Table 1: Table 1 Clinical trials on combination pharmacological therapy of chronic low back pain.

ReferenceTrial designDurationMain inclusion/exclusion criteriaPain typeIntervention(s) and dosePrincipal outcome

L. Romanò et al. [31]Prospective, randomized,
3-way cross-over study
4-weeks treatment with each therapy
12 week18–75 years
Chronic LBP for >6 months due to disc prolapse, lumbar spondylosis, and/or spinal stenosis
Minimum VAS >40 mm (on a scale of 0–100 mm)
Patients with neurological disease excluded
MixedCelecoxib 3–6 mg/kg/die + placebo
and
Pregabalin 1 mg/kg/die for the first week, then 2–4 mg/kg/die + placebo
and
Celecoxib 3–6 mg/kg/die + pregabalin 1 mg/kg/die for the first week, then 2–4 mg/kg/die
Combination therapy was more effective than either monotherapy for mean pain reduction (assessing using 0–100 mm VAS)

Gatti et al., [32]Prospective,
observational, and
open-label study
6 weekChronic LBP (46 months)
Moderate to severe (>3 on a 0–10 VAS)
Pain not responsive to previous systemic or local analgesic treatment
Osteoarticular,
nociceptive pain (Group A)
or
neuropathic pain (Group B)
Group A
Previous treatment discontinued: Oxycodone 5 mg + paracetamol 325 mg/8 hours
Group B
Previous treatment (except gabapentin). Fixed combination of oxycodone 5mg + paracetamol 325 mg/8 hours
Group A
73.9% and 78.3% (assessed using 0–10 VAS), respectively
Group B
All patients reported improved or stable neuropathic pain symptoms except pain preventing sleep

Pota et al., [33]Prospective,
observational, and
open-label study
2 monthChronic LBP (33 months)Mixed
Month 1: Buprenorphine TDS 35  g/ml
Month 2: Buprenorphine TDS 35  g/ml + pregabalin 150 mg
or
Buprenorphine TDS 35  g/ml + placebo
Significant reductions in pain(assessed using 0–100 VAS) were observed after month 1
Significant reductions in painafter month 2 were only observed in the combination group

Khoromi et al., [34]Single-centre,
cross-over,
randomized trial
9 week18–65 years
Lumbar radiculopathy
Average leg pain score >4 (0–10 cm VAS)
Patients with polyneuropathy and peripheral vascular disease associated with symptoms of numbness, or patients with burning painin the lower extremities, were excluded
Neuropathic
Morphine 15–90 mg
and
Nortriptyline 25–100 mg
and
Morphine 15–90 mg nortriptyline 25–100 mg
No significant reductions in mean leg pain (assessed using 0–10 VAS) or other leg or back pain were observed in any treatment group
Pain reduction relative to placebo was 14% for nortriptyline, 7% for morphine, and 7% for combination therapy

Peloso et al., [35]Multi-centre,
randomized,
double-blind study
21-day washout period,
91-day double-blind treatment period
> 18 years
Chronic LBP
Pain intensity >40 (0–100 mm VAS)
Patients with neurologic deficits in lower extremities,
symptomatic disk herniation, severe spinal stenosis, or spondy lolisthesis excluded
NociceptiveTramadol 37.5–300 mg + paracetamol 325–2600 mg
or
Placebo
Mean final pain intensity scores (assessed using 0–100 mm VAS) were significantly lower with combination therapy (47.4) than with placebo (62.9; ), as were mean final pain relief scores (assessed on 6-point Likertscale: 1.8 and 0.7, resp., )

Ruoff et al., [36]Multi-centre,
randomized,
double-blind,
parallel group study
21-day washout period,
10-day titration period,
81-day treatment period
25–75 years
Chronic LBP
Pain intensity >40 (0–100 mm VAS)
MixedTramadol 37.5–300 mg + paracetamol 325–2600 mg
OR
Placebo
Significantly lower final meanpain score (assessed by 0–100 mm VAS) with combination therapy than with placebo
CR=controlled release; LBP: low back pain; Mixed: mixed nociceptive and neuropathic pain; TDS: Transdermal delivery system; VAS: visual analogue scale.