Joanna M Zakrzewska and Mark E Linskey: Trigeminal neuralgia—gaps in the evidence

This blog is part of a series of blogs linked with BMJ Clinical Evidence, a database of systematic overviews of the best available evidence on the effectiveness of commonly used interventions.

Trigeminal neuralgia is a rare condition that causes excruciating intermittent short-lasting, usually unilateral facial pain especially provoked by light touch.

Although the criteria for diagnosis appear to be clear cut, there have been no case control studies to validate them, and there is no cohort data on progression of the disorder. This is especially important as—while the disorder is generally progressive over time—in more than 50% of cases this progression is interspersed with unpredictable remissions that can last six months or longer. In addition, the rate of progression can be extremely variable among patients. Currently, there are no biomarkers but magnetic resonance imaging with and without contrast of the brain is providing more data to help with decision making.

Management is further complicated in that both drug and surgical options are available. The disease can suddenly become extremely acute with longer lasting bouts of pain, and there are no studies on how these should be managed. In emergency circumstances, patients are often given opioids which provide little, if any, pain relief.

The most effective drugs for this condition are anticonvulsants but the design of drug trials is complicated by the fact that the gold standard drug carbamazepine takes up to three weeks to be fully eliminated, and the disease is so severe that it is unethical to use a placebo. New designs are therefore needed and have currently been attempted.

If efficacy and tolerability of the drugs become difficult, patients can undergo a variety of surgical procedures but there is insufficient evidence to help patient and healthcare professionals decide when this should occur. Within the field of surgical management of this condition, the recently updated BMJ Clinical Evidence overview identified a Cochrane review that, however, reported only three higher-quality randomised controlled trials (RCTs) of surgical treatments.[1][2] They focus on a comparison of different surgical techniques and do not include the procedure with the longest pain relief period, microvascular decompression. Within the surgical managements used, there are widely differing techniques, some of which are destructive and can lead to sensory loss, and others which are non-destructive but involve a major neurosurgical procedure.

RCTs of surgical trials are difficult to conduct but high-quality cohort follow-up studies by independent observers (for example using psychometrically-tested questionnaires comparing several different procedures) could be done. Some guidelines on how such a trial could be conducted have been published. [3]

It should be noted that there are different thresholds for treatment success for medical and surgical trials: pharmacological success is usually achieved by a greater than 50% improvement of baseline pain, whereas success of surgical procedures is most often defined as being pain-free, ideally off all medications. As a result, while the evidence for effectiveness of pharmacological management may be stronger than that for surgical interventions, the magnitude of therapeutic effect is much larger for surgical interventions. Given the marked disparity in therapeutic effect magnitude between medical and surgical interventions, a RCT comparing medical therapy against surgical interventions may raise ethical concerns up-front, as well as a high risk of significant unidirectional cross-over in an intent-to-treat analysis paradigm.

In view of the lack of high quality large trials, people with rare diseases such as trigeminal neuralgia should be managed in multi-disciplinary centres which are research-led, perform regular audits and so have built up experience with larger cohorts. There also needs to be more collaborative work between these centres to pool data and so provide more evidence-based therapies.

Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: JMZ has undertaken consultancy for a drug trial (drug not mentioned in this article) by Convergence Pharmaceuticals.

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