Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating complication of cancer treatment, characterized by neuropathic pain, sensory disturbances, and functional impairment that can substantially reduce quality of life. Neurotoxicity induced by chemotherapeutic agents affects peripheral nerves, dorsal root ganglia, and supporting structures, contributing to persistent pain and neurological dysfunction. This systematic review evaluated the efficacy and safety of antidepressants, particularly duloxetine and amitriptyline, in the management of CIPN-related pain. Following PRISMA guidelines and registration in PROSPERO (CRD42024608551), a systematic search of PubMed, Scopus, and Web of Science was conducted for studies published between November 2019 and October 2025. This time frame was selected to capture contemporary evidence and recent developments in multimodal treatment strategies, while acknowledging that foundational studies establishing the efficacy of duloxetine predate this period. Clinical and observational studies involving adult patients with CIPN were included. Of 892 records identified, 11 studies met the eligibility criteria. Duloxetine demonstrated clinically meaningful reductions in neuropathic pain, as assessed by VAS, NRS, and CTCAE measures. Topical amitriptyline also showed promising analgesic effects, although the available evidence remains limited. Combination therapies involving duloxetine and agents such as tapentadol, pregabalin, mirogabalin, or amitriptyline were associated with additional reductions in pain intensity; however, current evidence remains insufficient to establish additive or synergistic effects. Overall, antidepressant therapy was generally well tolerated, with predominantly mild and manageable adverse events. Current evidence supports antidepressants, particularly duloxetine, associated with reductions in pain intensity in heterogeneous studies, whereas evidence for CIPN prevention remains inconclusive. These findings support their continued use in clinical practice and highlight the need for larger, well-designed randomized controlled trials to optimize treatment strategies and further define the role of combination therapies in CIPN management.

Amitriptyline is in the tricyclic antidepressant (TCA) drug classification and acts by blocking the reuptake of both serotonin and norepinephrine neurotransmitters. Amitriptyline is an FDA-approved medication to treat depression in adults. The non-FDA approved indications are anxiety, post-traumatic stress disorder, insomnia, chronic pain (diabetic neuropathy, fibromyalgia), irritable bowel syndrome, interstitial cystitis (bladder pain syndrome), migraine prophylaxis, postherpetic neuralgia, and sialorrhea. This activity reviews the indications, contraindications, activity, adverse events, and other key elements of amitryptiline in the clinical setting related to the essential points needed by members of an interprofessional team managing the care of patients with indications that can benefit from amitriptyline therapy.

Several studies have supported Dr Gideon Koren’s 1993 landmark article, “Medications Which Can Kill a Toddler with One Tablet or Teaspoonful.” Although each study has its own merits, most focus solely on pediatric overdoses, and few provide an exhaustive reference list for real-time evaluation of ingestions in children and adults. The following xenobiotics warrant special attention because of their potential to cause serious outcomes, even after exposure to small volumes. This list does not imply that all pediatric exposures to these agents result in fatality, and the absence of a xenobiotic from this list does not indicate that it is necessarily safe. α1-Adrenergic agonists and imidazoline receptor agonists: Clonidine, guanfacine, naphazoline, oxymetazoline, tetrahydrozoline, xylazine (veterinary). Sulfonylureas: Chlorpropamide, glyburide, glipizide, glimepiride. Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, nicardipine, nimodipine; β-Blockers: Metoprolol, labetalol, propranolol, sotalol. Tricyclic antidepressants: Imipramine, desipramine, amitriptyline, nortriptyline. Opioids: Codeine, hydrocodone, methadone, morphine, heroin. Antidiarrheals: Diphenoxylate plus atropine, loperamide. Salicylates and methyl salicylate: Oil of wintergreen, bismuth subsalicylate, mentholated balms, paramao or lawang root oil . Antipsychotics: Loxapine, thioridazine, chlorpromazine. Antimalarials: Chloroquine, hydroxychloroquine, quinine, primaquine. Antiarrhythmics: Quinidine, disopyramide, procainamide, flecainide, amiodarone. Camphor: A terpenoid used as an analgesic, antipruritic agent, and component of cooling gels, ointments, balms, mothballs, household fragrances, and essential oils. Oral camphor use occurs in some regions for religious ceremonies, traditional remedies, aphrodisiacs, or lactation suppression. Nonalkaloid toxic lignan: Podophyllin, podofilox. Unique plant toxins: Colchicine. Oral acetylcholinesterase inhibitors: Rivastigmine, donepezil, galantamine, carbamate pesticides. Methylxanthines: Theophylline, 1,3-dimethylxanthine, caffeine. Other opioids: Buprenorphine, fentanyl. Toxic alcohols: Methanol, ethylene glycol, diethylene glycol. Caustics and other household products: Acidic or alkaline household products, hydrofluoric acid, selenious acid, acetonitrile, methylene chloride. Accidental overdoses continue to occur regularly despite the implementation of various safety measures, including widespread public education, the use of childproof containers, and easy access to poison control centers. In the US, poison control centers receive more than 2.4 million calls annually, with more than 50% involving children younger than 6 years. Most pediatric accidental ingestions involve household cleaning products and analgesics, followed by cosmetics, foreign objects, and dietary supplements. Adult overdoses may be unintentional but often involve larger total doses or high-risk medications, including opioids and sedative-hypnotics. America's Poison Centers identify the 5 most common substance classes as analgesics, household cleaners, antidepressants, cosmetic or personal care items, and cardiovascular drugs. The number of ingestions involving cleaning products increased sharply during the COVID-19 pandemic but has since declined.

Cerebellar and medullary stroke can cause persistent nausea and vomiting that may be resistant to initial antiemetic monotherapy and interfere with oral intake and recovery. Evidence guiding management remains limited. We report a 48-year-old man with diabetes mellitus and acute-to-subacute infarcts involving the inferomedial right cerebellum and posterior right medulla who presented with 10 days of persistent nausea and vomiting accompanied by focal neurologic symptoms. Diabetic gastroparesis was considered, but abdominal imaging and gastric emptying scintigraphy did not support a contributory gastrointestinal cause. Ondansetron and metoclopramide provided only limited or temporary relief. Symptoms improved after sequential escalation to ondansetron, chlorpromazine, prochlorperazine, and amitriptyline; transdermal scopolamine was included in the discharge regimen. Nausea and vomiting were nearly resolved before discharge and fully resolved by three-month follow-up. Because multiple medications were introduced over a short interval and natural neurologic recovery may have contributed, the effect of any individual agent or combination cannot be determined. This case suggests that receptor-diverse pharmacotherapy may be considered when initial treatment fails while underscoring the need for further study of efficacy, safety, and medication sequencing.

Terbinafine (TBNF), a lipophilic anti-fungal agent prescribed for onychomycosis distributes extensively into adipose, skin and peripheral tissues. TBNF and metabolite desmethyl terbinafine (DMT) are potent inhibitors of CYP2D6. A combination of prolonged half-life and CYP2D6 inhibition causes clinically significant interactions with drugs involving CYP2D6 metabolism that may persist for weeks after dosing cessation. A physiologically based pharmacokinetic (PBPK) model for TBNF and DMT incorporating in vitro and clinical information was developed and verified to predict their steady state pharmacokinetics. Experimentally determined Kiu,CYP2D6 for TBNF and DMT enabled to predict the interaction with CYP2D6 substrates Desipramine, Amitriptyline and Nortriptyline. The PBPK model predicted steady-state plasma concentration-time profiles of TBNF and DMT after daily administration of 250 mg and 125 mg TBNF were in agreement with the observed data, including sustained plasma concentrations after dosing cessation. This enabled prediction of drug interactions with the CYP2D6 substrates during and after termination of TBNF dosing. The distribution of TBNF into adipose and skin acts as a depot leading to its slow re-distribution back into plasma, followed by sequential metabolism to DMT and CYP2D6 inhibition. The model was validated against data from three independent drug interaction reports. This PBPK framework can be applied in different clinical pharmacology settings for drugs characterized by extensive distribution, formation rate limited metabolism and enzyme inhibition. The framework provides applicability in informing the rational design of clinical trials where sustained plasma drug levels warrant patient monitoring long after termination of dosing.

Migraine is one of the most common chronic health problems in children and adolescents, resulting in high levels of functional disability. Symptoms frequently persist into and impact the course of adulthood for affected individuals. Current practice recommendations include a combined therapy approach of preventive medication and cognitive behavioral therapy (CBT); however, no trials have systematically assessed whether a combined therapy approach is superior to a cognitive behavioral monotherapy intervention. The REACH (Responding With Evidence and Access for Childhood Headaches) trial will compare the impact of a CBT monotherapy to a combined treatment for prevention of migraine in youth, while addressing barriers to CBT access by utilizing a teletherapy approach. The study will include youth with migraine between the ages of 10 and 17 years from 15 sites across the United States, who will be randomly assigned to a CBT + pill (amitriptyline) group or CBT-alone group. Both groups will complete six sessions of telehealth CBT, as well as three booster sessions, over the course of 6 months. Participants will report on headache and migraine frequency and related disability via a daily headache diary before (28-day baseline), during, and after completion of the intervention (the last 28 days on the protocol). The CBT + pill group will also undergo a dose titration of clinically prescribed amitriptyline throughout the active treatment phase. Primary treatment outcomes are a ≥50% reduction in headache days and reduction in migraine-related disability (i.e., Pediatric Migraine Disability Assessment score ≤20). Findings of the REACH study may confirm current practice guidelines or provide evidence of comparable effectiveness of combined therapy and CBT monotherapy for prevention of migraine. This trial is designed to reinforce current guidelines for preventive headache management strategies in youth with migraine. The study will also advance knowledge by determining whether CBT alone, without the potential side effects of medication, is sufficient.