Table 2.

NeuPSIG recommendations based on the GRADE classification.²

Drug	Total daily dose and dose regimen	GRADE strength of recommendation	Tolerability and safety	Cost
First line
Gabapentin	1200–3600 mg, in three divided doses	STRONG	Moderate–high	Low–moderate
Gabapentin extended release or enacarbil	1200–3600 mg, in two divided doses	STRONG	Moderate–high	Low–moderate
Pregabalin	300–600 mg, in two divided doses	STRONG	Moderate–high	Low–moderate
SNRIs, duloxetine, or venlafaxinea	Duloxetine 60–120 mg Venlafaxine extended release 150–225 mg	STRONG	Moderate	Low–moderate
TCAsb	25–150mg, once a day or in two divided doses	STRONG	Low–moderate	Low
Second line
Capsacin 8% patchesc N.B. Indication = peripheral neuropathic pain	1–4 patches to the painful area for 30–60 min every 3 months	WEAK	Moderate–high N.B. Potential safety concerns over sensation with long–term use	Moderate–high
Lidocaine plasters N.B. Indication = peripheral neuropathic pain	1–3 5% plasters to region of pain one per day for up to 12 h	WEAK	High	Moderate–high
Tramadol	200–400 mg, in three divided dose (or two for extended release)	WEAK	Low–moderate	Low
Third line
Botulinum toxin A N.B. Specialist use, Indication = peripheral neuropathic pain, third line because the quality of evidence is weak	50–200 units to the painful area every 3 months	WEAK
Strong opioids	Individual titration	WEAK
Recommendations AGAINST use
Cannabinoids N.B. Because of negative trial results, potential misuse, diversion, long-term mental health risks		WEAK
Valproate		WEAK
Levetiracetam N.B. Because of generally negative trials and safety concerns		STRONG
Mexiletine N.B. Because of generally negative trials and safety concerns		STRONG

Sustained-release oxycodone and morphine are the opioids most studied. Long-term use may be associated with abuse, cognitive impairment, and endocrine and immunological changes. Prescription requires risk assessment strict monitoring and treatment agreements. GRADE, Grading of Recommendations Assessment, Development, and Evaluation; SNRI, selective serotonin and norepinephrine reuptake inhibitor; TCA, tricyclic antidepressants.

^aDuloxetine is the most studied and therefore the most recommended SNRI.

^bThe tertiary amine TCAs (amitriptyline, imipramine, clomipramine) are not recommended at doses greater than 75 mg day⁻¹ in >65 yr because of major anticholinergic and sedative adverse effects, and an increased risk of sudden cardiac death at doses >100 mg day⁻¹.

^cThe long-term safety of repeated application of high-concentration capsaicin patches is not clearly established. They may exacerbate progressive neuropathy by degeneration of epidermal nerve fibres.