Table 3.
Medication (class) | Mechanism of action | Starting dosage | Maximum dosage | Side Effects | Precaution and contraindications |
---|---|---|---|---|---|
First-Line Agents | |||||
(Tricyclic Antidepressants) Nortriptyline, Desipramine Use a tertiary amine TCAs only if a secondary are not available Ref. 112–119 Nortriptyline/Desipramine are FDA-approved for treatment of symptoms of depression |
Monoamine reuptake inhibition, sodium channel blockade and anticholinergic effects | 10–25 mg at bedtime | 100 mg at bedtime | Dry mouth, constipation, somnolence, anticholinergic effects, weight gain | Cardiac disease, prostatic adenoma and seizure disorder High doses should be avoid in adults>65 years of age |
Carbamazepine (Anticonvulsant) Ref. 120,121 FDA-approved for epilepsy, trigeminal neuralgia, and manic and mixed episodes of bipolar disorder |
Sodium channel– blocker | 200mg daily | 400–800mg/day, divided in 2–3 doses | Hyponatremia, Drowsiness, headache, Dizziness, rash and nausea | Concomitant use of MAO inhibitors Cardiac or hepatic disease Renal failure Prostatic hyperplasia |
Second-Line Agents | |||||
Low-Dose Naltrexone (Opioid Antagonist) Ref. 122–124 FDA-approved at higher doses (50 mg to 300 mg) for treatment of drug and alcohol addiction |
At low doses has an antiinflammatory effect, reducing the proinflammatory cytokines Modulating microglial activity Opioid antagonist - μ-opioid and κ-opioid receptors |
1.5 mg at bed time | 4.5 mg/bedtime | Headache, vivid dreams, nightmares, tachycardia and anxiety | Past organ transplant and use of immunosuppressive drugs |
Tramadol (Opioid Agonist) Ref. 110,111,125 FDA-approved for treatment of moderate to moderately severe pain |
μ-receptor agonist and monoamine reuptake inhibitor | 50mg/day | 100 mg/day in divided doses every 3–7 days as tolerated | Nausea, vomiting, constipation, dizziness, and somnolence | History of substance abuse, suicide risk and antidepressant in elderly patients |
Third-Line Agents | |||||
Calcium channel α 2-δ ligands - Gabapentin (Anticonvulsants) FDA-approved for treatment of post-herpetic neuralgia Pregabalin (Anticonvulsant) Ref. 113, 126–136 FDA-approved for treatment of neuropathic pain and fibromyalgia |
Act on the α2δ subunit of voltage-gated calcium channels, which decrease central sensitization | 100–300 mg three times/day 50mg three times/day or 75mg twice a daily |
2400 mg/day 300 mg/day |
Sedation, dizziness, peripheral edema | Reduced dose in renal insufficiency |
(Serotonin-noradrenaline reuptake inhibitors) Duloxetine Ref. 137–139 FDA-approved for treatment of diabetic peripheral neuropathic pain and fibromyalgia |
Serotoninnoradrenaline reuptake inhibitors | 30 mg/day | 60 mg twice/day | Nausea, abdominal pain, constipation | Hepatic disorders Use of tramadol hypertension |
Mexiletine (Sodium Channel Blocker) Ref. 140 FDA approved for treatment of cardiac arrhythmia |
Voltage-gated sodium channel blocker Lidocaine analogue Class IB anti-arrhythmic |
225–675 mg/day | 675 mg/day | Nausea, headache, sleep disturbances, tiredness, Gastritis is the most common side effect | Hepatic impairment Severe heart failure Sinus node dysfunction or intraventricular conduction defect |