28 August 1971 S.A. MEDICAL JOURNAL 945 As yet there is no generally accepted table for com­ 5. South African Bureau of Standards (1970): SABS Publication 083­ 1970. Pretoria: GOVl Printer. pensation purposes' based, for example on the percentage of 6. Organization for Health Research (T 0) (1963): Geluidspectra hearing impairment and resultant disability, which might 'T1 rt.fdelingSaudiOgrammen in de Nederlandse Indus/rie. The Hague: be calculated by the abovementioned method and related 7. Glorig, A., DLxon Ward, W. and Nixon, l. (1961): Arch. Otolaryng. 74, 413. (Copyright 1961, American Medical Association.) to the wage a worker was earning at the time of examina­ 8. Bell, A. (1966): W.H:O. Public Health Paper 30. Geneva: WHO. 9. Bums, W. and Robmson, D. W. (1970): Hearing and Noise in tion for considering his claim. Although this may be re­ Industry. London: HMSO. garded as desirable, it is not a medical problem and may 10. Organization for Health Research (TNO) (1962): Recommendations for Noise Measurement in the Industry. The Hague: TNO. be left to the appropriate authority in each country. 11. Glorig, A. (1961): 1. Laryng., 75, 447. 12. Laevens, J. (1969): T. soc. Geneesk., 47, 194. 13. American Industrial Hygiene Association (1966): Industrial Noise Manual. Southfield, Mich.: AlliA. I should like to thank Mr G. V. Meij of the South African 14. Lindeman, H. E. and Van Leeuwen, P. (1967): T. soc. Geneesk., 45, Bureau of Standards, Pretoria, for checking the manuscript. 814. 15. National Safety Council (1967): Fundamentals of Industrial H}giene. Chicago: NatIonal Safety Council. 16. Report of the Intersociety Committee (1967): Amer. Industr. Hyg. REFERENCES Assoc. 1., 28, 418. 17. Meij. G. V. (1968): The Certificated Engineer, p. 272. I. S.A. National Council for the Deaf (1962): Report on the Second 18. Mel), G. V., Hendrikse, W. J. and Breed, J. A.: Standardized Loudness National Conference on Noise. Balance Method of Determining Auenuacion of Ear-Protectors. Pretoria: 2. Van der Sandt, W. (1970): S. Afr. Med. l., 44, 558. SABS. 3. International Wrought Copper Council, London (1968): Imroduction 19. Committee on Medical Rating of Physical Impairment AMA (1961): to the Srudy of Noise in Industry. Surrey, UK: Unwin. 1. AIDer. Med. Assoc., 177, 489. (Copyright 1961, American Medical 4. American Academy of Ophthalmology and Otolaryngology (1969): Association.) Guide for Conservation of Hearing in Noise. Rochester. Minn.: AAOO. 20. Heron, T. G. (1968): S. Afr. Med. l., 42, 558. Chlorpromazine, Clotiapine and Thioridazine- A C10mparative Clinical Trial on Bantu Psychotic Patients * A. J. VAN WYK, Professor of Psychiatry, University of Pretoria, AND G. F. T. MARAIS, Psychiatric Clinical Assistant, Weskoppies Hospital, Pretoria SUMMARY No side-effects were seen with thioridazine and extra­ pyramidal side-effects caused by the other two drugs In a non-blind assessment of 3 neuroleptic drugs, chlor­ were easily controlled by dose reduction. promazine (Largactil), thioridazine (Melleril) and c1otia­ pine (Etomine), we found Etomine to be the drug of S. Air. Med. J., 45, 945 (1971). choice when the diagnosis is in doubt between a toxic psychosis or schizophrenia. This drug also offered the Early in 1968, the drug clotiapine (Etomine, Wander) highest discharge rate, 77'7% at 12 weeks compared with became available in South Africa for clinical trials. At that 73'5% in the thioridazine group, and 55'5% in the chlor­ stage the available literature'" indicated that because of its promazine group. quick action, it might be useful in increasing patient turn­ over rate, especially in the Bantu wards where we have a No clouding of consciousness was seen in the clotia­ high admission rate. pine group, whereas it was troublesome in the chlorpro­ mazine group in patients having received high parenteral It was decided to launch a clinical investigation, com­ doses. paring its effects with chlorpromazine and thioridazine, two well-known and often used neuroleptics in the Bantu 'Date received: 26 April 1971. wards. 14 946 S.-A. MEDIESE TYDSKRIF 28 Augustus 1971 METHOD remained symptom free for the following 4 weeks, were they discharged. No patients were discharged on medica­ Because of the administrative and staff shortage problems tion but a letter to the district surgeon stating the treat­ we could not introduce any 'blind' procedures into the ment which had been received, was given to all discharged trial. However, we hoped that by using a fair number of to be handed in to their district surgeon on arrival home. patients and following them through until discharge, we might nevertheless be able to gather enough data for a global evaluation of the 3 drugs. RESULTS All patients were physically healthy adult Bantu males suffering from acute psychoses. No epileptic or depressive Figs. 1 and 2 show the differences in action m the two psychoses were included and on subsequent analysis it main diagnostic categories. was found needful to divide all patients into two broad diagnostic groups, e.g. schizophrenia and toxic psychosis (Table I). ..•...... ;,.;;;./................. TABLE I. NUMBER OF PATIENTS y ••••.•. : -~ . -/ --"" :-~""":: . Treatment Schizophrenia Toxic Total ,//~-------~ psychosis -- Clotiapine c,c' (Etomine) 28 8 36 .:,c, Thioridazine .:, 21. // (Melleril) 21 10 31 :15':/ Chlorpromazine IoII1US >< >< CRLORP1IOMAZUIB (Largactil) 25 9 34 x_>< CLOTHI&PINIl " ••• " THIORIDJ,ZUIII Allocation to either of the 3 drug groups was at random Fig. 1. Results in schizophrenia. and all patients were handled by the same staff and the same clinical investigator throughout the trial. Diagnoses were confirmed before final diagnostic grouping. --?/:::::.~_=-__=__::::.__=-=-_=__...=-::= ..2 Psychosis ratings were done before treatment and there­ after weekly for 12 weeks or until discharge. The psychosis rating scale was a very simplified tabulation of the usual ...-""'" important psychiatric signs and symptoms with which .r········- - . Bantu patients present. All patients were scored from 1 ......... " (normal) through 5 (severely disordered) on 5 diagnostic criteria, e.g. orientation~ insight, delusions, hallucinations and general behaviour. .•.... No patients received concurrent electroconvulsive or ........ antiparkinsonism therapy during the trial. 10 ..... I."llJIU x--x CHLORPllOIUZINB ]1_]1 CLOTIfIAPUI. Dosage ", •.• x TIiIOll.ID£ZI!I!" Toxic All patients received an initial maximum recommended Fig. 2. Results in toxic psychosis. dose of each drug. Dosage was reduced when improve­ ment or side-effects began to occur. Ootiapine: 40 mg t.d.s. oraUy. Because of restlessness It is interesting to note, in the schizophrenic group, a and agitation in 11 patients the initial treatment was definite lag in the chlorpromazine curve below the other limited to a single dose on the first day (120 mg), given two drugs. Also in the toxic group there is a definite lag intravenously, to be followed only on the second day with in the thioridazine curve below the other two drugs. the normal daily dosage orally. When calculating a discharge rate after 12 weeks treat­ Chlorpromazine: 200 mg t.d.s. oraUy. Due to agitation ment we obtained the results shown in Table n. and restlessness, 4 patients received an initial dose of 100 mg intramuscularly, followed after 8 hours and 16 hours with oral medication, to make up the total daily dosage of TABLE 11. PERCENTAGE PATIENTS DISCHARGED 600 mg. Thioridazine: 200 mg t.d.s. oraUy. 10 patients received Toxic Total 300 mg t.d.s. on the first day to alleviate agitatiQn and Treatment psychosis Schizophrenia discharged restlessness. Chlorpromazine 26'1% 29'4% 55'5% Medication was discontinued when patients rated 'symp­ Clotiapine 16'7% 61'0% 77-7% tom free' for 2 consecutive weeks, and only when they Thioridazine ' 21'2% 52'3% 73'5% 28 August 1971 S.A. MEDICAL JOURNAL 947 DISCUSSION that clothiapine (Etomine, Wander) gives rapid response in both schizophrenia and toxic psychoses. By using either of The total rating of all symptoms before beginning treat­ the other two drugs at the time when exact diagnosis is ment (x) was computed for each patient. In addition, their still in doubt, one might find an unsatisfactory response. total rating of all symptoms after 1, 2 and more weeks of Furthermore, an advantage of clotiapine over the observation in hospital was determined. (yi, i = 1, 2, ....). other two drugs is the availability of a safe parenteral To obtain the measure of improvement under drug therapy solution. In none of the 11 patients treated with 120 mg (x - iy).lOO clotiapine intravenously did we notice untoward clinical we computed the rate Zi = . In the graphs side-effects either locally or systemically. They all promptly x ~ 5 calmed down and were put to bed. are represented the mean values of Zi computed from all We did notice an upsetting degree of mental clouding patients observed in week 1. The differences between mean in all 4 patients 24 hours after the intramuscular chlor­ values Zi of the 3 drug groups were then tested by Student's promazine injection. It was so severe that it was only I-test. The small numbers at the beginning and at the with difficulty that any information could be obtained from end of the curves represent the number of patients from them the next day. which the mean was computed. This clouding of consciousness was not present at all in This method has the disadvantage that patients who are patients that had received clothiapine intravenously the cured and discharged from hospital fall out of the cal­ previous day. Although they were heavily sedated, they culation. Their ratings after discharge are not known, and could give a good account and assessment of psychosis it would be wrong to assess them with the minimal rating was therefore much easier with them. for all following weeks. So those discharged early have No extrapyramidal side-effects were noticed in the a negative influence upon the improvement-curves.