Pregabalin overdose is generally considered to have a relatively benign clinical course. However, severe respiratory depression, coma, and life-threatening clinical deterioration have rarely been reported, particularly in patients with high-dose ingestion or delayed recognition. We present the case of a 26-year-old male who was found unconscious following suspected intentional ingestion of approximately 14 pregabalin 300 mg capsules (4.2 g). On arrival of the emergency medical team, the patient was found to be in out-of-hospital cardiac arrest with an initial rhythm of asystole. Return of spontaneous circulation was achieved after 20 minutes of cardiopulmonary resuscitation. On admission, profound metabolic acidosis (pH: 6.43) and severe hyperlactatemia (lactate: 29 mmol/L) were present. During follow-up, the patient developed rhabdomyolysis, acute kidney injury requiring renal replacement therapy, marked transaminase elevation compatible with ischemic hepatitis, and pancreatic enzyme elevation. Despite aggressive supportive treatment, the patient died on the fourth day due to refractory shock and multiorgan failure. Although pregabalin overdose is often benign, suspected high-dose ingestion may lead to profound central nervous system depression, loss of airway protective reflexes, aspiration, respiratory arrest, and fatal post-cardiac arrest multiorgan failure. Early airway protection and close hemodynamic monitoring are essential. We present a rare, fatal case of a young adult who developed multi-organ dysfunction syndrome following suspected severe pregabalin intoxication.

Background/Objectives: Glia-mediated inflammation contributes to a wide range of central nervous system (CNS) disorders, including epilepsy. Pregabalin (PGB) and cannabidiol (CBD) are CNS-acting drugs prescribed for various neuropsychiatric conditions, especially seizures. This study investigated the effects of PGB and CBD on glial properties in an astrocyte-microglia co-culture model of inflammation. Methods: Physiological (M5, containing 5-10% microglia) and pathological inflammatory astrocyte-microglia co-cultures (M30, containing 30-40% microglia) were collected from the postnatal brain hemispheres of Wistar rats (P0-P2) according to an established protocol and treated with different concentrations of PGB (3, 10, 30 and 60 µg/mL) for 24 h or CBD (50, 500 and 1000 ng/mL) for 1 h or 24 h. Metabolic activity was assessed by the MTT assay. Microglial phenotypes and astroglial connexin (Cx)43 expression were detected by immunocytochemistry. Results: In M5 co-cultures, short-term incubation (1 h) with high concentrations (1000 ng/mL) of CBD significantly reduced glial viability (p < 0.05), while no significant changes were observed in M30 co-cultures. After 24 h of incubation, M5 cultures exhibited a significant increase in metabolic activity at 50 ng/mL (p < 0.0001) and 500 ng/mL (p < 0.05), and a reduction at 1000 ng/mL (p < 0.05), suggesting impaired viability at high concentrations under physiological conditions. The distribution of microglial phenotypes in physiological M5 co-cultures incubated with CBD remained unchanged. In M30 co-cultures, CBD incubation for 1 and 24 h significantly reduced microglial activation and promoted a shift from reactive, phagocytic to homeostatic, ramified microglial phenotype (p < 0.05, p < 0.01, p < 0.0001). In contrast, PGB did not affect glial cell viability, microglial phenotypes or Cx43 expression in physiological and inflammatory co-cultures, indicating that the mechanisms of action of PGB probably do not include modulation of glial cells in vitro. Conclusions: The inhibition of microglial reactivity by CBD suggests potential positive effects on the neuroinflammatory component involved in the pathogenesis of CNS disorders such as epilepsy.

This article summarizes the top 20 research studies of 2025 identified as POEMs (patient-oriented evidence that matters). Treating male sex partners of female patients with oral and topical medication reduces recurrence of bacterial vaginosis. Anti-influenza drugs do not reduce hospitalizations or mortality. COVID-19 vaccines still improve mortality and reduce hospitalizations. Influenza vaccines are safe in pregnancy. Vaginal estrogen appears to be safe in breast cancer survivors. Women with normal bone density given zoledronic acid every 5 years have fewer fractures. Early post-partum insertion of a long-acting reversible contraceptive is associated with fewer pregnancies vs delayed insertion. Early medication abortion before pregnancy confirmation is safe and effective. After stent placement in patients with atherosclerotic coronary vascular disease who are taking an anticoagulant, adding aspirin worsens outcomes. After catheter ablation for atrial fibrillation, discontinuing anticoagulants after 1 year is safe if atrial arrhythmia does not recur, whereas left atrial appendage closure is superior to oral anticoagulation. For patients with provoked venous thromboembolism and at least one ongoing risk factor, 12 months of apixaban is better than 3 months. Clopidogrel is slightly more effective than aspirin for the secondary prevention of myocardial infarction and stroke over 3 years. Intensive blood pressure lowering decreases cardiovascular events but increases rates of hypotension and syncope, and there are concerns about the applicability of the data to the United States. Duloxetine, milnacipran, and pregabalin provide meaningful pain reduction in adults with fibromyalgia. Amyloid-directed monoclonal antibodies do not provide clinically meaningful cognitive benefits and may cause harms. Bright light therapy is effective for nonseasonal depression. Water exposure 6 hours after cutaneous surgery does not increase the risk of complications. A meta-analysis of platelet-rich plasma injections for knee osteoarthritis concluded that high-quality studies found no meaningful pain improvement. Using an oral challenge to rule out sulfonamide allergy is safe when used with a risk assessment tool.

Crisugabalin (HSK16149) is a next-generation α2δ ligand developed to preserve the mechanistic rationale of gabapentinoids while refining target engagement and exposure-related tolerability constraints. We performed a translational review of molecular/structural studies, in vivo pharmacology and behavioural safety assessments, phase I clinical pharmacology and randomized clinical trials in diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN), with searches across major bibliographic databases and trial registries updated through June 2026. Evidence was synthesized qualitatively along a molecular-to-clinical sequence. Structural and kinetic studies indicate stable engagement of the α2δ1 binding site, with slower dissociation from α2δ1 than from α2δ2. In rodent models, crisugabalin demonstrated antinociceptive efficacy with a wider separation between antinociceptive and motor-impairing doses relative to pregabalin and no clear abuse liability signals across standard paradigms. Human phase I data show rapid absorption (Tmax ~ 1.5-1.7 h), dose-proportional exposure, slight accumulation and predominant renal elimination. A high-fat meal delayed absorption without materially changing overall exposure, whereas renal impairment produced graded exposure increases supporting consideration of dose adjustment as renal function declines. Clinically, a seamless adaptive phase II/III trial in DPNP and a confirmatory phase III trial in PHN demonstrated significant reductions in pain intensity at 40-80 mg/day; dizziness was the most frequent dose-related adverse event. Current evidence supports crisugabalin as a class-refinement strategy with consistent short-term efficacy in DPNP and PHN and predictable clinical pharmacology. Generalizability beyond Chinese populations, longer-term outcomes and comparative effectiveness relative to established therapies remain key gaps.

A cocrystal of pregabalin and octanoic acid shows two phase transitions when temperature is lowered. These transitions were followed using differential scanning calorimetry. Both transitions are single-crystal to single-crystal allowing the study of these transitions using single-crystal X-ray diffraction at different temperatures. The crystal structures of the different forms were determined. Negative thermal expansion is observed along the shortest unit-cell axis in form III. Ultimately, subsequent transitions to form II and form I lead to positive thermal expansion in every principal strain axis.

Fibromyalgia (FM) is a chronic, multifactorial pain syndrome involving widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive dysfunction, significantly reducing the quality of life of patients. FM is classified under MG30.01, representing chronic widespread pain, within the broader classification of chronic primary pain according to the International Classification of Diseases, 11th Revision. FM has a complex, multifactorial pathophysiology involving peripheral and central mechanisms that contribute to its marked clinical heterogeneity. Currently, FM is diagnosed primarily through clinical assessment using widely accepted criteria, such as the American College of Rheumatology criteria, most recently revised in 2016, which evolved from the widely used 2010/2011 diagnostic framework. A thorough differential diagnosis is required to distinguish FM from a wide range of rheumatic, neurological, endocrine, psychiatric, and other medical disorders. FM management requires a multidisciplinary approach. Non-pharmacological interventions, including patient education, exercise (eg, aerobic and resistance training), and psychological therapies, such as cognitive behavioral therapy, are recommended as first-line treatments. Pharmacological therapies, including pregabalin, duloxetine, milnacipran, and cyclobenzaprine, are Food and Drug Administration-approved and provide clinically meaningful benefits to patients with FM. Although tramadol may be considered, the use of other opioids is generally not recommended because of their limited efficacy and potential risks. Despite the availability of current diagnostic criteria and treatment options, achieving a consistent diagnosis and optimal outcomes in patients remains challenging. Therefore, this narrative review aims to provide a concise, updated, and clinically relevant overview of the current evidence regarding the pathogenesis, diagnosis, and multidisciplinary management of FM to improve diagnostic accuracy and support individualized patient management. Furthermore, future directions should prioritize improving diagnostic precision and developing mechanism-based interventions targeting the underlying pathophysiology of FM.

Cancer pain remains inadequately controlled in some patients despite opioid therapy, particularly when neuropathic or mixed pain mechanisms are present. This systematic review evaluated the efficacy and safety of non-opioid or adjuvant analgesics used alongside opioids in adults with chronic cancer pain. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for English-language randomized controlled trials published from January 2010 to August 2025. Two reviewers independently selected studies, extracted data, and assessed risk of bias using Cochrane Risk of Bias 2 (RoB 2). Ten trials involving 1,344 participants were included. In one trial, duloxetine was associated with clinically meaningful pain-response rates, although its primary mean pain-score analysis was not statistically significant. Low-dose gabapentin plus imipramine reduced pain and rescue-morphine use. Pregabalin reduced the morphine dose required to maintain pain control in one crossover trial, while other pregabalin studies showed numerical or non-significant benefits. Neither nabiximols trial met its primary efficacy endpoint, and nefopam did not significantly improve pain response or morphine consumption. Risk of bias was low in two trials, raised some concerns in one, and was high in seven. Overall, the evidence remains heterogeneous and insufficient to support a standard multimodal pharmacological regimen. Selected antidepressant and gabapentinoid strategies, particularly in neuropathic cancer pain, may benefit selected patients.

Gabapentin is widely prescribed for neuropathic and radicular pain syndromes. While somnolence and dizziness are well-recognized adverse effects, severe vivid nightmares may constitute an underreported psychiatric side effect that can significantly impair quality of life and treatment adherence. We present two cases of gabapentin-induced severe vivid nightmares in patients treated for spinal pain syndromes. Management strategies included medication discontinuation and transition to pregabalin. Both patients experienced resolution of nightmares following intervention. This report reviews the existing literature on gabapentin's effects on sleep architecture and discusses potential mechanisms, clinical implications, and management approaches.

While clinicians commonly prescribe neuromodulators for the treatment of refractory or unexplained chronic cough, no trials have directly compared these treatments. Furthermore, although guidelines recommend non-pharmacological management involving physiotherapy and speech-language therapy, few trials have evaluated its effectiveness.