1
586 distribution are more easily distinguished from pathological sequelae. The limitations of frontal-plane electrocardiography are well evidenced by the paper of Woods et al. and emphasise the necessity for a better electrocardiographic technique. Vectorcardiography presents special diffi- culties. These difficulties are overcome with the ABC display. Department of Physiology, University of Melbourne. E. R. TRETHEWIE. TRANYLCYPROMINE SIR,-So far there have been 8 deaths associated with tranylcypromine (’Parnate ’). 3 of the patients who died were having imipramine at the same time, 2 had amphetamines, 2 were on tranylcypromine plus trifluo- perazine (’ Parstelin ’), and 1 had tranylcypromine only. Cerebral haemorrhage was confirmed in 3 cases and suspected in 1. In addition, 3 patients with intracranial bleeding who recovered have been reported, and Dorrell 1 2 mentions that there are 4 more cases known but still unpublished. Many other patients while on treatment with tranylcypromine had sudden attacks of violent and throbbing headache accompanied by hypertension and at least some of the following features: acute fear, palpita- tions, tachycardia or bradycardia, nausea, vomiting, giddiness, sweating, photophobia, stiff neck and other neurological signs, faintness, and collapse. There is no agreement regarding the frequency of the side- effects. Lees and Burke 3 reported 11 out of 60 patients (18%) in a clinical trial with parnate, but Macdonald 4 reported only 14 cases of severe headache in 600 patients treated, and Milligan 5 also mentions a very low incidence. Simultaneous administration of imipramine (’ Tofranil ’) or amphetamines seems to be particularly dangerous although Morgan 6 has reported the case of a patient who received large doses of parnate and amphetamine without ill-effects. Blackwell 1 has drawn attention to a possible association between the eating of cheese and the symptoms in patients taking tranylcypromine and has described 11 patients in whom typical attacks came on shortly after eating cheese. Womack 9 has recorded the case of a healthy youth who died of acute circulatory collapse less than two hours after eating cheese. Recently and within a short time 5 patients attending the Hill End day hospital who were taking tranylcypromine or phenelzine had typical attacks of severe headache. In view of the reports of Blackwell 7 and Womack 9 10 we decided to make a retrospective inquiry into the dietetic habits of these patients. 1. Female, 49, on phenelzine (’Nardil’) 15 mg. t.d.s. and chlordiazepoxide (’ Librium’) 10 mg. t.d.s. for three months had a typical crisis at home. She eats cheese about twice a month and does not remember whether she had eaten it before the attack. 2. Female, 47, on phenelzine 30 mg. t.d.s. and chlordiazepoxide 10 mg. t.d.s. for three weeks had three very severe attacks at home and a milder one in the day hospital. She eats cheese almost every day, always with the evening meal. The attacks came at noon or in the morning and not shortly after eating cheese. 3. Female, 40, on parstelin 1 tablet t.d.s. for six months followed by tranylcypromine 10 mg. t.d.s. and chlordiaze- poxide 10 mg. t.d.s. for ten days had a severe crisis one evening. She eats cheese almost every evening, but she is quite sure that she did not have cheese that day. 1. Dorrell, W. Lancet, 1963, i, 388. 2. Dorrell, W. ibid. Aug. 10, 1963, p. 300. 3. Lees, F., Burke, C. W. ibid. 1963, i, 13. 4. Macdonald, R. ibid. p. 269. 5. Milligan, W. L. ibid. p. 442. 6. Morgan, D. H. ibid. p. 389. 7. Blackwell, B. ibid. p. 167. 8. Blackwell, B. ibid. Aug. 24, 1963, p. 414. 9. Womack, A. M. Brit. med. J. Aug. 10, 1963, p. 366. 10. Womack, A. M. Lancet, Aug. 31, 1963, p. 463. 4. Female, 57, on parstelin 1 tablet t.d.s. since Oct. 29, 1962. She had an attack on Jan. 8, 1963, in the morning. She is very fond of cheese, but she eats it with the evening meal, and, therefore, she had not had it before the attack that day. 5. Male, 50, an outpatient, on parstelin 1 tablet t.d.s. since Feb. 25, 1963. He had several violent attacks of throbbing headache between April 3 and July 7. He did not relate these attacks to parstelin. He often eats cheese at lunch and is sure that at least three of the attacks took place after lunch, but he had several other attacks at different times of the day, some of them on days when he had not eaten cheese. There were 9 patients on tranylcypromine during the same period who did not develop side-effects. Of these, 2 never eat cheese, 1 eats cheese only occasionally, 4 eat cheese 1-4 times weekly, and 2 eat cheese almost every day. There were 2 patients on phenelzine who did not develop side-effects, of whom 1 eats cheese occasionally and the other eats cheese twice weekly. Judged by this series, although not extensive or con- clusive enough, one would think that there is no clear relation between eating cheese and the typical side-effects of tranylcypromine. Cheese is such a common article of diet that obviously most patients on long-term treatment with monoamineoxidase inhibitors are bound to eat cheese during the course of treatment, and, of course, some of them will have by coincidence attacks of severe headache shortly after eating cheese. More research is needed. Hill End Hospital, St. Albans, Herts. L. ARENILLAS. SiR,ňThere has been much correspondence in your columns recently describing intracranial bleeding in association with the use of tranylcypromine, and I should like to describe one further case lately under our care. A man aged 67 had been depressed for several years after the death of his wife, and had been treated with various anti- depressant agents. On June 26, 1963, he was started on tranylcypromine and trifluoperazine (’Parstelin’) by his general practitioner. On July 7 while in a restaurant he had very severe occipital headache which radiated to the forehead and was associated with vomiting. He was taken to the casualty department of a nearby hospital, but apparently no abnormal signs were then found. It is of interest to note that the casualty officer told the patient that his symptoms were probably due to parstelin and referred him to his own general practitioner. The headache continued and was associated with severe neck stiffness. On July 12 he was seen by Dr. L. J. Grant, and a clinical diagnosis of subarachnoid haemorrhage was made. He was admitted to hospital for further investigations. On examination he was alert and cooperative and his blood- pressure was 140/80 mm. Hg. He had severe neck stiffness and a positive Kernig’s sign. The tendon reflexes of the right arm and leg were a little brisker than those of the left and the right plantar response was equivocal. A lumbar puncture was per- formed on July 13, and the cerebrospinal fluid was xantho- chromic with total protein 90 mg. per 100 ml., moderate excess of globulin, 50 red cells per c.mm., and less than 3 lymphocytes per c.mm. An electroencephalogram and skull X-ray were normal. Although the patient had previously had mild occasional headaches, he had never experienced one of this intensity which persisted to some extent for approximately 19 days, but he continued to complain of back pain for a further fortnight. He eventually made a complete recovery. Because of the patient’s age and general condition no further investigations were undertaken. It seems reasonable to conclude that this is another case of intracranial bleeding associated with parstelin administration. National Temperance Hospital, London, N.W.1. DOREEN GREENE.

TRANYLCYPROMINE

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586

distribution are more easily distinguished from pathologicalsequelae.The limitations of frontal-plane electrocardiography

are well evidenced by the paper of Woods et al. and

emphasise the necessity for a better electrocardiographictechnique. Vectorcardiography presents special diffi-culties. These difficulties are overcome with the ABC

display.Department of Physiology,University of Melbourne. E. R. TRETHEWIE.

TRANYLCYPROMINE

SIR,-So far there have been 8 deaths associated withtranylcypromine (’Parnate ’). 3 of the patients whodied were having imipramine at the same time, 2 hadamphetamines, 2 were on tranylcypromine plus trifluo-perazine (’ Parstelin ’), and 1 had tranylcypromine only.Cerebral haemorrhage was confirmed in 3 cases and

suspected in 1. In addition, 3 patients with intracranialbleeding who recovered have been reported, and Dorrell 1 2mentions that there are 4 more cases known but still

unpublished. Many other patients while on treatment withtranylcypromine had sudden attacks of violent and

throbbing headache accompanied by hypertension and atleast some of the following features: acute fear, palpita-tions, tachycardia or bradycardia, nausea, vomiting,giddiness, sweating, photophobia, stiff neck and other

neurological signs, faintness, and collapse.There is no agreement regarding the frequency of the side-

effects. Lees and Burke 3 reported 11 out of 60 patients (18%)in a clinical trial with parnate, but Macdonald 4 reported only14 cases of severe headache in 600 patients treated, andMilligan 5 also mentions a very low incidence. Simultaneousadministration of imipramine (’ Tofranil ’) or amphetaminesseems to be particularly dangerous although Morgan 6 hasreported the case of a patient who received large doses ofparnate and amphetamine without ill-effects.

Blackwell 1 has drawn attention to a possible associationbetween the eating of cheese and the symptoms in patientstaking tranylcypromine and has described 11 patients in whomtypical attacks came on shortly after eating cheese. Womack 9has recorded the case of a healthy youth who died of acutecirculatory collapse less than two hours after eating cheese.

Recently and within a short time 5 patients attending theHill End day hospital who were taking tranylcypromine orphenelzine had typical attacks of severe headache. In view ofthe reports of Blackwell 7 and Womack 9 10 we decided to makea retrospective inquiry into the dietetic habits of these patients.

1. Female, 49, on phenelzine (’Nardil’) 15 mg. t.d.s.and chlordiazepoxide (’ Librium’) 10 mg. t.d.s. for threemonths had a typical crisis at home. She eats cheese abouttwice a month and does not remember whether she hadeaten it before the attack.

2. Female, 47, on phenelzine 30 mg. t.d.s. and

chlordiazepoxide 10 mg. t.d.s. for three weeks had three

very severe attacks at home and a milder one in the dayhospital. She eats cheese almost every day, always with theevening meal. The attacks came at noon or in the morningand not shortly after eating cheese.

3. Female, 40, on parstelin 1 tablet t.d.s. for six monthsfollowed by tranylcypromine 10 mg. t.d.s. and chlordiaze-poxide 10 mg. t.d.s. for ten days had a severe crisis oneevening. She eats cheese almost every evening, but she isquite sure that she did not have cheese that day.

1. Dorrell, W. Lancet, 1963, i, 388.2. Dorrell, W. ibid. Aug. 10, 1963, p. 300.3. Lees, F., Burke, C. W. ibid. 1963, i, 13.4. Macdonald, R. ibid. p. 269.5. Milligan, W. L. ibid. p. 442.6. Morgan, D. H. ibid. p. 389.7. Blackwell, B. ibid. p. 167.8. Blackwell, B. ibid. Aug. 24, 1963, p. 414.9. Womack, A. M. Brit. med. J. Aug. 10, 1963, p. 366.

10. Womack, A. M. Lancet, Aug. 31, 1963, p. 463.

4. Female, 57, on parstelin 1 tablet t.d.s. since Oct. 29,1962. She had an attack on Jan. 8, 1963, in the morning.She is very fond of cheese, but she eats it with the eveningmeal, and, therefore, she had not had it before the attackthat day.

5. Male, 50, an outpatient, on parstelin 1 tablet t.d.s.since Feb. 25, 1963. He had several violent attacks of

throbbing headache between April 3 and July 7. He didnot relate these attacks to parstelin. He often eats cheeseat lunch and is sure that at least three of the attacks took

place after lunch, but he had several other attacks at differenttimes of the day, some of them on days when he had noteaten cheese.There were 9 patients on tranylcypromine during the same

period who did not develop side-effects. Of these, 2 never eatcheese, 1 eats cheese only occasionally, 4 eat cheese 1-4 timesweekly, and 2 eat cheese almost every day. There were 2

patients on phenelzine who did not develop side-effects, ofwhom 1 eats cheese occasionally and the other eats cheesetwice weekly.

Judged by this series, although not extensive or con-clusive enough, one would think that there is no clearrelation between eating cheese and the typical side-effectsof tranylcypromine. Cheese is such a common article ofdiet that obviously most patients on long-term treatmentwith monoamineoxidase inhibitors are bound to eat cheese

during the course of treatment, and, of course, some ofthem will have by coincidence attacks of severe headacheshortly after eating cheese. More research is needed.

Hill End Hospital,St. Albans, Herts. L. ARENILLAS.

SiR,ňThere has been much correspondence in yourcolumns recently describing intracranial bleeding inassociation with the use of tranylcypromine, and I shouldlike to describe one further case lately under our care.A man aged 67 had been depressed for several years after the

death of his wife, and had been treated with various anti-

depressant agents. On June 26, 1963, he was started ontranylcypromine and trifluoperazine (’Parstelin’) by his

general practitioner. On July 7 while in a restaurant he hadvery severe occipital headache which radiated to the foreheadand was associated with vomiting. He was taken to the casualtydepartment of a nearby hospital, but apparently no abnormalsigns were then found. It is of interest to note that the casualtyofficer told the patient that his symptoms were probably due toparstelin and referred him to his own general practitioner. Theheadache continued and was associated with severe neckstiffness. On July 12 he was seen by Dr. L. J. Grant, and aclinical diagnosis of subarachnoid haemorrhage was made. Hewas admitted to hospital for further investigations.On examination he was alert and cooperative and his blood-

pressure was 140/80 mm. Hg. He had severe neck stiffness anda positive Kernig’s sign. The tendon reflexes of the right armand leg were a little brisker than those of the left and the rightplantar response was equivocal. A lumbar puncture was per-formed on July 13, and the cerebrospinal fluid was xantho-chromic with total protein 90 mg. per 100 ml., moderateexcess of globulin, 50 red cells per c.mm., and less than 3lymphocytes per c.mm. An electroencephalogram and skullX-ray were normal.

Although the patient had previously had mild occasionalheadaches, he had never experienced one of this intensity whichpersisted to some extent for approximately 19 days, but hecontinued to complain of back pain for a further fortnight. Heeventually made a complete recovery. Because of the patient’sage and general condition no further investigations were

undertaken.

It seems reasonable to conclude that this is anothercase of intracranial bleeding associated with parstelinadministration.

National Temperance Hospital,London, N.W.1. DOREEN GREENE.