Table 4Benefits and Comparative Benefits of Pharmacological Therapies

Key question/intervention Recommendation Strength of recommendation Quality of evidence

PICO 4. For patients with lumbar spinal stenosis, should nonsteroidal anti-inflammatory drugs (NSAID) be used for patients with lumbar spine stenosis?

NSAIDs For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of NSAIDs for any duration. Conditional/Weak Low (⊕⊕OO)

Definition: Anti-inflammatory drugs in the form of NSAIDs (eg, naproxen 250–500 mg or ibuprofen 400–600 mg 3–4 times or twice daily) with treatment duration from 4 to 12 wk.

Included studies: We did not identify any RCT investigating the effect of NSAID in patients with NC caused by LSS (Appendix 6, Table 4). Patients with LSS often presents with LBP. The panel considered indirect evidence from 2 systematic reviews (Enthoven et al (2016), ³⁵ Machado et al (2017) ⁷⁹) reporting a statistically, but non-clinically significant immediate and short-term benefit favoring NSAIDs compared to placebo in reducing LBP. NSAIDs increased the risk of gastrointestinal adverse effect.⁷³^,⁷⁴.

Comment: The panel determined a low certainty in the evidence, with small desirable effects (many of the estimates did not meet MCID), and a moderate risk of undesirable effects reported.

Remarks: Consider possible drug interactions and potential differences in gastro-intestinal, liver, cardiovascular and renal toxicity, and the person's risk factors, including age. ⁶²^,¹³⁹

PICO 5. For patients with lumbar spinal stenosis, should adjunctive analgesics (methylcobalamin, paracetamol) versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?

Adjunctive Analgesics (Methylcobalamin, Paracetamol) For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of Methylcobalamin or Paracetamol (acetaminophen). Conditional/weak Consensus-based

Definition: Pain medication in the form of oral Methylcobalamin/vitamin B12 (0.5 mg, 3 times/d for 6 mo) or paracetamol (max 4 grams daily for 4-12 wk).

Studies considered: One RCT by Waikakul et al (2000) ¹³² compared oral Methylcobalamin along with usual care to conventional treatment only (education, activity modification, strengthening exercises for the trunk and abdominal muscles, physical therapy, and NSAIDs, analgesics and muscle relaxant as needed), and another RCT by Rodrigues et al (2014) ¹⁰⁴ compared Paracetamol to either oral corticoid (1 mg/kg/d with a 1/3 dose reduction weekly) or placebo for 3 wk.

Primary outcomes: Walking distance (Meters), pain (VAS), functional disability (RMDQ and 6-min walk test), quality of life (SF-36).

Key results: No between group difference was observed in those trials.

Comments: The panel determined a very low certainty in the evidence, with uncertain desirable effects and a risk of undesirable effects. The panel decided to pursue consensus-based recommendation.

Remarks: Paracetamol cannot be recommended at this time for neurogenic pain. Further, Paracetamol is unlikely to provide clinical benefit for concurrent acute or chronic LBP. Other treatment options should be considered in case of persistent and function-limiting symptoms considering potential adverse effects.

PICO 6. Should Adjunctive Analgesics (Calcitonin) be Used for Patients with LSS vs other therapies or placebo?

Adjunctive analgesics (Calcitonin) For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of Calcitonin. Conditional/Weak Consensus-based

Definition: Pain medication in the form of nasal salmon calcitonin spray or intramuscular calcitonin (variable doses)

Studies considered: A review of four small RCTs by Podichetty (2011) ¹⁰⁰ found no significant improvement when comparing calcitonin with placebo for pain (VAS) or walking distance. About 5% of patients reported minor transient side effects (nausea and flushing).

Primary outcomes: Pain (VAS) and walking distance (Meters).

Comments: Although the panel considered this review, it was eventually excluded from the analysis due to a lack of reported data with unclear pooled estimates. The panel decided to pursue consensus-based recommendation.
Remarks: Calcitonin releases β-endorphins and can be used as an analgesic agent. The most frequently reported transient minor adverse events were nausea and flushing. Other treatment options should be considered in case of persistent and function-limiting symptoms.

PICO 7. For patients with lumbar spinal stenosis, should serotonin–norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs)‡ versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?

SNRIs or TCAs For patients with LSS and neurogenic claudication with or without LBP, we suggest to consider a trial of serotonin–norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs). Conditional/Weak Consensus-based

Definition: SNRIs and TCA are a class of anti-depressant medication commonly used to treat chronic pain.
Included studies: No RCT investigated the effect of SNRIs or TCAs in patients with NC.
Studies considered: The panel considered indirect evidence on the use of SNRIs and TCAs in chronic LBP and neuropathic pain. ⁵⁹ ^, ⁶⁵^,¹⁰²^,¹¹⁷^, ¹²⁸^, ¹³⁰^, ¹³⁶
Comment: The panel pursued a consensus-based recommendation, with moderate risk of adverse events considered. The panel concludes that a trial of SNRI or TCA should be considered in patients with LSS causing NC with LBP.
Remarks: Consider side effects including, but not limited to, cognitive and physical function, cardiovascular issues and postural instability (eg, falls).

PICO 8. For patients with lumbar spinal stenosis, should opioid versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?

Opioids For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of opioids as first line treatment. Conditional/Weak Consensus-based

Definition: Opioids (eg, morphine 10 mg 3–4 times/d, oxycodone 5–10 mg twice/d or tramadol 50–100 mg 3–4 times/d in addition to non-opioid pain medication and with a treatment duration from 4 to 12 wk) ¹⁰⁵.
Studies included: No eligible RCTs investigated the effect of opioids for the treatment of NC caused by LSS.
Studies considered: The panel considered indirect evidence from opioid therapy guidelines for chronic noncancer pain ¹⁹, and consensus-based recommendation from the DHA guideline on managing LSS ¹⁰⁵.
Comment: The panel pursued a consensus-based recommendation, with strong risk of adverse events considered. Opioids may only be used for patients who have failed to respond to the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. ¹⁹^,³⁷ While the potential benefit of opioids for neurogenic claudication due LSS is unknown, there is strong evidence for the potential side effects of opioid use ¹⁹^,¹⁰².
Remarks: Should a trial of opioids be considered in selected patients who have persistent, problematic pain despite optimized non-opioid therapy, caution should be used with respect to side effects including, but not limited to cognition, balance, narcotic habituation, overdose and death ¹⁹^,¹⁰².

PICO 9. For patients with lumbar spinal stenosis, should muscle relaxants be used to decrease pain, and improve function, quality of life, and return to function?

Muscle relaxants For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of muscle relaxants. Conditional/Weak Consensus-based

Definition: Skeletal muscle relaxants (eg, tizanidin 2–4 mg 3–4 times/d, chlorzoxazone 250 mg 3–4 times/d) for 4–12 wk ¹⁰⁵.
Studies included: No RCTs investigated the use of muscle relaxants in patients with NC caused by LSS.
Studies considered: Patients with LSS often presents with LBP. The panel considered indirect evidence from systematic reviews (van Tulder, et al (2003),¹²⁹ Chou et al (2017),²⁴ and guidelines ¹⁰²^,¹⁰⁵ addressing the management of LBP. For acute LBP, there was moderate to strong evidence that different muscle relaxants performed similarly to each other, and are more effective than placebo for short-term pain relief for patients. However, evidence was insufficient to determine effects on function. For chronic LBP, there was insufficient evidence with inconsistent results and methodological shortcomings to determine the effects of muscle relaxants. Adverse events however were significantly more prevalent in the muscle relaxants group (RR = 1.50; 95% CI, 1.14 to 1.98), and especially the central nervous system (RR = 2.04; 95% CI, 1.23 to 3.37).
Comment: The panel pursued a consensus-based recommendation, with known undesirable consequences greater than the uncertain desirable effects of muscle relaxants. For patients with LSS causing NC with LBP, the panel determined there was a low certainty of evidence, with existing studies focusing on LBP of various etiologies. Muscle relaxants may provide short-term pain relief for acute and subacute LBP, though adverse events secondary to muscle relaxant use should be considered.
Remarks: Important to differentiate true muscle relaxants vs psychogenic relaxants. Psychogenic relaxants are more commonly prescribed and may help improve sleep. For patients with claudication type pain, it is important to consider the anti-spasm properties of these agents. Risks of transient adverse events should be considered and patients should be monitored. van Tulder et al (2003),¹²⁹ Chou et al (2017),²⁴

PICO 10. For patients with lumbar spinal stenosis, should anti-seizure neuropathic medication (pregabalin) versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?

Pregabalin For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of pregabalin for short-term reduction in pain and improved function. Conditional/Weak Consensus-based

Definition: Medication for neurogenic pain (eg, fixed and flexible doses of Pregabalin between 75 mg/d and 600 mg/d)
Studies considered A non-inferiority RCT by Kim et al (2016) ⁶¹ compared limaprost, pregabalin or a combination of limaprost and pregabalin.

Primary outcomes: Functional disability (ODI), leg pain (VAS), walking distance (Meters).

Key results: There was no between-group difference in disability between the pregabalin and limaprost (MD: 3.39 (95% CI, -1.28 to 8.06) at 2 mo. Limaprost did not result in inferior outcomes compared with treatment with pregabalin or pregabalin+limaprost on the ODI. There were no differences in the improvement of leg pain or walking distance among the 3 groups. All groups reported drug-related adverse events. Compared with the limaprost group, the pregabalin, and limaprost+pregabalin groups showed a significantly higher incidence of drug related adverse events.

Comment: The panel pursued a consensus-based recommendation, with uncertain desirable effects and a risk of undesirable effects reported.

Remarks: Despite their widespread use, recent systematic reviews, meta-analysis and guidelines advise against the use of anti-seizure neuropathic medication (eg, pregabalin and gabapentin) due to limited evidence and significant risk of adverse effects without any demonstrated benefit ³⁴^,¹⁰²^,¹¹¹.

PICO 11: For patients with lumbar spinal stenosis, should anti-seizure neuropathic medication (gabapentin)‡ versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?

Gabapentin For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of gabapentin. Conditional/Weak Very low
⊕OOO)

Definition: Medication for neurogenic pain (eg, Gabapentin 300 mg 3 times/d, increasing to 900 mg, 3 times/d)

Studies included: One small RCT by Yaksi et al (2007) ¹⁴⁰ compared gabapentin to placebo (Appendix 6, Table 5).This trial was identified in 2 systematic reviews (Ammendolia et al 2013, ⁶ and the Danish National Guideline by Rousing et al (2019) ¹⁰⁵.

Primary outcomes: Leg pain (VAS), walking distance (Meters)

Key results: A statistically significant improvement in leg pain and walking distance in favor of gabapentin at 3 and 4 mo follow-up, but the effect size did not reach clinical significance. Patients in both groups were treated with therapeutic exercises, lumbosacral corset with steel bracing, and NSAIDs. This trial reported that some participants randomized to the gabapentin group (no data specified) experienced mild to moderate drowsiness or dizziness, or both.

Comments: The panel determined very low certainty in the evidence. Because of this lack of evidence and moderate risk of side effects the recommendation did not favor gabapentin neurogenic pain medication.
Remarks: Despite their widespread use, recent systematic reviews, meta-analysis and guidelines advise against the use of anti-seizure neuropathic medication (eg, pregabalin and gabapentin) for managing patients with associated due to limited evidence and significant risk of adverse effects without any demonstrated benefit ³⁴^,⁴⁵^,¹⁰²^,¹¹¹.

PICO 12. In patients who underwent spinal fusion with or without decompression, should Epidural Steroid Injections (ESI) versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?

Epidural steroid injections (ESI) For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of epidural steroidal injections for short-term reduction in pain and improved function. Conditional/Weak High
(⊕⊕⊕⊕)

Definition: Lumbar epidural steroid injections can be performed using 3 approaches: translaminar, caudal, or interlaminar. Injections typically contain a glucocorticoid (eg, triamcinolone (60–120 mg), betamethasone (6–12 mg), dexamethasone (8–10 mg), or methylprednisolone (60 to 120 mg) with or without an anesthetic (eg, 1–3 mL of 0.25% to 1% lidocaine) under fluoroscopic guidance ³⁹.
Studies included: One RCT by Friedly et al (2014) ³⁹ compared 2 injections of either epidural steroid injection (glucosteroid plus lidocaine) or lidocaine alone. This trial was identified in a systematic review and meta-analysis by Liu et al (2015) ⁷⁴ which included 10 RCTs comprising 1010 patients (mixed population) comparing ESI and local anesthetic (Appendix 6, Table 6).

Outcomes: Function (RMDQ, walking ability), pain (VAS).
Key results: Friedly et al (2014) ³⁹ found no short (6 wk) or long-term (up to 12 mo) between-group differences in either function (RMDQ) or pain. Responder analysis revealed that about a third of patients in both arms were RMDQ responders and about half were pain responders (≥30% improvement at 6 wk). Repeated epidural injections of either type did not offer any additional long-term benefit if the injections in the first 6 wk did not improve pain. ESI was not superior to lidocaine alone. In the Liu et al (2015)⁷⁴ review, ESIs did not significantly improve pain or function (walking ability) compared with local anesthetic alone. Few adverse events were reported in the trials included in the Liu et al (2015) review.⁷⁴ However, a review by Kerezoudis et al (2018) ⁶⁵ and case reports of complications following interlaminar epidural steroid injections ¹¹² suggest that ESIs can lead to decreased bone mineral density and increased risk for vertebral fracture.

Comment: The panel determined that there was moderate certainty in the evidence, with unclear desirable effect (some of the estimates did not meet MCID) and small undesirable effects with rare reporting of adverse events. Results differed depending on study design, approach (transforaminal, interlaminar, or caudal), outcome measures, and comparison groups evaluated. Resource, cost, and training requirements to perform epidural steroid injections are not inconsequential and this treatment is not readily available in all areas, particularly in remote or smaller centers.

Remarks: Epidural steroidal injections may have minor adverse events such as subarachnoid entries, nerve root irritation, or pain and swelling at the site of injection. Patients with more severe structural changes as less likely to respond and may be at higher risks of adverse events.

SSS, Swiss spinal stenosis questionnaire; ZCQ Zurich claudication questionnaire; SF-36, Short Form 36; NPRS, The Numeric Pain Rating Scale; RMDQ, Roland Morris Disability Questionnaire; ODI, Oswestry disability index; CBT, cognitive-behavioral therapy; MD, mean difference; MCID, minimal clinically important difference; RCT, randomized controlled trial; RR, relative risk.

PICO questions, recommendations, definitions of interventions, supporting evidence, comments and remarks regarding LSS.

Key question/intervention	Recommendation	Strength of recommendation	Quality of evidence
PICO 4. For patients with lumbar spinal stenosis, should nonsteroidal anti-inflammatory drugs (NSAID) be used for patients with lumbar spine stenosis?
NSAIDs	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of NSAIDs for any duration.	Conditional/Weak	Low (⊕⊕OO)
Definition: Anti-inflammatory drugs in the form of NSAIDs (eg, naproxen 250–500 mg or ibuprofen 400–600 mg 3–4 times or twice daily) with treatment duration from 4 to 12 wk.
Included studies: We did not identify any RCT investigating the effect of NSAID in patients with NC caused by LSS (Appendix 6, Table 4). Patients with LSS often presents with LBP. The panel considered indirect evidence from 2 systematic reviews (Enthoven et al (2016), ³⁵ Machado et al (2017) ⁷⁹) reporting a statistically, but non-clinically significant immediate and short-term benefit favoring NSAIDs compared to placebo in reducing LBP. NSAIDs increased the risk of gastrointestinal adverse effect.⁷³^,⁷⁴.
Comment: The panel determined a low certainty in the evidence, with small desirable effects (many of the estimates did not meet MCID), and a moderate risk of undesirable effects reported.
Remarks: Consider possible drug interactions and potential differences in gastro-intestinal, liver, cardiovascular and renal toxicity, and the person's risk factors, including age. ⁶²^,¹³⁹
PICO 5. For patients with lumbar spinal stenosis, should adjunctive analgesics (methylcobalamin, paracetamol) versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?
Adjunctive Analgesics (Methylcobalamin, Paracetamol)	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of Methylcobalamin or Paracetamol (acetaminophen).	Conditional/weak	Consensus-based
Definition: Pain medication in the form of oral Methylcobalamin/vitamin B12 (0.5 mg, 3 times/d for 6 mo) or paracetamol (max 4 grams daily for 4-12 wk).
Studies considered: One RCT by Waikakul et al (2000) ¹³² compared oral Methylcobalamin along with usual care to conventional treatment only (education, activity modification, strengthening exercises for the trunk and abdominal muscles, physical therapy, and NSAIDs, analgesics and muscle relaxant as needed), and another RCT by Rodrigues et al (2014) ¹⁰⁴ compared Paracetamol to either oral corticoid (1 mg/kg/d with a 1/3 dose reduction weekly) or placebo for 3 wk.
Primary outcomes: Walking distance (Meters), pain (VAS), functional disability (RMDQ and 6-min walk test), quality of life (SF-36).
Key results: No between group difference was observed in those trials.
Comments: The panel determined a very low certainty in the evidence, with uncertain desirable effects and a risk of undesirable effects. The panel decided to pursue consensus-based recommendation.
Remarks: Paracetamol cannot be recommended at this time for neurogenic pain. Further, Paracetamol is unlikely to provide clinical benefit for concurrent acute or chronic LBP. Other treatment options should be considered in case of persistent and function-limiting symptoms considering potential adverse effects.
PICO 6. Should Adjunctive Analgesics (Calcitonin) be Used for Patients with LSS vs other therapies or placebo?
Adjunctive analgesics (Calcitonin)	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of Calcitonin.	Conditional/Weak	Consensus-based
Definition: Pain medication in the form of nasal salmon calcitonin spray or intramuscular calcitonin (variable doses)
Studies considered: A review of four small RCTs by Podichetty (2011) ¹⁰⁰ found no significant improvement when comparing calcitonin with placebo for pain (VAS) or walking distance. About 5% of patients reported minor transient side effects (nausea and flushing).
Primary outcomes: Pain (VAS) and walking distance (Meters).
Comments: Although the panel considered this review, it was eventually excluded from the analysis due to a lack of reported data with unclear pooled estimates. The panel decided to pursue consensus-based recommendation. Remarks: Calcitonin releases β-endorphins and can be used as an analgesic agent. The most frequently reported transient minor adverse events were nausea and flushing. Other treatment options should be considered in case of persistent and function-limiting symptoms.
PICO 7. For patients with lumbar spinal stenosis, should serotonin–norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs)‡ versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?
SNRIs or TCAs	For patients with LSS and neurogenic claudication with or without LBP, we suggest to consider a trial of serotonin–norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs).	Conditional/Weak	Consensus-based
Definition: SNRIs and TCA are a class of anti-depressant medication commonly used to treat chronic pain. Included studies: No RCT investigated the effect of SNRIs or TCAs in patients with NC. Studies considered: The panel considered indirect evidence on the use of SNRIs and TCAs in chronic LBP and neuropathic pain. ⁵⁹ ^, ⁶⁵^,¹⁰²^,¹¹⁷^, ¹²⁸^, ¹³⁰^, ¹³⁶ Comment: The panel pursued a consensus-based recommendation, with moderate risk of adverse events considered. The panel concludes that a trial of SNRI or TCA should be considered in patients with LSS causing NC with LBP. Remarks: Consider side effects including, but not limited to, cognitive and physical function, cardiovascular issues and postural instability (eg, falls).
PICO 8. For patients with lumbar spinal stenosis, should opioid versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?
Opioids	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of opioids as first line treatment.	Conditional/Weak	Consensus-based
Definition: Opioids (eg, morphine 10 mg 3–4 times/d, oxycodone 5–10 mg twice/d or tramadol 50–100 mg 3–4 times/d in addition to non-opioid pain medication and with a treatment duration from 4 to 12 wk) ¹⁰⁵. Studies included: No eligible RCTs investigated the effect of opioids for the treatment of NC caused by LSS. Studies considered: The panel considered indirect evidence from opioid therapy guidelines for chronic noncancer pain ¹⁹, and consensus-based recommendation from the DHA guideline on managing LSS ¹⁰⁵. Comment: The panel pursued a consensus-based recommendation, with strong risk of adverse events considered. Opioids may only be used for patients who have failed to respond to the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. ¹⁹^,³⁷ While the potential benefit of opioids for neurogenic claudication due LSS is unknown, there is strong evidence for the potential side effects of opioid use ¹⁹^,¹⁰². Remarks: Should a trial of opioids be considered in selected patients who have persistent, problematic pain despite optimized non-opioid therapy, caution should be used with respect to side effects including, but not limited to cognition, balance, narcotic habituation, overdose and death ¹⁹^,¹⁰².
PICO 9. For patients with lumbar spinal stenosis, should muscle relaxants be used to decrease pain, and improve function, quality of life, and return to function?
Muscle relaxants	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of muscle relaxants.	Conditional/Weak	Consensus-based
Definition: Skeletal muscle relaxants (eg, tizanidin 2–4 mg 3–4 times/d, chlorzoxazone 250 mg 3–4 times/d) for 4–12 wk ¹⁰⁵. Studies included: No RCTs investigated the use of muscle relaxants in patients with NC caused by LSS. Studies considered: Patients with LSS often presents with LBP. The panel considered indirect evidence from systematic reviews (van Tulder, et al (2003),¹²⁹ Chou et al (2017),²⁴ and guidelines ¹⁰²^,¹⁰⁵ addressing the management of LBP. For acute LBP, there was moderate to strong evidence that different muscle relaxants performed similarly to each other, and are more effective than placebo for short-term pain relief for patients. However, evidence was insufficient to determine effects on function. For chronic LBP, there was insufficient evidence with inconsistent results and methodological shortcomings to determine the effects of muscle relaxants. Adverse events however were significantly more prevalent in the muscle relaxants group (RR = 1.50; 95% CI, 1.14 to 1.98), and especially the central nervous system (RR = 2.04; 95% CI, 1.23 to 3.37). Comment: The panel pursued a consensus-based recommendation, with known undesirable consequences greater than the uncertain desirable effects of muscle relaxants. For patients with LSS causing NC with LBP, the panel determined there was a low certainty of evidence, with existing studies focusing on LBP of various etiologies. Muscle relaxants may provide short-term pain relief for acute and subacute LBP, though adverse events secondary to muscle relaxant use should be considered. Remarks: Important to differentiate true muscle relaxants vs psychogenic relaxants. Psychogenic relaxants are more commonly prescribed and may help improve sleep. For patients with claudication type pain, it is important to consider the anti-spasm properties of these agents. Risks of transient adverse events should be considered and patients should be monitored. van Tulder et al (2003),¹²⁹ Chou et al (2017),²⁴
PICO 10. For patients with lumbar spinal stenosis, should anti-seizure neuropathic medication (pregabalin) versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?
Pregabalin	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of pregabalin for short-term reduction in pain and improved function.	Conditional/Weak	Consensus-based
Definition: Medication for neurogenic pain (eg, fixed and flexible doses of Pregabalin between 75 mg/d and 600 mg/d) Studies considered A non-inferiority RCT by Kim et al (2016) ⁶¹ compared limaprost, pregabalin or a combination of limaprost and pregabalin.
Primary outcomes: Functional disability (ODI), leg pain (VAS), walking distance (Meters).
Key results: There was no between-group difference in disability between the pregabalin and limaprost (MD: 3.39 (95% CI, -1.28 to 8.06) at 2 mo. Limaprost did not result in inferior outcomes compared with treatment with pregabalin or pregabalin+limaprost on the ODI. There were no differences in the improvement of leg pain or walking distance among the 3 groups. All groups reported drug-related adverse events. Compared with the limaprost group, the pregabalin, and limaprost+pregabalin groups showed a significantly higher incidence of drug related adverse events.
Comment: The panel pursued a consensus-based recommendation, with uncertain desirable effects and a risk of undesirable effects reported.
Remarks: Despite their widespread use, recent systematic reviews, meta-analysis and guidelines advise against the use of anti-seizure neuropathic medication (eg, pregabalin and gabapentin) due to limited evidence and significant risk of adverse effects without any demonstrated benefit ³⁴^,¹⁰²^,¹¹¹.
PICO 11: For patients with lumbar spinal stenosis, should anti-seizure neuropathic medication (gabapentin)‡ versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?
Gabapentin	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of gabapentin.	Conditional/Weak	Very low ⊕OOO)
Definition: Medication for neurogenic pain (eg, Gabapentin 300 mg 3 times/d, increasing to 900 mg, 3 times/d)
Studies included: One small RCT by Yaksi et al (2007) ¹⁴⁰ compared gabapentin to placebo (Appendix 6, Table 5).This trial was identified in 2 systematic reviews (Ammendolia et al 2013, ⁶ and the Danish National Guideline by Rousing et al (2019) ¹⁰⁵.
Primary outcomes: Leg pain (VAS), walking distance (Meters)
Key results: A statistically significant improvement in leg pain and walking distance in favor of gabapentin at 3 and 4 mo follow-up, but the effect size did not reach clinical significance. Patients in both groups were treated with therapeutic exercises, lumbosacral corset with steel bracing, and NSAIDs. This trial reported that some participants randomized to the gabapentin group (no data specified) experienced mild to moderate drowsiness or dizziness, or both.
Comments: The panel determined very low certainty in the evidence. Because of this lack of evidence and moderate risk of side effects the recommendation did not favor gabapentin neurogenic pain medication. Remarks: Despite their widespread use, recent systematic reviews, meta-analysis and guidelines advise against the use of anti-seizure neuropathic medication (eg, pregabalin and gabapentin) for managing patients with associated due to limited evidence and significant risk of adverse effects without any demonstrated benefit ³⁴^,⁴⁵^,¹⁰²^,¹¹¹.
PICO 12. In patients who underwent spinal fusion with or without decompression, should Epidural Steroid Injections (ESI) versus another treatment be used to decrease pain, and improve function, quality of life, and return to function?
Epidural steroid injections (ESI)	For patients with LSS and neurogenic claudication with or without LBP, we do not suggest the use of epidural steroidal injections for short-term reduction in pain and improved function.	Conditional/Weak	High (⊕⊕⊕⊕)
Definition: Lumbar epidural steroid injections can be performed using 3 approaches: translaminar, caudal, or interlaminar. Injections typically contain a glucocorticoid (eg, triamcinolone (60–120 mg), betamethasone (6–12 mg), dexamethasone (8–10 mg), or methylprednisolone (60 to 120 mg) with or without an anesthetic (eg, 1–3 mL of 0.25% to 1% lidocaine) under fluoroscopic guidance ³⁹. Studies included: One RCT by Friedly et al (2014) ³⁹ compared 2 injections of either epidural steroid injection (glucosteroid plus lidocaine) or lidocaine alone. This trial was identified in a systematic review and meta-analysis by Liu et al (2015) ⁷⁴ which included 10 RCTs comprising 1010 patients (mixed population) comparing ESI and local anesthetic (Appendix 6, Table 6).
Outcomes: Function (RMDQ, walking ability), pain (VAS). Key results: Friedly et al (2014) ³⁹ found no short (6 wk) or long-term (up to 12 mo) between-group differences in either function (RMDQ) or pain. Responder analysis revealed that about a third of patients in both arms were RMDQ responders and about half were pain responders (≥30% improvement at 6 wk). Repeated epidural injections of either type did not offer any additional long-term benefit if the injections in the first 6 wk did not improve pain. ESI was not superior to lidocaine alone. In the Liu et al (2015)⁷⁴ review, ESIs did not significantly improve pain or function (walking ability) compared with local anesthetic alone. Few adverse events were reported in the trials included in the Liu et al (2015) review.⁷⁴ However, a review by Kerezoudis et al (2018) ⁶⁵ and case reports of complications following interlaminar epidural steroid injections ¹¹² suggest that ESIs can lead to decreased bone mineral density and increased risk for vertebral fracture.
Comment: The panel determined that there was moderate certainty in the evidence, with unclear desirable effect (some of the estimates did not meet MCID) and small undesirable effects with rare reporting of adverse events. Results differed depending on study design, approach (transforaminal, interlaminar, or caudal), outcome measures, and comparison groups evaluated. Resource, cost, and training requirements to perform epidural steroid injections are not inconsequential and this treatment is not readily available in all areas, particularly in remote or smaller centers.
Remarks: Epidural steroidal injections may have minor adverse events such as subarachnoid entries, nerve root irritation, or pain and swelling at the site of injection. Patients with more severe structural changes as less likely to respond and may be at higher risks of adverse events.