Megaloblastic anaemia associated with anticonvulsant therapy.

In 1954 Badenoch described two cases of megaloblastic anaemia which developed in epileptics while under treatment with phenytoin sodium and phenobarbitone, and subsequently I2 further cases have been recorded (Hawkins and Meynell, 1954; Chalmers and Boheimer, I954; Rhind and Varadi, I954; Webster, 1954; Berlyne, Levene and McGlashan, 1955; Ryan and Forshaw, I955; Vaishnava, I955). Six of these patients were taking phenytoin sodium only, four patients were taking phenytoin sodium and phenobarbitone, and two patients were taking primidone in addition to phenytoin sodium and phenobarbitone (Chalmers and Boheimer, 1954; Berlyne et al., I955). It is unlikely that the anticonvulsant drugs were responsible for the anaemia in two of these patients, one of whom probably had megaloblastic anaemia of pregnancy (Vaishnava, 1955) and the other probably had pernicious anaemia (Chalmers and Boheimer, 1954). More recently Girdwood (I956) and Girdwood and Lenman (I956) have described two cases in which megaloblastic anaemia developed during treatment with primidone and phenobarbitone, and Fuld and Moorhouse (1956) reported two cases in which the anaemia developed during primidone therapy alone. One case has been reported in which a severe megaloblastic anaemia developed during treatment with large doses of amylobarbitone and quinalbarbitone (Hobson, Selwyn and Mollin, 1956). The present report is of another patient who developed megaloblastic anaemia during treatment with phenytoin sodium and phenobarbitone, and also of the subsequent progress of two of our original patients (Ryan and Forshaw, I955). One of the original patients, who has continued to take 2 gr. phenobarbitone daily, has now been observed for over three years since stopping vitamin B12 therapy and the anaemia has not returned. The other patient, who has continued to take 3 gr. phenobarbitone daily, relapsed eight months after stopping folic acid treatment. She responded to a second course of folic acid treatment and a relapse has not occurred during the subsequent io months. Case Report A married woman, aged 60, was admitted to Whiston Hospital in August I955. She had been feeling tired and depressed and had been breathless on exertion for about nine months. Her diet had been poor for many years. For about 12 years she had suffered from epilepsy. At first the epileptic attacks were infrequent and she did not take any anti-convulsant drugs, but more recently the attacks became more frequent and during the last year she had been taking 2 gr. phenobarbitone and 300 mg. phenytoin sodium daily. On examination she was thin (weight 7 st. 7 lb.), there was pallor of the skin and mucous membranes, and her temperature was oo00 F. The tongue and gums were normal, the spleen was not palpable and there were no abnormal neurological signs. Both a chest X-ray and a barium meal X-ray were normal.