Current and future pharmacological agents for the treatment of back pain

Figures & data

Table 1. Summary of therapeutic benefits and adverse effects of pharmacological options for patients with low back pain. Data is in absolute units on the 0–100 scale unless otherwise specified.

Pharmacological therapy	Effect size (95% CI) on a 0–100 scale for pain/SMD/RR	Level of evidence	Comments
Acetaminophen/ Paracetamol	0.0 (–9.7, 9.7) [17]	Low
NSAIDs	−6.97 (−10.74, −3.19) [14]	Low	No increase in AE with NSAIDs compared to placebo
Gabapentinoids	2.2 (−5, 7.7) [23]	Very low	A meta-analysis of 3 studies that compared gabapentin against placebo did not show a difference between gabapentin, pregabalin and placebo [23] but did not include a crossover study that showed superiority of gabapentin to pregabalin [24]
TCA	SMD: 0.10 (−0.51, 0.31) [18]	Low
SSRI	SMD: 0.11 (−0.17, 0.39) [18]	Low
SNRI	RR: 1.41 (1.11, 1.78)* [15]	Moderate
Muscle relaxants including BZD	−21.3, (−29.0, −13.5) [21]	Low	Data positive for acute pain relief; no evidence for long-term outcomes or radicular pain
Opioids	All opioids: −10.1 (−12.8, −7.4) for short-term benefit [27] SMD for Tramadol: −0.55 (−0.66, −0.44) SMD for transdermal buprenorphine: −2.47 (−2.69, −2.25) SMD for strong opioids: −0.43 (−0.52, −0.33) [26]	Moderate	Higher incidence of nausea, dizziness, constipation, vomiting, somnolence and dry mouth with opioids compared to placebo. No longer considered first-line treatment for any chronic pain condition.

*Likelihood of 50% or greater relief of low back pain after 12 weeks.

AE: adverse effects; BZD: benzodiazepines; NSAIDs: non-steroidal anti–inflammatory drugs; RR: relative risk; SMD: standardized mean difference; SNRI: serotonin–norepinephrine reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: Tricyclic antidepressants.

Table 2. New pharmacotherapeutic agents evaluated in studies for treating low back pain with or without radicular pain.

1st Author, year (study type – number of participants)	Main results
Nerve growth factor inhibitors (tanezumab, fulranumab, fasinumab)
Katz 2011 (RCT – 216) Kivitz 2013 (RCT – 1347) Sanga 2011 (RCT – 389) Tiseo 2014 (RCT – 157)	Tanezumab, but not Fulranumab or Fasinumab, more efficacious than placebo or naproxen AE: arthralgias, headache, para/hyperesthesia, abnormal peripheral sensation, and dizziness
Cannabinoids (CBD, THC+CBD)
Mondello 2018 (Retrospective – 11) Silveira 2014 (Animal study −19)	The addition of THC-CBD resulted in effective pain management in all 11 people who had failed to respond to SCS for neuropathic FBSS Injection of CBD into inflamed intervertebral discs attenuated degeneration in response to induced injury AEs: dizziness, drowsiness, attention deficits, dry mouth, headaches, migraines, nausea, vomiting, palpitations, forgetfulness, urinary retention, fatigue, balance difficulty, myalgias, weakness, hot flushes
Bisphosphonates: denosumab, minodronate, pamedronate, zoledronate
Fujimoto 2017 (CS – 113) Koivisto 2014 (RCT – 40) Sakai 2014 (CS – 397) Tetsunaga 2017 (CS – 80) Pappagallo 2014 (RCT – 44)	Participants had LBP secondary to osteoporosis (without or with vertebral fractures) or degenerative spondylosis Newer bisphosphonates require less frequent administration and reduce intensity of LBP in the short term, decrease bone metabolism markers, and may increase bone mineral density Acute-phase reactions (fever, flu-like symptoms, arthralgia) seen with bisphosphonates
New opioids: cebranopadol
Christoph 2017 (RCT – 360)	Combines nociceptin/orphanin FQ peptide and opioid peptide receptor agonism Demonstrated analgesic efficacy, with significant and clinically relevant improvements in pain over placebo (comparable to tapentadol), along with both improved sleep and functionality in patients with LBP Low incidence of AE
Ketamine
Amr 2011 (RCT – 200) Patil 2012 (CS – 7)	Epidural S(+) ketamine enhanced analgesic effects of steroids and local anesthetics and reduced disability in patients with LBP and radicular pain Subanesthetic intravenous ketamine (mean dose 0.9 mg kg^−1) in severe refractory pain states reduced pain for over 3 weeks Epidural ketamine may be associated with neurotoxicity
Botulinum toxin
Machado 2016 (RCT – 37) Cogne 2017 (RCT – 19) Ney 2006 (CS – 60) Jabbari 2006 (CS – 75) Foster 2001 (RCT – 31)	Higher doses (>200 units per session with 40–50 units per site) may decrease intensity of LBP and improve quality of life Analgesic effect mediated by chemical denervation of local muscles and inhibition of release of inflammatory mediators and pain neurotransmitters Most studies were sponsored by industry Beneficial clinical response to the first injection predicts response to reinjection Patients on opioids do not respond as well as opioid-naive subjects AE: Mild flu-like reaction lasting a few days

AE: adverse effects; CBD: cannabidiol; CS: case series; FBSS: failed back surgery syndrome; LBP: low back pain; RCT: randomized controlled trial; SCS: spinal cord stimulation; THC: delta-9-tetrahydrocannabinol.

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