Severe Lithium Toxicity due to the Use of Unauthorized Weight Loss Medication

Abstract

A 39-year-old female patient, followed in outpatient care for bipolar I disorder, effectively treated with lithium since January 2022 (a dose of 18 mmol 2× per day and latest plasma concentrations around 0.85 mmol/L during the last months), and flurazepam (30 mg/j) for sleep onset difficulties, was referred to the emergency department for involuntary admission on August 13 by her psychiatrist for suspicion of a manic episode with mixed features.

Upon arrival at the psychiatric emergency department, the patient was confused, with disorganized thinking, disoriented as far as the situation, the place and the time, a marked psychomotor slowing, bilateral miosis, spontaneous tremors, jaw dysarthria and muscle rigidity. She reported taking lithium as prescribed (18 mmol 2×/day), flurazepam (30 mg per day), and a weight-loss treatment which she had procured, without prescription, online (of a composition unknown to the patient). Biological tests revealed acute kidney injury (KDIGO III), with elevated lithium levels at 3.94 mmol/L, hypokalemia at 2.6 mmol/L, and hypophosphatemia at 0.22 mmol/L. A prolonged QTc of 570 ms was also noted. A brain CT scan ruled out any intracranial hemorrhage.

Lithium remains a cornerstone in managing bipolar disorder due to its efficacy in stabilizing mood fluctuations. However, its narrow therapeutic index necessitates rigorous monitoring, as interactions with other substances can precipitate toxicity. This case exemplifies the dangers associated with unregulated weight-loss supplements, which may contain undisclosed pharmacologically active ingredients [2]. The toxicological analysis of the patient's weight-loss product revealed the presence of fluoxetine, furosemide, hydrochlorothiazide, metformin, and sibutramine. The inclusion of diuretics such as furosemide and hydrochlorothiazide is particularly concerning, as they can reduce renal lithium clearance, leading to elevated serum lithium levels and potential toxicity. Additionally, sibutramine, an appetite suppressant withdrawn from the market due to cardiovascular risks, and fluoxetine, a selective serotonin reuptake inhibitor, can further complicate the clinical picture through their own side effect profiles and potential interactions. The prevalence of dietary supplements adulterated with pharmaceutical agents is a growing public health concern. A study assessing the US Food and Drug Administration's Tainted Supplements Database from 2007 through 2016 identified numerous products marketed for weight loss containing undeclared substances, including sibutramine and various diuretics [3]. These adulterated supplements pose significant health risks, especially when consumed without medical supervision. According to research, nonprescription weight-loss product use remains common, despite the potential for severe adverse effects [4]. Additionally, a systematic review identified a high prevalence of adolescent use of nonprescription weight-loss products, further emphasizing the necessity of stricter regulations and public awareness campaigns [5].

Patients with bipolar disorder may seek over-the-counter weight-loss products to address medication-associated weight gain, often without disclosing this to their healthcare providers. This behavior underscores the necessity for clinicians to proactively inquire about all substances patients are taking, including non-prescription products. Failure to do so can result in a confirmation bias, where new or worsening symptoms are misattributed solely to psychiatric causes, potentially overlooking underlying non-psychiatric issues such as medication interactions or toxicities. Beyond the pharmacological interaction with diuretics, rapid weight loss and associated volume depletion may have further reduced renal lithium clearance, thereby promoting lithium accumulation. Psychoeducation plays a pivotal role in preventing such adverse events. Educating patients on the potential risks of unapproved supplements and the importance of reporting all ingested substances can aid in early identification of toxicity. Moreover, informing patients about the early signs of lithium overdose—including gastrointestinal disturbances, tremors, confusion, and neuromuscular excitability—can facilitate prompt medical attention and intervention.

In conclusion, this case highlights the imperative for comprehensive medication reconciliation and patient education in those receiving lithium therapy. Clinicians must maintain a high index of suspicion for potential interactions with over-the-counter products and provide thorough education on the risks associated with unregulated supplements and the early manifestations of lithium toxicity.

The data that support the findings of this study are available from the corresponding author upon reasonable request.