The National Institute for Clinical Excellence (NICE) guidelines for treatment of mania recommend that consideration be given to olanzapine and semisodium valproate as first-line treatments (NICE, 2003). They state that valproate can rarely cause severe liver damage and assert that liver function should be assessed before and during therapy, saying ‘tests that reflect protein synthesis, particularly prothrombin time are most relevant’. They continue: ‘Blood tests (blood cell count, including platelet count, bleeding time and coagulation tests) are therefore recommended’. Most readers will be familiar with the concept of the bleeding time only through the immortal lines delivered by James Robertson Justice in the film Doctor in the House (1954). It is a rarely indicated test of platelet function which requires making a 3 cm cut on a patient's forearm and timing how long it takes for the bleeding to stop. Clearly such a test would not be acceptable to a substantial proportion of patients with mania.
The recommendation seems a non sequitur. Saying that valproate can cause liver damage and that ‘therefore’ these investigations should be performed does not make sense because, with the exception of the coagulation tests, they are not indicators of hepatic function. In fact, the investigations are not recommended by the British National Formulary (BNF) but in the summary product characteristics for semisodium valproate (available at http://emc.medicines.org.uk). It is here that it is stated that valproate can cause the frequent occurrence of thrombocytopenia, and it is here that the investigations listed are recommended.
It would strain credulity to believe that British doctors routinely measure bleeding time prior to initiating valproate therapy. Yet if a patient were to suffer ill effects, then having ignored recommendations found both in the summary product characteristics and in NICE guidelines could make an action for negligence difficult to defend.
Even setting aside the bleeding time, the advice to perform more straightforward investigations remains problematic. Faced with a manic patient, one is unlikely to feel enthusiastic about holding off treatment until a prothrombin time has been obtained. Instead, one will be tempted to choose an alternative treatment which can be started immediately, such as haloperidol. The BNF does not recommend that these blood tests be performed before starting valproate and there is no evidence base to show that carrying them out pre-treatment will produce a better outcome. The advice seems to have been included in the NICE guidelines in a thoughtless way, without regard to the possibility that unnecessary investigations will make a particular treatment option less acceptable to both doctors and patients. If recommendations about treatment are to be evidence-based, then so must be the recommendations about accompanying investigations.
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