. 2011 Feb;2(1):27–38. doi: 10.1177/2042018810391900

Supplemental Table.

Medication details.

Tier I	Tricyclic antidepressants
Side effects
Common	Dry mouth; constipation; dizziness/orthostatic hypotension; urinary retention; sedation; blurred vision; weight loss (imipramine, desipramine); weight gain (amitriptyline, imipramine, desipramine); sexual side effects (imipramine)		Mechanism of action: SNRI
			T_1/2
Serious	Cardiac dysrhythmia; myocardial infarction; worsening depression and suicidality; may alter glucose regulation (imipramine, desipramine)		Amitriptyline	9–27 h
Contraindications	MAOI use within 2 weeks; cardiac history (including recent MI, heart failure, and arrhythmias, prolonged corrected QT); glaucoma		Imipramine	6–18 h
			Desipramine	7–60h
Dosing			Pregnancy category: C-D^*
Starting	Amitriptyline	10–25mg/day	Cost
	Imipramine	10–25mg/day	Amitriptyline	$
	Desipramine	10–25mg/day
Average effective	Amitriptyline	100mg/day	Imipramine	$
	Imipramine	150mg/day
	Desipramine	100 mg/day
Titration	Weekly as tolerated		Desipramine	$$
Monitoring			Generic available: Y
Baseline	ECG for patients with history if cardiac disease or age >40
Periodic	Periodic screening for depression
Special populations
Rental disease	Use with caution		DM medication drug-drug Interactions: N
Liver disease	Use with caution	Hepatic metabolism
Geriatrics	High risk (imipramine max dose should not exceed 100 mg/day in elderly patients)

Tier I	Duloxetine
Side effects
Common	Nausea; somnolence; dizziness; loss of appetite; constipation; may lower serum glucose; weight loss; weight gain; sexual side effects		Mechanism of action: SNRI
Serious	Abnormal bleeding; hepatotoxicity; worsening depression/suicidality; serotonin syndrome		T_1/2: 12h
Contraindications	Uncontrolled narrow-angle glaucoma; concurrent treatment MAOI		Pregnancy category: C
Dosing			Cost: $$$$
Starting	20-60 mg/day
Average effective	60 mg/day
Titration	As tolerated
Monitoring			Generic available: N
Baseline	Blood work: chemistry; liver function tests and glycated hemoglobin (HbAi c or A1C); screening for hypertension and depression
Periodic	Periodic screening for depression
Special populations
Rental disease	Dosage reduction may be required for mild to moderate renal impairment Not recommended for CrCI < 30 ml/min or ESRD		DM medication drug-drug Interactions: N
Liver disease	Hepatic metabolism	Not recommended for use in hepatic impairment
Geriatrics	No special dosing recommended
Tier I	Pregabalin
Side effects
Common	Dizziness; somnolence; peripheral edema; constipation; xerostomia; headache; weight gain		Mechanism of action: acts on voltage-gated calcium channels
Serious	Angioedema
Contraindications	Use with caution in patients with congestive heart failure		T_1/2: 6.3 h
Dosing			Pregnancy category: C
Starting	50 mg three times a day
Average effective	100 mg three times a day		Cost: $$
Titration	Can be rapidly titrated within a week
Monitoring			Generic available: N
Baseline	N/A
Periodic	Periodic screening for depression
Special populations
Rental disease	-		DM medication drug-drug interactions: Y May increase fluid retention in patients concomitantly treated with thiazolidinedione
Liver disease	Use with caution	Reduce total daily dose in proportion to renal impairment
Geriatrics	No special dosing recommended
Tier I	Gabapentin
Side effects
Common	Dizziness; somnolence; weight gain; sexual side effects		Mechanism of action: unknown^‡
Serious	Stevens-Johnson syndrome; worsening depression/suicidality		T_1/2: 5–7h
Contraindications			Pregnancy category: C
Dosing			Cost: $$
Starting	300mg/day every night or divided into three times a day
Average effective	800mg three times a day (maximum dose of 3600mg/day divided over three times a day)
Titration	As tolerated
Monitoring			Generic available: Y
Baseline	N/A
Periodic	Periodic screening for depression
Special populations
Rental disease	Reduce total daily dose in proportion to renal impairment		DM medication drug-drug interactions: N
Liver disease	–
Geriatrics	–
Tier II	Venlafaxine
Side effects
Common	Nausea; somnolence; headache; weight loss; sexual side effects		Mechanism of action: SNRI
Serious	Hyponatremia; gastrointestinal hemorrhage; bleeding abnormalities; neuroleptic malignant syndrome; serotonin syndrome; worsening depression/suicidality		T_1/2:5±2h
Contraindications	Recent MAOI use		Pregnancy category: C
Dosing			Cost: $$$
Starting	Venlafaxine immediate release 37.5mg twice a day or venlafaxine extended release 75mg/day
Average effective	Venlafaxine immediate release 112.5mg twice a day or venlafaxine extended release 150-225mg/day
Titration	As tolerated
Monitoring			Generic available: Y
Baseline	Serum cholesterol; screening for hypertension and depression
Periodic	Periodic screening for depression; blood pressure monitoring
Special populations
Rental disease	Use with caution	Reduce total daily dose by 25% in mild to moderate renal impairment (CrC110-70 ml/min); reduce total daily dose by 50% if on hemodialysis	DM medication drug-drug interactions: N
Liver disease	Hepatic metabolism	Reduce total daily dose by 50% in mild to moderate renal impairment
Geriatrics	No special dosing recommended but may benefit from lower initial dosing
Tier II	Carbamazepine
Side effects
Common	Dizziness; drowsiness; dry mouth; ataxia; nausea; vomiting; hyponatremia; pancytopenia; abnormal liver function; sexual side effects		Mechanism of action: inhibition of voltage-dependent sodium channels
Serious	Dysrhythmia; congestive heart failure; Stevens-Johnson syndrome; toxic epidermal necrolysis; nephrotoxicity; hypocalcemia, hyponatremia; blood dyscrasia including aplastic anemia		T_1/2:12–17h
Contraindications	Blood dyscrasias; dermatologie reactions; presence of HLA-B^*1502 allele is a contraindication, however guidelines for routine screening of Asian patients has not been established		Pregnancy category: D
Dosing			Cost: $$$
Starting	200mg/day
Average effective	300mg/day or twice a day
Titration	Over 2 weeks
Monitoring			Generic available: Y
Baseline	Complete blood count; liver function tests; chemistry; thyroid function tests; screening for depression
Periodic	Complete blood count; liver function tests; chemistry; thyroid function tests; carbamazepine levels^§; screening for depression		DM medication drug-drug interactions: Y Concurrent use of carbamazepine and repaglinide may cause lower serum repaglinide concentrations
Special populations
Rental disease	Use with caution	No dose adjustment recommended
Liver disease	Hepatic metabolism; Use with caution	No dose adjustment recommended
Geriatrics	No special dosing recommended
Tier II	Valproate
Side effects
Common	Headache; somnolence; dizziness; nausea; dyspepsia; abdominal pain; tremor; hair loss; weight loss; weight gain		Mechanism of action:increases effects at GABA
Serious	Pancreatitis; thrombocytopenia; hepatic failure		receptor
			T_1/2: 9–16h
Contraindications	Hepatic failure; pancreatitis; urea cycle disorders		Pregnancy category: D^\|\|
Dosing			Cost: $$
Starting	500mg/day or 300 mg twice a day
Average effective	500–600 mg twice a day
Titration	As tolerated
Monitoring			Generic available: Y
Baseline	Liver function tests; complete blood count; prothrombin time; partial thromboplastin time; ammonia; screening for depression
Periodic	Liver function tests; complete blood count; prothrombin time; partial thromboplastin time; ammonia; valproate levels; screening for depression
Special populations
Rental disease	No significant effect on metabolism, however Rental disease may influence protein binding and clearance		DM medication drug-drug interactions: N
Liver disease	Hepatic metabolism	Use with caution Dose reduction required Contraindicated in severe liver disease
Geriatrics	No special dosing recommended but may benefit from lower initial dosing
Tier III	Oxcarbazepine
Side effects
Common	Abdominal pain; nausea; vomiting; ataxia; dizziness; headache; nystagmus; somnolence; tremor; vertigo; diplopia; rhinitis; fatigue; weight loss; weight gain		Mechanism of action:oxcarbazepine and its active metabolite monohydroxy metabolite block voltage-sensitive sodium channels and modulate voltage-activated calcium channels
Serious	Hyponatremia; Stevens-Johnson syndrome; toxic epidermal necrolysis; angioedema
Contraindications	–
Dosing			T_1/2: oxcarbazepine 2h; monohydroxy metabolite (active metabolite) 9h
Starting	300mg/day
Average effective	1200mg/day divided into twice or three times a day dosing		Pregnancy category: C
Titration	Weekly titration to twice a day dosing Slow titration for patients with CrCI < 30ml/min		Cost: $$$$$
Monitoring			Generic available: Y
Baseline	Serum sodium
Periodic	Serum sodium; periodic screening for depression
Special populations

Rental disease	For CrCI <30ml/min: initial dose should be half the starting dose with slow titration		DM medication drug-drug interactions: N
Liver disease	Hepatic metabolism	No dose adjustment recommended for mild to moderate impairment. No data available for severe liver disease
Geriatrics	No special dosing recommended
Tier III	Lamotrigine
Side effects
Common	Nausea; abdominal pain; headache; drowsiness; dizziness; weight loss		Mechanism of action: stabilization of neural membranes through voltage-gated sodium channels; and inhibition of presynaptic release of glutamate
Serious	Stevens-Johnson syndrome; toxic epidermal necrolysis; hepatic failure; anemia/thrombocytopenia/pancytopenia
Contraindications	–
Dosing
Starting	25mg/day		T_1/2:25–33h
Average effective	150–200 mg twice a day		Pregnancy category: C
Titration	Slow; 25mg increase per week. More rapid titration is contraindicated because of concern for Stevens-Johnson syndrome		Cost: $$$$$
Monitoring			Generic available: Y
Baseline	N/A
Periodic	Periodic screening for depression and rash
Special populations
Rental disease	Renal metabolism	Use with caution; dosage reduction may be required	DM medication drug-drug interactions: N
Liver disease	Hepatic metabolism	Use with caution; dosage reduction may be required
Geriatrics	No special dosing recommended
Tier III	Alpha lipoic acid
Side effects
Common	Paresthesias; muscle cramps; platelet dysfunction; headache; rash; nausea; vomiting; vertigo		Mechanism of action: antioxidant
Serious	Hypoglycemia		T_1/2:30min
Contraindications	Unknown		Pregnancy category: unknown
Dosing			Cost ^¶: N/A
Starting	300mg twice a day (or 200mg three times a day)
Average effective	600mg once daily or divided twice a day
Titration	N/A
Monitoring			Generic available: N/A
Baseline	Unknown
Periodic	Periodic screening for depression
Special populations
Rental disease	Unknown		DM medication drug-drug interactions: unknown; may interact with insulin and oral hypoglycemics
Liver disease	Unknown
Geriatrics	Unknown
Breakthrough pain	Lidocaine patch
Side effects
Common	Local skin irritation; itching; edema; rash; urticaria; blisters; angioedema		Mechanism of action: decreased neuronal membrane permeability to sodium ions
Serious	Allergic/anaphylactoid reaction
Contraindications	Skin breakdown in area of application
Dosing
Starting	One patch applied to painful area. Patch may remain in place for up to 12h in any 24h period		T_1/2: unknown^#
Average effective	As above		Pregnancy category: B
Titration	N/A		Cost^**: $$$$$
Monitoring			Generic available: N
Baseline	N/A
Periodic	Check skin for reactions at site of patch
Special populations
Rental disease	No special dosing recommended		DM medication drug-drug interactions: N
Liver disease	No special dosing recommended
Geriatrics	No special dosing recommended
Breakthrough pain	Capsaicin
Side effects
Common	At site of application: itching; burning; stinging; erythema; cough; nausea		Mechanism of action: depletes stores of peripheral nerve substance P and prevents reaccumulation
Serious	Hypertension
Contraindications	Skin breakdown in area of application
Dosing			T_1/2: 1.64h
Starting	N/A		Pregnancy category: C
Average effective	0.075% capsaicin patch or cream applied 3-4 times per day PRN		Cost^‡‡: $–$$$
Titration	N/A
Monitoring			Generic available: Y
Baseline	N/A
Periodic	Check skin for reactions at site of patch
Special populations
Rental disease	No special dosing recommended		DM medication drug-drug interactions: N
Liver disease	No special dosing recommended
Geriatrics	No special dosing recommended
Breakthrough pain	Tramadol
Side effects
Common	Flushing; pruritus; constipation; nausea; vomiting; dyspepsia; xerostomia; dizziness; headache; somnolence; insomnia; weight loss; sexual side effects		Mechanism of action: tramadol and its active metabolite bind to central u-opiate receptors and inhibit ascending pain pathways; also inhibits serotonin and norepinephrine reuptake.
Serious	Dyspnea; respiratory depression; myocardial infarction; pancreatitis; seizure; serotonin syndrome
Contraindications	Acute intoxication with CNS depressants (alcohol, hypnotics, opioids, or psychotropic drugs)
Dosing			T_1/2: ^§§ tramadol: −6–8h; active metabolite: 7–9h
Starting	50mg/day PRN
Average effective	50–200mg/day divided twice daily PRN		Pregnancy category: C
Titration	To be used PRN		Cost: $^\|\|\|\|
Monitoring			Generic available: Y
Baseline	N/A
Periodic	Monitor for tolerance and abuse
Special populations
Rental disease	For CrCI <30ml/min: – immediate release: 50-100mg every 12h; maximum: 200 mg/day – extended release should not be used		DM medication drug-druginteractions: N
Liver disease	Hepatic metabolism	For cirrhosis: – immediate release: 50mg every 12h – extended release should not be used
Geriatrics	Use with caution	>65 years: start with lower doses >75 years: do not exceed 300 mg/day of immediate release formulation

Imipramine is pregnancy category D.

^‡

May act on voltage-gated calcium channels and impact the release of excitatory neurotransmitters.

^§

Owing to hepatic autoinduction, serum levels must be monitored until stable.

^||

Known teratogen.

^¶

Prices vary based on distributors.

Half-life of topical lidocaine is not known. It is not clear if it is metabolized in the skin. The half-life of intravenous lidocaine is 1.5-2.5 hours.

^**

Cost listed is for 30 patches of Lidoderm.

^‡‡

Cost based on price per tube of 0.075% capsaicin cream or packages of four patches used four times a day although this is not the recommended dosing.

^§§

T_1/2: prolonged in elderly, hepatic and renal impairment.

^||||

Listed cost is for 90 tablets of 50mg tramadol immediate release.

Key for costs: $, US$0-50; $$, US$51-100; $$$, US$101-150; $$$$, US$151-200; $$$$$, >US$201. CrCI, creatinine clearance; DM, diabetes mellitus; ESRD, end-stage Rental disease; MAOI, monoamine oxidase inhibitors; MI, myocardial infarction; PRN, pro re nata; SNRI, serotonin-norepinephrine reuptake inhibitor.