1. Pharmacotherapy
Eric J. Visser

2. Lets review the drug cupboard

3. Paracetamol Does it work?
Not sure how paracetamol works?
- COX-2, ‘cannabinoid’, serotonin?
Mainstay analgesic in most chronic pain protocols
Not much good for MSS pain?
- exception: older patients?
Adverse effects (liver, warfarin; NSAID-like?)
Rx for acute LBP
- especially as combination drug with NSAID/coxib, tramadol, codeine (NNT 3)
Machado GC et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ Mar 31;350:h1225. doi: /bmj.h1225.

4. Tramadol Good for acute & chronic LBP
1/3rd opioid, 1/3rd SSRI (serotonin), 1/3rd SNRI (nor adrenaline)
1st line for acute & chronic LBP (NNT 4)
Effective for neuropathic pain (NNT 4)
↓ Respiratory depression & constipation
OK with TCAs, SSRIs, SNRIs; ‘sensible doses’; no seizures
Accumulates in renal impairment
Pro-drug, 11 active metabolites
Won’t work in 10% of patients (like codeine, cytochrome P450 2D6)

5. Tapentadol SR Like tramadol without the serotonin
‘Weak’ opioid (S8) & NARI in one molecule
-noradrenaline is main pain-inhibiting neurotransmitter
2nd line for chronic pain?
Effective in nociceptive & neuropathic pain (NNT 4)
↓ Constipation
↓ Side effects than tramadol?
Minimal accumulation in renal impairment
OK with TCAs, SSRIs, SNRIs
Tapentadol SR 50 mg ~ 10 mg oxycodone po ~ 20 mg morphine po

6. NSAIDs & coxibs Effective (NNT 3) Rapid-acting formulations ARE better
Rx acute pain flare-ups (days-fortnight)
Do NOT use long-term for chronic pain
Renal & gastric risk (NSAIDs) (PPI)
Hypertension & cardiovascular risk
Naproxen-best cardiovascular risk (MI)
Celecoxib-best overall risk profile (gut, bleeding, CVS)

7. Antidepressants & anticonvulsants
TCAs: NOT effective for CLBP
Duloxetine (SNRI): moderately effective (noradrenaline effect)
- chronic LBP
- neuropathic pain (NNT 4) (radicular leg pain?)
Gabapentinoids (pregabalin, gabapentin)
Not effective for LBP
Radicular leg pain?

8. Opioids don’t work well in CLBP (NNT = 8, NNH = 4) (Level I)
Opioids for CLBP?
Opioids don’t work well in CLBP (NNT = 8, NNH = 4) (Level I)
Adverse effects (tolerance, hyperalgesia, overuse, addiction)
Poor risk vs benefit
Opioids ‘contraindicated’ in CNSLBP (especially < 60s)
Consider in > 60s with spondylosis (more side effects?)
Opioid prescribing is always an ongoing therapeutic trial (90 days)
3Ts: tramadol SR, tapentadol SR, transdermal buprenorphine
Ceiling dose is ≤ 90 mg oral morphine equivalents/day (no more)
Chaparro LE et al. Opioids compared with placebo or other treatments for chronic low back pain: an update of the Cochrane Review. Spine (Phila Pa 1976) ;39(7):

9. Transdermal buprenorphine patch
Mu partial agonist, kappa antagonist
No ceiling effect for analgesia
Use it like any other opioid
Safer respiratory profile
Safer renal profile (no accumulation)
Better dose control....only 1 patch per week

10. What about Bob? Above the ceiling dose
Bob has ‘’opioid non-responsive pain’’
Taper & cease
Opioid rotation
- tapentadol (wean morphine slowly-may get withdrawal)
- oxycodone/naloxone CR
- transdermal buprenorphine patch

11. Radicular (neuropathic) leg pain Analgesics don’t work? (level I)
TCAs, opioids & NSAIDs don’t work
Pregabalin?
Duloxetine?
2nd line, tramadol SR or tapentadol SR
3rd line, transdermal buprenorphine
Oral steroids?
Natural history; improvement in 3-6 months
Pinto RZ et al. Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis. BMJ Feb 13;344:e497. doi: /bmj.e497.

12. Acute-on-chronic LBP flare-ups
Rx as per acute LBP guidelines
Comfort measures (heat)
Continue baseline analgesia
Celecoxib mg bd for ≤ 4 days?
Paracetamol w/ tramadol IR (or codeine?) prn
Short-term IR opioid? (oxycodone) (≤ 4 days)
Orphenadrine (?) or baclofen for muscle spasms (avoid diazepam)
Four-hour rule for prn analgesia: ≤ 4/24 prn, ≤ 4 x daily, ≤ 4 days

13. Summary An inconvenient truth
Pharmacotherapy: part of a multimodal pain Mx approach
Not much works for CLBP or radicular leg pain
Avoid opioids in CNSLBP (HARM > help)
- consider in > 60s with spondylosis; or spondylitis
- 3Ts: tramadol, tapentadol, transdermal buprenorphine
- opioid ceiling dose = 90 mg oral morphine/eq per day
- ‘opioid-non responsive pain’ (taper & cease, opioid rotation)
Radicular pain: pregabalin, duloxetine, tramadol, tapentadol?
Acute pain: celecoxib, paracetamol-combo prn
Start low & go slow (↓ side effects)

14. Thank you

15. Pharmacotherapy for chronic NSLBP Learning objectives
Pharmacotherapy must always be part of a multimodal pain Mx approach
CLBP is often a ‘mixed’ pain (nociceptive & neuropathic pain elements)
Analgesics are NOT that effective for CLBP
Analgesics are NOT that effective for radicular leg pain
Opioids are (essentially) contraindicated in CNSLBP (especially in < 60s)
Exceptions: > 60s with ‘degenerative’ spinal pain (spondylosis), or patient w/ ‘inflammatory spinal pain’ (spondylitis)
Preferred opioids, 3Ts: tramadol, tapentadol, transdermal buprenorphine
Mx acute-on-chronic LBP flare-ups (multimodal, COX-2, paracetamol-analgesic combo)
Avoid benzodiazepines
Always titrate medications: ‘’start low and go slow’’

16. Visser MED 200 UNDA pain pharmacology 2015
Adverse effects of long-term opioids
Classical side effects (respiratory, sedation, dizziness, nausea, constipation)
Overuse (chemical-coping, addiction) (+ reward centre, dopamine)
Opioid-induced hyperalgesia & tolerance (the pain gets worse)
Endocrine changes (testosterone, osteoporosis)
Immune modulation (activates glia via Toll-like receptors)
Cortical changes on fMRI (cognitive, anxiety, mood, motivation)
Increased all cause mortality
Poor QoL, social & health outcomes
>150mg oral morphine equivalents per day = really bad outcomes
Visser MED 200 UNDA pain pharmacology 2015