Trigeminal neuralgia (TN) is defined by the International Association for the Study of Pain, as a sudden, usually unilateral, severe brief stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve (Merskey 1994). The International Headache Society (Anonymous 1988), lays down the following criteria for TN:

A. Paroxysmal attacks of facial or frontal pain which last a few seconds to less than two minutes.

B. Pain with at least four of the following characteristics:
1. distribution along one or more divisions of the trigeminal nerve;
2. sudden, intense sharp, superficial, stabbing or burning in quality;
3. pain intensity severe;
4. precipitation from trigger areas, or by certain daily activities such as eating, talking, washing the face or cleaning the teeth;
5. between paroxysms the patients is entirely asymptomatic.

C. No neurological deficit.

D. Attacks are stereotyped in the individual patient.

E. Exclusion of other causes of facial pain by history, physical examination and special investigation when necessary.

The diagnosis of TN is based on clinical findings although there have not been any case controlled studies to validate diagnostic methods. A careful history and examination can distinguish between TN and other disorders that cause facial pain (Zakrzewska 2002 (a)).

Trigeminal neuralgia has an annual occurrence rate of 3 to 5 per 100,000 people. It is found more often in women than in men (age‐adjusted ratio, 1.74:1) and is most common from age 50 to 69 years. Attacks are more commonly on the right (Yoshimasu 1972; Katusic 1990).

The aetiology of TN is not clear. There are obvious problems in determining the causes of a syndrome, formulated on the basis of subjective pain rather than hard signs or laboratory abnormalities. However, in the last three decades, evidence has been mounting that in a large proportion of cases, compression of the trigeminal nerve root at or near the dorsal root entry zone by a blood vessel is a major causative or contributing factor (Devor 2002). Compression is not always found and so it is necessary to look for other factors. In a few cases, TN is due to multiple sclerosis. Other, rare causes include infiltration of the nerve root, trigeminal ganglion or nerve by a tumour or amyloid, and small infarcts or angiomas in the pons or medulla (Cheng 1993). Once all of these possibilities have been excluded, there remains a small proportion of patients in whom the aetiology is undetermined (Nurmikko 2001).

Spontaneous remission of TN is common, but the disorder is often progressive. Remission may last for months or even years, but, as the attacks become more frequent, the patient may develop persistent pain between episodes. Attacks may come in clusters and can completely disrupt activities of daily living if left untreated (Katusic 1990; Zakrzewska 2002 (b)).

Antiepileptic drugs have been used in pain management since the 1960s. The clinical impression is that they are useful for neuropathic pain, especially when the pain is lancinating or burning (Jacox 1994; Wiffen 2002). From three placebo‐controlled studies of carbamazepine in TN, a Cochrane systematic review deduced a number needed to treat (95%) confidence interval (CI)) for effectiveness of 2.5 (CI 2.0‐3.4). Lamotrigine has been used in a randomised controlled trial as an add on therapy and this small trial found that addition of lamotrigine was effective (Zakrzewska 1997). Little evidence supports a beneficial role of other antiepileptic drugs such as clonazepam, gabapentin, phenytoin and sodium valproate for TN (Wiffen 2002). The long‐term effects of carbamazepine have been evaluated in one study only, showing either loss of effect or problems with tolerability in one half of patients after 10 years (Taylor 1981). A long‐term cohort study on oxcarbazepine suggests that the pain increases with time rather than the drug becoming less effective (Zakrzewska 2002 (b)).

Several non‐antiepileptic drugs have been used to treat TN since the 1980s. Conventional analgesics such as aspirin, codeine and non‐steroidal anti‐inflammatory drugs are not used since experience suggests that they are not helpful. Drugs used include: baclofen, pimozide, racemic ketamine, proparacaine and tocainide. Baclofen is a gamma‐aminobutyric acid receptor agonist that has the least serious adverse effects (Steardo 1984). A double blind crossover study showed a significant decrease in the number of TN attacks when treated with baclofen, even in patients who had become unresponsive to carbamazepine (Fromm 1984; Cheshire 1997; Turp 1996). Pimozide is a neuroleptic that has shown significant relief of pain when compared with carbamazepine in a double blind crossover trial. Patients in this study had been diagnosed as having TN for at least two years and were treated with carbamazepine or pimozide. Adverse effects were common with pimozide, but mild, and no patients stopped the treatment because of side effects (Lechin 1989). Racemic ketamine, an anaesthetic, showed some benefit when treating acute pain but was ineffective for pain lasting more than five years (Mathisen 1995). The use of topical ophthalmic anaesthetics, such as proparacaine, has been reported to relieve TN pain in some patients, but a randomised trial showed no change in the frequency or severity of attacks (Kondziolka 1994). The analgesic effect of tocainide was also reported in 1987 (Lindstrom 1987). There is no known systematic review of non‐antiepileptic drug treatment for trigeminal neuralgia. Sindrup and Jensen (Sindrup 1999) have done a systematic review of drugs used in TN and there is also a review in Clinical Evidence that is updated every eight months at www. clinicalevidence. org (Zakrzewska 2001).

The aim of this review is to review systematically all randomised controlled trials (RCTs) and quasi‐randomised controlled trials, which examine the effectiveness of non‐antiepileptic drugs for TN.