A Case of Lithium Toxicity Masked by Behavioral Symptoms in a Psychiatric Patient

A 14-year-old female with a history of bipolar disorder, depression, and hypothyroidism presented to the emergency department with her mother for a psychiatric evaluation.

Her mother expressed concern that the patient had been "pocketing" her medications—lithium, quetiapine, and levothyroxine—by hiding them in her cheek and spitting them out over the past two weeks. On some of these occasions, the mother found her hiding the medication and was able to flush them down the toilet. Otherwise, medications were kept locked away to prevent independent access by the patient.

Additionally, the mother reported the patient had recently been eating poorly, often hiding her food. The mother was concerned this behavior might indicate a suicide attempt, as the patient had previously attempted to starve herself.

Over the past few days, the patient had exhibited increasingly erratic behavior, including episodes of violence followed by withdrawal. Family members noted this pattern had occurred multiple times before, and it was assumed that much of the patient's altered mental state was due to behavioral issues.

On physical examination in the ED, the patient was awake and alert, though her motor movements were slowed. She demonstrated diminished responsiveness to external stimuli and would not give verbal responses. Her oral mucous membranes were dry. She exhibited mild hyperreflexia in addition to inducible clonus in her lower extremities. Her vital signs were within normal limits.

Laboratory tests, including glucose, CBC, TSH, free T4, salicylate level, acetaminophen level, urine drug screen, urine pregnancy test, and ECG, all came back within normal limits. However, CMP revealed an elevated creatinine level of 1.30 mg/dL and hyponatremia with a sodium of 128 mEq/L. A lithium level was also obtained, which was elevated at 6.7 mEq/L.

Consultations with pediatric nephrology and toxicology were promptly initiated, and the patient was admitted to the pediatric ICU for fluid resuscitation and hemodialysis (HD).

Discussion

Distinguishing between medical and psychiatric causes of altered mental status (AMS) can be challenging, as the two may present with similar clinical manifestations.¹ As a result, patients with underlying psychiatric conditions who present with AMS are at heightened risk for misdiagnosis, though data on the frequency of such misdiagnoses remains limited.

Emergency physicians must maintain a high level of suspicion for potential organic or alternative causes of AMS in psychiatric patients, even when the clinical history strongly suggests a psychiatric etiology. This caution is especially critical in pediatric populations, where symptoms may be less apparent or misattributed to behavioral issues. Particular attention should be paid to physical exam findings, such as hyperreflexia and clonus in this case. These findings may help expand the differential diagnosis.

Physicians must also be vigilant when managing patients on high-risk medications, such as lithium, which has a narrow therapeutic index of 0.8–1.2 mEq/L.² Lithium toxicity, if not promptly recognized and addressed, can lead to catastrophic consequences. Severe intoxication may present with seizures, coma, hemodynamic instability, and even death.³ Additionally, physicians should be acutely aware of lithium’s renal excretion, as any degree of kidney impairment in a patient on lithium therapy can precipitate toxicity.

In any patient presenting with AMS who is prescribed lithium, obtaining a serum lithium level should be a part of the workup in the ED if available.

It is important to note that serum lithium levels do not fully reflect intracellular concentrations, where lithium exerts its pharmacologic effects. Consequently, treatment decisions should not be based solely on lithium levels but must also consider the patient's clinical symptoms.⁴

Treatment

Hemodialysis (HD) is the preferred treatment for severe lithium toxicity. Guidance on indications for HD is provided by the Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup. 

Per EXTRIP guidelines, extracorporeal treatment (ECTR) for lithium poisoning is recommended:

• If kidney function is impaired and the lithium is greater than 4.0 mEq/L  
• In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of lithium levels

Additionally, ECTR is suggested: 

• If the lithium level is greater than 5.0 mEq/L 
• If confusion is present 
• If the expected time to obtain a lithium level less than 1.0 mEq/L with optimal management is greater than 36 hours⁵

Case Conclusion

The patient underwent intermittent HD until her lithium levels declined and stabilized. Gradually, her mental status returned to baseline. Psychiatry was consulted and patient did admit to intentional lithium ingestion with suicidal intent. She described becoming physically ill in the days following ingestion, likely leading to her dehydration and worsening of lithium toxicity.

The initial differential diagnosis for this patient was broad. Dehydration raised the possibility of metabolic disturbances, while medication nonadherence suggested a potential exacerbation of hypothyroidism. The presence of lithium use raised concerns for lithium toxicity or serotonin syndrome, the latter of which can be precipitated by lithium.³ Although a psychiatric etiology for the AMS remained on the differential, it was ultimately considered a diagnosis of exclusion.

Obtaining a lithium level was paramount to the patient’s clinical course. Despite a history that did not strongly suggest lithium overdose and minimal physical exam findings indicative of lithium toxicity, the lithium level was crucial for guiding appropriate treatment. Without this diagnostic step, the patient may not have received timely HD, potentially leading to devastating consequences.

Clinical Pearls

• Maintain a high index of suspicion for medical causes of AMS in psychiatric patients. 
  Psychiatric symptoms may mask underlying medical causes of AMS. Always consider and rule out non-psychiatric causes such as toxicologic, metabolic disturbances, or medication-related issues. Look for subtle physical exam findings that can aid in the diagnosis.
• Obtain a lithium level in patients with AMS who are on lithium therapy. 
  Lithium toxicity can go unrecognized in patients with AMS. A reassuring history or vague symptoms should not deter the clinician from obtaining a lithium level when AMS is present in a patient taking lithium.
• Consider HD in patients with lithium toxicity. 
  In cases of lithium toxicity, HD is recommended (1) if kidney function is impaired and the lithium is greater than 4.0 mEq/L or (2) in the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of lithium levels.

References

1. Welch KA, Carson AJ. When psychiatric symptoms reflect medical conditions. Clin Med (Lond). 2018;18(1):80-87.
2. Chokhawala K, Lee S, Saadabadi A. Lithium. StatPearls. Jan 14, 2024. Accessed January 27, 2025.
3. Dunne FJ. Lithium toxicity: the importance of clinical signs. Br J Hosp Med (Lond). 2010;71(4):206-210.
4. Hedya SA, Avula A, Swoboda HD. Lithium toxicity. StatPearls. June 26, 2023. Accessed January 27, 2025.
5. Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2015;10(5):875-887.