The effect of single-application topical ophthalmic anesthesia in patients with trigeminal neuralgia. A randomized double-blind placebo-controlled trial. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. The effects of streptomycin/lidocaine block on trigeminal neuralgia: a double blind crossover placebo controlled study. Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? A prospective double-blind, randomized study.
To evaluate the reported benefit of ipsilateral single-application ophthalmic anesthetic eyedrops in patients with typical trigeminal neuralgia, a randomized double-blind placebo-controlled trial was performed. Forty-seven patients were randomly assigned to receive two drops of either proparacaine (25 cases) or saline placebo (22 cases). The experimental and placebo groups were equivalent in regard to patient age, distribution of trigeminal neuralgia pain, duration of pain, current medication regimens, and number of prior procedures performed. Pain response was assessed at 3, 10, and 30 days after instillation using two pain rating scales and a measure of pain frequency. Treatment failure was defined in advance as any of the following: a lack of clinical response, the need for an increase in medication, or the need for surgery. No significant difference in outcomes was found between the two groups either when using a verbal pain rating scale (p = 0.24) or when comparing overall pain status (unchanged, improved throughout the study period, or temporarily improved) (p = 0.98). No difference in the frequency of trigeminal neuralgia attacks between the two treatment groups (scaled within five levels of pain frequency) was detected (p = 0.09). During follow-up monitoring, 11 patients in the test drug group and 14 in the placebo group required surgery because of persistent pain (p = 0.24). The results of this study indicate that single-application topical ophthalmic anesthesia reduces neither the severity nor the frequency of pain in comparison to placebo administration. Although a simple and safe treatment, the single application of topical ophthalmic eyedrops provides no short- or long-term benefit to patients with trigeminal neuralgia. Lamotrigine is a chemically novel antiepileptic drug which has not been adequately assessed for its antineuralgic properties. It was used in a double-blind placebo controlled crossover trial in 14 patients with refractory trigeminal neuralgia. Patients continued to take a steady dose of carbamazepine or phenytoin throughout the trial over a 31-day period. Each arm of the trial lasted 2 weeks with an intervening 3-day washout period. The maintenance dose of lamotrigine was 400 mg. Lamotrigine was superior to placebo (P = 0.011) based on analysis of a composite efficacy index which compared the numbers of patients assigned greater efficacy on lamotrigine with those assigned greater efficacy on placebo. Efficacy for one treatment over another was determined according to a hierarchy of: (i) use of escape medication; (ii) total pain scores; or (iii) global evaluations. Eleven of the 13 patients eligible for inclusion in the composite efficacy index showed better efficacy on lamotrigine compared with placebo. Global evaluations further suggested that patients did better on lamotrigine than placebo (P = 0.025). The adverse reactions with both lamotrigine and placebo were predominantly dose-dependent effects on the central nervous system. A 14th patient withdrew from the study due to severe pain during the placebo arm of the trial. It would appear that lamotrigine has antineuralgic properties. This study investigated the long term effect of a peripheral sensory block using streptomycin sulphate on trigeminal neuralgia. A total of twenty subjects, thirteen with idiopathic trigeminal neuralgia (ITN) and seven with traumatic trigeminal neuralgia (TTN) were studied. A double-blind placebo controlled randomized design was used. After the clinical assessment subjects were randomly assigned to receive either 1 g of streptomycin with 3 ml 2% lidocaine, or 3 ml lidocaine alone. The injections were performed adjacent to the branches that served the painful site. These were intraoral injections, more specifically infraorbital and inferior alveolar blocks. Patients received five blocks of either streptomycin/lidocaine or lidocaine alone for a period of five consecutive weeks. On the sixth week they were crossed over. Measures of pain intensity and pain frequency were used to assess treatment outcome. Patients also recorded their side-effects. Repeated measures analysis of variance was used to compare the treatment outcomes between the active and placebo groups. There was no statistically significant differences in the treatment outcomes regarding frequency and intensity of pain attacks. The sensory function of the treated nerves was also not affected. Side effects including facial swelling and pain were a common finding in the patients receiving streptomycin. This study demonstrated no beneficial effects of streptomycin blockade for idiopathic and traumatic trigeminal neuralgia. To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief.
                Eighty-seven patients with typical trigeminal neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43) isocenters. The median follow-up was 26 months (range 1-36).
                Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7% +/- 5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p = 0.23). Improved pain relief correlated with younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p = 0.018).
                Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications.
Of the four studies identified, one had low and three an unclear risk of bias. There is insufficient evidence from randomized controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.