Emergency Situations

22 Emergency Situations

A number of emergency situations may arise from iatrogenic effects of psychotropic medications. Such situations demand rapid identification. Discontinuation of a suspected causal agent often leads to resolution of many suspected iatrogenic emergencies, although a number of situations require specific forms of medical management. Table 22–1 provides a summary of common adverse psychotropic drug effects that may constitute medical emergencies.

Overdoses of psychotropic medications constitute their own form of medical emergency. Apart from the underlying psychiatric implications of an overdose (e.g., suicide attempts), some agents with relatively wide therapeutic indices may cause little more than an exaggeration of the adverse effects sometimes seen at lower dosages (e.g., sedation, nausea, emesis, headache, tremor). Others may cause more grave end-organ damage that requires vigilant monitoring of cardiovascular status, seizure risk, or renal or CNS sequelae. One must also bear in mind certain drug-specific idiosyncrasies in the setting of overdose: for example, after a toxic overdose of lithium carbonate, high penetration of lithium salts into brain and bone are prone to cause persistent risk for cardiac, renal, or neurotoxic lithium effects for weeks or months after serum lithium levels become undetectable.

Although it is beyond the scope of this summary to provide a comprehensive discussion of emergency medical management and detailed consequences of medication overdoses, Table 22–2 describes common signs and symptoms associated with overdoses of specific psychotropic drugs, as well as basic elements of their management. Notably, however, in the case of toxic overdose ingestions, gastric lavage procedures have generally not shown superior outcomes to the use of activated charcoal alone, and lavage generally is not recommended beyond 60 minutes after an acute ingestion.

TABLE 22–1.Emergency management of serious adverse drug effects
Emergent adverse effect	Clinical description	Associated agents	Management
Cardiovascular
Hypertensive crisis	Blood pressure exceeding 180/110; may include headache, dyspnea, mental status changes.	MAOIs, SNRIs	Discontinue causal agent.
Cutaneous
Purpura	Nonblanching hemorrhagic eruptions beneath the skin.	Carbamazepine	Indicative of thrombocytopenia; discontinue likely causal agent and refer for medical management.
Stevens-Johnson syndrome or toxic epidermal necrolysis	Blistering, burnlike lesions on mucocutaneous tissues; facial edema, lymphadenopathy.	Bupropion, carbamazepine, lamotrigine	Discontinue likely causal agent. Steroids may be indicated early in the course of disease but are contraindicated later in course. Do not rechallenge after a serious rash.
Gastrointestinal
Acute pancreatitis	Acute abdominal presentation; diagnose by clinical examination and elevated serum lipase and amylase. A history of pancreatitis unrelated to divalproex is not a known contraindication or predisposing risk factor for developing pancreatitis from divalproex.	Divalproex	Discontinue divalproex and do not reintroduce. Medical management mainly involves taking no food by mouth accompanied by intravenous hydration and rest.
Hematological
Aplastic anemia	—	Carbamazepine, clozapine	Discontinue offending agent. Monitor for the development of and treat infections (e.g., pharyngitis) that arise in the setting of an immunocompromised state. Bone marrow typically replenishes within 21 days without the need for further intervention.
Neurological
Acute dystonia	Markedly increased muscle tone and rigidity in extremities; difficulty swallowing or clearing salivary secretions may indicate laryngospasm.	All FGAs, particularly higher-potency agents that lack anticholinergic effects (e.g., haloperidol, fluphenazine)	Administer oral or intramuscular anticholinergic agents (e.g., diphenhydramine or benztropine).
Seizure	—	All FGAs, SGAs, bupropion	Maintain airway and safety; avoid aspiration or head injury.
Systemic
Aseptic meningitis	Systemic illness involving high fever, nuchal rigidity, nausea, vomiting, photophobia, confusion, depressed sensorium.	Lamotrigine	Discontinue lamotrigine.
Neuroleptic malignant syndrome	Fever, abdominal cramping, muscle rigidity; elevated CK (typically >1,000 IU/L).	All antipsychotics	Discontinue the antipsychotic; hydrate; administer dantrolene for marked autonomic instability that does not respond adequately to supportive treatment.
Serotonin syndrome	Clonus	SSRIs, SNRIs, tramadol	Discontinue serotonergic drugs; hydrate, maintain airway, consider cooling blankets.
Note. CK=creatine kinase; FGA=first-generation antipsychotic; MAOI=monoamine oxidase inhibitor; SGA=second-generation antipsychotic; SNRI=serotonin-norepinephrine reuptake inhibitor; SSRI=selective serotonin reuptake inhibitor.

TABLE 22–2.Clinical features associated with medication overdoses, and management^a
Agent	Maximum reported dose in overdose	Medical consequences	Management
Atomoxetine	1,400 mg	Gastrointestinal symptoms, somnolence, dizziness, tremor, abnormal behavior; reports of seizures, hyperactivity, agitation; rare QTc prolongation, disorientation, hallucinations.	Gastric lavage with administration of activated charcoal if recent ingestion. Monitor cardiac and vital signs.
Buspirone	375 mg	Nausea, vomiting, dizziness, miosis, gastric distress.	Gastric lavage if recent ingestion. Monitor vital signs. No specific management strategies apart from general supportive measures.
Anticonvulsants and lithium
Carbamazepine	>6,000 mg	Neuromuscular disturbances, irregular breathing, respiratory depression, tachycardia, hyper- or hypotension, shock, QRS prolongation and ventricular arrhythmias, impaired level of consciousness (including drowsiness or coma), nystagmus, mydriasis, seizures, nausea, vomiting, anticholinergic effects.	Maintain adequate airway; gastric lavage with activated charcoal may be considered; monitor cardiac rhythm and vital signs.
Divalproex	Maximum dose not reported; maximum recommended dose in epilepsy=60 mg/kg; maximum reported serum valproate level= 2,120 μg/mL	Fever, hallucinations, somnolence (CNS depression at doses > 200 mg/kg [valproate > 180 μg/mL]), hyperammonemia, tachycardia, heart block, coma; fatalities reported.	Supportive measures, gastric lavage with emesis. Naloxone (0.8–2.0 mg) may reverse the CNS depressant effects of divalproex.
Gabapentin	49,000 mg	Ataxia, labored breathing, ptosis, sedation, hypoactivity, excitation, double vision, slurred speech, drowsiness, lethargy, diarrhea; no fatalities reported.	Supportive care, cardiovascular monitoring, gastric lavage. Gabapentin is dialyzable.
Lamotrigine	15,000 mg (oral LD₅₀=250 mg/kg in rats)	Dizziness, diplopia or blurry vision, rotatory or downbeat nystagmus, truncal ataxia, cognitive disorganization; fatalities reported.	Supportive care, cardiovascular monitoring, induction of emesis, gastric lavage.
Lithium	Not reported; serum levels>3 mEq/L may produce seizures, coma, and death; maximum recommended dose=2,400 mg/day	Neurotoxicity (ataxia, nystagmus, tremor, slow shuffling gait, myoclonic jerks, confusion and disorientation), GI symptoms (nausea, vomiting, abdominal cramps, diarrhea), and cardiac toxicity (including sinus bradycardia and sinoatrial- or atrioventricular block that can produce complete heart block [Serinken et al. 2009]); reports of pulmonary edema; mortality results from CNS toxicity and subsequent cardiovascular collapse.	Consequences of lithium toxicity may persist for weeks or even months after serum lithium levels become undetectable. Following acute overdose, measurement of plasma lithium–erythrocyte lithium ratios may reveal higher lithium in plasma than erythrocytes. Management involves hydration, gastric lavage (although activated charcoal does not bind lithium well and tends not to be recommended), and cardiac monitoring; hemodialysis is rarely necessary for serum lithium levels <2.5 mEq/L but is usually required for levels >6 mEq/L, or for lower levels in medically debilitated patients or patients with coma, convulsions, cardiovascular symptoms, or respiratory failure.
Oxcarbazepine	24,000 mg	Somnolence, hypotension, tremor, seizures, diplopia, dyspnea, miosis, nystagmus, decreased urine output; no fatalities reported.	Supportive care, gastric lavage with activated charcoal is recommended.
Topiramate	110,000 mg	Stupor or coma, severe metabolic acidosis, convulsions, drowsiness, speech disturbances, blurred vision, diplopia, cognitive impairment, lethargy, abnormal coordination, hypotension, abdominal pain, agitation, dizziness, depression; no reported fatalities.	Gastric lavage or induction of emesis if recent ingestion. Activated charcoal is not thought to absorb topiramate.
Antidepressants
Bupropion	17,500 mg	Seizure (~1/3 of cases), hallucinations, loss of consciousness, tachycardia.	Maintain adequate airway; cardiac monitoring; gastric lavage if soon after ingestion (but not induction of emesis), with administration of activated charcoal. EEG monitoring is advised for first 48 hours.
Citalopram	6,000 mg	Dizziness, sweating, nausea, vomiting, tremor, somnolence, tachycardia; QTc prolongation, nodal rhythms, ventricular arrhythmias, and torsades de pointes reported.	Maintain adequate airway; gastric lavage with activated charcoal may be considered; monitor cardiac rhythm and vital signs.
Desvenlafaxine	>600 mg	Tachycardia, somnolence, mydriasis, seizures, vomiting, hypotension, liver necrosis, rhabdomyolysis, serotonin syndrome; QTc or QRS prolongation and bundle branch block on ECG.	Maintain adequate airway; monitor cardiac rhythm and vital signs; gastric lavage if soon after ingestion.
Escitalopram	>1,000 mg	Seizures, coma, dizziness, hypotension, insomnia, acute renal failure, tachycardia; QTc prolongation and rare torsades de pointes on ECG.	Maintain adequate airway; cardiac monitoring; gastric lavage if soon after ingestion.
Fluoxetine	8,000 mg	Variable outcomes (e.g., full recovery) after 8,000-mg ingestion, although 34 fatalities reported by manufacturer following 633 monotherapy overdoses; signs of overdose include seizures, nausea, vomiting, tachycardia, somnolence; more severe overdoses may lead to visual and gait disturbances, confusion, unresponsiveness, nervousness, respiratory distress, tremor, hypertension, impotence, movement disorders, hypomania.	Maintain adequate airway; cardiac rhythm and vital sign monitoring; gastric lavage if soon after ingestion. Do not induce emesis. Beware of coingestion of TCAs and the pharmacokinetic potential for their increased accumulation.
Fluvoxamine	12,000 mg	Variable outcomes (e.g., full recovery after 12,000-mg ingestion but lethality after 1,400-mg ingestion); signs of overdose include GI upset, coma, hypokalemia, hypotension, respiratory difficulties, somnolence, tachycardia, bradycardia, QTc prolongation, first-degree AV block and other arrhythmias, seizures, tremor, hyperreflexia.	Maintain adequate airway; cardiac rhythm and vital sign monitoring; gastric lavage if soon after ingestion. Beware of coingestion of TCAs and the pharmacokinetic potential for their increased accumulation.
Levomilnacipran	360 mg	Not described; no fatalities reported.	Supportive care; no specific interventions recommended.
Mirtazapine	975 mg (Fawcett and Barkin 1998)	Disorientation, somnolence, impaired memory, tachycardia; no known potential for seizures or ECG abnormalities; unlikely fatality.	Maintain adequate airway; monitor cardiac rhythm and vital signs. Gastric lavage with activated charcoal if soon after ingestion. Induction of emesis is not recommended.
Nefazodone	11,200 mg	Nausea, vomiting, somnolence; fatalities reported when overdoses occurred in combination with other substances.	Maintain adequate airway; monitor cardiac rhythm and vital signs. Gastric lavage if soon after ingestion. Induction of emesis is not recommended.
Paroxetine	2,000 mg	Somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, dizziness.	Maintain adequate airway; gastric lavage if soon after ingestion (but not induction of emesis), with administration of activated charcoal.
TCAs	Not reported	Drowsiness, lethargy, confusion, tachycardia, hyper- or hypotension, urinary retention with desipramine (highest risk for fatality due to potent sodium channel blockade), nortriptyline, imipramine, amitriptyline, clomipramine, protriptyline, doxepin.	Cardiac monitoring; intravenous hydration (observe for hypotension due to sodium channel blockade); gastric lavage with activated charcoal if within first few hours after ingestion; intravenous administration of sodium bicarbonate (alkalinize urine) if QRS > 100 msec, ventricular arrhythmias; observe for seizure risk (highest in first several hours after ingestion; may require anticonvulsant benzodiazepines, phenobarbital, or other antiseizure therapy). Avoid β-blockers, calcium channel blockers, ipecac syrup.
Vilazodone	280 mg	Serotonin syndrome, lethargy, restlessness, hallucinations, disorientation.	Maintain adequate airway; monitor cardiac rhythm and vital signs. Gastric lavage with activated charcoal if soon after ingestion. Induction of emesis is not recommended.
Vortioxetine	75 mg	Nausea, dizziness, diarrhea, abdominal discomfort, pruritis, somnolence, flushing.	Supportive care.
Anxiolytics/Sedative-hypnotics
Benzodiazepines	Not reported	Somnolence, confusion, coma, hyporeflexia, hypotension, miosis or sluggish/delayed pupillary responses, nystagmus.	Supportive care including cardiovascular monitoring, gastric lavage, and intravenous hydration. Flumazenil may be administered to reverse sedative effects of benzodiazepines.
Buspirone	375 mg	Nausea, vomiting, dizziness, drowsiness, miosis, gastric distress; no fatalities reported.	Supportive care, cardiovascular monitoring.
Eszopiclone	270 mg	Somnolence, coma, rare fatalities when combined with other CNS drugs or alcohol.	Immediate gastric lavage where appropriate; IV fluids; flumazenil may be useful; monitor vital signs; general supportive care.
Ramelteon	Not reported	Somnolence.	General supportive care; gastric lavage where appropriate; IV fluids as needed.
Suvorexant	240 mg	Somnolence.	General supportive care; gastric lavage where appropriate; IV fluids as needed.
Tasimelteon	Not available	Somnolence.	General supportive care; gastric lavage where appropriate; IV fluids as needed.
Zaleplon	200 mg	CNS depression, drowsiness, coma, ataxia, hypotonia, hypotension, respiratory depression, rare fatalities.	General supportive care; gastric lavage where appropriate; IV fluids as needed; flumazenil may be appropriate; monitor vital signs.
Zolpidem	Not available	Somnolence, coma, cardiovascular and respiratory compromise, possible fatality.	General supportive care; gastric lavage where appropriate; IV fluids as needed; flumazenil may be useful (but may lead to convulsions); monitor vital signs.
Psychostimulants
Amphetamine	Deaths reported at dosages > 1.3 mg/kg	Restlessness, tremor, hyperreflexia, tachypnea, confusion, assaultiveness, hallucinations, panic, hyperpyrexia, rhabdomyolysis, convulsions, coma, arrhythmias, hypo- or hypertension, circulatory collapse, nausea, vomiting, diarrhea, abdominal cramps, death.	General supportive care; gastric lavage where appropriate; administration of activated charcoal; IV phentolamine may counteract hypertension, if necessary; chlorpromazine antagonizes the central stimulant effects of amphetamine and may be useful.
Methylphenidate	1,134 mg (Klampfl et al. 2010)	Vomiting, agitation, muscle twitching, seizures, confusion, psychosis, hyperhidrosis, headache, fever, tachycardia, palpitations, rhabdomyolysis, mydriasis, dry mouth, death.	General supportive care; gastric lavage where appropriate; administration of activated charcoal.
Modafinil	12,000 mg	Excitation, agitation, restlessness, insomnia, disorientation, confusion, hallucinations, nausea, diarrhea, tremor, tachycardia, bradycardia, hypertension, chest pain; no fatalities reported.	Supportive care, cardiovascular monitoring, induction of emesis or gastric lavage if not contraindicated.
SGAs
Aripiprazole	1,260 mg	Vomiting, somnolence, tremor, confusion, bradycardia, tachycardia, QTc prolongation, coma, respiratory failure, seizures.	Supportive care, cardiac monitoring; activated charcoal if given soon after ingestion may reduce serum levels.
Asenapine	400 mg	Agitation, confusion.	Maintain adequate airway; cardiac monitoring. Monitor for possible hypotension and circulatory collapse. Anticholinergic medication should be used if severe EPS occur.
Brexpiprazole	Not available	Not described.	Supportive monitoring, maintenance of airway; administration of activated charcoal if within 4 hours of overdose.
Cariprazine	48 mg	Orthostatic hypotension, sedation.	Supportive monitoring, maintenance of airway; no other specific intervention recommended.
Iloperidone	576 mg	Drowsiness, sedation, tachycardia, hypotension, EPS, QTc prolongation; no fatalities reported.	Maintain adequate airway; cardiac monitoring; gastric lavage if soon after ingestion with activated charcoal plus a laxative should be considered. Cardiac monitoring should include continuous electrocardiography due to the risk for arrhythmias. Monitor for seizure risk and dystonic reactions.
Lurasidone	560 mg	Recovery without medical sequelae.	Avoid α-adrenergic blocking agents or sympathomimetic drugs with β-agonist activity (e.g., epinephrine, dobutamine) to minimize risk for hypotension; avoid disopyramide, procainamide, or quinidine if arrhythmias occur, to minimize additive risk for QTc prolongation. No sequelae following single overdose case of 560 mg/day.
Olanzapine	1,500 mg	Agitation, dysarthria, tachycardia, EPS, reduced level of consciousness or coma; fatality from overdoses of olanzapine alone reported from doses as low as 450 mg.	Maintain adequate airway; cardiac monitoring; gastric lavage if soon after ingestion with activated charcoal plus a laxative should be considered. Cardiac monitoring should include continuous electrocardiography due to the risk for arrhythmias.
Paliperidone	405 mg	Gait unsteadiness, drowsiness, EPS, seizures, QTc prolongation, tachycardia, hypotension.	Maintain adequate airway; cardiac monitoring; gastric lavage if soon after ingestion. Anticholinergic agents should be used for severe EPS. Intravenous hydration may be necessary to counteract hypotension. Avoid parenteral epinephrine or dopamine because beta stimulation may exacerbate hypotension from paliperidone-induced alpha blockade.
Pimavanserin	Unavailable	Nausea, vomiting, possible QTc prolongation.	Immediate cardiovascular/continuous ECG monitoring; if antiarrhythmics are needed, avoid agents that may further prolong QTc (e.g., procainamide, quinidine, disopyramide).
Quetiapine	9,600 mg	Drowsiness, sedation, tachycardia, hypotension, hypokalemia, first-degree heart block; prolonged delirium described in adolescents.	Maintain adequate airway; cardiac monitoring; gastric lavage with activated charcoal and a laxative if soon after ingestion; continuous ECG monitoring.
Risperidone	360 mg	Drowsiness, sedation, tachycardia, hypotension, EPS, electrolyte abnormalities, seizures, QTc prolongation with QRS widening on ECG.	Maintain adequate airway; cardiac monitoring; gastric lavage with activated charcoal and a laxative if soon after ingestion; continuous ECG monitoring.
Ziprasidone	3,240 mg	Sedation, slurred speech, transient hypertension, EPS, somnolence, tremor, anxiety.	Maintain adequate airway; cardiac monitoring; gastric lavage if soon after ingestion.
Note. AV=atrioventricular; CNS=central nervous system; ECG=electrocardiogram; EEG=electroencephalogram; EPS = extrapyramidal symptoms; GI=gastrointestinal; IV=intravenous; SGA=second-generation antipsychotic; TCA=tricyclic antidepressant. ^aInformation based on manufacturers’ package insert materials.