- Email: [email protected]
TRANQUILLISERS IN PSYCHIATRY
281 and treated in every respect as. rheumatic carditis. It should be emphasised that steroid therapy is not a routine treatment in infections. It can be used without risk of damage only under protection of high doses of penicillin.
regarded
Infectious Diseases Hospital,
EVA PARKAS.
Budapest.
TRANQUILLISERS IN PSYCHIATRY
SIR,-Iwould like to make some comments on your leading article.1 You state: As regards the third (miscellaneous) group of tranquillisers, opinion is unanimous only about their ineffectiveWhile most tranquillisers other than ness in schizophrenia." the phenothiazine and reserpine derivatives have been shown to be of no value in schizophrenia, work in the past few years indicates that meprobamate may be effective in the treatment of psychoses. The effect of meprobamate on delusions and "
hallucinations is not well substantiated; but the drug appears effective in controlling restlessness, agitation, and tension in schizophrenic patients.2-5 Many observers noted that patients refractory to other tranquillisers (such as chlorpromazine or
reserpine) may respond to meprobamate alone, or may respond after meprobamate has been added to their previous regimen. 24 6v I would also take issue with your statement that " most agree that tranquillisers have proved a failure in the treatment of neuroses ". Data are still inadequate for evaluating the recently introduced minor tranquillisers ; not so with meprobamate. More than 2500 papers on meprobamate have been published in the literature in the past 5 years, and at least 65 of these reported double-blind investigations. Analysis of these studies demonstrated that when clinical evaluation was carried out for long enough, studies clearly defined, indications rationally chosen, experiments well designed, and patients closely observed, the therapeutic effectiveness of meprobamate in the neuroses was unequivocal. Its action could be clearly differentiated from placebo effects which wore off with continued administration.8-11 Scepticism about the value of tranquillisers may be fashionable. Time may well reveal meprobamate as one of the enduring drugs of medicine.
psychiatrists would
Cranbury, Jersey.
New
F. M. BERGER President, Wallace Laboratories.
LIFE AT HIGH ALTITUDES
SIR,-Readers of your leading article (Dec. 31)
may be
interested to know that students and staff of The Middle-
Hospital organised a high-altitude physiological expedition during the summer of 1960. An unbroken period of 24 days was spent at the Vallot Observatory at an altitude of 14,300 ft. on one of the ridges of Mont Blanc. The party was composed of 4 men and 3 women, and it is probable that few have previously spent such a long period at a similar height on this mountain. Mounsex
taineers will know that last summer was notable for bad weather in the Alps, and our party experienced a number of protracted blizzards and gained valuable experience in mountain-rescue work and in the treatment of cold injury in some of those to whom succour was given. The party ascended by helicopter to avoid the disturbing influence of exercise on acclimatisation to altitude, and to 1. Lancet, 1960, ii, 855. 2. Hollister, L. E., Elkins, H., Hiler, E. G., St. Pierre, R. Ann. N.Y. Acad. Sci. 1957, 67, 789. 3. Laird, D. M., Angelo, J. N., Hope, J. M. Dis. nerv. Syst. 1957, 18, 346. 4. McLaughlin, B. E. Penn. med. J. 1957, 60, 989. 5. Tucker, K., Wilensky, H. Amer. J. Psychiat. 1957, 113, 698. 6. Barsa, J. A. ibid. 1958, 115, 79. 7. Tybring, G. B. Wis. med. J. 1957, 56, 430. 8. Rickels, K., Clark, T. W., Ewing, J. H., Klingensmith, W. C., Morris, H. M., Smock, C. D. J. Amer. med. Ass. 1959, 171, 1649. 9. Hollister, L. E., Stannard, A. N., Drake, C. F. Dis. nerv. Syst. 1956,
17, 288.
10. Zukin, P., Arnold, De V. G., Kessler, C. R. 129, 193. 11. Brick, H., Doub, W. H., Jr., Perdue, W. 4, 48.
J.
Dis.
1959,
Ther.
1958,
nerv. ment.
C. J.
soc.
rapid transition from normal levels to the altitude at which was carried out. Only 1 member had been as high or higher before; but our experiences at height contrasted with those often recorded. No-one was ill, and all took an active part in transporting almost a ton of stores and equipment to the observatory from where the helicopter landed on the ridge above. This would have been a tough enough job at sealevel in view of the steep, iced slopes to be negotiated with heavy loads. It was not until the morning after our arrival that we became ill; and then the outstanding feature was headache, and ensure
the study
not nausea.
A full programme was undertaken and associated laboratory work is still in progress, but it is already evident that the efforts of the organisers of the expedition were well worth while. An account of the non-scientific aspects of the undertaking has appeared 1; and scientific reports are being prepared. The Middlesex Hospital, E. S. WILLIAMS. London, W.1.
ENTERIC-COATED TABLETS SIR,-In their letter of Jan. 7, Mr. Pirnie and Dr. Staffurth drew attention to the failure of certain entericcoated potassium tablets to dissolve, and suggested that
the British
Pharmacopmia standards should be revised. We recently completed a trial of aspirin coated with a celluloseester ; and our experience was not discouraging. An enteric coat is designed to impede dissolution in the stomach and hence avoid gastric irritation, while allowing to occur in the small bowel. Solution of the coat in the intestine should not be too prompt since pyloric renux may nullify its protective effect.2 To test the protective effect of the coating, we aspirated gastric contents at half-hourly intervals for 21/2 hours from 6 subjects who had taken six coated aspirin tablets ( ’Nu-seals’ ), each of 300 mg. aspirin. No salicylate was detected in any aspirate. Next, 9 subjects took six specially prepared barium-containing enteric-coated tablets before the first meal of the day, and the tablets were observed by abdominal radiography over nine hours or until they disappeared. Although the time taken for the tablets to leave the stomach varied considerably, they remained intact, with the exception of one which was breaking up at 6 hours. Intact tablets were never seen elsewhere than in the stomach; and there was good evidence that disintegration occurred fairly promptly beyond the pylorus. To obtain evidence that aspirin was adequately absorbed after release, plasma-salicylate levels were measured after a single dose of 1800 mg. aspirin, taken either as soluble aspirin tablets B.P., or as the coated preparation. Absorption was variable with both preparations; but the plasma levels were broadly comparable, although slightly lower over the first 6-8 hours with the enteric-coated tablets. In random bloodsamples from patients on maintenance treatment with 1800 mg. of aspirin b.d. the range of plasma-levels noted was about the same whether the preparation was soluble aspirin or entericcoated. 60 patients, mostly with rheumatoid arthritis, were treated with coated tablets, the dose varying according to their needs between four and eight tablets twice daily; none reported epigastric pain, nausea, vomiting, or gastrointestinal hmmorrhage. But 3 complained of lower abdominal pain about 2 hours after administration, which was ascribed to irritation of the lower bowel. We concluded that these enteric-coated tablets were a satisfactory means of carrying out high-dosage
break-up
salicylate therapy. We entirely agree that high standards should be set for the enteric coating of tablets, especially as it appears that such standards are attainable. But apart from poor absorption with certain types of coat, it does seem that many past disappointments resulted from expectations which the coats are not designed to fulfil. For instance, while they may delay absorption of a drug, they will not necessarily prolong the period of absorption or the therapeutic effect. Coated tablets are also susceptible to such factors as gastric delay, which must restrict 1. 2.
Williams, E. S., Edwards, R. Middx Hosp. J. 1960, 60, 167. Lazarus, J., Cooper, J. J. Pharm., Lond. 1959, 11, 257.
regarded
Infectious Diseases Hospital,
EVA PARKAS.
Budapest.
TRANQUILLISERS IN PSYCHIATRY
SIR,-Iwould like to make some comments on your leading article.1 You state: As regards the third (miscellaneous) group of tranquillisers, opinion is unanimous only about their ineffectiveWhile most tranquillisers other than ness in schizophrenia." the phenothiazine and reserpine derivatives have been shown to be of no value in schizophrenia, work in the past few years indicates that meprobamate may be effective in the treatment of psychoses. The effect of meprobamate on delusions and "
hallucinations is not well substantiated; but the drug appears effective in controlling restlessness, agitation, and tension in schizophrenic patients.2-5 Many observers noted that patients refractory to other tranquillisers (such as chlorpromazine or
reserpine) may respond to meprobamate alone, or may respond after meprobamate has been added to their previous regimen. 24 6v I would also take issue with your statement that " most agree that tranquillisers have proved a failure in the treatment of neuroses ". Data are still inadequate for evaluating the recently introduced minor tranquillisers ; not so with meprobamate. More than 2500 papers on meprobamate have been published in the literature in the past 5 years, and at least 65 of these reported double-blind investigations. Analysis of these studies demonstrated that when clinical evaluation was carried out for long enough, studies clearly defined, indications rationally chosen, experiments well designed, and patients closely observed, the therapeutic effectiveness of meprobamate in the neuroses was unequivocal. Its action could be clearly differentiated from placebo effects which wore off with continued administration.8-11 Scepticism about the value of tranquillisers may be fashionable. Time may well reveal meprobamate as one of the enduring drugs of medicine.
psychiatrists would
Cranbury, Jersey.
New
F. M. BERGER President, Wallace Laboratories.
LIFE AT HIGH ALTITUDES
SIR,-Readers of your leading article (Dec. 31)
may be
interested to know that students and staff of The Middle-
Hospital organised a high-altitude physiological expedition during the summer of 1960. An unbroken period of 24 days was spent at the Vallot Observatory at an altitude of 14,300 ft. on one of the ridges of Mont Blanc. The party was composed of 4 men and 3 women, and it is probable that few have previously spent such a long period at a similar height on this mountain. Mounsex
taineers will know that last summer was notable for bad weather in the Alps, and our party experienced a number of protracted blizzards and gained valuable experience in mountain-rescue work and in the treatment of cold injury in some of those to whom succour was given. The party ascended by helicopter to avoid the disturbing influence of exercise on acclimatisation to altitude, and to 1. Lancet, 1960, ii, 855. 2. Hollister, L. E., Elkins, H., Hiler, E. G., St. Pierre, R. Ann. N.Y. Acad. Sci. 1957, 67, 789. 3. Laird, D. M., Angelo, J. N., Hope, J. M. Dis. nerv. Syst. 1957, 18, 346. 4. McLaughlin, B. E. Penn. med. J. 1957, 60, 989. 5. Tucker, K., Wilensky, H. Amer. J. Psychiat. 1957, 113, 698. 6. Barsa, J. A. ibid. 1958, 115, 79. 7. Tybring, G. B. Wis. med. J. 1957, 56, 430. 8. Rickels, K., Clark, T. W., Ewing, J. H., Klingensmith, W. C., Morris, H. M., Smock, C. D. J. Amer. med. Ass. 1959, 171, 1649. 9. Hollister, L. E., Stannard, A. N., Drake, C. F. Dis. nerv. Syst. 1956,
17, 288.
10. Zukin, P., Arnold, De V. G., Kessler, C. R. 129, 193. 11. Brick, H., Doub, W. H., Jr., Perdue, W. 4, 48.
J.
Dis.
1959,
Ther.
1958,
nerv. ment.
C. J.
soc.
rapid transition from normal levels to the altitude at which was carried out. Only 1 member had been as high or higher before; but our experiences at height contrasted with those often recorded. No-one was ill, and all took an active part in transporting almost a ton of stores and equipment to the observatory from where the helicopter landed on the ridge above. This would have been a tough enough job at sealevel in view of the steep, iced slopes to be negotiated with heavy loads. It was not until the morning after our arrival that we became ill; and then the outstanding feature was headache, and ensure
the study
not nausea.
A full programme was undertaken and associated laboratory work is still in progress, but it is already evident that the efforts of the organisers of the expedition were well worth while. An account of the non-scientific aspects of the undertaking has appeared 1; and scientific reports are being prepared. The Middlesex Hospital, E. S. WILLIAMS. London, W.1.
ENTERIC-COATED TABLETS SIR,-In their letter of Jan. 7, Mr. Pirnie and Dr. Staffurth drew attention to the failure of certain entericcoated potassium tablets to dissolve, and suggested that
the British
Pharmacopmia standards should be revised. We recently completed a trial of aspirin coated with a celluloseester ; and our experience was not discouraging. An enteric coat is designed to impede dissolution in the stomach and hence avoid gastric irritation, while allowing to occur in the small bowel. Solution of the coat in the intestine should not be too prompt since pyloric renux may nullify its protective effect.2 To test the protective effect of the coating, we aspirated gastric contents at half-hourly intervals for 21/2 hours from 6 subjects who had taken six coated aspirin tablets ( ’Nu-seals’ ), each of 300 mg. aspirin. No salicylate was detected in any aspirate. Next, 9 subjects took six specially prepared barium-containing enteric-coated tablets before the first meal of the day, and the tablets were observed by abdominal radiography over nine hours or until they disappeared. Although the time taken for the tablets to leave the stomach varied considerably, they remained intact, with the exception of one which was breaking up at 6 hours. Intact tablets were never seen elsewhere than in the stomach; and there was good evidence that disintegration occurred fairly promptly beyond the pylorus. To obtain evidence that aspirin was adequately absorbed after release, plasma-salicylate levels were measured after a single dose of 1800 mg. aspirin, taken either as soluble aspirin tablets B.P., or as the coated preparation. Absorption was variable with both preparations; but the plasma levels were broadly comparable, although slightly lower over the first 6-8 hours with the enteric-coated tablets. In random bloodsamples from patients on maintenance treatment with 1800 mg. of aspirin b.d. the range of plasma-levels noted was about the same whether the preparation was soluble aspirin or entericcoated. 60 patients, mostly with rheumatoid arthritis, were treated with coated tablets, the dose varying according to their needs between four and eight tablets twice daily; none reported epigastric pain, nausea, vomiting, or gastrointestinal hmmorrhage. But 3 complained of lower abdominal pain about 2 hours after administration, which was ascribed to irritation of the lower bowel. We concluded that these enteric-coated tablets were a satisfactory means of carrying out high-dosage
break-up
salicylate therapy. We entirely agree that high standards should be set for the enteric coating of tablets, especially as it appears that such standards are attainable. But apart from poor absorption with certain types of coat, it does seem that many past disappointments resulted from expectations which the coats are not designed to fulfil. For instance, while they may delay absorption of a drug, they will not necessarily prolong the period of absorption or the therapeutic effect. Coated tablets are also susceptible to such factors as gastric delay, which must restrict 1. 2.
Williams, E. S., Edwards, R. Middx Hosp. J. 1960, 60, 167. Lazarus, J., Cooper, J. J. Pharm., Lond. 1959, 11, 257.