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Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain (strength of recommendation [SOR]: A, at least 2 good-quality randomized controlled trials [RCTs] and/or meta-analyses). Opioids have demonstrated pain relief in 3 RCTs (SOR: A, consistent RCTs). Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia (SOR: B, recommendations from meta-analyses and lower-quality RCTs).
Evidence summary
Postherpetic neuralgia (PHN) is defined as pain lasting 1 to 3 months after resolution of acute herpes zoster (shingles) rash. It occurs in approximately 10% to 15% of patients and can cause significant morbidity.
Tricyclic antidepressants provide effective pain relief
Five systematic reviews have concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN.1-5 Amitriptyline, the best studied TCA, provides at least moderate pain relief in two-thirds of patients with a pooled number needed to treat (NNT) for TCAs of 2.64 (95% confidence interval [CI], 2.1-3.54)5 (TABLE).
Selective serotonin reuptake inhibitors—including fluoxetine, paroxetine, citalopram, and sertraline—have been studied in a variety of neuropathic pain syndromes, but not for treating PHN.1
TABLE
What’s the NNT for drugs used to treat postherpetic neuralgia?
| CLASS | DRUG | DOSE | NNT | SIDE EFFECTS |
|---|---|---|---|---|
| Tricyclic antidepressants5 | Amitriptyline | Up to 150 mg/d (mean 120 mg/d) | 2.64 | Sedation, dry mouth, blurred vision, constipation, urinary retention |
| Nortriptyline | Up to 150 mg/d (mean 89 mg/d) | |||
| Desipramine | Up to 150 mg/d (mean 65-73 mg/d) | |||
| Anticonvulsants3,5 | Gabapentin | 1800-3600 mg/d | 2.8-5.3 | Somnolence, dizziness, edema, dry mouth |
| Pregabalin | 150-600 mg/d | 4.93 | ||
| Opioids5 | Oxycodone | Variable | 2.67 | Constipation, nausea, vomiting, sedation, dizziness, dependence |
| Long-acting morphine/methadone | 15-225 mg/d (morphine) (mean 91 mg/d for morphine, 15 mg/d for methadone) | 2.67 | ||
| Tramadol | 100-400 mg/d (mean 275 mg/d) | 4.76 | Dependence | |
| Topicals5 | Capsaicin 0.075% cream | Applied 3-4 times per day | 3.26 | Burning skin |
| Lidocaine 5% extended release patch | Max 3 patches per day | 2.0 | Mild skin reaction | |
| NNT, number needed to treat. | ||||
Anticonvulsants help, too
Five systematic reviews found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS).2-6 Pregabalin is also effective, with an NNT of 4.93 (95% CI, 3.34-6.07) for up to 50% pain reduction.7,8 Limited data are available concerning the effectiveness of valproate.5
A look at the role of narcotics
Four systematic reviews found that controlled-release oxycodone reduced pain by 50%, based on the VAS.2-5 Another systematic review reported only limited evidence of effectiveness.6 In pooled results from systematic reviews, opioids decreased pain by 50% on the VAS (NNT=2.67; 95% CI, 2.10-3.77).6
An RCT of 76 patients demonstrated that morphine, with methadone as backup, both reduced the intensity of pain and relieved pain more than placebo.9
Tramadol, a selective opioid agonist, showed moderate effectiveness in a small RCT (N=125), with an NNT of 4.76 (95% CI, 2.61-26.97).3,5,6 The mean pain intensity, degree of pain relief, and amount of rescue medication required were all better in the tramadol group than the placebo group.
Evidence for topical therapy is limited
The anesthetic lidocaine patch 5% has shown efficacy in PHN with allodynia based on 3 RCTs of lower quality (short duration, recruitment of patients who had improved on lidocaine previously, no report of baseline levels of pain); the NNT was 2 (95% CI, 1.4-3.3).10 A systematic review of these 3 RCTs concluded that evidence is insufficient to recommend the lidocaine patch as treatment for PHN.10
Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85).2-6 Blinding was limited in these studies because of the stinging associated with treatment.
Recommendations
A 2004 practice parameter of the American Academy of Neurology recommends TCAs (amitriptyline, nortriptyline, desipramine, and maprotiline), gabapentin, pregabalin, opioids, topical lidocaine, and capsaicin to treat PHN (level of evidence: A), but notes that amitriptyline has significant cardiac effects in the elderly compared with nortriptyline and desipramine.3
In 2006, the European Federation of Neurological Societies determined that TCAs, gabapentin, pregabalin, and opioids had established efficacy (level of evidence: A), but recommended opioids as second-line therapy because of potential adverse events with long-term use.4 The federation’s guidelines designate capsaicin, tramadol, topical lidocaine, and valproate as drugs with lower efficacy or limited strength of evidence (level of evidence: B). Nevertheless, they recommend considering topical lidocaine for elderly patients with allodynia and small areas of pain.4
1. saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007;(4):CD005454.-
2. Alper BS, Lewis PR. Treatment of postherpetic neuralgia: a systematic review of the literature. J Fam Pract. 2002;51:121-128.
3. Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63:959-965.
4. Attal N, Cruccu G, Haanpaa M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006;13:1153-1169.
5. Hempenstall K, Nurmikko TJ, Johnson RW, et al. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2:e164.-
6. Wareham DW. Postherpetic neuralgia. BMJ Clin Evid. 2007;12:905-918.
7. van Seventer R, Feister HA, Young JP, et al. efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin. 2006;22:375-384.
8. Dworkin RH, Corbin AE, Young JP, Jr, et al. Pregabalin for the treatment of postherpetic neuralgia; a randomized, placebo-controlled trial. Neurology. 2003;60:1274-1283.
9. Raja SN, Haythornwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2002;59:1015-1021.
10. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;(2):CD004846.-
Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain (strength of recommendation [SOR]: A, at least 2 good-quality randomized controlled trials [RCTs] and/or meta-analyses). Opioids have demonstrated pain relief in 3 RCTs (SOR: A, consistent RCTs). Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia (SOR: B, recommendations from meta-analyses and lower-quality RCTs).
Evidence summary
Postherpetic neuralgia (PHN) is defined as pain lasting 1 to 3 months after resolution of acute herpes zoster (shingles) rash. It occurs in approximately 10% to 15% of patients and can cause significant morbidity.
Tricyclic antidepressants provide effective pain relief
Five systematic reviews have concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN.1-5 Amitriptyline, the best studied TCA, provides at least moderate pain relief in two-thirds of patients with a pooled number needed to treat (NNT) for TCAs of 2.64 (95% confidence interval [CI], 2.1-3.54)5 (TABLE).
Selective serotonin reuptake inhibitors—including fluoxetine, paroxetine, citalopram, and sertraline—have been studied in a variety of neuropathic pain syndromes, but not for treating PHN.1
TABLE
What’s the NNT for drugs used to treat postherpetic neuralgia?
| CLASS | DRUG | DOSE | NNT | SIDE EFFECTS |
|---|---|---|---|---|
| Tricyclic antidepressants5 | Amitriptyline | Up to 150 mg/d (mean 120 mg/d) | 2.64 | Sedation, dry mouth, blurred vision, constipation, urinary retention |
| Nortriptyline | Up to 150 mg/d (mean 89 mg/d) | |||
| Desipramine | Up to 150 mg/d (mean 65-73 mg/d) | |||
| Anticonvulsants3,5 | Gabapentin | 1800-3600 mg/d | 2.8-5.3 | Somnolence, dizziness, edema, dry mouth |
| Pregabalin | 150-600 mg/d | 4.93 | ||
| Opioids5 | Oxycodone | Variable | 2.67 | Constipation, nausea, vomiting, sedation, dizziness, dependence |
| Long-acting morphine/methadone | 15-225 mg/d (morphine) (mean 91 mg/d for morphine, 15 mg/d for methadone) | 2.67 | ||
| Tramadol | 100-400 mg/d (mean 275 mg/d) | 4.76 | Dependence | |
| Topicals5 | Capsaicin 0.075% cream | Applied 3-4 times per day | 3.26 | Burning skin |
| Lidocaine 5% extended release patch | Max 3 patches per day | 2.0 | Mild skin reaction | |
| NNT, number needed to treat. | ||||
Anticonvulsants help, too
Five systematic reviews found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS).2-6 Pregabalin is also effective, with an NNT of 4.93 (95% CI, 3.34-6.07) for up to 50% pain reduction.7,8 Limited data are available concerning the effectiveness of valproate.5
A look at the role of narcotics
Four systematic reviews found that controlled-release oxycodone reduced pain by 50%, based on the VAS.2-5 Another systematic review reported only limited evidence of effectiveness.6 In pooled results from systematic reviews, opioids decreased pain by 50% on the VAS (NNT=2.67; 95% CI, 2.10-3.77).6
An RCT of 76 patients demonstrated that morphine, with methadone as backup, both reduced the intensity of pain and relieved pain more than placebo.9
Tramadol, a selective opioid agonist, showed moderate effectiveness in a small RCT (N=125), with an NNT of 4.76 (95% CI, 2.61-26.97).3,5,6 The mean pain intensity, degree of pain relief, and amount of rescue medication required were all better in the tramadol group than the placebo group.
Evidence for topical therapy is limited
The anesthetic lidocaine patch 5% has shown efficacy in PHN with allodynia based on 3 RCTs of lower quality (short duration, recruitment of patients who had improved on lidocaine previously, no report of baseline levels of pain); the NNT was 2 (95% CI, 1.4-3.3).10 A systematic review of these 3 RCTs concluded that evidence is insufficient to recommend the lidocaine patch as treatment for PHN.10
Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85).2-6 Blinding was limited in these studies because of the stinging associated with treatment.
Recommendations
A 2004 practice parameter of the American Academy of Neurology recommends TCAs (amitriptyline, nortriptyline, desipramine, and maprotiline), gabapentin, pregabalin, opioids, topical lidocaine, and capsaicin to treat PHN (level of evidence: A), but notes that amitriptyline has significant cardiac effects in the elderly compared with nortriptyline and desipramine.3
In 2006, the European Federation of Neurological Societies determined that TCAs, gabapentin, pregabalin, and opioids had established efficacy (level of evidence: A), but recommended opioids as second-line therapy because of potential adverse events with long-term use.4 The federation’s guidelines designate capsaicin, tramadol, topical lidocaine, and valproate as drugs with lower efficacy or limited strength of evidence (level of evidence: B). Nevertheless, they recommend considering topical lidocaine for elderly patients with allodynia and small areas of pain.4
Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain (strength of recommendation [SOR]: A, at least 2 good-quality randomized controlled trials [RCTs] and/or meta-analyses). Opioids have demonstrated pain relief in 3 RCTs (SOR: A, consistent RCTs). Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia (SOR: B, recommendations from meta-analyses and lower-quality RCTs).
Evidence summary
Postherpetic neuralgia (PHN) is defined as pain lasting 1 to 3 months after resolution of acute herpes zoster (shingles) rash. It occurs in approximately 10% to 15% of patients and can cause significant morbidity.
Tricyclic antidepressants provide effective pain relief
Five systematic reviews have concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN.1-5 Amitriptyline, the best studied TCA, provides at least moderate pain relief in two-thirds of patients with a pooled number needed to treat (NNT) for TCAs of 2.64 (95% confidence interval [CI], 2.1-3.54)5 (TABLE).
Selective serotonin reuptake inhibitors—including fluoxetine, paroxetine, citalopram, and sertraline—have been studied in a variety of neuropathic pain syndromes, but not for treating PHN.1
TABLE
What’s the NNT for drugs used to treat postherpetic neuralgia?
| CLASS | DRUG | DOSE | NNT | SIDE EFFECTS |
|---|---|---|---|---|
| Tricyclic antidepressants5 | Amitriptyline | Up to 150 mg/d (mean 120 mg/d) | 2.64 | Sedation, dry mouth, blurred vision, constipation, urinary retention |
| Nortriptyline | Up to 150 mg/d (mean 89 mg/d) | |||
| Desipramine | Up to 150 mg/d (mean 65-73 mg/d) | |||
| Anticonvulsants3,5 | Gabapentin | 1800-3600 mg/d | 2.8-5.3 | Somnolence, dizziness, edema, dry mouth |
| Pregabalin | 150-600 mg/d | 4.93 | ||
| Opioids5 | Oxycodone | Variable | 2.67 | Constipation, nausea, vomiting, sedation, dizziness, dependence |
| Long-acting morphine/methadone | 15-225 mg/d (morphine) (mean 91 mg/d for morphine, 15 mg/d for methadone) | 2.67 | ||
| Tramadol | 100-400 mg/d (mean 275 mg/d) | 4.76 | Dependence | |
| Topicals5 | Capsaicin 0.075% cream | Applied 3-4 times per day | 3.26 | Burning skin |
| Lidocaine 5% extended release patch | Max 3 patches per day | 2.0 | Mild skin reaction | |
| NNT, number needed to treat. | ||||
Anticonvulsants help, too
Five systematic reviews found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS).2-6 Pregabalin is also effective, with an NNT of 4.93 (95% CI, 3.34-6.07) for up to 50% pain reduction.7,8 Limited data are available concerning the effectiveness of valproate.5
A look at the role of narcotics
Four systematic reviews found that controlled-release oxycodone reduced pain by 50%, based on the VAS.2-5 Another systematic review reported only limited evidence of effectiveness.6 In pooled results from systematic reviews, opioids decreased pain by 50% on the VAS (NNT=2.67; 95% CI, 2.10-3.77).6
An RCT of 76 patients demonstrated that morphine, with methadone as backup, both reduced the intensity of pain and relieved pain more than placebo.9
Tramadol, a selective opioid agonist, showed moderate effectiveness in a small RCT (N=125), with an NNT of 4.76 (95% CI, 2.61-26.97).3,5,6 The mean pain intensity, degree of pain relief, and amount of rescue medication required were all better in the tramadol group than the placebo group.
Evidence for topical therapy is limited
The anesthetic lidocaine patch 5% has shown efficacy in PHN with allodynia based on 3 RCTs of lower quality (short duration, recruitment of patients who had improved on lidocaine previously, no report of baseline levels of pain); the NNT was 2 (95% CI, 1.4-3.3).10 A systematic review of these 3 RCTs concluded that evidence is insufficient to recommend the lidocaine patch as treatment for PHN.10
Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85).2-6 Blinding was limited in these studies because of the stinging associated with treatment.
Recommendations
A 2004 practice parameter of the American Academy of Neurology recommends TCAs (amitriptyline, nortriptyline, desipramine, and maprotiline), gabapentin, pregabalin, opioids, topical lidocaine, and capsaicin to treat PHN (level of evidence: A), but notes that amitriptyline has significant cardiac effects in the elderly compared with nortriptyline and desipramine.3
In 2006, the European Federation of Neurological Societies determined that TCAs, gabapentin, pregabalin, and opioids had established efficacy (level of evidence: A), but recommended opioids as second-line therapy because of potential adverse events with long-term use.4 The federation’s guidelines designate capsaicin, tramadol, topical lidocaine, and valproate as drugs with lower efficacy or limited strength of evidence (level of evidence: B). Nevertheless, they recommend considering topical lidocaine for elderly patients with allodynia and small areas of pain.4
1. saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007;(4):CD005454.-
2. Alper BS, Lewis PR. Treatment of postherpetic neuralgia: a systematic review of the literature. J Fam Pract. 2002;51:121-128.
3. Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63:959-965.
4. Attal N, Cruccu G, Haanpaa M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006;13:1153-1169.
5. Hempenstall K, Nurmikko TJ, Johnson RW, et al. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2:e164.-
6. Wareham DW. Postherpetic neuralgia. BMJ Clin Evid. 2007;12:905-918.
7. van Seventer R, Feister HA, Young JP, et al. efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin. 2006;22:375-384.
8. Dworkin RH, Corbin AE, Young JP, Jr, et al. Pregabalin for the treatment of postherpetic neuralgia; a randomized, placebo-controlled trial. Neurology. 2003;60:1274-1283.
9. Raja SN, Haythornwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2002;59:1015-1021.
10. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;(2):CD004846.-
1. saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007;(4):CD005454.-
2. Alper BS, Lewis PR. Treatment of postherpetic neuralgia: a systematic review of the literature. J Fam Pract. 2002;51:121-128.
3. Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63:959-965.
4. Attal N, Cruccu G, Haanpaa M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006;13:1153-1169.
5. Hempenstall K, Nurmikko TJ, Johnson RW, et al. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2:e164.-
6. Wareham DW. Postherpetic neuralgia. BMJ Clin Evid. 2007;12:905-918.
7. van Seventer R, Feister HA, Young JP, et al. efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin. 2006;22:375-384.
8. Dworkin RH, Corbin AE, Young JP, Jr, et al. Pregabalin for the treatment of postherpetic neuralgia; a randomized, placebo-controlled trial. Neurology. 2003;60:1274-1283.
9. Raja SN, Haythornwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2002;59:1015-1021.
10. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;(2):CD004846.-
Evidence-based answers from the Family Physicians Inquiries Network