Low back pain (LBP) is one of the most common symptoms leading to primary care physician visits in the United States [1–3] and can be challenging to manage, since it is not a distinct disease entity and manifests with a diverse range of symptoms and severity. Healthcare providers play a pivotal role in guiding patients experiencing LBP toward effective treatment strategies.

An estimated up to 84% of adults will experience LBP [4], with a notable 25%–39% of U.S. adults reporting LBP episodes within the past 3 months [5, 6]. Ineffective management of LBP is associated with significant costs, since LBP is the leading cause of disability globally and ranks high among reasons for work absences and reduced productivity [7–11].

Acute LBP is usually considered non-specific, which means that it cannot be attributed to a specific disease or spinal pathology with certainty; it is often self-resolving [12], and individuals often manage their symptoms without seeking medical care [1, 13, 14]. LBP typically encompasses pain, stiffness, and/or discomfort in the lumbosacral region, commonly attributed to causes such as muscle sprains, ligament strains, herniated discs, osteoarthritis, scoliosis, traumatic injury, sciatica, and lumbar spinal stenosis. LBP may radiate to other parts of the body; individuals may experience symptoms such as muscle, hip, or leg pain, which can manifest as sharp, dull, aching, or burning sensations. The pain may vary in intensity and pattern, being intermittent, constant, or waxing/waning, and be accompanied by bilateral lower extremity paresthesia or exacerbated by movement [15–17].

LBP is classified according to its duration: acute (<4 weeks), subacute (4–12 weeks), and chronic (>12 weeks) [10, 16]. Acute LBP is the most common and often caused by mechanical issues or soft-tissue damage due to poor posture, prolonged sitting, improper lifting, muscle sprains, and injury or trauma. Patients with persistent symptoms often see continued improvement in the subacute phase; in primary care settings, an estimated 32% of patients transition from acute to chronic LBP [18]. This emphasizes the importance of effective treatment strategies during the acute and subacute periods to prevent the transition to chronic LBP, which accounts for much of the burden and costs of LBP.

Established guidelines recommend non-pharmacological approaches as the first line of treatment, followed by pharmacological treatments only if non-pharmacological methods are ineffective or based on patient preference [10, 19–22]. Non-pharmacological approaches can include education on proper body mechanics, clinician-directed exercise programs (including formal physical therapy), local heat, massage/manipulation, acupuncture, electromyography biofeedback, low-level laser therapy, and cognitive behavior therapy [10].

Since many episodes of LBP are self-resolving, many individuals do not seek medical attention and may manage their symptoms over days to weeks using a combination of non-pharmacological and over-the-counter (OTC) pharmacological approaches. If these do not provide sufficient pain relief, they will often follow up with their healthcare professional. This provides an opportunity for healthcare professionals to assess and advise patients on appropriate pain relief options based on their distinct safety and efficacy profiles. This guidance can educate patients on proper dosing, precautions, and selection of the agent most suitable for their circumstances and needs. Both healthcare professionals and patients would benefit from an enhanced understanding of the benefits and risks of LBP treatment options, especially for those who are, or may be, at risk of adverse events or impacted by suboptimal treatment.

Guidelines published by the American College of Physicians (ACP) and endorsed by the American Academy of Family Physicians recommend non-steroidal anti-inflammatory drugs (NSAIDs) and skeletal muscle relaxers (SMRs) as first-line pharmacologic treatments for acute or subacute LBP [10, 23], as do the North American Spine Society and Department of Veterans Affairs [19, 20, 24]. The US Centers for Disease Control and Prevention (CDC) also support non-opioid medications, including NSAIDs, for LBP [25]. These guidelines do not distinguish between the various NSAIDs (e.g., naproxen, ibuprofen, and aspirin) [10, 19, 20, 24]. There are important differences between NSAIDs that can make one more suitable for an individual patient, as will be discussed later. Moreover, research across multiple types of pain models suggest that a single dose of naproxen is superior to other NSAIDs (ibuprofen and aspirin) and acetaminophen in terms of duration of pain relief [26–32], albeit there are studies suggesting that other NSAIDs may be superior to naproxen in some specific pain conditions [33, 34]. The occurrence of adverse events from OTC doses of naproxen is similar to that of placebo, with the most commonly reported mild-to-moderate adverse events related to the GI system [26–32]. In the context of managing LBP, naproxen alone demonstrated superior efficacy compared to combination therapies including: diazepam plus naproxen, cyclobenzaprine plus naproxen, oxycodone/acetaminophen plus naproxen, orphenadrine plus naproxen, or methocarbamol plus naproxen [35–38].

In a comprehensive review of 15 clinical practice guidelines containing recommendations for treating acute LBP, Oliveira et al. (2018) found a consensus highlighting NSAIDs as the primary choice for non-specific LBP [21]. Another analysis of clinical guidelines also found that they consistently recommend NSAIDs as the first-line pharmacological therapy [22], while international clinical practice guidelines provide conflicting recommendations for the use of SMRs [39].

Due to the lack of demonstration of meaningful effectiveness advantages with opioids in providing pain relief when compared to NSAIDs and the potential risks associated with long-term opioid use after treating acute pain, opioids are not recommended as first-line therapy for common acute pain conditions, including LBP [25, 40, 41], with one recent clinical study finding no significant difference in acute LBP severity between the opioid and placebo groups [42]. Opioids continue to serve an important role in managing pain related to severe traumatic injuries and major surgeries and in other instances when NSAIDs and other treatments are contraindicated or not likely to be effective.

For patients with an inadequate response to non-pharmacologic therapy, NSAIDs are recommended as the exclusive first-line pharmacologic therapy, and SMRs are not recommended for chronic LBP [10]. Although guidelines for second-line pharmacologic therapy vary, they consistently recommend that opioids be a last resort, after a careful discussion of risks and realistic benefits with patients—when other treatments have failed, contraindication to NSAIDs exist, or the potential benefits outweigh the risks [10, 19, 20, 24].

In their analyses of clinical practice guidelines containing recommendations for the treatment of chronic LBP, investigators found a consensus highlighting NSAIDs as the primary choice for managing chronic non-specific LBP [21, 22].

While acetaminophen has an established role in pain management, clinical guidelines do not recommend it for treating LBP based on studies showing that it is ineffective at improving LBP outcomes versus placebo [10, 19, 20, 24, 43]. This lack of efficacy may be due to acetaminophen being a weaker analgesic than NSAIDs and with minimal anti-inflammatory activity, despite some overlapping mechanisms with NSAIDs [44, 45].

Topical analgesic medications have a long history of use for managing a variety of acute and chronic pain conditions. Topical formulations provide localized delivery of active ingredients such as NSAIDs, anesthetics, and counterirritants such as menthol, methyl salicylate, and capsaicin. Studies indicate that topical NSAIDs, high concentration capsaicin, and lidocaine are effective for some pain conditions, with efficacy being highly dependent on the specific formulation and condition [46, 47]. By delivering high local drug concentrations at the site of pain while minimizing systemic absorption, they are optimal for pain confined to discrete areas like specific joints or skeletal muscles [48].

Since many non-specific LBP cases involve referred pain radiating from areas beyond the back itself, the effects of topical therapies directly applied to the low back can be limited. Currently, there is limited evidence supporting large or long-lasting analgesic effects from topical agents in treating LBP, especially relative to systemic pharmacological options like oral NSAIDs [49].

NSAIDs are well-established for pain management. Comprehensive reviews and clinical guidelines consistently support the view that, relative to placebo, NSAIDs reduce pain and improve function in patients with acute and chronic LBP; as a result, they are recommended as the first-line pharmacological therapy for LBP [10, 19, 20, 24, 49–51]. Moreover, studies have confirmed that NSAIDs, including naproxen, are as or more effective compared to other drugs alone or in combination with NSAIDs for the treatment of LBP [35–37, 52, 53].

Non-selective NSAIDs, such as naproxen and ibuprofen, work primarily by reversibly inhibiting the cyclooxygenase (COX) enzymes COX-1 and COX-2, which convert arachidonic acid into various compounds such as prostaglandins F2α (PGF2α) and E2 (PGE2) that are responsible for the pain and inflammation associated with many conditions [54–57]. While COX-1 is constitutively expressed and has key roles in the kidneys, gastrointestinal (GI) tract, and platelets, COX-2 expression is primarily induced during inflammation. This mechanism of action results in analgesic, anti-inflammatory, and antipyretic effects that make NSAIDs highly effective in treating a variety of pain conditions [54, 55].

While prescription NSAID regimens require healthcare provider supervision and per-patient assessment due to their risks, OTC equivalent regimens have an improved safety profile such that healthcare professional supervision is only required in some cases. The lower OTC doses and shorter treatment durations are associated with fewer side effects that are typically reversible upon discontinuation. However, as with any medication, risk cannot be entirely eliminated [58]. NSAIDs available as OTC formulations, such as naproxen sodium, have an established role in managing various types of pain, including LBP.

As mentioned previously, there are important distinctions between NSAIDs that can determine the suitability of one over another for an individual patient. Notably, studies indicate that a single dose of naproxen is superior to other NSAIDs (ibuprofen and aspirin) and acetaminophen in terms of duration of pain relief across several pain conditions [26–30, 32]. Moreover, naproxen has a pharmacokinetic profile that allows for a dosing interval of 8–12 h to achieve a sustained therapeutic effect. In contrast, other OTC NSAIDs must be readministered at 4–6-h intervals, which aligns with their maximum daily dosage and half-life. Naproxen’s extended dosing time frame reduces an individual’s overall “pill burden,” which has been identified as a factor linked to enhanced patient adherence [59] and enhances the consistency of serum concentrations, thereby delivering continuous pain relief while mitigating potential adverse effects tied to local exposure, peak concentrations, and subtherapeutic phases associated with fluctuations in pharmacokinetics [60]. It is noted that some epidemiological data suggest a slightly increased risk of GI bleeding with the use of low-dose naproxen compared with low-dose ibuprofen [61], which may possibly be attributed in part to its longer half-life [62], although a more recent analysis of controlled studies is not in agreement, finding no difference in adverse event profiles, including GI adverse events, between these regimens [31].

With longer duration of pain relief and comparable safety profile to other OTC NSAIDs, combined with an improved dosing regimen, naproxen is an ideal choice for OTC NSAID LBP management. The following sections provide additional details on naproxen in that context.

Guidelines recommend against opioids as first-line pharmacological therapy, yet these continue to be prescribed for LBP despite their unfavorable safety profile and general lack of evidence to support their effectiveness [40, 100–102]. Moreover, published studies have demonstrated that NSAIDs are as or more effective compared to opioids or opioids combined with NSAIDs for relief of LBP, despite the latter being associated with addiction and overdose-related mortality, a risk that has increased alongside prescription rates [40]. In one study, adding oxycodone/acetaminophen to naproxen 500 mg twice daily found no improvement in efficacy (pain relief and functional improvement) over naproxen alone for acute LBP prompting the authors to conclude that “These findings do not support use of these additional medications [beyond naproxen] in this setting” [35]. Moreover, the SPACE RCT compared opioids against non-opioids (including NSAIDs) for improving pain-related function in subjects with hip/knee osteoarthritis and chronic back pain. Over a 12 months period, opioids did not exhibit superior improvements in pain-related function compared to non-opioids [52].

Opioids are not recommended as first-line treatment choice for many common acute pain conditions because of the potential risks associated with their long-term use post-treatment. Opioids for acute pain can inadvertently lead to prolonged usage if prescribers provide large supplies or prescriptions are continuously refilled, resulting in drug dependence [40, 103]. Limited evidence supports improved pain or function with long-term use of opioids for several chronic pain conditions for which they are commonly prescribed, including chronic non-specific LBP. In some cases, evidence indicates worse outcomes associated with prolonged opioid usage for these conditions [10, 104]. Moreover, studies that have assessed opioids for chronic LBP have not addressed the risk for addiction, abuse, or overdose, although data show a dose-dependent relationship between opioid use for chronic pain and serious harms [105]. Furthermore, an analysis of patients who visited an emergency department with LBP showed that they were significantly more likely to return within 6–12 months with LBP complaints if they were prescribed an opioid at discharge compared to patients who were not. Receiving opioids at discharge also doubled the odds of return within 12 months, while receiving NSAIDs reduced the odds by 60% [106].

Data from the CDC indicate that in 2021 there were 16,706 reported deaths involving prescription opioids; almost 5 times higher than in 1999 [107]. The use of opioids carries many possible adverse effects, some of which are serious and life-threatening. GI effects like constipation, nausea, and vomiting are well-known risks associated with long-term opioid use [108, 109]. Additional but less frequent adverse effects include cardiovascular depression (bradycardia, hypotension), headaches, hypothermia, inability to urinate, muscle and bladder spasms, muscle rigidity, flushing, and involuntary muscle twitching and/or jerking. Opioid-induced hyperalgesia, an effect that heightens rather than dulls pain, has also been reported as a potential adverse effect [110, 111].

To reduce dependence on opioids, it is important that healthcare providers prioritize non-opioid treatment approaches, explore comprehensive pain management strategies, and adhere to established clinical guidelines, which generally recommend non-pharmacological approaches as the initial treatment for LBP, followed by NSAIDs as the first-line pharmacological therapy. Opioids should be considered the last resort due to the uncertain efficacy and risks associated with addiction and overdose. It is important to establish an adequate treatment plan concordant with established guidelines to reduce the risk of opioid dependence or transitioning from acute/subacute pain to chronic pain.

Centrally acting SMRs are approved for acute musculoskeletal conditions, and their prescribing doubled between 2005 and 2016 [112]. They are the third most commonly prescribed drug for LBP [39]. Although they are generally effective for acute LBP, the body of evidence originates from specific SMRs, their comparative efficacy to NSAIDs and other analgesics remains unknown, and evidence is lacking to support their use for chronic LBP [39, 113, 114]. Furthermore, it was shown that combining SMRs (i.e., orphenadrine or methocarbamol) to 500 mg by mouth naproxen (twice daily) for acute LBP did not increase efficacy (pain relief and functional improvement) when compared to naproxen plus placebo [36].

Based on moderate-quality evidence, the ACP recommends NSAIDs or SMRs as first-line pharmacological treatment for acute LBP [10], although the evidence does not support the view that SMRs improve functional recovery [115]. Studies have shown that SMRs introduce adverse events without significantly reducing LBP [39, 116]. SMRs have well-established central nervous system adverse effects, such as drowsiness and dizziness, and, due to limited long-term efficacy and safety data coupled with the potential risk for abuse, dependence, and overdose, their use is generally recommended for a maximum of 2-3 weeks [117–119]. Despite these limitations, one estimate suggests that 18.5% of LBP patients receive an SMR (unfortunately, the investigators were not able to distinguish between acute and chronic LBP) [120] and SMR use was found to increase rapidly between 2005 and 2016 [112]. This trend that may have taken hold as healthcare providers and patients seek alternatives to opioids for the management of LBP and other conditions. Overall, it is important to exercise caution when recommending SMRs for LBP, since the evidence suggests they may only be effective for acute and subacute LBP, and caution is especially warranted for patients with comorbidities, underlying conditions, or a history of substance abuse [112, 121].

Although the data supporting antidepressants’ efficacy remains uncertain, estimates indicate that roughly 25% of U.S. primary care physicians prescribe them for LBP [122]. The rationale is that individuals with chronic LBP often exhibit concurrent depression, and addressing the depression can raise pain tolerance. Some antidepressants are believed to have analgesic mechanisms distinct from their mood-elevating ones, and their sedative effects are thought to ameliorate insomnia in patients with chronic LBP. Nevertheless, the evidence does not generally support antidepressants for LBP treatment, as several studies have observed only a marginal and clinically non-significant benefit, primarily with SNRIs [21, 122–125]. Furthermore, antidepressants are associated with a variety of side effects, including dry mouth, constipation, drowsiness, dizziness, weight gain, and sexual issues, which collectively are a common reason for patients’ discontinuation of them [126, 127].

Corticosteroids possess both anti-inflammatory and immunosuppressant properties, and their side effect profiles can be extensive and affect many organ systems [128]. In general, no differences in efficacy for pain have been reported between systemic corticosteroids and placebo; a small effect on function in patients with radicular LBP has been observed, but the effects in individuals with non-radicular LBP remain uncertain [10, 129, 130]. Before initiating corticosteroids for LBP, healthcare providers should consider their potential adverse effects and patients’ underlying comorbidities to ensure any potential benefits outweigh the harms.

Antiseizure medications are commonly prescribed to treat LBP despite inconclusive evidence for the treatment of LBP [10, 21, 123, 124, 131] despite their increased risk of adverse events, including suicidality [132–134].