sustained-release).

Clinical features rather than absolute serum lithium levels should guide treatment. [1]

Diuretics, osmotic agents, and carbonic anhydrase inhibitors are contraindicated in lithium poisoning, as they can worsen hypovolemia and increase lithium retention. [1]

Valproate poisoningtoggle arrow icon

Clinical features [1][21]

Diagnostics [1][22][23]

Valproate poisoning is diagnosed based on history, clinical features, and serum valproate levels.

Management [1][21]

Initial management

Indications for hemodialysis [24]

Referencestoggle arrow icon

  1. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. Goldfrank's Toxicologic Emergencies, 11th edition. McGraw-Hill Education ; 2019
  2. Patel J, Berezowski I, Mazer-Amirshahi M, Frasure SE, Tran QK, Pourmand A. Valproic Acid Overdose: Case Report and Literature Review. J Emerg Med. 2022; 63 (5): p.651-655.doi: 10.1016/j.jemermed.2022.07.009 . | Open in Read by QxMD
  3. Isbister GK, Balit CR, Whyte IM, Dawson A. Valproate overdose: a comparative cohort study of self poisonings. Br J Clin Pharmacol. 2003; 55 (4): p.398-404.doi: 10.1046/j.1365-2125.2003.01772.x . | Open in Read by QxMD
  4. Spiller HA, Spiller H, Krenzelok EP, et al. Multicenter Case Series of Valproic Acid Ingestion: Serum Concentrations and Toxicity. J Toxicol Clin Toxicol. 2000; 38 (7): p.755-760.doi: 10.1081/clt-100102388 . | Open in Read by QxMD
  5. Ghannoum M, Laliberté M, Nolin TD, et al. Extracorporeal treatment for valproic acid poisoning: Systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol. 2015; 53 (5): p.454-465.doi: 10.3109/15563650.2015.1035441 . | Open in Read by QxMD
  6. Prisco L, Sarwal A, Ganau M, Rubulotta F. Toxicology of Psychoactive Substances. Crit Care Clin. 2021; 37 (3): p.517-541.doi: 10.1016/j.ccc.2021.03.013 . | Open in Read by QxMD
  7. Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen's Emergency Medicine 10th edition- Concepts and Clinical Practice E-Book. Elsevier Health Sciences ; 2022
  8. Levine M, Ruha AM. Overdose of Atypical Antipsychotics. CNS Drugs. 2012; 26 (7): p.601-611.doi: 10.2165/11631640-000000000-00000 . | Open in Read by QxMD
  9. Minns AB, Clark RF. Toxicology and Overdose of Atypical Antipsychotics. J Emerg Med. 2012; 43 (5): p.906-913.doi: 10.1016/j.jemermed.2012.03.002 . | Open in Read by QxMD
  10. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020; 142 (16_suppl_2).doi: 10.1161/cir.0000000000000916 . | Open in Read by QxMD
  11. Bruccoleri RE, Burns MM. A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening. J Med Toxicol. 2015; 12 (1): p.121-129.doi: 10.1007/s13181-015-0483-y . | Open in Read by QxMD
  12. Van Kernebeek MW, Ghesquiere M, Vanderbruggen N, Verhoeven E, Hubloue I, Crunelle CL. Rivastigmine for the treatment of anticholinergic delirium following severe procyclidine intoxication. Clin Toxicol. 2020; 59 (5): p.447-448.doi: 10.1080/15563650.2020.1818768 . | Open in Read by QxMD
  13. Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016; 4 (1).doi: 10.1186/s40345-016-0068-y . | Open in Read by QxMD
  14. Grandjean EM, Aubry JM. Lithium: Updated Human Knowledge Using an Evidence-Based Approach. CNS Drugs. 2009; 23 (4): p.331-349.doi: 10.2165/00023210-200923040-00005 . | Open in Read by QxMD
  15. Thanacoody R, Caravati EM, Troutman B, et al. Position paper update: Whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol. 2014; 53 (1): p.5-12.doi: 10.3109/15563650.2014.989326 . | Open in Read by QxMD
  16. Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal treatment for lithium poisoning: rystematic review and recommendations from the EXTRIP workgroup. CJASN. 2015; 10 (5): p.875-887.doi: 10.2215/​CJN.10021014 . | Open in Read by QxMD
  17. Thanacoody HKR, Thomas SHL. Tricyclic Antidepressant Poisoning. Toxicol Rev. 2005; 24 (3): p.205-214.doi: 10.2165/00139709-200524030-00013 . | Open in Read by QxMD
  18. Kerr GW. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001; 18 (4): p.236-241.doi: 10.1136/emj.18.4.236 . | Open in Read by QxMD
  19. Waring WS. Clinical use of antidepressant therapy and associated cardiovascular risk. Drug Healthc Patient Saf. 2012: p.93.doi: 10.2147/dhps.s28804 . | Open in Read by QxMD
  20. Dear JW, Bateman DN. Antidepressants. Medicine. 2016; 44 (3): p.135-137.doi: 10.1016/j.mpmed.2015.12.027 . | Open in Read by QxMD
  21. Schreffler SM, Marraffa JM, Stork CM, Mackey J. Sodium Channel Blockade With QRS Widening After an Escitalopram Overdose. Pediatr Emerg Care. 2013; 29 (9): p.998-1001.doi: 10.1097/pec.0b013e3182a314b7 . | Open in Read by QxMD
  22. Shepherd G, Velez LI, Keyes DC. Intentional bupropion overdoses. J Emerg Med. 2004; 27 (2): p.147-151.doi: 10.1016/j.jemermed.2004.02.017 . | Open in Read by QxMD
  23. Howell C, Wilson AD, Waring WS. Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases. Br J Clin Pharmacol. 2007; 64 (2): p.192-197.doi: 10.1111/j.1365-2125.2007.02849.x . | Open in Read by QxMD
  24. Batista M, Dugernier T, Simon M, et al. The spectrum of acute heart failure after venlafaxine overdose. Clin Toxicol. 2013; 51 (2): p.92-95.doi: 10.3109/15563650.2012.763133 . | Open in Read by QxMD

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