Researchers led by Alice Treloar and Susanna B. Park of the University of Sydney set out to test whether brief patient-reported questionnaires could be woven into everyday cancer care at two oncology centres in Sydney, Australia. Between March 2022 and November 2023, they recruited 159 adults who were receiving or about to receive neurotoxic chemotherapy, including platinum, taxane, anti-microtubule, vinca alkaloid, and bortezomib-based regimens. The screening package, dubbed CIPN-Screen, combined three short patient-reported outcome measures: the two-item sensory neuropathy subscale of the National Cancer Institute’s PRO-CTCAE, the two-item Patient Neurotoxicity Questionnaire, and the 11-item EviQ online neurotoxicity instrument. Anyone reporting symptoms was invited to complete the longer 20-item EORTC QLQ-CIPN-20 questionnaire to characterise the impact of their symptoms in more detail.

The crucial difference between the two sites was how patients were asked to participate. At the first centre, clinical staff approached patients during chemotherapy visits and offered a QR code or paper copy, a model that depended entirely on busy nurses and doctors remembering to hand out surveys. At the second centre, patients were enrolled once and then received an automated text message reminder before every chemotherapy appointment, requiring no ongoing input from clinical staff whatsoever. The contrast in results was striking. The staff-driven site produced just 109 completed screens across 75 participants, with a median of a single screen per person. The text-message site generated 646 screens among 84 participants, with a median of eight screens per patient, all completed online.

In total, 755 screening episodes were collected, and the data they yielded paint a sobering picture of neuropathy in the chemotherapy population. Just over 56 percent of screens identified CIPN symptoms, and 18.3 percent detected moderate to severe symptoms on the PRO-CTCAE scale. Roughly a third of screens at both centres indicated that the neuropathy was having a functional impact. Patients reported that nerve symptoms interfered with sleep, breathing, buttoning clothes, working, and walking. Notably, the proportion of symptomatic patients and the severity distribution were almost identical between the two centres, despite their very different demographics and delivery methods, suggesting the screening tools themselves were capturing something real and consistent.

Acceptability, the make-or-break factor for any screening programme, was overwhelmingly positive. Across all screens, 92 percent of respondents agreed or strongly agreed that CIPN-Screen was easy to complete, 91.6 percent found it easy to understand, and 85.6 percent said it helped them describe their symptoms. Acceptability held steady regardless of age, sex, or chemotherapy type, and it did not fade with repeated use: responses to the acceptability questions did not change significantly between the first and sixth screens. Interestingly, however, patients with moderate to severe symptoms rated the tool slightly less favourably than those with mild or no symptoms, particularly on the question of whether it helped them describe what they were feeling. The authors speculate that very brief questionnaires may not capture the full range of symptoms experienced by the worst-affected patients, who may also need more clinical input than a short survey can trigger.

The study also demonstrated something scientifically important: the screening tool was responsive to change. Among 52 participants at the text-message centre who completed seven consecutive screens over a median of 49 days, the proportion reporting CIPN symptoms rose from 27 percent at the first screen to 63 percent by the seventh, a statistically significant trajectory that tracked the cumulative neurotoxicity of ongoing treatment. In other words, the brief questionnaires did not merely snapshot a moment; they charted the emergence and worsening of nerve damage across a chemotherapy course. This longitudinal sensitivity is exactly what clinicians would need to make informed decisions about dose modification before irreversible damage sets in.

The three short instruments also agreed strongly with one another, with correlation coefficients of 0.84 or higher for most pairwise comparisons, and the PRO-CTCAE severity grades differentiated scores on the longer CIPN-20 questionnaire with high statistical significance. This internal consistency matters because it suggests clinics could reasonably pick a single brief instrument rather than deploying a battery of surveys. Prior Delphi consensus work has indicated that questionnaires longer than three items rate poorly for feasibility in busy infusion units, so a validated two-item screener that correlates well with comprehensive instruments is an attractive proposition for real-world oncology.

Patients, however, are only half of the implementation equation. The researchers also surveyed 31 clinicians, including medical and nursing staff and allied health personnel, using the adapted Organisational Readiness for Implementing Change questionnaire. Both centres scored in the mid-range for readiness for change, with mean scores of 43.5 and 46.4. Encouragingly, the highest-rated items concerned motivation: around 85 to 89 percent of clinicians at each site agreed that their colleagues wanted to implement CIPN screening. The weakest link was confidence in navigating the organisational politics of implementation, where agreement fell to between 39 and 46 percent. The authors argue that this gap between willingness and organisational confidence is precisely where tailored implementation strategies, staff training, and integration with electronic medical records must focus.

The study has honest limitations. It was a clinical implementation study rather than a randomised trial, so delivery methods differed by site and the cohorts skewed young and female, dominated by breast cancer patients at the text-message centre. Screening information was not fed back into clinical decisions, so the researchers could not measure whether enhanced screening actually reduced dose interruptions or chronic neuropathy, and no neurological examination was performed to confirm diagnoses. The authors also note that automated electronic collection could disadvantage patients less comfortable with digital tools, and that CIPN itself can impair the hand function needed to complete electronic surveys.

Even so, the central message is hard to ignore. A two-item questionnaire, delivered by an automated text message tied to a chemotherapy appointment, achieved near-perfect completion rates, detected symptom evolution over time, and required almost no clinician labour. International guidelines already endorse electronic symptom monitoring in cancer care, and large real-world programmes in Europe have shown high patient compliance and meaningful reductions in symptom burden. What this study adds is a concrete demonstration that CIPN screening specifically can be automated, scaled, and tolerated by patients across age groups and treatment types. The next step, the researchers say, is embedding such tools into electronic medical records with real-time delivery of results to treating clinicians, and pairing screening with guided clinical pathways so that a flagged symptom actually changes management. For the millions of cancer survivors living with numb hands and unsteady feet, a routine text message that catches nerve damage early could make the difference between a temporary side effect and a lifelong disability.

Subject of Research: Feasibility and acceptability of patient-reported screening for chemotherapy-induced peripheral neuropathy in routine cancer care

Article Title: Feasibility of clinical implementation and acceptability of patient-reported screening for chemotherapy-induced peripheral neuropathy (CIPN)

Article References: Treloar, A., Grimison, P., Choi, V., Young, J., Mayer, K., Li, T., Boyle, F., King, T., Mizrahi, D., Horvath, L. G., Goldstein, D., & Park, S. B. (2026). Feasibility of clinical implementation and acceptability of patient-reported screening for chemotherapy-induced peripheral neuropathy (CIPN). Supportive Care in Cancer, 34(11), Article 1073. https://doi.org/10.1007/s00520-026-11296-4

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11296-4

Keywords: chemotherapy-induced peripheral neuropathy, CIPN, patient-reported outcome measures, cancer screening, supportive care, text message reminders, PRO-CTCAE, oncology, neurotoxicity, cancer survivors, clinical implementation, symptom monitoring

The scale of the problem is enormous. The review’s authors report that roughly 34 percent of patients worldwide experience CIPN six months or longer after finishing chemotherapy, with prevalence peaking at around 68 percent during the first month after treatment. Symptoms arise because neurotoxic drugs damage the myelin sheaths, axons, and neuronal cell bodies of the dorsal root ganglia, triggering neuroinflammation, elevated pro-inflammatory cytokines, apoptosis, and altered neuronal excitability. Clinicians distinguish positive symptoms, such as allodynia, hyperalgesia, dysesthesia, and paresthesia, from negative symptoms like numbness and motor dysfunction. In severe cases, the condition forces oncologists to reduce chemotherapy doses or abandon potentially curative regimens altogether, making effective symptomatic treatment a genuine clinical priority.

International guidelines from the American Society of Clinical Oncology and the European Society for Medical Oncology currently identify duloxetine, a serotonin-norepinephrine reuptake inhibitor, as the only pharmacological option supported by strong evidence for painful CIPN, though its use remains off-label. The foundational evidence came from a randomized placebo-controlled trial by Smith and colleagues, later confirmed by Hirayama and coworkers in a large open-label Japanese study. Yet clinical practice has moved on, with growing interest in combination and multimodal approaches, and the comparative evidence base had never been systematically consolidated. The new review set out to fill exactly that gap, synthesizing studies published between 2019 and 2025 under contemporary diagnostic and reporting standards.

Methodologically, the review was rigorous and transparent. Two investigators independently searched PubMed, Web of Science, and Scopus following PRISMA guidelines and the PICO framework, with the protocol registered on PROSPERO. From 892 initial records, 374 duplicates were removed, and successive rounds of screening excluded pre-2019 publications, preclinical studies, reviews, editorials, and inaccessible or irrelevant articles. Eleven clinical studies survived the selection process, spanning randomized double-blind placebo-controlled trials, a non-inferiority trial, prospective pilot work, retrospective observational cohorts, and individual case reports. Risk of bias was assessed with the Cochrane RoB 2 tool for randomized trials and the Newcastle-Ottawa Scale for observational studies, and most randomized trials showed low risk across the key domains of randomization, blinding, and outcome measurement.

The patient populations were heterogeneous, reflecting the diversity of oncology practice. Enrolled individuals had breast, gastrointestinal, lung, hematological, head and neck, genitourinary, and other malignancies, with sample sizes ranging from single-patient case reports to more than 230 participants. The antidepressants evaluated included duloxetine at daily doses of 20 to 60 milligrams, oral amitriptyline at 10 to 20 milligrams, topical 10 percent amitriptyline gel, and venlafaxine, alongside combination regimens pairing duloxetine with mirogabalin at 5 to 25 milligrams daily or tapentadol at 50 to 500 milligrams daily. Pain outcomes were tracked with the Numerical Rating Scale, the Visual Analogue Scale, and the Brief Pain Inventory, while neuropathy severity was graded using CTCAE criteria, the Total Neuropathy Score, and the DN4 questionnaire.

The results for duloxetine monotherapy were strikingly consistent. In one double-blind placebo-controlled trial in non-metastatic breast cancer patients receiving paclitaxel, duloxetine cut average pain scores on the Numerical Rating Scale from 4.19 to 2.63 over eight weeks, while CTCAE neuropathy grades fell from 1.48 to 0.79, a statistically significant difference against placebo. A second placebo-controlled trial in gastrointestinal cancer patients treated with oxaliplatin similarly found that duloxetine prevented worsening of peripheral sensory neuropathy, with grade scores improving from 0.86 to 0.62. In a broader randomized trial across multiple tumor types, 44.1 percent of duloxetine-treated patients achieved a clinically significant pain reduction of at least 30 percent, compared with only 18.2 percent on placebo, and 32.4 percent achieved reductions of 50 percent or more versus 3.0 percent of placebo patients. A retrospective observational study was the outlier, reporting only a modest, statistically insignificant Visual Analogue Scale change, likely reflecting uncontrolled dosing and confounding.

Combination therapies generated the most eye-catching numbers, though the authors are careful about interpretation. In a randomized study of 72 breast cancer patients, duloxetine paired with electrostimulation reduced average pain scores from about 6.1 to 3.6 in two weeks. A single case report described mirogabalin plus duloxetine lowering pain scores from 8 to 1 and CTCAE grade from 3 to 1. In a randomized non-inferiority trial of 114 patients, tapentadol combined with duloxetine reduced the Numerical Rating Scale from 7.51 to 2.87, statistically equivalent to tapentadol alone. A prospective randomized comparison of 89 patients found duloxetine outperforming pregabalin on both pain and DN4 neuropathy scores, with duloxetine dropping scores from roughly 7 to 4 over four weeks. Meanwhile, a retrospective cohort in lung cancer showed duloxetine plus low-dose mirogabalin reducing median pain scores from 5.5 to 4.0. Importantly, adverse events remained mild across all regimens, limited mainly to nausea, constipation, dizziness, and transient somnolence, and combination treatments did not increase side-effect burdens relative to monotherapy.

One of the more intriguing findings concerned topical amitriptyline. In a prospective pilot study of 44 patients treated with bortezomib or oxaliplatin, a 10 percent topical amitriptyline emulsion applied twice daily for six months reduced Visual Analogue Scale scores from 7 to 2, with the difference reaching high statistical significance. Topical delivery may offer localized analgesia with far better tolerability than systemic tricyclic therapy, which is otherwise limited by dry mouth, weight gain, and drowsiness. The evidence base remains small, but the result hints at a practical option for patients who cannot tolerate oral agents, and it underscores how routes of administration may reshape the pharmacology of otherwise old drugs.

Why should antidepressants relieve nerve pain at all? The review explains the mechanistic logic. SNRIs like duloxetine and tricyclics like amitriptyline enhance both serotonergic and noradrenergic transmission, strengthening descending inhibitory pathways, particularly noradrenergic projections from the locus coeruleus to the spinal dorsal horn that suppress pain signals before they reach consciousness. Selective serotonin reuptake inhibitors, by contrast, fail to engage these noradrenergic circuits, which may explain their inconsistent efficacy in neuropathic pain. Preclinical work supports these mechanisms, with duloxetine, amitriptyline, and pregabalin all reducing pain behaviors in animal models, although translational gaps persist, especially for pregabalin and venlafaxine, which perform better in the laboratory than in the clinic, likely because animal models incompletely reproduce human CIPN and because dosing and timing differ.

The authors are candid about limitations. Study heterogeneity in design, populations, and outcome measures precluded quantitative meta-analysis, several trials were small, and the restriction to English-language open-access studies published after 2019 may have introduced bias and excluded foundational duloxetine trials, which the authors discussed as context rather than primary evidence. Combination benefits remain hypothesis-generating, since most multimodal studies lacked appropriate comparator arms to disentangle whether effects are additive, synergistic, or driven by a single component. Prevention, too, remains unproven; current evidence supports antidepressants only for treating established CIPN. Still, the message for patients and clinicians is clear and cautiously optimistic: duloxetine stands as the first-line pharmacological option, topical amitriptyline deserves larger trials, and well-designed randomized studies of combination strategies could finally deliver the relief that millions of cancer survivors still lack.

Subject of Research: The efficacy of antidepressants, particularly duloxetine, in managing chemotherapy-induced peripheral neuropathic pain

Article Title: The Role of the Antidepressants in Managing Chemotherapy‐Induced Neuropathic Pain: A Systematic Review

Article References: Caminiti, R., Mazza, V., Nucera, S., Oppedisano, F., Passacatini, L. C., Maiuolo, J., Malafoglia, V., Giorgio, A., Soluri, A., Pileggi, C., Tomino, C., Mollace, V., Ilari, S., & Muscoli, C. (2026). The Role of the Antidepressants in Managing Chemotherapy‐Induced Neuropathic Pain: A Systematic Review. Pharmacology Research & Perspectives, 14(5), Article e70327. https://doi.org/10.1002/prp2.70327

Image Credits: AI Generated

DOI: 10.1002/prp2.70327

Keywords: chemotherapy-induced peripheral neuropathy, CIPN, duloxetine, antidepressants, neuropathic pain, systematic review, SNRI, amitriptyline, cancer survivors, pain management, mirogabalin, tapentadol