Grozdena Yilmaz

Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a scoping review following PRISMA-ScR. MEDLINE/PubMed, CINAHL, and APA PsycInfo were searched (January 2020–31 May 2025). Eligible human and animal studies evaluated ketamine, esketamine, or norketamine in the context of diabetes (type 1 [T1DM], type 2 [T2DM], gestational [GDM]), or DN, and reported psychiatric, analgesic, metabolic, or mechanistic outcomes. Two reviewers independently screened and charted data; no formal risk-of-bias assessment was performed. Results: Eleven studies met inclusion criteria: four human case reports/series (three T1DM, one T2DM), one randomized trial in GDM, two narrative reviews of topical ketamine for DN, and four preclinical rodent studies using streptozotocin- or diet-induced diabetes models. Short-term improvements were reported for treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative analgesia in GDM. Glycemic effects varied across settings, with both hyperglycemia and hypoglycemia reported. Mechanistic and clinical drug–drug and drug-disease interactions (particularly involving metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and CYP3A4/CYP2B6 modulators) remain insufficiently studied. We outline a forward-looking population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK-PD) research agenda, including priority covariates (eGFR, hepatic function, inflammatory status, HbA1c, genotype, co-medications) and sparse-sampling windows for future model-informed precision dosing. Conclusions: Current evidence supports cautious, selective use of ketamine for refractory depression and DN within multidisciplinary diabetes care. Purpose-built popPK/PK-PD studies in both human and preclinical diabetic models cohorts are needed to quantify variability, define drug–disease–drug interactions and glycemic risk, and inform individualized dosing strategies.

Kidney stones typically present as renal colic in emergency departments (EDs), where patients experience severe pain and often require parenteral therapy for symptom management. The economic burden associated with managing kidney stones exceeds USD 5 billion annually in the US and accounts for more than a million visits to EDs each year. There is clear evidence emphasizing the need for innovative and alternative pain control options for patients with renal colic. Recent randomized controlled trials suggest that intranasal (IN) and intravenous (IV) ketamine are as effective as parenteral NSAIDs and opioids in treating renal colic. However, the limited studies available show inconsistent results regarding the analgesic effects of ketamine. In this study, we reviewed the mechanism of action of ketamine for kidney stones, its efficacy in treating acute renal colic, and the potential adverse side effects of ketamine treatment. A population, intervention, comparison, and outcome (PICO)-related question was formulated to guide our research inquiry: “What are the effects of IV or IN ketamine, as a single agent or as an adjuvant (I), in adult patients diagnosed with acute renal colic (P) on pain scale scores and adverse side effects (O) compared to NSAIDs and/or opioids (C)?”