Advancing chronic low back pain management: Insights from amitriptyline and duloxetine comparison

Abstract

Chronic low back pain (CLBP) is a leading cause of disability worldwide, yet optimal pharmacological management remains debated. This letter to the editor appraises the observational study by Sardar et al, which compared amitriptyline and duloxetine in a tertiary rehabilitation setting. The study, involving 254 patients, demonstrated that amitriptyline provided rapid early pain relief, while duloxetine offered more sustained pain reduction at 12 weeks with fewer anticholinergic and sedative side effects. These findings are consistent with existing evidence supporting duloxetine’s efficacy and tolerability in chronic pain management. Although the absence of a placebo group limits causal inference, the study underscores the importance of individualized treatment strategies. We recommend further randomized controlled trials to validate these findings and strengthen evidence-based guidelines for CLBP management.

Key Words: Chronic low back pain; Amitriptyline; Duloxetine; Visual analog scale; Sedatives

Core Tip: This manuscript highlights the comparative effectiveness of amitriptyline and duloxetine for chronic low back pain (CLBP). While amitriptyline provides rapid early pain relief, duloxetine offers more durable reduction with fewer side effects, making it preferable for sustained management. The study’s real-world approach, using robust statistical adjustments and patient-centered outcomes, emphasizes the importance of personalized treatment strategies in chronic pain. These findings support duloxetine as a promising option and underscore the need for further randomized trials to refine evidence-based guidelines for CLBP management.

TO THE EDITOR

I read with great interest the article by Sardar et al[1], titled "Comparative effectiveness of amitriptyline vs duloxetine in the treatment of chronic low back pain: An observational study". This well-executed observational study provides valuable insights into the comparative efficacy and safety of amitriptyline and duloxetine for managing chronic low back pain (CLBP), a debilitating condition affecting millions globally[2].

The authors’ rigorous methodology, involving 254 patients in a tertiary rehabilitation setting and employing robust statistical tools like analysis of variance to adjust for baseline differences, is commendable[1]. Their findings highlight that while amitriptyline offers rapid pain relief in the early weeks, duloxetine achieves superior sustained pain reduction at 12 weeks, as measured by the visual analog scale[1]. This aligns with prior evidence suggesting duloxetine’s efficacy in CLBP, particularly at 60 mg daily, with improvements in pain and quality of life[3]. A recent meta-analysis further supports duloxetine’s role in chronic pain management, noting its favorable side effect profile compared to tricyclic antidepressants (TCAs)[4].

Amitriptyline’s rapid onset, observed at 1 and 4 weeks, may be attributed to its broader pharmacological effects, including sedative properties beneficial for sleep disturbances in CLBP[5]. However, its higher incidence of anticholinergic side effects, such as dry mouth and drowsiness, contrasts with duloxetine’s milder profile, potentially improving long-term adherence[1,6]. These findings echo systematic reviews indicating that serotonin and norepinephrine reuptake inhibitors (SNRIs) like duloxetine have fewer off-target effects than TCA[7].

The global burden of CLBP underscores the importance of such studies, as it remains a leading cause of disability[8]. The absence of a placebo group, a noted limitation, aligns with challenges in pain research where placebo effects are significant[9]. Nevertheless, the study’s use of the brief pain inventory and strict adherence monitoring strengthens its real-world applicability[1]. Previous trials, including a randomized controlled trial on low-dose amitriptyline, have shown mixed results, with some failing to demonstrate significant benefits over placebo[10]. In contrast, duloxetine’s consistent pain reduction in studies supports its preferential use in certain patient populations[11].

The authors’ call for future randomized trials to confirm these findings is timely, given the variability in clinical guidelines on antidepressant use for CLBP[12]. For instance, some guidelines recommend duloxetine as a second-line therapy, while others question the efficacy of TCAs[13]. This study’s contribution to personalized medicine is notable, suggesting that treatment choice should consider patient-specific factors like tolerance for side effects and comorbidities[1].

Beyond the findings of Sardar et al[1], it is important to place these results in the context of the broader evidence base. Several systematic reviews and meta-analyses have reported low to very low certainty evidence for antidepressants overall in non-specific low back pain and have questioned a clinically meaningful benefit on pain or disability; SNRIs (including duloxetine) show at best small effects on pain that may be of limited clinical importance, and TCAs (including amitriptyline) have inconsistent effects across trials[14,15]. The heterogeneity in published results likely reflects differences in study populations, baseline disability, follow-up duration, outcome measures, dosing strategies, and methodological quality, factors that complicate direct comparisons and generalizability.

A brief mechanistic and tolerability discussion helps explain the clinical differences observed. Duloxetine, a serotonin–norepinephrine reuptake inhibitor, is thought to exert analgesic effects by augmenting descending inhibitory pain pathways via increased synaptic serotonin and norepinephrine, which can reduce central pain sensitization; several mechanistic and clinical studies support this mode of action and its dose-dependent analgesic effects[16]. In contrast, amitriptyline’s broader pharmacology, including anticholinergic, antihistaminic and sedative effects in addition to monoamine reuptake inhibition, may explain its earlier effects on sleep and pain but also accounts for a higher burden of anticholinergic adverse effects that limit tolerability, particularly in older adults[17]. Notably, randomized trials of low-dose amitriptyline have not consistently shown benefit over comparators[10], while duloxetine trials often show modest pain reduction but with higher rates of adverse effects and discontinuation at some doses[7]. These mechanistic and tolerability differences highlight the need to tailor antidepressant selection and dosing to patient age, comorbidity, and tolerance for side effects.

In summary, Sardar et al’s study provides meaningful real-world evidence that while amitriptyline offers rapid short-term relief, duloxetine achieves more durable pain reduction with fewer side effects in patients with CLBP[1]. These findings are consistent with meta-analyses demonstrating duloxetine’s efficacy and favorable tolerability profile compared to TCAs[3,4,7]. Given the mixed results of randomized controlled trials on low-dose amitriptyline[10] and the consistent benefits observed with duloxetine across chronic pain conditions[11], duloxetine appears to be a more suitable long-term therapeutic option for selected patients.

We recommend that clinicians consider duloxetine as a preferential agent in patients requiring sustained pain management, particularly where tolerability and adherence are concerns. However, further high-quality randomized controlled trials with larger and more diverse populations are warranted to confirm these observational findings and guide harmonization of international clinical guidelines[12,13]. Strengthening the evidence base will be crucial for optimizing personalized pharmacological strategies in CLBP.