Citations

Background: Lithium is a mainstay treatment for bipolar disorder, but its narrow therapeutic index and susceptibility to pharmacokinetic interactions make appropriate monitoring crucial. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are increasingly prescribed for type 2 diabetes and weight management. Scarce evidence exists on the potential interaction between semaglutide and lithium. Methods: We present 3 cases involving patients on stable lithium regimens who were initiated on semaglutide, reviewing potential mechanisms underlying the interaction between them. Findings: In 2 cases, lithium levels increased significantly, leading to toxicity despite stable renal function and no changes in concurrent medications. In the third case, preemptive reductions in lithium dosage mitigated toxicity, although lithium levels remained higher than anticipated. Mechanistic hypotheses that might contribute to semaglutide-associated elevated lithium levels include altered kidney function, dehydration from reduced oral intake, vomiting, or diarrhea, and delayed gastric emptying. Conclusions: To our knowledge, this is one of the first documented case series describing a potential interaction between semaglutide and lithium in the medical literature. These cases underscore the importance of vigilant monitoring when combining lithium with semaglutide, and potentially other GLP-1 RAs. Baseline renal function, hydration status, and lithium levels should be assessed before initiating semaglutide, and lithium levels should be monitored more frequently during therapy. Clinicians prescribing semaglutide to patients on lithium should exercise caution, monitor for signs of toxicity, and provide appropriate patient education. Further research is needed to elucidate the mechanisms of this potential interaction and its clinical significance.

Background: Pneumocystis jirovecii pneumonia (PJP) is life-threatening for immunocompromised patients. No consensus exists on PJP prophylaxis for immunosuppressed patients without HIV, transplant, or cancer. Methods: We retrospectively reviewed the electronic health records of adult immunosuppressed patients with PJP diagnosed between 1990 and 2020 at Mayo Clinic. Patients with HIV, solid organ transplants, or cancer were excluded. Demographic data, treatments, and outcomes were manually abstracted. Results: The most common indications for immunosuppression were rheumatoid arthritis (19.7%), vasculitis (18.1%), and interstitial lung disease (ILD) not related to connective tissue disease (17.6%). Despite having high risk of PJP, 86.0% of patients did not receive PJP prophylaxis. Corticosteroids were the most common immunosuppressive agent used (84.5%), with 64.4% of patients receiving high-dose treatment. Nonbiologic disease-modifying antirheumatic drugs were used for 49.7%, including methotrexate (51.0%), azathioprine (22.9%), and hydroxychloroquine (11.5%). Biologics were prescribed for 25.4%, primarily rituximab (59.2%) and infliximab (22.4%). Hospitalization occurred for 76.7% of patients; 70.3% required intensive care unit (ICU) admission, and 46.6% received mechanical ventilation. The in-hospital mortality rate was 30.4% overall and 53.6% for patients on ventilation. Predictors of death included ILD [odds ratio (OR), 4.61; 95% CI, 1.75-13.00], ICU admission (OR, 3.60; 95% CI, 1.19-11.08), and ventilator use (OR, 3.46; 95% CI, 1.30-9.79). Biologic use was associated with lower odds of death (OR, 0.34; 95% CI, 0.11-0.89). Conclusions: Most patients in our cohort did not receive PJP prophylaxis, and outcomes were poor with high mortality rates. Standardized risk stratification and prophylaxis protocols are needed to improve outcomes.

Since the discovery of the first psychoactive medications, their psychiatric and medical uses have overlapped. Designating a medication psychiatric or psychotropic is thus arbitrary, based on its most common usage, but labeling it so obscures the full range of its pharmacologic activity and clinical utility. Psychotropic medications (PMs) are frequently used to treat medical conditions or symptoms in the areas of neurology (e.g., migraine, seizure disorder), dermatology (e.g., itching), gastroenterology, and chronic pain, among many others. It is important for both primary care and specialty physicians to be aware of the potential non-psychiatric indications for the use of common PMs such as antidepressants, antipsychotics, and anxiolytics. This review examines the potential benefits and risks of PMs when used for non-psychiatric indications, highlighting how their pharmacologic effects on neurotransmitters contribute to both therapeutic outcomes and adverse effects. It also provides guiding principles for prescribers, including the importance of adjusting doses based on the specific indication, monitoring for harmful side effects, considering age-related factors, and addressing the risks associated with polypharmacy.

Abstract Background Despite advances in diagnosis and management, the interstitial lung disease (ILD) lexicon is plagued by ambiguous and inconsistent terminology that complicates communication and impedes knowledge generation. The objective of this Fleischner Society Consensus Statement was to produce standardized terminology for ILD multidisciplinary diagnoses and major phenotypes. Methods Interviews with 10 experts were used to identify ILD clinical diagnoses and major phenotypes. The preferred terms for each entity and potential alternatives were identified, alongside the rationale for the preferred term. Entities with more than one potential term were the subject of an online modified Delphi survey posed to the 29 committee members, aiming to achieve consensus. Committee members rated their agreement with the initially preferred term—5 (strongly agree), 4 (agree), 3 (neutral/unsure), 2 (disagree), and 1 (strongly disagree)—with the option to provide additional comments. Median score ≥4 and interquartile range ≤1 were considered consensus agreement. Terms not reaching agreement were discussed by video conference, followed by an additional survey that incorporated feedback. Results From the 60 initial terms, there were two root terms that required upfront consensus before survey initiation (ILD and interstitial pneumonia) and another eight terms that had no alternative suggested by the committee or in the literature. Agreement was met by 47/50 terms (94%) in Round 1 of the survey. The three terms (6%) that did not reach agreement met agreement in Round 2. Conclusions This document provides standardized recommended terms for ILD multidisciplinary diagnoses and major phenotypes that will facilitate communication among clinicians, researchers, patients, and other stakeholders.

Abstract Introduction Alice in Wonderland Syndrome (AIWS) is an uncommon condition manifesting visual and somatosensory disturbances in which patients may perceive objects, including their own bodies, as larger or smaller than they are. In adults, AIWS typically is associated with migraine and epilepsy but has been reported as an adverse effect of topiramate, which is used to treat both illnesses, making it difficult to ascertain whether illness or medication causes altered perceptions. Reported is a case of topiramate-associated AIWS, which adds to the limited reports published on this unique phenomenon. Case Report A 40-year-old woman admitted to a 3-week pain rehabilitation program to treat chronic migraine reported macrosomatognosia that she retrospectively recalled beginning during titration of topiramate. The symptoms of AIWS resolved after the topiramate was discontinued. An assessment with the Naranjo ADR Probability Scale indicated a possible association between topiramate and macrosomatognosia. Discussion In this patient with migraine, the onset of AIWS coincided with titration of topiramate, providing a clue that its emergence may have been an adverse drug reaction rather than the underlying illness. Consistent with previous reports, AIWS resolved shortly after topiramate was discontinued, lending credence to this conclusion. However, the mechanism of AIWS is unknown and may be multifactorial, leaving the possibility that migraine predisposed the patient to develop AIWS from topiramate. Conclusion The long association of AIWS with migraine and epilepsy makes it possible that cases caused by medications used to treat these illnesses, like topiramate, are underreported. Awareness of the temporal relationships between the course of illness and the timing of drug therapy can help guide the recognition of AIWS as a potential adverse event.

Abstract This retrospective analysis examined 15 years of autologous stem cell transplantation (ASCT) for light chain (AL) amyloidosis at the Mayo Clinic (2010-2024). We aimed to assess ASCT utilization trends, factors influencing practice changes, and current indications amid newer therapies. Four hundred and forty-one ASCTs were divided into cohort 1 (2010-2019) and cohort 2 (2020-2024), revealing a significant ASCT reduction in cohort 2 (385 vs 56, average 71% annual decrease). Cohort 2 patients were older, more likely to have relapsed/refractory disease, and had higher baseline bone marrow plasma cell burden compared to cohort 1. Pre-ASCT induction was more frequent in cohort 2 (89.3% vs 56.4%), with daratumumab (Dara)–cyclophosphamide-bortezomib-dexamethasone (CyBorD) replacing CyBorD as the predominant induction regimen. Lymphoma-based regimens were also more common in cohort 2 (15.1% vs 5.3%, P = .02). Day-100 satisfactory hematological response improved in cohort 2 (91.1% vs 72.7%, P = .001), although hematological complete response rates did not significantly differ (50.9% vs 38.8%, P = .09). In summary, there is a decrease in the utilization of ASCT in AL amyloidosis. This procedure is primarily reserved for patients with suboptimal responses, relapsed/refractory disease, lymphoplasmacytic clones (predominantly immunoglobulin M amyloidosis), or high bone marrow plasma cell burden (myeloma phenotype). This study underscores a significant shift in ASCT practice, driven by novel therapies, emphasizing more personalized management in AL amyloidosis.

BACKGROUND: The impact of covert cerebrovascular disease on falls in the general population is not well-known. Here, we determine the time to a first fall following incidentally detected covert cerebrovascular disease during a clinical neuroimaging episode. METHODS: This longitudinal cohort study assessed computed tomography (CT) and magnetic resonance imaging from 2009 to 2019 of patients aged >50 years registered with Kaiser Permanente Southern California which is a healthcare organization combining health plan coverage with coordinated medical services, excluding those with before stroke/dementia. We extracted evidence of incidental covert brain infarcts (CBI) and white matter hyperintensities/hypoattenuation (WMH) from imaging reports using natural language processing. We examined associations of CBI and WMH with falls requiring medical attention, using Cox proportional hazards regression models with adjustment for 12 variables including age, sex, ethnicity multimorbidity, polypharmacy, and incontinence. RESULTS: We assessed 241 050 patients, mean age 64.9 (SD, 10.42) years, 61.3% female, detecting covert cerebrovascular disease in 31.1% over a mean follow-up duration of 3.04 years. A recorded fall occurred in 21.2% (51 239/241 050) during follow-up. On CT, single fall incidence rate/1000 person-years (p-y) was highest in individuals with both CBI and WMH on CT (129.3 falls/1000 p-y [95% CI, 123.4–135.5]), followed by WMH (109.9 falls/1000 p-y [108.0–111.9]). On magnetic resonance imaging, the incidence rate was the highest with both CBI and WMH (76.3 falls/1000 p-y [95% CI, 69.7–83.2]), followed by CBI (71.4 falls/1000 p-y [95% CI, 65.9–77.2]). The adjusted hazard ratio for single index fall in individuals with CBI on CT was 1.13 (95% CI, 1.09–1.17); versus magnetic resonance imaging 1.17 (95% CI, 1.08–1.27). On CT, the risk for single index fall incrementally increased for mild (1.37 [95% CI, 1.32–1.43]), moderate (1.57 [95% CI, 1.48–1.67]), or severe WMH (1.57 [95% CI, 1.45–1.70]). On magnetic resonance imaging, index fall risk similarly increased with increasing WMH severity: mild (1.11 [95% CI, 1.07–1.17]), moderate (1.21 [95% CI, 1.13–1.28]), and severe WMH (1.34 [95% CI, 1.22–1.46]). CONCLUSIONS: In a large population with neuroimaging, CBI and WMH are independently associated with greater risks of an index fall. Increasing severities of WMH are associated incrementally with fall risk across imaging modalities.

Abstract Purpose Clozapine is primarily metabolized by cytochrome P450 (CYP) 1A2 and to a lesser extent by CYP2C19, CYP2D6, and CYP3A4. The global pandemic of coronavirus disease 2019 (COVID-19) and use of nirmatrelvir/ritonavir brought forth new challenges for those caring for patients prescribed clozapine. Prescribing information describes a consideration for a clozapine dose reduction while monitoring for adverse reactions when clozapine is used with nirmatrelvir/ritonavir. Other drug information resources consider the combination a contraindication. A case is reported in which therapeutic drug monitoring demonstrated a lack of interaction between clozapine and nirmatrelvir/ritonavir. The complexities of infection-associated clozapine toxicity are discussed and a review is provided of CYP3A4 drug and gene interactions with clozapine. Summary A 75-year-old woman with schizophrenia, prescribed clozapine 200 mg by mouth at bedtime, was initiated on nirmatrelvir/ritonavir after developing a mild COVID-19 infection. Two days later, the patient was brought to the emergency department after an unwitnessed fall. Clozapine toxicity was included in the differential diagnosis, although no other signs or symptoms of elevated clozapine levels were present. Nirmatrelvir/ritonavir was discontinued. Clozapine was withheld for 1 day while a clozapine level was pending, but this measurement revealed no interaction when compared to a baseline level of clozapine. Conclusion Although there are hypothetical concerns when initiating a CYP3A4 inhibitor with concomitant clozapine, the information derived from this case does not clearly support an interaction with the addition of nirmatrelvir/ritonavir during mild COVID-19 infection. It is important to understand the risks of withholding clozapine, although fortunately no psychiatric concerns developed. In reviewing the literature, CYP3A4 inhibitors or genetic polymorphisms seem to have a minimal impact on clozapine levels, although clinical monitoring is warranted.