Treatment of Postherpetic Neuralgia

Oral therapies

Oral therapies evaluated were tricyclic antidepressants, gabapentin, oxycodone, tramadol, dextromethorphan, memantine, acyclovir, lorazepam, and fluphenazine (Table 1).

Tricyclic antidepressants have been shown to be effective in multiple small short-term crossover trials. Amitriptyline was highly effective in 2 placebo-controlled trials.^16,17 In 1 of these trials, amitriptyline was more effective than lorazepam.¹⁶ In another trial, amitriptyline was more effective than fluphenazine (a phenothiazine) and glycopyrrolate placebo.¹⁸ Nortriptyline was as effective as amitriptyline in a comparison trial,¹⁹ while maprotiline was not.²⁰ Desipramine was highly effective in a trial using benztropine as an “active placebo” in that the anticholinergic properties of benztropine were used to match the side effects of desipramine.²¹ In all these studies, the analgesic effects of tricyclic antidepressants appeared independent of antidepressant effects. No randomized trial data were collected to assess the use of antidepressants for longer than 8 weeks.

Gabapentin, an anticonvulsant, was effective in a single large placebo-controlled trial.²² The number needed to treat (NNT) was 3.2 for the outcome of moderate or better pain relief and 13.9 for the outcome of no pain during the eighth week of treatment. The proportion of patients whose pain was much improved or who had no pain was not reported.

Controlled-release oxycodone was effective in a crossover trial in which 45% of patients had previously used opioids.²³ Tramadol may be effective but was not compared against placebo.²⁴ High-dose dextromethorphan, an N-methyl-D-aspartate (NMDA) receptor antagonist, was not shown to be effective for PHN in a small crossover trial.²⁵ Memantine, another NMDA antagonist, was also ineffective.²⁶ Acyclovir did not show any greater efficacy than placebo in a small trial.²⁷ Lorazepam and fluphenazine did not show statistically significant benefit in comparison with placebo in the amitriptyline trials.^16,18

Other therapies

Other therapies evaluated were vincristine iontophoresis, acupuncture, intrathecal methylprednisolone, and subcutaneous administration of a mixture of gangliosides (Table 1).

Iontophoresis is a process whereby topical medications are applied via electricity. Vincristine iontophoresis was no more effective than saline iontophoresis in one small trial.²⁸ Vincristine and dimethylsulfoxide iontophoresis was effective at reducing but not eliminating pain in another small trial.²⁹ Dimethylsulfoxide may have an independent analgesic effect.³⁰

Acupuncture was no more effective than mock transcutaneous electrical nerve stimulation (TENS) in 1 trial,³¹ while a smaller trial suggested a short-term effect.³²

Intrathecal methylprednisolone acetate plus lidocaine was highly effective for achieving good or excellent results (pain relief > 50%) in patients with longstanding PHN refractory to multiple conventional therapies.³³ All patients whose response to methylprednisolone was poor (8%) had had PHN for more than 5 years. The intrathecal route appears more effective than the epidural route of administration.³⁴

A mixture of gangliosides given by subcutaneous injection was more effective than placebo, but poor tolerability and derivation from bovine brain tissue severely limit its acceptability.³⁵

Sympathetic blocks using bupivacaine were more effective than intravenous lidocaine infusions in 1 trial,³⁶ but results were not reported in a fashion that conveys the proportion of patients who improved significantly.

Discussion

Effective therapies

The therapy for which evidence for efficacy is best is tricyclic antidepressants. Three placebo-controlled RCTs demonstrated that only 2 to 3 patients with PHN need to be treated to achieve 1 good or excellent result (NNT = 2-3). Since none of these studies lasted longer than 8 weeks, the long-term efficacy of antidepressants for the treatment of PHN is unknown. Follow-up of 10 patients who did well in 1 antidepressant trial found that only 2 patients were still doing well at 2 years.¹⁹

Other therapies shown to be effective in 1 or 2 trials are topical capsaicin 0.075%, gabapentin, and controlled-release oxycodone. For these studies, it is difficult to determine the number needed to treat for “meaningful” clinical benefit, although gabapentin demonstrated superiority to placebo in numerous quality-of-life measures.

For patients with severe PHN refractory to other treatments, 2 trials support benefit from intrathecal methylprednisolone and 1 trial suggests benefit from bupivacaine sympathetic blocks. Cost data for selected therapies are presented in Table 2.

TABLE 2
COSTS OF SELECTED DRUG THERAPIES