Common Psychiatric Medications: Pearls & Pitfalls for the ED

Authors: Paul Zentko, MD (EM Resident Physician, Mount Sinai St. Luke’s-West Hospital) and Christopher Hahn, MD (Emergency Medicine Attending Physician, Assistant Residency Director, Mount Sinai St. Luke’s-West Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case

A 22-year-old female presents to your emergency department with fever for 8 days.  She was diagnosed with influenza early in the course after a positive nasal swab.  The symptoms have not changed, and she is now having pain in her right upper back and not tolerating food or drink.  Vitals signs are blood pressure 111/71, Temp 102.2 F (oral), HR 122, RR 21, O2 sat 97%. She had taken 650 mg acetaminophen 2 hours prior to arrival.  Her only past medical history is bipolar disorder well controlled.  She is nontoxic, appropriately ill-appearing given her vital signs.  She has decreased breath sounds on the right side to auscultation.  You initiate a sepsis workup with blood cultures, antibiotics, IV fluids, and toradol for fever, and chest x-ray confirms a dense right lower lobe pneumonia.  Aside from WBC 14.2 and lactate 2.2, the labs are within normal limits.  She remains stable in the ED and is admitted to the observation unit for 24 hours of IV antibiotics and hydration.  Eight hours after admission she develops tremors, lethargy, and mild diarrhea, and neuro exam is notable for hyperreflexia.

Background

Emergency physicians encounter psychiatric medications in a variety of ways on any given shift.  The acutely agitated patient who does not respond to verbal de-escalation may be chemically sedated, frequently with antipsychotics or benzodiazepines. Another, more common occurrence, is encountering a patient with a psychiatric history or one who is prescribed a drug for their emotional and/or mental health.  In fact, in 2013 nearly 1 in 6 adults in the U.S. filled a prescription for a psychiatric medication, most commonly antidepressants, sedatives/hypnotics, anxiolytics, or antipsychotics.¹  Amongst all adult ED visits for adverse drug reactions, it is estimated approximately 10% are related to psychiatric drugs.²  Whether these drugs are listed in your patient’s medication list or a patient comes with an acute adverse reaction or overdose, it is critical to be familiar with several common psychiatric medications.

Selective Serotonin Reuptake Inhibitors (SSRI)

Approximately 7% of adults in the U.S. experience a major depressive episode in a given year.³  SSRIs are often a first line treatment for depression due to a favorable side effect profile when compared to other antidepressants, especially tricyclics or monoamine oxidase inhibitors.⁴  A wide range of conditions can be treated with these drugs including depression, panic disorder, anorexia/bulimia, alcoholism, and obsessive compulsive disorder. Citalopram (Celexa), Escitalopram (Lexapro), Sertraline (Zoloft), Fluoxetine (Prozac), and Paroxetine (Paxil) are some of the more common antidepressants prescribed today.  SSRIs generally have a similar side effect profile. Common side effects of SSRIs at therapeutic doses include insomnia, myalgias, headaches, dizziness, rashes, GI upset, and sexual dysfunction.

What the emergency physician should know about SSRIs

In the ED we frequently evaluate for toxic effects of these drugs.  SSRIs are relatively well tolerated and generally have a high toxicity ratio.  An overdose of SSRI by itself is rarely fatal unless taken in extremely large doses.  They are unlikely to have serious side effects, even up to thirty times recommended dosing.⁵  Nausea, vomiting, dizziness, blurry vision, CNS depression, and tachycardia are typical symptoms in most acute ingestions.  Coingestion with alcohol or other substances increase risk of dangerous sequelae.  Having a high clinical suspicion for serotonin syndrome is critical, as numerous medications have the potential, in combination with SSRIs, to induce this condition.  A detailed medication list should be obtained if possible.  Classic symptoms of serotonin syndrome include agitation, myoclonus, altered mental status, diaphoresis, muscle rigidity, hyperthermia, tremor, and hyperreflexia.  Isolated ingestions of SSRI, however, rarely cause serotonin syndrome.  This emDocs post and this ToxCard have more on serotonin syndrome.

Two members of the SSRI class with dangerous toxic effects are citalopram and escitalopram.  These specific drugs are known to increase risk of seizure and QT prolongation in a dose dependent manner, usually with seizures occurring early, whereas subsequent EKG changes may be delayed up to 24 hours.^6,7 Seizures occur relatively infrequently with SSRIs in general, however, they can be relatively common (approximately 13%) in isolated citalopram overdoses.⁸

Management of acute ingestion of SSRI is mainly supportive.  Obtain an EKG to screen for cardiotoxic effects of other potentially co-ingested drugs. Discuss the case with poison control or toxicology. Consider giving activated charcoal, as it may reduce risk of QT prolongation if given early after ingestion.   In general, small overdoses of a known quantity are generally easily managed with close observation and do not warrant specific treatment or admission.  Citalopram and escitalopram, especially in higher doses, may need longer observation or admission, as neurotoxic and cardiotoxic effects are dose dependent and may have delayed effects.

Patients who abruptly stop taking their SSRI may experience discontinuation syndrome with nonspecific symptoms like dizziness, nausea, lethargy, and paresthesias.  Continuing the medication and discontinuing on a taper can reduce symptoms.

Two members of the SSRI class with dangerous toxic effects are citalopram and escitalopram.  These specific drugs are known to increase risk of seizure and QT prolongation in a dose dependent manner, usually with seizures occurring early, whereas subsequent EKG changes may be delayed up to 24 hours.^6,7 Seizures occur relatively infrequently with SSRIs in general, however they can be relatively common (approximately 13%) in isolated citalopram overdoses.⁸

Management of acute ingestion of SSRI is mainly supportive.  Obtain an EKG to screen for cardiotoxic effects of other potentially co-ingested drugs. Discuss the case with poison control or toxicology. Consider giving activated charcoal as it may reduce risk of QT prolongation if given early after ingestion.   In general, small overdoses of a known quantity are generally easily managed with close observation and do not warrant specific treatment or admission.  Citalopram and escitalopram, especially in higher doses, may need longer observation or admission, as neurotoxic and cardiotoxic effects are dose dependent and may have delayed effects.

Patients who abruptly stop taking their SSRI may experience discontinuation syndrome with nonspecific symptoms like dizziness, nausea, lethargy, and paresthesias.  Continuing the medication and discontinuing on a taper can reduce symptoms.

Lithium

Another drug emergency physicians frequently come across is lithium.  A simple drug with complex mechanisms of action and numerous toxic effects, it is relatively common, as approximately 1 in 1000 people in developed countries are prescribed a form of lithium.⁹  It is effective in treating and preventing mania and depression seen in bipolar disorder, augmenting an established antidepressant regimen, and demonstrating anti-suicidal effects.  Emergency physicians must consider if their patient is on a formulation of this drug, otherwise unforeseen medication interactions may cause harm.

Lithium excretion occurs almost exclusively by the kidneys and is similar to sodium in being reabsorbed at a high rate in proximal tubules.  Development of lithium toxicity can therefore occur in situations that increase renal sodium absorption including low sodium intake and dehydration.  Furthermore, progressive chronic renal failure, advancing age with associated reduced GFR, and numerous drugs which affect kidney function (thiazides, NSAIDs, aminoglycosides, bactrim, etc) are known risk factors for lithium toxicity.^9-11  Emergency physician must be aware of the risk of iatrogenic lithium toxicity when ordering or prescribing medications with renal effects.

What the emergency physician should know about lithium toxicity and adverse effects

The therapeutic window for lithium is narrow, with 1.2 mmol/L generally being the acceptable upper limit of normal.  Acute ingestions present early with GI symptoms of diarrhea, nausea, and vomiting.  Neurologic symptoms are typically a late finding in acute toxicity, as lithium slowly redistributes to the central nervous system.  You may see confusion, tremors, ataxia, and agitation. An EKG may show T wave changes, but it is uncommon to have significant cardiac dysfunction in acute lithium overdose.¹¹²  Chronic toxicity typically demonstrates neurologic symptoms early, such as progression of an existing tremor, hyperreflexia, clonus, ataxia, altered mental states, seizures, or encephalopathy.

Systemic manifestations of chronic lithium use may lead to renal dysfunction including nephrogenic diabetes insipidus or tubulointerstitial nephropathy.  Thyroid dysfunction, mainly hypothyroidism, can occur.  In pregnancy, lithium may lead to multiple fetal impairments including Ebstein’s anomaly, hypothyroidism, and neurotoxic sequela previously discussed.

ED Management

After initial evaluation and stabilization of airway, breathing, and circulation, determine if the patient has an acute or chronic lithium exposure and if the formulation is immediate or sustained release. Immediate release formulations are rapidly absorbed.  Activated charcoal does not adsorb lithium effectively and should only be considered as treatment for a possible coingestant.  For sustained release formulations, whole bowel irrigation is the only decontamination method to show efficacy.¹³  Give IV fluids to correct intravascular volume loss that results from vomiting/diarrhea in acute poisoning.  IV fluids will help restore renal function in chronic poisoning resulted from an acute kidney injury.  Hemodialysis should be started for any patient with severe neurotoxic symptoms, toxicity in the setting of advanced renal failure, or patients who cannot tolerate fluid replacement to increase filtration in the kidneys (congestive heart failure, cirrhosis, etc).

Obtain a lithium level in acute or chronic lithium exposure, but the level should not be used as a marker of toxicity by itself. The history, symptoms, and clinical presentation should guide therapy.  Check electrolytes and renal function.  Consider obtaining serum and urine electrolytes and osmolality if nephrogenic diabetes insipidus is suspected due to hypernatremia.  Consider checking thyroid function if hypothyroidism is suspected.

Antipsychotics

A relatively new class of medications developed in the mid 1900s, these drugs are widely used in a variety of ways. Treatment of positive and negative symptoms of schizophrenia, intractable hiccups, acute agitation in intoxicated persons, agitation in the elderly or cognitively impaired, and increasing reported use for functional abdominal pain or cannabinoid-induced hyperemesis are a few.  These drugs are more commonly classified as “typical” or “atypical”.  Typical antipsychotics classically treated positive symptoms of schizophrenia, but without significant improvement in negative symptoms.  In addition, they were associated with a higher rate of extrapyramidal side effects and neuroleptic malignant syndrome.  In comparison to typical antipsychotics, the atypical drugs tend to control both positive and negative symptoms of schizophrenia.  The side effect profile is more favorable with less risk of extrapyramidal symptoms.

What the emergency physician should know about antipsychotics

Antipsychotics in general have increased risk of sudden cardiac death.¹³  Some antipsychotics have a greater tendency of QT prolongation.  In the acutely agitated patient requiring chemical sedation, some common medications used are haloperidol, olanzapine (Zyprexa), and ziprasidone (Geodon).  A comprehensive overview on safely sedating agitated patients is seen here.  If it is suspected or known that a patient takes antipsychotics, then obtain an EKG once it is safe to do so, especially if multiple doses of an antipsychotic were administered for sedation.  An EKG is quick, easy to obtain, and allows early identification for those at risk of torsades due to prolonged QT.  These patients should be placed on a monitor to identify associated arrhythmia if QT is prolonged.  In the non-agitated patient, use caution when administering or prescribing medications in the ED.  QT prolonging agents such as quinolones for pneumonia, or repeat doses of ondansetron for nausea and vomiting, pose a risk at well.  Consider providing another drug without QT prolonging effects if possible.

Maintain a high clinical suspicion for neuroleptic malignant syndrome (NMS) in ill appearing patients on antipsychotics.  This dangerous complication occurs more commonly at therapeutic or recently adjusted doses.  Symptoms typically occur over several days and usually less than two weeks within starting treatment.  Classic symptoms are hyperthermia, autonomic dysfunction, altered mental status, and rigidity.  While sharing a similar presentation to NMS, serotonin syndrome differs from NMS due to a prevalence of myoclonus and hyperreflexia, in addition to a much shorter time course to symptom onset (hours).  For more on differentiating NMS and SS, see this emDocs post and this ToxCard.

Acute overdose of antipsychotics is managed with symptomatic treatment, with special attention to potential cardiovascular and central nervous system effects.  Hypotension can be treated with fluids and vasopressors as needed.  QRS widening on EKG may be seen and managed with boluses of sodium bicarbonate, similar to a TCA ingestion.  CNS depression ranging from mild lethargy to coma is possible.  Anticholinergic toxidromes may be seen, even in atypical antipsychotics overdoses, resulting in tachycardia, urinary retention, and dry skin. Respiratory depression requiring intubation is rare in single drug ingestions.

Case Conclusion

Repeat blood work shows an increase in creatinine from 1.1 to 1.9.  It is noted that the patient takes lithium, and a serum level is within normal limits at 0.9.  It is suspected the toradol initially given in the ED caused acute kidney injury in the setting of her infection, resulting in lithium toxicity.  The patient is upgraded to a full admission and resuscitated with fluids, withholding her lithium, and provided symptom control. She is discharged 2 days later with normalized renal function and complete resolution of her symptoms.

Pearls

-Psychotropic drugs have multiple potential adverse effects. Take a moment to consider what drugs a patient takes at home and what you offer them in the ED.

–Citalopram and Escitalopram are different from other SSRIs; beware of seizures and QT on EKG.

-Use caution when administering medications with renal effects to someone taking lithium.

Pitfalls

-Failure to take a thorough medication history in patients taking psychotropic drugs.

-Not considering that lithium is primarily renally excreted.

-Failing to obtain an EKG for a chemically sedated patient when multiple doses of antipsychotics are given (or when the patient is known to be taking a QT prolonging agent).

-Failing to consider serotonin syndrome or neuroleptic malignant syndrome in the ill appearing patient on psychotropic drugs.

Dr. Katy Hanson has a great review of psychiatric medications, from Hanson’s Anatomy:

References/Further Reading:

1. Moore, T. and Mattison, D. (2017). Adult Utilization of Psychiatric Drugs and Differences by Sex, Age, and Race. JAMA Internal Medicine, 177(2), p.274

2. Hampton, L., Daubresse, M., Chang, H., Alexander, G. and Budnitz, D. (2014). Emergency Department Visits by Adults for Psychiatric Medication Adverse Events. JAMA Psychiatry, 71(9), p.1006

3. nih.gov. (2018). NIMH » Major Depression. [online] Available at: https://www.nimh.nih.gov/health/statistics/major-depression.shtml [Accessed 23 May 2018].

4. Nierenberg, A., Ostacher, M., Huffman, J., Ametrano, R., Fava, M. and Perlis, R. (2008). A Brief Review of Antidepressant Efficacy, Effectiveness, Indications, and Usage for Major Depressive Disorder. Journal of Occupational and Environmental Medicine, 50(4), pp.428-436.

5. Barbey, JT, Roose, SP (1998). SSRI Safety in Overdose. Journal of Clinical Psychiatry, 59(15), pp. 42-8.

6. Isbister, G., Friberg, L., Stokes, B., Buckley, N., Lee, C., Gunja, N., Brown, S., MacDonald, E., Graudins, A., Holdgate, A. and Duffull, S. (2007). Activated Charcoal Decreases the Risk of QT Prolongation After Citalopram Overdose. Annals of Emergency Medicine, 50(5), pp.593-600.e46.

7. Personne, M., Sjöberg, G. and Person, H. (1997). Citalopram Overdose-Review of Cases Treated in Swedish Hospitals. Journal of Toxicology: Clinical Toxicology, 35(3), pp.237-240.

8. Reichert, C., Reichert, P., Monnet-Tschudi, F., Kupferschmidt, H., Ceschi, A. and Rauber-Lüthy, C. (2014). Seizures after single-agent overdose with pharmaceutical drugs: Analysis of cases reported to a poison center. Clinical Toxicology, 52(6), pp.629-634.

9. Greller HA. Lithium. In: Goldfrank’s Toxicologic Emergencies 9th edition. Nelson LS, et al (Eds). New York, NY, McGraw-Hill 2011.

10. Demers, R. (1971). Electrocardiographic T-Wave Changes During Lithium Carbonate Treatment. JAMA: The Journal of the American Medical Association, 218(3), p.381. From https://www.uptodate.com.

11. Offerman, S., Alsop, J., Lee, J. and Holmes, J. (2010). Hospitalized lithium overdose cases reported to the California Poison Control System. Clinical Toxicology, 48(5), pp.443-448. From https://www.uptodate.com.

12. Smith, S., Ling, L. and Halstenson, C. (1991). Whole-bowel irrigation as a treatment for acute lithium overdose. Annals of Emergency Medicine, 20(5), pp.536-539. From https://www.uptodate.com.

13. Ray, W., Chung, C., Murray, K., Hall, K. and Stein, C. (2009). Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. New England Journal of Medicine, 360(3), pp.225-235.