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ORAL CONTRACEPTIVES AND DEPRESSION
1209 LENGTH OF STAY OF
while
51 PATIENTS WITH DEPRESSION OR MANIA
were receiving lithium carbonate. The favourable in the 51 Camberwell patients seems to be a consequence of the exclusion of patients who had been admitted only once or not at all during 1965 and 1966 (see accompanying figure). The data on the length of stay are presented in the accompanying table. The division into subgroups of depression had perforce to depend on the final diagnosis reached by different psychiatrists, but whatever their shortcomings these data show that the patients with reactive depression had a worse prognosis than did those patients with endogenous or unspecified depression. The average length of stay of patients with endogenous depression during 1965 and 1966 was 146.6 days (73-3 days per year) and during 1967 and 1968 72’4 (36-2 days per year). Therefore, these patients stayed 74’2 days less during the latter period. This result is statisti-
they
outcome
cally significant (p < 002). These data are presented to show that the remarkable results of Baastrup and Schou could possibly have been arrived at by the design of the experiment. This would not be harmful if psychiatrists viewed the use of lithium only with cautious optimism, but many still seem to have an unjustified conviction of its prophylactic value. Institute of Psychiatry, London S.E.5.
B. M. SARAN.
ORAL CONTRACEPTIVES AND DEPRESSION SIR,-In 1967 two correspondents 12 pointed out the possible association of depression with the taking of oral contraceptives, and later the same year Daly et awl. suggested some possible reasons for this. I should like to suggest a further possible explanation for the precipitation or aggravation of depression in certain women taking oral contraceptives. Dewhurst ’has postulated that a dysfunction of tryptophan metabolism is implicated in the onset of certain types of depression, and it has also been suggested that one of the mechanisms involved is a shift of tryptophan metabolism from the serotonin pathway to the kynurenine pathway.5-7 Price et a].’ have shown that the use of steroid hormones for ovulation control results in a disturbance of tryptophan metabolism along the kynurenine pathway. Similar disturbances occur during pregnancy, just before menstruation, and with the administration of cortisone.5 Since cortisone, oral contraceptives, and pregnancy all have in common the possibility of 1. Tharkudas, H. Lancet, 1967, i, 1164. 2. McGregor, C. M. ibid. p. 1231. 3. Daly, R. J., Kane, F. J., Jr., Ewing, J. A. ibid. 1967, ii, 444. 4. Dewhurst, W. G. Nature, Lond. 1968, 218, 1130. 5. Green, A. R., Curzon, G. ibid. 1968, 220, 1095. 6. Mandell, A. J., Spooner, C. E. Science, N.Y., 1968, 162, 1442. 7. Lapin, L. P., Oxenkrug, G. F. Lancet, Jan. 18, 1969, p. 132. 8. Price, J. M., Thornton, M. J., Mueller, L. M. Am. J. clin. Nutr.
20, 452.
1967,
severe depression in susceptible patients, and are also known to upset tryptophan metabolism, then, if tryptophan metabolism is shown to be associated with control of mood, it would be more credible that these effects are mediated in some way through an upset of tryptophan metabolism than to believe that this is just mere coincidence. The fact that progestogens given alone do not cause this disturbance of tryptophan metabolism9 and are also reported not to cause depression 10 would lend weight to this view. Whereas the disturbance of tryptophan metabolism by hydrocortisone is supposedly caused by the activation of tryptophan pyrollase5 oral contraceptives (and presumably pregnancy and menstruation) apparently create a functional deficiency of pyridoxine, for the disturbance of tryptophan metabolism along the kynurenine pathway is corrected by giving supplementary pyridoxine.8 Apparently the steroid hormones have the effect of loosening the binding of some pyridoxine to its enzyme. Since the decarboxylation of tryptophan to tryptamine and serotonin is also dependent on pyridoxine it would be interesting to know whether giving supplemental pyridoxine would protect patients on oral contraceptives from becoming depressed. In this regard one patient in her 4th month of pregnancy had her symptoms of depression and irritability completely resolved five days after starting on pyridoxine 50 mg. daily. Similarly, another young woman who became extremely irritable and difficult to live with during the second half of her menstrual cycle ceased to have these episodes soon after starting on pyridoxine. These are only straws in the wind, but it does seem that the matter merits further investigation.
precipitating
Madison, Wisconsin,
FRANK WINSTON.
U.S.A.
EARLY TRAUMATIC EPILEPSY
SIR,-Of the patients described by Professor Jennett (May 24, p. 1023), how many had their first fits within 1 week after blunt head injuries: 273 (tables II, III) or 331 (table v) ? How many in weeks 2-8: 66 (tables 11, III) or 41 (table v) ? How many in weeks 1-8: 331 (the opening words of the paper), 339 (paragraph 3, tables 11, III), 372 (table v) ? Granted, one can guess, by weighing evidence, which the correct figures probably are; but who wants that task ? In table vi where do all those patients with " No early epilepsy " come from ? Table iv shows that, of patients having their first fits in weeks 2-8, 41 were followed up for 4 years, and, of those having them more than 3 months after injury, 158 were followed up for 4 years, making a total of only 199 (or 223 even if 24 with missile injuries are added). Those followed up for
if
more
than 4 years,
as
in table vi, should therefore be
anything fewer than 199. How can they be 240 ? Why are patients who had their first fits up to
8 weeks after injury, and those who had them more than 3 months after injury, selected for discussion ? Why exclude the period from 9 to 12 weeks ? Or was it included for the purposes of table vi only, and is that how the figure 240 is reached ? London S.W.20. JOHN PENMAN.
** This letter has been shown to Professor Jennett, who writes as follows: Dr. Penman is correct in one point; 331 in the summary should read 339. As for the rest of his comments I can only regret the unhappy outcome of my attempt to make an argument clear by omitting details which seemed irrelevant to the main theme. I can, however, assure him that each table is internally consistent. But attempts to compare different tables can lead only to confusion; thus tables n and ill include all cases in a consecutive series, table iv is limited to cases followed for 4 years, whilst table v excludes those with "
9. Brown, R. R., Rose, P. P., Price, J. M., Wolff, H. Proc. N. Y. Acad. Sci. (in the press). 10. Carranza-Acevedo, J. Lancet, 1967, ii, 104.
while
51 PATIENTS WITH DEPRESSION OR MANIA
were receiving lithium carbonate. The favourable in the 51 Camberwell patients seems to be a consequence of the exclusion of patients who had been admitted only once or not at all during 1965 and 1966 (see accompanying figure). The data on the length of stay are presented in the accompanying table. The division into subgroups of depression had perforce to depend on the final diagnosis reached by different psychiatrists, but whatever their shortcomings these data show that the patients with reactive depression had a worse prognosis than did those patients with endogenous or unspecified depression. The average length of stay of patients with endogenous depression during 1965 and 1966 was 146.6 days (73-3 days per year) and during 1967 and 1968 72’4 (36-2 days per year). Therefore, these patients stayed 74’2 days less during the latter period. This result is statisti-
they
outcome
cally significant (p < 002). These data are presented to show that the remarkable results of Baastrup and Schou could possibly have been arrived at by the design of the experiment. This would not be harmful if psychiatrists viewed the use of lithium only with cautious optimism, but many still seem to have an unjustified conviction of its prophylactic value. Institute of Psychiatry, London S.E.5.
B. M. SARAN.
ORAL CONTRACEPTIVES AND DEPRESSION SIR,-In 1967 two correspondents 12 pointed out the possible association of depression with the taking of oral contraceptives, and later the same year Daly et awl. suggested some possible reasons for this. I should like to suggest a further possible explanation for the precipitation or aggravation of depression in certain women taking oral contraceptives. Dewhurst ’has postulated that a dysfunction of tryptophan metabolism is implicated in the onset of certain types of depression, and it has also been suggested that one of the mechanisms involved is a shift of tryptophan metabolism from the serotonin pathway to the kynurenine pathway.5-7 Price et a].’ have shown that the use of steroid hormones for ovulation control results in a disturbance of tryptophan metabolism along the kynurenine pathway. Similar disturbances occur during pregnancy, just before menstruation, and with the administration of cortisone.5 Since cortisone, oral contraceptives, and pregnancy all have in common the possibility of 1. Tharkudas, H. Lancet, 1967, i, 1164. 2. McGregor, C. M. ibid. p. 1231. 3. Daly, R. J., Kane, F. J., Jr., Ewing, J. A. ibid. 1967, ii, 444. 4. Dewhurst, W. G. Nature, Lond. 1968, 218, 1130. 5. Green, A. R., Curzon, G. ibid. 1968, 220, 1095. 6. Mandell, A. J., Spooner, C. E. Science, N.Y., 1968, 162, 1442. 7. Lapin, L. P., Oxenkrug, G. F. Lancet, Jan. 18, 1969, p. 132. 8. Price, J. M., Thornton, M. J., Mueller, L. M. Am. J. clin. Nutr.
20, 452.
1967,
severe depression in susceptible patients, and are also known to upset tryptophan metabolism, then, if tryptophan metabolism is shown to be associated with control of mood, it would be more credible that these effects are mediated in some way through an upset of tryptophan metabolism than to believe that this is just mere coincidence. The fact that progestogens given alone do not cause this disturbance of tryptophan metabolism9 and are also reported not to cause depression 10 would lend weight to this view. Whereas the disturbance of tryptophan metabolism by hydrocortisone is supposedly caused by the activation of tryptophan pyrollase5 oral contraceptives (and presumably pregnancy and menstruation) apparently create a functional deficiency of pyridoxine, for the disturbance of tryptophan metabolism along the kynurenine pathway is corrected by giving supplementary pyridoxine.8 Apparently the steroid hormones have the effect of loosening the binding of some pyridoxine to its enzyme. Since the decarboxylation of tryptophan to tryptamine and serotonin is also dependent on pyridoxine it would be interesting to know whether giving supplemental pyridoxine would protect patients on oral contraceptives from becoming depressed. In this regard one patient in her 4th month of pregnancy had her symptoms of depression and irritability completely resolved five days after starting on pyridoxine 50 mg. daily. Similarly, another young woman who became extremely irritable and difficult to live with during the second half of her menstrual cycle ceased to have these episodes soon after starting on pyridoxine. These are only straws in the wind, but it does seem that the matter merits further investigation.
precipitating
Madison, Wisconsin,
FRANK WINSTON.
U.S.A.
EARLY TRAUMATIC EPILEPSY
SIR,-Of the patients described by Professor Jennett (May 24, p. 1023), how many had their first fits within 1 week after blunt head injuries: 273 (tables II, III) or 331 (table v) ? How many in weeks 2-8: 66 (tables 11, III) or 41 (table v) ? How many in weeks 1-8: 331 (the opening words of the paper), 339 (paragraph 3, tables 11, III), 372 (table v) ? Granted, one can guess, by weighing evidence, which the correct figures probably are; but who wants that task ? In table vi where do all those patients with " No early epilepsy " come from ? Table iv shows that, of patients having their first fits in weeks 2-8, 41 were followed up for 4 years, and, of those having them more than 3 months after injury, 158 were followed up for 4 years, making a total of only 199 (or 223 even if 24 with missile injuries are added). Those followed up for
if
more
than 4 years,
as
in table vi, should therefore be
anything fewer than 199. How can they be 240 ? Why are patients who had their first fits up to
8 weeks after injury, and those who had them more than 3 months after injury, selected for discussion ? Why exclude the period from 9 to 12 weeks ? Or was it included for the purposes of table vi only, and is that how the figure 240 is reached ? London S.W.20. JOHN PENMAN.
** This letter has been shown to Professor Jennett, who writes as follows: Dr. Penman is correct in one point; 331 in the summary should read 339. As for the rest of his comments I can only regret the unhappy outcome of my attempt to make an argument clear by omitting details which seemed irrelevant to the main theme. I can, however, assure him that each table is internally consistent. But attempts to compare different tables can lead only to confusion; thus tables n and ill include all cases in a consecutive series, table iv is limited to cases followed for 4 years, whilst table v excludes those with "
9. Brown, R. R., Rose, P. P., Price, J. M., Wolff, H. Proc. N. Y. Acad. Sci. (in the press). 10. Carranza-Acevedo, J. Lancet, 1967, ii, 104.