TABLE 2
| 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 |
||
| T1/2 | ||||
| Serious | Cardiac dysrhythmia; myocardial infarction; worsening depression and suicidality; may alter glucose regulation (imipramine, desipramine) | Amitriptyline | 9–27 hrs | |
| Contraindications | MAOI use within 2 weeks; cardiac history (including recent MI, HF, and arrhythmias, prolonged QTC); glaucoma | Imipramine | 6–18hrs | |
| Desipramine | 7–60 hrs | |||
| Dosing | Pregnancy Category: C–D * | |||
| Starting: | Amitriptyline | 10–25 mg/day | Cost | |
| Imipramine | 10–25 mg/day | Amitriptyline | $ | |
| Desipramine | 10–25 mg/day | |||
| Average Effective | Amitriptyline | 100 mg/day | Imipramine | $ |
| Imipramine | 150 mg/day | |||
| Desipramine | 100mg/day | |||
| Titration | Weekly as tolerated | Desipramine | $$ | |
| Monitoring | Generic Available: Y | |||
| Baseline | ECG for patients with history if cardiac disease or age > 40 | |||
| Periodic | Periodic screening for depression | |||
| Special Populations | ||||
| Renal Disease | Use with caution | DM medication Drug-Drug Interactions: N | ||
| Liver Disease | Use with caution | Hepatic metabolism | ||
| Geriatrics | High Risk (Imipramine max dose should not exceed 100 mg/day in elderly patients) | |||
| TIER I | Duloxetine | ||
|---|---|---|---|
| Side Effects | |||
| Common | Nausea; somnolence; dizziness; loss of appetite; constipation; may lower serum glucose; weight loss; weight gain; sexual side effects | Mechanism of Action: SNRI | |
| Serious | Abnormal bleeding; hepatotoxicity; worsening depression/suicidality; serotonin syndrome | T1/2: 12 hours | |
| Contraindications | Uncontrolled narrow-angle glaucoma; concurrent treatment MAOI | Pregnancy Category: C | |
| Dosing | Cost: $$$$ | ||
| Starting | 20–60 mg/day | ||
| Average Effective | 60 mg/day | ||
| Titration | As tolerated | ||
| Monitoring | Generic Available: N | ||
| Baseline | Blood work: chemistry; liver function tests and glycated hemoglobin (Hb A1C); screening for hypertension and depression | ||
| Periodic | Periodic screening for depression | ||
| Special Populations | |||
| Renal Disease | Dosage reduction may be required for mild-to-moderate renal impairment NOT recommended for CrCL < 30 ml/min or ESRD |
DM medication Drug-Drug Interactions: N | |
| Liver Disease | Hepatic metabolism | NOT recommended for use in hepatic impairment | |
| Geriatrics | No special dosing recommended | ||
| TIER I | Pregabalin | ||
|---|---|---|---|
| Side Effects | |||
| Common | Dizziness; somnolence; peripheral edema; constipation; xerostomia; headache; weight gain | Mechanism of Action: Acts on voltage-gated calcium channels | |
| Serious | Angioedema | ||
| Contraindications | - (use with caution in patients with congestive heart failure) | T1/2: 6.3 hours | |
| Dosing | Pregnancy Category: C | ||
| Starting | 50 mg TID | ||
| Average Effective | 100 mg TID | Cost: $$ | |
| Titration | Can be rapidly titrated within a week | ||
| Monitoring | Generic Available: N | ||
| Baseline | N/A | ||
| Periodic | Periodic screening for depression | ||
| Special Populations | |||
| Renal 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 | T1/2:5–7 hours |
| Contraindications | - | Pregnancy Category: C |
| Dosing | Cost: $$ | |
| Starting | 300 mg/day QHS or divided into TID | |
| Average Effective | 800 mg TID (maximum dose of 3600 mg/d divided TID) | |
| Titration | As tolerated | |
| Monitoring | Generic Available: Y | |
| Baseline | N/A | |
| Periodic | Periodic screening for depression | |
| Special Populations | ||
| Renal Disease | Reduce total daily dose in proportion to renal impairment | DM medication Drug-Drug Interactions: N |
| Liver Disease | - | |
| Geriatrics | - | |
| TIER II | Venlafaxine | ||
|---|---|---|---|
| Side Effects | |||
| Common | Nausea; somnolence; headache; weight loss; sexual side effects | Mechanism of Action: SNRI | |
| Serious | Hyponatremia; gastrointestinal hemorrhage ; bleeding abnormalities; neuroleptic malignant syndrome; serotonin syndrome; worsening depression/suicidality | T1/2:5 ± 2 hours | |
| Contraindications | Recent MAOI use | Pregnancy Category: C | |
| Dosing | Cost: $$$ | ||
| Starting | Venlafaxine immediate release 37.5 mg b.i.d. OR Venlafaxine ER 75 mg/day | ||
| Average Effective | Venlafaxine immediate release 112.5 mg b.i.d OR Venlafaxine ER 150–225 mg/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 | |||
| Renal Disease | Use with caution | Reduce total daily dose by 25% in mild-to-moderate renal impairment (Clcr 10–70 mL/minute); 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-moderate 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 | T1/2:12–17 hours | |
| Contraindications | Blood dyscrasias; dermatologic 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: $$$ | ||
| Starting | 200 mg/day | ||
| Average Effective | 300 mg/day or BID | ||
| Titration | Over 2 weeks | ||
| Monitoring | Generic Available: Y | ||
| Baseline | Complete blood count; liver function tests; chemistry; thyroid function tests; screening for depression | ||
| Periodic | Complete blood count; liver function tests; chemistry; thyroid function tests; carbamazepine levels*; screening for depression |
DM medication Drug-Drug Interactions: Y Concurrent use of Carbamazepine and Repaglinide may cause lower serum Repaglinide concentrations |
|
| Special Populations | |||
| Renal Disease | Use with caution | No dose adjustment recommended | |
| Liver Disease | Hepatic metabolism; Use with caution |
No dose adjustment recommended | |
| Geriatrics | No special dosing recommended | ||
| TIER II | Valproate | ||
|---|---|---|---|
| Side Effects | |||
| Common | Headache; somnolence; dizziness; nausea; dyspepsia; abdominal pain; tremor; hair loss; weight loss; weight gain | Mechanism of Action: Increases effects at GABA receptor | |
| Serious | Pancreatitis; thrombocytopenia; hepatic failure | T1/2:9–16 hours | |
| Contraindications | Hepatic failure; pancreatitis; urea cycle disorders | Pregnancy Category: D* | |
| Dosing | Cost: $$ | ||
| Starting | 500 mg per day or 300 mg BID | ||
| Average Effective | 500–600 mg BID | ||
| 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 | |||
| Renal Disease | No significant effect on metabolism, however renal 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 it's 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 | - | T1/2: Oxcarbazepine 2 hours; monohydroxy metabolite (active metabolite) 9 hours | |
| Dosing | |||
| Starting | 300 mg/ day | ||
| Average Effective | 1200 mg/day divided into BID or TID dosing | Pregnancy Category: C | |
| Titration | Weekly titration to BID dosing Slow titration for patients with CrCl < 30 mL/min |
Cost: $$$$$ | |
| Monitoring | Generic Available: Y | ||
| Baseline | Serum sodium | ||
| Periodic | Serum sodium; periodic screening for depression | ||
| Special Populations | |||
| Renal Disease | For Clcr <30 mL/minute: initial dose should be ½ the starting dose with slow titration | DM medication Drug-Drug Interactions: N | |
| Liver Disease | Hepatic metabolism | No dose adjustment recommended for mild-moderate impairment. No data available for severe liver disease. | |
| Geriatrics | No special dosing recommended | ||
| TIER III | Lamotrigine | ||
|---|---|---|---|
| Side Effects | |||
| Common | Nausea; abdominal pain; headache; drowsiness; dizziness; weight loss | Mechanism of Action: Stabilization of neural membranes through voltage-gated sodium channels; and inhibition of presynaptic release of glutamate | |
| Serious | Stevens-Johnson syndrome; toxic epidermal necrolysis; hepatic failure; anemia/thrombocytopenia/pancytopenia | ||
| Contraindications | - | ||
| Dosing | |||
| Starting | 25 mg/day | T1/2:25–33 hours | |
| Average Effective | 150–200 mg BID | Pregnancy Category: C | |
| Titration | Slow; 25 mg increase per week. More rapid titration is contraindicated due to concern for Stevens-Johnson syndrome. | Cost: $$$$$ | |
| Monitoring | Generic Available: Y | ||
| Baseline | N/A | ||
| Periodic | Periodic screening for depression and rash | ||
| Special Populations | |||
| Renal Disease | Renal metabolism | Use with caution; dosage reduction may be required | DM medication Drug-Drug Interactions: N |
| Liver Disease | Hepatic metabolism | Use with caution; dosage reduction may be required | |
| Geriatrics | No special dosing recommended | ||
| TIER III | Alpha Lipoic Acid | |
|---|---|---|
| Side Effects | ||
| Common | Paresthesias; muscle cramps; platelet dysfunction; headache; rash; nausea; vomiting; vertigo | Mechanism of Action: Antioxidant |
| Serious | Hypoglycemia | T1/2:30 minutes |
| Contraindications | Unknown | Pregnancy Category: Unknown |
| Dosing | Cost*: N/A | |
| Starting | 300 mg BID (or 200 mg TID) | |
| Average Effective | 600 mg once daily or divided BID | |
| Titration | N/A | |
| Monitoring | Generic Available: N/A | |
| Baseline | Unknown | |
| Periodic | Periodic screening for depression | |
| Special Populations | ||
| Renal Disease | Unknown | DM medication Drug-Drug Interactions: Unknown; may interact with insulin and oral hypoglycemics |
| Liver Disease | Unknown | |
| Geriatrics | Unknown | |
| Breakthrough Pain | Lidocaine Patch | |
|---|---|---|
| Side Effects | ||
| Common | Local skin irritation; itching; edema; rash; urticaria; blisters; angioedema | Mechanism of Action: Decreased neuronal membrane permeability to sodium ions |
| Serious | Allergic/anaphylactoid reaction | |
| Contraindications | Skin breakdown in area of application | |
| Dosing | ||
| Starting | 1 patch applied to painful area. Patch may remain in place for up to 12 hours in any 24 hour period. | T1/2: Unknown* |
| Average Effective | As above | Pregnancy Category: B |
| Titration | N/A | Cost**: $$$$$ |
| Monitoring | Generic Available: N | |
| Baseline | N/A | |
| Periodic | Check skin for reactions at site of patch | |
| Special Populations | ||
| Renal Disease | No special dosing recommended | DM medication Drug-Drug Interactions: N |
| Liver Disease | No special dosing recommended | |
| Geriatrics | No special dosing recommended | |
| Breakthrough Pain | Capsaicin | |
|---|---|---|
| Side Effects | ||
| Common | At site of application: itching; burning; stinging; erythema; cough; nausea | Mechanism of Action: Depletes stores of peripheral nerve substance P and prevents reaccumulation |
| Serious | Hypertension | |
| Contraindications | Skin breakdown in area of application | |
| Dosing | T1/2:1.64 hours | |
| Starting | N/A | Pregnancy Category: C |
| Average Effective | 0.075% Capsaicin patch or cream applied 3–4 times per day PRN | Cost:* $-$$$ |
| Titration | N/A | |
| Monitoring | Generic Available: Y | |
| Baseline | N/A | |
| Periodic | Check skin for reactions at site of patch | |
| Special Populations | ||
| Renal 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 μ-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 |
T1/2:* Tramadol: ~6–8 hours; Active metabolite: 7–9 hours |
||
| Starting | 50 mg/day PRN | ||
| Average Effective | 50–200 mg/day divided BID 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 | |||
| Renal Disease | For Clcr <30 mL/minute: -Immediate release: 50–100 mg Q12 hours; Maximum: 200 mg/day -Extended release should NOT be used |
DM medication Drug-Drug Interactions: N | |
| Liver Disease | Hepatic metabolism | For cirrhosis: -Immediate release: 50 mg Q12 hours? -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 |
|
| Key for Costs | |
|---|---|
| KEY | |
| $ | $0–50 |
| $$ | $51–100 |
| $$$ | $101–150 |
| $$$$ | $151–200 |
| $$$$$ | > $201 |
*
Imipramine is pregnancy category D
*
May act on voltage-gated calcium channels and impact the release of excitatory neurotransmitters
*
Due 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 IV lidocaine is 1.5–2.5.
**
Cost listed is for 30 patches of Lidoderm
*
Cost based on price per tube of 0.075% capsaician cream or packages of 4 patches used QID daily although this is not the recommended dosing
*
T1/2: prolonged in elderly, hepatic and renal impairment
**
Listed cost is for 90 tablets of 50 mg Tramadol Immediate Release