First and second line drugs for NP
| Drug class | Dosage and titration (S: starting dosage, T: titration, M: maximum dosage) | Side and adverse effects | Advantages | Disadvantages, contraindications and precautions |
|---|---|---|---|---|
| TCAsA | Sedation, drowsiness, dry mouth, blurred vision, constipation, urinary retention, weight gain, hypomania (side effects are reduced with low starting dosage and slow titration). | May improve depression (higher dosage needed) and sleep disturbances. | Cardiac diseases (the rate of sudden cardiac death is not enhanced for dosages of amitriptyline or its equivalent up to 100 mg/day), prostatic hypertrophy, glaucoma, seizures, risk of suicide, concurrent use of tramadol or MAOIs may increase the risk of serotonin syndrome. Use lower starting dosage and slower titration in older patients. | |
| Amitriptyline | S: 6–10 mg at bedtime, T: increase by 2–5 mg every 2–3 days, M: 75 mg. | |||
| Nortriptyline | S: 10–25 mg at bedtime, T: increase by 10–25 mg every 5–7 days, M: 100 mg. | |||
| Desipramine | ||||
| α2-δ Ligands | Dizziness or drowsiness, sedation, peripheral oedema, weight gain. | May improve anxiety and sleep disturbance, no significant pharmacokinetic interactions. | Renal failure (dosage and titration should be adapted according to creatine clearance). Long titration and many pills a day may be necessary for gabapentin to obtain NP reduction. | |
| Gabapentin | S: 300 mg at bedtime, T: increase by 300 mg every 2–3 days, M: 1200 mg tid. | |||
| Pregabalin | S: 75 mg at bedtime; T: increase by 75 mg every 2–3 days, M: 300 mg bid. | |||
| SNRIs | Nausea (may be reduced taking the drug after a meal), dizziness, sedation, agitation, withdrawal syndrome after abrupt discontinuation. | May improve depression and anxiety. Some guidelines26 29 indicate them as first choice for diabetic NP. | Liver dysfunction, renal failure, risk of suicide, concurrent use of tramadol or MAOIs may increase the risk of serotonin syndrome. | |
| Duloxetine | S: 30 mg (after a meal), T: increase to 60 mg after 1 week, M: 120 mg. | |||
| Venlafaxine | S: 37.5 mg, T: increase to 75 mg after 1 week, then by 37.5–75 mg each week, M: 225 mg. | |||
| Topical lidocaine | Local side effects (erythema, rash), no systemic ones. | May be effective on allodynia. | Hypersensitivity to local anaesthetics. Do not use on inflamed or injured skin or mucous membranes. | |
| 5% patch | S: 1–3 patches for a maximum of 12 h/day, M: 3 patches for a maximum of 12 h/day | |||
| Tramadol | S: 50 mg qd/bid, T: increase by 50–100 mg (in divided doses) every 3–7 days, M: 400 mg (100 mg qid), consider 300 mg for older patients. | Nausea, vomiting, sedation, constipation, drowsiness, dizziness. | Rapid NP reduction, effective on nociceptive and mixed pain. | Substance abuse, risk of suicide, seizures, respiratory depression, concurrent use of tricyclic antidepressants, SNRIs, SSRIs or MAOIs may increase the risk of serotonin syndrome. Use slower titration in older patients. |
| Opioids Morphine Oxycodone Hydromorphone Oxymorphone Methadone Buprenorphine Fentanyl Tapentadol | S: 10–15 mg morphine every 4 h or as needed (equianalgesic dosage for other opioidsB), T: after 1–2 weeks convert total daily dosageB to long-acting opioids (short-acting medication may be continued as needed), M: no maximum dosage (up to 300 mg morphine used in NP). | Nausea, vomiting, flushing and itching (usually short-lasting), sedation, confusion, constipation (may be reduced with oral opioids+naloxone formulations), drowsiness, dizziness, hypogonadism. | Rapid NP reduction, effective on nociceptive and mixed pain. Tapentadol has also NRI effect. | Substance abuse, respiratory depression, risk of suicide. Use slower titration and lower dosages in older patients and chronic obstructive pulmonary disease. Consider referral to a pain specialist for higher dosages. Short-acting (lollipop or sublingual) formulations are useful for breakthrough pain. Opioid patches are not the first choice way of administration and should not be used in opioid-naive patients. For tapentadol, concurrent use of TCAs, SNRIs, SSRIs or MAOIs may increase the risk of serotonin syndrome. |
| AEDs | ||||
| Carbamazepine | S: 100 mg tid, T: increase by 100 mg every 3–5 days, M: 1600 mg. | Drowsiness, SJS, TEN, SIADH, aplastic anaemia. | First line drug in trigeminal neuralgia. | Risk of SJS or TEN is higher in Asian patients carrying HLA-B*1502 allele. Monitor CBC. |
| Oxcarbazepine | S: 300 mg, T: increase by 600 mg every week, M: 2400 mg. | Drowsiness, dizziness, headache, SIADH. | First line drug in trigeminal neuralgia. | Better tolerated than carbamazepine. Use lower starting dosage and slower titration in older patients. |
| Lamotrigine | S: 25 mg, T: increase 25 mg every 2 weeks, M: 400 mg. | Drowsiness, blurred vision, SJS, TEN, DRESS. | First line drug in central poststroke pain. | Adverse reactions are reduced with slow titration. It may take many weeks to reach effective dosage. |
A=TCAs dosages effective on NP are generally lower than those used for depression. Dosages higher than those reported here are usually poorly tolerated in older patients, but may be used in younger ones (side effects and ECG abnormalities should be monitored). B=Equianalgesic opioid charts are available as pocket-sized cards and opioids calculator/converter apps are available for iPhone and Android mobile devices.
AEDs, antiepilepsy drugs; bid, twice daily; CBC, complete blood count; DRESS, drug reaction with eosinophilia and systemic symptoms; MAOIs, monoamine oxidase inhibitors; NP, neuropathic pain; NRI, norepinephrine reuptake inhibitor; qd, daily; qid, four times a day; SIADH, syndrome of inappropriate antidiuretic hormone; SJS, Stevens-Johnson syndrome; SNRIs, serotonin-norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants; TEN, toxic epidermal necrosis; tid, three times a day.