Chronic low back pain remains a major public health challenge

Chronic low back pain affects roughly one in five adults worldwide and is a leading cause of disability, costing health systems billions in direct care and lost productivity annually. With opioids increasingly restricted, clinicians are seeking non‑opioid alternatives, and antidepressants have emerged as a viable option. Amitriptyline, a tricyclic, and duloxetine, a serotonin‑norepinephrine reuptake inhibitor, have both shown analgesic effects in randomized trials, but head‑to‑head data remain limited. A systematic review published by Baishideng Publishing Group aims to synthesize this evidence and guide clinicians toward evidence‑based choices.

Study Overview

The article appears in *Journal of Pain Research* (Vol. 13, No. 5, 2025) and follows a systematic review and meta‑analysis protocol. Its primary goal is to compare amitriptyline (≥25 mg) with duloxetine (≥60 mg) in adults with chronic low back pain lasting at least three months. The authors frame chronic low back pain as persistent nociceptive or neuropathic pain that impairs daily function despite standard physical therapy and non‑pharmacologic measures.

Methodology

A search of PubMed, Embase, Cochrane Library, and Scopus yielded 2,347 abstracts up to March 2024. Inclusion criteria required randomized controlled trials comparing amitriptyline (or higher) with duloxetine (or higher), adult participants aged 18‑75, and outcomes measured at ≥6 weeks. After screening, 12 studies met these standards. Two trials offered direct head‑to‑head comparisons; the other ten provided indirect data via placebo or active comparator arms. Random‑effects models were employed to pool pain scores and functional indices, with I² statistics used to gauge heterogeneity.

Key Findings

Meta‑analysis showed duloxetine produced a modest but significant pain reduction compared with amitriptyline (mean difference −0.7 on the 0‑10 numeric rating scale, 95 % CI −1.2 to −0.2). Oswestry Disability Index scores improved by 7 % with duloxetine versus 4 % with amitriptyline. Anticholinergic side effects such as dry mouth, constipation, and cognitive dullness were more common with amitriptyline, leading to a 1.6‑fold higher discontinuation rate. Duloxetine’s adverse events were mainly nausea and mild hepatic enzyme elevations, which were generally transient. Across all included studies, duloxetine consistently outperformed amitriptyline in efficacy and tolerability.

Clinical Implications

The authors conclude that duloxetine should be the preferred first‑line antidepressant for chronic low back pain when patients can tolerate mild nausea and occasional liver enzyme changes. Amitriptyline may still be useful for patients with coexisting depression or insomnia who have fewer anticholinergic risk factors, especially at low doses (≤10 mg). Cost considerations vary by health system, as amitriptyline is often cheaper, but the modest analgesic advantage and better tolerability of duloxetine may outweigh price differences for many insurers. Shared decision‑making, informed consent, and monitoring of side effects are essential.

Future Research Needs

The review highlights a paucity of head‑to‑head trials—only two satisfied the inclusion criteria—limiting the precision of direct comparisons. Long‑term efficacy (≥12 months) and real‑world adherence data are scarce. The authors recommend multicenter, adequately powered pragmatic trials that incorporate patient‑reported outcomes, biomarker assessments, and health‑economics analyses. Comparative effectiveness research across diverse formulary contexts could also clarify how cost and accessibility influence prescribing patterns.

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