Lithium absorption unpredictability after bariatric surgery: When different ways of administration of mood stabilizers should be prescribed

Dear Editors, I am writing to highlight the pharmacokinetic challenges that arise in the management of lithium therapy following bariatric surgery (BS). This is particularly relevant given the anatomical alterations caused by these procedures, which include restrictive, malabsorptive, and combined techniques. Obese patients undergoing BS frequently have psychiatric comorbidities, including bipolar disorder, which necessitate mood stabilization therapies. However, the pharmacokinetics of psychiatric medications, especially lithium, can be significantly altered postoperatively due to changes in absorption, metabolism, and excretion.[1] Lithium remains the gold-standard treatment for bipolar disorder, particularly in preventing suicidality. However, its low therapeutic index requires meticulous monitoring. Post-BS patients, especially those undergoing malabsorptive procedures, present a unique challenge in lithium management. While the literature is sparse, most available reports document lithium intoxication following bariatric procedures, underscoring the risk of unpredictable absorption and blood level fluctuations.[2-4] These risks are heightened in patients who undergo malabsorptive procedures, which can significantly decrease drug bioavailability. In the case I present, a 38-year-old female patient with a diagnosis of bipolar I disorder underwent a malabsorptive bariatric procedure 2 years prior. Post surgery, she was started on oral lithium carbonate (900 mg/day) for mood stabilization. However, despite adherence to therapy, her lithium serum levels fluctuated dramatically, ranging from 0.2 mEq/L to 1.0 mEq/L, making therapeutic management exceedingly difficult. Notably, these fluctuations occurred despite consistent dosing and regular bimonthly monitoring. Given her highly variable serum lithium levels and mood instability (characterized by mood swings from depression to hypomania), it was hypothesized that the malabsorptive nature of the surgery had led to unpredictable lithium absorption. This hypothesis aligns with previous findings suggesting that malabsorptive procedures, such as gastric bypass, can compromise the absorption of lithium due to reduced transit time and altered luminal pH in the gastrointestinal tract. Some studies indicate increased pH and altered bile acid concentrations in the stomach post surgery, which can interfere with the solubility and absorption of lithium salts.[5] To address this therapeutic challenge, a switch from oral lithium to intramuscular long-acting aripiprazole (400 mg/month), a mood stabilizer with more predictable pharmacokinetics, was proposed. This transition followed a 2-week oral trial of aripiprazole (20 mg/day) in addition to lithium to ensure tolerance. After switching to intramuscular aripiprazole, the patient demonstrated marked clinical improvement, with stabilization of mood and a more predictable therapeutic response. This case underscores the need for clinicians to remain vigilant in monitoring post-BS patients on lithium, given the potential for absorption variability and the narrow therapeutic window of the drug. Furthermore, alternative drug delivery methods, such as long-acting injectables, should be considered in cases where oral administration leads to unpredictable pharmacokinetics. In conclusion, this case highlights the importance of considering the type of bariatric procedure when managing psychopharmacological treatments, particularly those with low therapeutic indices like lithium. Additional research is required to establish standardized protocols for the psychiatric management of post-BS patients to ensure both efficacy and safety. Ethic approval and consent to partecipate Full written informed consent was obtained from the patient and anonymity was preserved according to the Department ethic protocol. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.