News Author: Megan Rauscher
CME Author: Désirée Lie, MD, MSEd
May 19, 2006 — For patients with idiopathic, treatment-refractory trigeminal neuralgia, subcutaneous sumatriptan produces rapid and significant pain relief that lasts for about 8 hours without serious adverse reactions, according to results of a study conducted in Japan.
"Mechanical compression of the trigeminal root by an artery is thought to cause trigeminal neuralgia," Dr. Akifumi Kanai and colleagues from Kitasato University School of Medicine explain in the April issue of the journal Headache.
"We hypothesize that the basic mechanism for the analgesic effect of sumatriptan on trigeminal neuralgia is activation of 5-HT1B/1D receptors, leading to the improvement of neurogenic inflammation in trigeminal root," Dr. Kanai noted in comments to Reuters Health.
In a randomized, double-blind, cross-over trial, Dr. Kanai's team examined the possible effectiveness of subcutaneous injection of sumatriptan (3 mg in 1 mL) compared with 1 mL saline in the treatment of refractory trigeminal neuralgia in 24 patients. Paroxysmal pain triggered by touching or moving the face was assessed before and 15 minutes after each treatment session, which were separated by a week.
Subcutaneous sumatriptan significantly decreased visual analogue scale pain scores from 8.3 to 2.4 cm (p < 0.01), according to the investigators. Pain scores did not change with placebo injection.
Twenty patients described their pain as moderately or slightly better after sumatriptan treatment, compared with only one after saline injection. The analgesic effect of sumatriptan lasted for a median of 7.9 hours (range: 1-20 hours).
"No potentially serious side effects were reported," the investigators say. Blood pressure was elevated by 15% in two cases for about 15 minutes after sumatriptan injection, and five patients experienced fatigue and/or nausea.
Dr. Kanai concluded, "In patients with trigeminal neuralgia refractory to previous treatment, if they have no serious chronic diseases including contraindications of sumatriptan such as ischemic heart disease and cerebral infarction, subcutaneous sumatriptan can offer effective analgesia without serious adverse effects."
In an editorial, Dr. Julio Pascual of University Hospital in Salamanca, Spain, notes that, if replicated, the findings "would offer several practical consequences."
He says the rapid onset of relief is an advantage, but subcutaneous injection — at least twice a day — is a disadvantage.
Dr. Pascual suggests sumatriptan might be ideal as short-term treatment until drugs like carbamazepine begin to act, or as rescue treatment.
He concludes by calling for a trial to test oral or intranasal triptans for trigeminal neuralgia.
Headache. 2006;46:577-584
Idiopathic trigeminal neuralgia is characterized by paroxysmal shooting, stabbing, or electric shock like pain triggered by light stimuli, such as touch or facial movement. Although the pain lasts only for seconds, it may recur multiple times daily, and the maxillary and mandibular divisions of the trigeminal nerve are most commonly affected. According to the current authors, antiepileptic drugs, such as carbamazepine, phenytoin, and valproate, have been the standard of care, but onset of action may be long with pain relief occurring within 48 hours. Further, carbamazepine therapy has several adverse effects, including drowsiness, ataxia, dizziness, and diplopia, and it is not well-tolerated among older patients. Other treatment options include surgical methods: glycerol injection, radiofrequency lesions, and microvascular decompression. However, sumatriptan may be the most effective treatment of trigeminal neuralgia because it has a high affinity for 5-HT receptors and, according to the current authors, has the advantage of being tolerated in the elderly with few adverse effects. It also can be administered orally, by subcutaneous injection, or by intranasal spray.
The current trial is a double-blind, placebo-controlled, crossover study to examine the effectiveness of subcutaneous sumatriptan in controlling the pain of trigeminal neuralgia and the duration and quality of pain control in patients with intractable pain refractory to other treatment.
Inclusion criteria were International Headache Classification definition of trigeminal neuralgia without sensory or motor symptoms in the affected region with extensive testing showing no cause for the trigeminal neuralgia and paroxysmal pain for at least 3 months with intensity of more than 4 of 10 on a 10-cm visual analogue scale (VAS).
On the VAS, 0 was equivalent to no pain and 10 represented the worst pain.
Exclusion criteria were other neurologic disease, psychiatric conditions, or chronic medical conditions, use of 5-HT agonists within 1 month, or contraindication to sumatriptan use.
Consecutive patients were recruited for 6 months from the outpatient setting of a university hospital.
Conventional treatments were discontinued 12 hours before the study.
24 patients (20 women and 4 men) were randomized to receive either 3 mg in 1 mL of sumatriptan subcutaneously or identical saline placebo for the first group.
After 7 days, patients crossed over and received the alternative treatment in the second group.
VAS score of paroxysmal pain in response to touching of the face or facial movement before and 15 minutes after treatment was assessed as the primary outcome.
Mean age was 63 years (range, 42 - 80 years), mean body weight was 55 kg, mean duration of trigeminal neuralgia was 4.5 years (range, 3 months - 32 years), and baseline VAS score at entry was 8.1 to 8.4.
All patients had been treated previously with carbamazepine, and 15 had discontinued treatment due to adverse effects.
No patient was lost to follow-up.
Subcutaneous sumatriptan reduced the VAS score from 8.3 ± 2.1 cm before treatment to 2.4 ± 3.0 cm, whereas placebo did not change the VAS score.
Among 24 patients, only 8% who received placebo reported a decrease of 2 cm in VAS score, whereas 83% reported a similar decrease after subcutaneous sumatriptan.
50% of patients who received sumatriptan became pain free within 15 minutes of administration of sumatriptan.
The mean duration of pain relief for patients who responded to sumatriptan was 7.9 hours.
30 minutes after administration of subcutaneous injection, patients were asked to describe the quality of the pain as unchanged, improved throughout the observation period, or temporarily improved.
Significantly more patients reported durable improvement over the observation period of 30 minutes in the sumatriptan treatment period (20 vs 2 in the placebo treatment period).
There were no serious adverse effects associated with treatment. In 2 patients, blood pressure increased 15% within 15 minutes of sumatriptan administration.
Adverse effects included fatigue in 5 patients and nausea in 2 patients in the sumatriptan group but resolved within a few hours.
There was no morbidity associated with the subcutaneous injection.
Medical treatment of trigeminal neuralgia includes antiepileptic drugs, sumatriptan, and glycerol injection, whereas surgical options include radiofrequency lesions and microvascular decompression.
Subcutaneous sumatriptan given to patients with intractable trigeminal neuralgia is associated with immediate pain improvement of at least 2 cm on a VAS in 80% of patients, and the average duration of pain relief is 7.9 hours.
Updated 5-22-06