Neither tricyclic antidepressants (TCAs) nor opioids are indicated for the treatment of PHN, but both are widely used and have demonstrated efficacy in clinical trials. Head-to-head trials of TCAs and opioids failed to show significant differences in pain relief, though patients did prefer opioids over TCAs.
13 Patients older than 18 years with pain lasting at least 3 months after resolution of rash (N = 76) were randomly assigned to receive one of six treatments, each of which included 8-week periods of a TCA, an opioid, and placebo, with 1-week drug-free washout periods between the test periods.
The TCA studied was nortriptyline hydrochloride, 10 mg to 160 mg (average dose, 89 mg), with an option of desipramine hydrochloride (average dose, 63 mg) if nortriptyline was not tolerated. The study opioid was controlled-release morphine sulfate, 15 mg/d to 240 mg/d (average dose, 91 mg/d), with an option for methadone hydrochloride (average dose, 15 mg/d) if morphine was not tolerated. The study drugs were uptitrated from starting (lowest) dose via biweekly dose increases until the patient had maximal pain relief or dose-limiting adverse events.
13
Both TCAs and opioids offered significantly greater pain relief than placebo; there was a nonsignificant (
P = .06) tendency for the reduction in pain ratings to be greater with an opioid than with a TCA. Patients receiving an opioid had an average 38.2% reduction in pain, whereas patients receiving a TCA had a 31.9% reduction and patients receiving placebo had an 11.2% reduction (
Figure 3). Commensurate with the greater reduction in pain, more patients preferred opioids (54%) than TCAs (30%;
P = .02); the remainder preferred placebo. The preference for TCAs over placebo was not significant (
P = .08).
13 Once dose levels were established, opioids were associated with a significantly greater incidence of constipation, nausea, and drowsiness than placebo; the first two were also significantly more common with opioids than with TCAs (
P = .01, opioids vs TCAs). Tricyclic antidepressants were associated with more dizziness than placebo.
13 The strong patient preference for opioids over TCAs suggests that even though opioids are associated with a greater incidence of certain adverse events than TCAs, the pain relief they offer is such that this benefit outweighs the adverse events.