BLUF (Bottom Line Up Front)
This study systematically reviewed 301 randomized controlled trials (RCTs) and 377 treatment comparisons assessing the efficacy of 56 different non-surgical and non-interventional treatments for acute (<12 weeks) and chronic (≥12 weeks) low back pain against placebo. The findings indicate that only 10% of the treatments provided statistically significant but small pain relief beyond placebo. For acute low back pain, NSAIDs were the only treatment with moderate-certainty evidence of efficacy. For chronic low back pain, exercise, spinal manipulative therapy, taping, antidepressants, and TRPV1 agonists were identified as efficacious, though the effect sizes were small. In contrast, glucocorticoid injections, paracetamol, and antibiotics did not provide meaningful pain relief, challenging their widespread clinical use. The majority of treatments had inconclusive evidence due to small sample sizes, imprecision, and methodological flaws, underscoring the need for higher-quality placebo-controlled trials to inform clinical guidelines for low back pain management.
Purpose of the Study
This study aimed to:
- Evaluate the effectiveness of non-surgical and non-interventional treatments for low back pain compared to placebo.
- Identify treatments that provide significant pain relief beyond placebo effects.
- Determine the level of evidence certainty for each treatment and classify them as efficacious, not efficacious, or inconclusive.
Subjects and Research Methodology
- Number of RCTs analyzed: 301
- Number of treatment comparisons: 377
- Number of treatments assessed: 56
- Study population: Adults (≥18 years) with non-specific low back pain, categorized as either acute (<12 weeks)or chronic (≥12 weeks).
- Databases searched: MEDLINE, CINAHL, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials (search period: inception to April 14, 2023).
- Risk of Bias Assessment: PEDro Scale (0–10 points); trials scoring ≤6 were classified as high risk.
- Data Analysis:
- Random effects meta-analysis to estimate treatment effects on pain intensity (0–100 scale).
- GRADE (Grading of Recommendations Assessment) approach to determine evidence certainty (High, Moderate, Low, Very Low).
Findings
1. Efficacious Treatments (Provide Pain Relief Beyond Placebo)
- Acute Low Back Pain:
- NSAIDs: Moderate-certainty evidence of small but significant pain relief.
- Chronic Low Back Pain:
- Exercise: Moderate-certainty evidence of small pain reductions.
- Spinal Manipulative Therapy: Moderate-certainty evidence of small pain reductions.
- Taping: Moderate-certainty evidence of small pain reductions.
- Antidepressants: Moderate-certainty evidence of small pain reductions.
- TRPV1 Agonists: Moderate-certainty evidence of small pain reductions.
2. Non-Efficacious Treatments (No Meaningful Pain Relief Beyond Placebo)
- Acute Low Back Pain:
- Exercise, glucocorticoid injections, and paracetamol had moderate-certainty evidence of no effect.
- Chronic Low Back Pain:
- Antibiotics and anesthetics had moderate-certainty evidence of no effect.
3. Inconclusive Treatments (Insufficient Evidence Due to Small Sample Size or Study Limitations)
- Acute Low Back Pain:
- 10 non-pharmacological treatments (e.g., acupuncture, heat therapy, massage, TENS, laser therapy, spinal manipulative therapy).
- 10 pharmacological treatments (e.g., cannabinoids, opioids, muscle relaxants, immunoglobulins).
- Chronic Low Back Pain:
- 22 non-pharmacological treatments (e.g., biofeedback, dry cupping, diathermy, extracorporeal shockwave therapy, transcutaneous electrical nerve stimulation (TENS)).
- 16 pharmacological treatments (e.g., opioids, muscle relaxants, probiotics, antibody injections, bisphosphonates).
Analysis and Interpretation of Findings
This review provides a comprehensive synthesis of placebo-controlled trials evaluating non-surgical and non-interventional treatments for low back pain. The findings confirm that only a small subset of these treatments demonstrated statistically significant pain relief beyond placebo, and the effects were generally small. NSAIDs were the only treatment with moderate-certainty evidence of efficacy for acute low back pain, while for chronic low back pain, exercise, spinal manipulative therapy, taping, antidepressants, and TRPV1 agonists were found to be effective, though with small effect sizes.
Conversely, glucocorticoid injections, paracetamol, and antibiotics did not provide meaningful pain relief, despite their frequent use in clinical settings. The majority of treatments had inconclusive evidence, largely due to small sample sizes, methodological weaknesses, and imprecision. A major limitation in the current evidence base is the high risk of bias, with 62% of studies classified as high risk. Common methodological issues included lack of therapist blinding (69%), failure to conduct intention-to-treat analysis (50%), and unconcealed allocation (46%), reducing confidence in many of the reported effects.
Furthermore, the review highlights the challenges in designing placebo-controlled trials for behavioral, psychological, and exercise-based treatments, which may contribute to the lower certainty of evidence for these interventions. Given that placebo effects themselves may contribute to small analgesic benefits, distinguishing between actual treatment effects and non-specific effects remains critical for guiding clinical decisions.
Conclusion
The findings indicate that only one in ten common non-surgical and non-interventional treatments for low back pain are efficacious, and even these provide only small analgesic effects beyond placebo. NSAIDs remain the only moderately effective treatment for acute low back pain, while exercise, spinal manipulative therapy, taping, antidepressants, and TRPV1 agonists provide small but statistically significant benefits for chronic low back pain.
Many widely used treatments, including glucocorticoid injections, paracetamol, and antibiotics, were found to be ineffective, questioning their routine clinical use. The majority of treatments lack conclusive evidence, primarily due to small sample sizes, methodological limitations, and inconsistent trial designs, emphasizing the need for higher-quality, placebo-controlled research. Future trials should focus on improving study design, increasing sample sizes, and ensuring methodological rigor to refine treatment guidelines and improve pain management strategies for low back pain.
Bibliography
Cashin, A. G., Furlong, B. M., Kamper, S. J., De Carvalho, D., Machado, L. A. C., Davidson, S. R. E., Bursey, K. K., Abdel Shaheed, C., & Hall, A. M. (2025). Analgesic effects of non-surgical and non-interventional treatments for low back pain: A systematic review and meta-analysis of placebo-controlled randomized trials. BMJ Evidence-Based Medicine.