Parturient montes?

The National Institute for Clinical Excellence (NICE) whose unofficial acronyms are much funnier and one (the National Institute for the Control of Expenditure) probably more accurate has just, at the time of writing, produced its final appraisal determination on newer drugs for epilepsy in adults (we still await—how typical—the one for children). This final determination on newer drugs compares them against the older standard drugs for epilepsy. This is obvious, but raises several problems. Firstly, valproate and carbamazepine are chosen as the older comparators. One can see why since all new drugs are compared against them in double blind trials. But there is very little mention of phenobarbitone (an effective third world anticonvulsant) or of phenytoin (still widely used in this country). Perhaps some comparison should have been made. Secondly, it is also important to remember that valproate and carbamazepine were introduced into the epilepsy world at a time when double blind controlled trials did not have the supremacy they have today and when standards for measuring efficacy were different. Thirdly it is also important to remember that in terms just of efficacy the older and the newer drugs cannot be separated, despite determined efforts to do so. The newer drugs stand or fall by their other properties and side effects, not by their efficacy. The “newer” drugs for epilepsy are a strange mixture of the new and what I would term the older; can drugs like lamotrigine and gabapentin, approaching the end of their patent protection life, really be though of as new? It is an odd reflection of the status of epilepsy in British medical thinking that such drugs could be considered “new”—they would not be in the case of hypertension, for instance. The mix of “new” drugs includes those licensed for monotherapy (lamotrigine and topiramate) with those not so licensed. Should they be lumped with those other drugs which are not licensed either because they tried and failed, never bothered or are too new, or, perhaps more sensibly, assessed separately? The appraisal concludes under the title of “Guidance” that the old drugs (valproate and carbamazepine) should be tried first unless there are (1) contraindications to the drugs, (2) they could interact with other drugs, notably oral contraceptives, (3) they are already known to be poorly tolerated by the individual, (4) the person is a woman of child-bearing potential. This rule applies also to the elderly (in whom new onset seizures are common) and those with learning difficulty, in whom epilepsy is even more common and often difficult to treat. It is also recommended that people should be treated with monotherapy and that “combination therapy (adjunctive or “add on” therapy) should only be considered when sequential attempts at monotherapy with antiepileptic drugs have not resulted in seizure freedom”. Since the second or subsequent drug will be added into the first failed drug (and there may be an interaction between them) there will be a time when the patient will be taking two drugs. The first drug should then be withdrawn; but one does not usually do this at once since time must elapse to ensure that the second drug really is effective. By this time the patient may well be near seizure freedom for a year and be eligible for a driving licence and unwilling to risk losing it again by drug withdrawal, particularly if side effect free. Untidy perhaps and not scientific—but human nature tends to be. At one time whole conferences were devoted to “rational