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. Pimozide therapy for trigeminal neuralgia. Neuronavigator-guided percutaneous radiofrequency thermocoagulation in the treatment of intractable trigeminal neuralgia. Controlled sequential trials of carbamazepine in trigeminal neuralgia. Controlled trial of lamotrigine (Lamictal) for refractory partial seizures. Double-blind, placebo-controlled trial of lamotrigine in combination with other medications for neuropathic pain.
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. Pimozide was compared with carbamazepine in a double-blind crossover trial in 48 patients with trigeminal neuralgia who were refractory to medical therapy. Pimozide treatment produced greater reduction in trigeminal neuralgia symptoms than carbamazepine treatment. All of the pimozide-treated patients improved, while only 56% of carbamazepine-treated patients were relieved of their pain. Although both drugs provoked some adverse effects, it was not necessary to interrupt the trial in any case. After this 24-week trial, all patients began receiving pimozide and were followed up according to an open-label study design. In all cases, the pimozide dosage was progressively reduced until the minimal effective dose was reached. Central and peripheral mechanisms that may underlie pimozide-induced improvement are discussed. Percutaneous radiofrequency thermocoagulation of the trigeminal ganglion (PRTTG) is regarded as the first choice for most patients with trigeminal neuralgia (TN) because of its safety and feasibility. However, neuronavigator-guided PRTTG has been seldom reported. The purpose of this study was to assess the safety and efficacy of neuronavigator-guided PRTTG for the treatment of intractable TN.
                Between January 2000 and December 2004, 54 patients with intractable TN were enrolled into this study and were randomly divided into two groups. The patients in navigation group (n = 26) underwent PRTTG with frameless neuronavigation, and those in control group (n = 28) received PRTTG without neuronavigation. Three months after the operation, the efficacy, side effects, and complications of the surgery were recorded. The patients in the control group were followed up for 10 to 54 months (mean, 34 +/- 5), and those in the navigation group were followed up for 13 to 58 months (mean, 36 +/- 7). Kaplan-Meier analyses of the pain-free survival curves were used for the censored survival data, and the log-rank test was used to compare survival curves of the two groups.
                The immediate complete pain-relief rate of the navigation group was 100%, whereas it was 95% in the control. The proportion of sustained pain-relief rates at 12, 24 and 36 months after the procedure were 85%, 77%, and 62% in the navigation group, and 54%, 40%, and 35% in the control. Recurrences in the control group were more common than that in the navigation group. Annual recurrence rate in the first and second years were 15% and 23% in the navigation group, and 46%, 60% in the control group. No side-effect and complication was noted in the navigation group except minimal facial hypesthesia.
                Neuronavigator-guided PRTTG is a safe and promising method for treatment of intractable TN with better short- and long-term outcomes and lower complication rate than PRTTG without neuronavigation. nan The antiepileptic effect of lamotrigine (LTG) was assessed in a double-blind, placebo-controlled crossover trial in 24 adult patients with refractory partial seizures. LTG or placebo was added to existing antiepileptic drugs (AEDs). The dose of LTG varied from 75 to 400 mg daily. Three patients did not complete the trial. One was withdrawn from the trial with ataxia, tiredness, dyspnea, and diplopia while receiving LTG and died 18 days later of invasive carcinoma involving the liver. A second patient was withdrawn during baseline for contravening admission criteria, and a third received LTG in error during both treatment periods. Twenty-one patients (12 men and 9 women) completed the trial. An analysis of seizure counts in the 12-week treatment period with LTG showed a statistically significant reduction in seizures as compared with placebo for total seizures (p less than 0.002), partial seizures (p less than 0.002), and secondarily generalized seizures (p less than 0.05). The analysis of total seizure days showed a significant reduction during LTG treatment (p less than 0.002). There were no statistically significant changes in plasma concentrations of phenytoin (PHT), carbamazepine (CBZ), primidone (PRM), or phenobarbital (PB) between the two treatment periods. The most common adverse events reported during the trial were diplopia, drowsiness, tiredness, ataxia, and headache, but although these were more frequent during LTG treatment, the differences from placebo were not statistically significant. No hematological or biochemical changes were noted. This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and tolerability of lamotrigine added to gabapentin, a tricyclic antidepressant, or a nonopioid analgesic in patients whose neuropathic pain was inadequately controlled with these medications. Patients with neuropathic pain from diabetic peripheral neuropathy, postherpetic neuralgia, traumatic/surgical nerve injury, incomplete spinal cord injury, trigeminal neuralgia, multiple sclerosis, or HIV-associated peripheral neuropathy, who had a mean weekly pain score > or =4 on an 11-point numerical rating scale, were randomized to receive a flexible dose of lamotrigine 200, 300, or 400mg daily (n=111) or placebo (n=109) for up to 14 weeks (including eight weeks of dose escalation) in addition to their prestudy regimen of gabapentin, a tricyclic antidepressant, or a nonopioid analgesic. No statistically significant difference in the mean change in pain-intensity score from baseline to Week 14 (primary endpoint) was detected between lamotrigine and placebo (P=0.67). Differences between lamotrigine and placebo were not statistically significant for secondary efficacy assessments, including mean changes from baseline in the Short-Form McGill Pain Questionnaire, the Neuropathic Pain Scale, rescue medication use, and the percentages of patients rated as much improved or very much improved at the end of treatment on the Clinician Global Impression of Change scale and the Patient Global Impression of Change scale. Lamotrigine was generally well tolerated. Lamotrigine (up to 400 mg/day) added to gabapentin, a tricyclic antidepressant, or a nonopioid analgesic did not demonstrate efficacy as an adjunctive treatment of neuropathic pain but was generally safe and well tolerated.
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.