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October 1988, Volume 38, Issue 10

Original Article


Muhammad Shafique  ( Departments of Biochemistry, Quaid.i-Azam Medical College and B.V. Hospital, Bahawalpur. )
Iqbal Ahmad Khan  ( Departments of Pathology, Quaid.i-Azam Medical College and B.V. Hospital, Bahawalpur. )
Matloob Hussain Akhtar  ( PMRC Research Centre, Quaid.i-Azam MedicalCollege and B.V. Hospital, Bahawalpur. )
Ibrar Hussain  ( Departments of Psychiatry, Quaid.i-Azam Medical College and B.V. Hospital, Bahawalpur. )


Serum lipids and Jipoprotein levels were determined in 35 schizophrenics treated with Phenothia­zine, 30 with butyrophenone and 22 with both drugs for six to twelve months. Total cholesterol, VLD L — cholesterol and LDL cholesterol levels were significantly elevated in patients on phenothiazine and LDL cholesterol in patients on butyrophenone. VLD L and LD L — cholesterol levels were significantly higher and HDL cholesterol levels lower in patients on combined therapy (JPMA 38 : 259 1988).


Heavy doses of tranquilizers for prolonged periods are used for the treatment of Schizopbrema. Phenothiazines and Butyrophenones alone or in combination are known to affect serum lipid levels.1-7 Except for occasional reports8, data on -biochemical profile of Schizophrenics in Pakistan is scarce. This study reports serum lipids and lipoprotein levels in Sthizophrenics treated with major tranquilizers.


Eighty seven male schizophrenics attending Psychiatric outpatient department of Bahawal Victoria Hospital were selected for this study. Their ages ranged from 30 . 50 years and they had been regularly receiving major tranquilizers for 6 — 12 months. Thirty five were on Chior­promazine (300 — 500 mg/day), 30 on Halo­peridol (10 — 30 mg/day) and 22 on a com­bined therapy. None had been taking other medi­cations known to affect lipid levels. Patients with complications including diabetes mellitus and liver disease were excluded. Thirty male subjects of comparable age group and socioeconomic status, who were free from any physical or mental illness, served as controls.
Blood samples were drawn from all these cases after an overnight fast. The serum was separated and analysed for total lipids by sufo­phosphovanillin reaction9, total cholesterol by Watson’s10, triacyiglycerol by the method of Giegel et al11, HDL-cholesterol by Lopes- Virellatechnique12 and LDL-cholesterol by Burstein and Samaille’s method13. VLDL- cholesterol was calculated with the help of Wilson’s formula14. Statistical differences between mean values of results were assessed by student’s ‘t’ test.


The age and weight were similar for the patient groups and controls (Table-I).

There was a significant rise in mean total serum cholesterol concentrations (P< 0.05) in phen­othiazine group (Table II). The mean total choIes~ terol concentrations in the patients on butyro­phenone and on combined therapy, were also higher than in the controls, but the difference was not significant. There was non-significant difference in the levels of total lipids and triacy­iglycerol in all patients as compared to that of control group (Table II).

There was a significant rise in VLDL­cholesterol (P < 0.05) and LDL-cholesterol (P<0.02) in patients on phenothiazine but the reduction in HDL-cholesterol concentration was not significant (Table III)

in group of patients TABLE-l. General characteristics including number, Age,Wt. of Controls and Schizophrenic Patients treated with major Tranquilizers. Values represent Mean S.D. on butyrophenone. Patients on combined therapy (phenothiazine and butyrophenone) had signi­ficantly higher levels of VLDL-cholesterol, (P <0.02), LDL-cholesterol (P<0.01) and signi­fIcantly lower levels of HDL-cholesterol (P<0.05) than the contrql group (Table III).


The mechanism by which major tranqui­lizers disturb lipid levels is not yet established. Chiorpromazine has a strong adrenergic blocking action and butyrophenones have also been reported to block the central effects of catechola­ mines15.. The patients who receive B-blockers have a higher serum lipids, which partially result from increased free fatty acids release from the adipose tissue16. Our results indicate that there was significant increase in total cholesterol and VLDL­cholesterol concentrations in the phenothiazine group which confinns the previous results1. Phenotbiazines in our study were also found to be associated with significant rise in LDL-cholesterol and non-significant fall in HDL-cholesterol values which were not in agreement with the latest study of Sasaki et ap who observed no significant dif­ference in mean LDL-cholesterol and significant reduction in HDL.cholesterol as compared to controls. The significant elevation in the concen­tration of tricyiglycerol was demonstrated pre­viously with the use of phenothiazines3,7 which is not supported by our study. Total lipids were estimated but both the drugs did not affect thejr levels significantly.
Butyrophenones have been reported to lower serum total cholesterol6 and HDL-choles­terol7 significantly in men but in our patients, butyrophenone has not been shown to be associated with significant changes in total choles­terol, VLDLcholesterol, HDL-cholesterol and triacylglycerol. But why butyrophenone only increased LDL-cholesterol fraction is not known.
In our study, the patients receiving mixed therapy, both a phenothiazine and butyrophenone had higher levels of VLDL-cholesterol, LDL­cholesterol and lower levels of HDL-cholesterol. This may be due to prolonged period of therapy.


1. Clark, M. , Dubowski, K. and Colmore, J. The effect of chiorpromazune on serum cholesterol in chronic schizophrenic patients. Clin. Phar­macol. Ther., 1970; 11:883.
2. Clark, M,L. and Johnson, P.C. Amenorrhea and elevated level of serum cholesterol produced by trifluomethylated phenothiazine (SKF 5354—A). 3. Clin. Endocrinol. Metab., 1960; 20:641.
3. Sasaki, J., Kumagae, G., Sata, T., Ikeda, M., Tsutsumi, S. and Arakawa, K. Seasonal variation of serum high density lipoprotein cholesterol levels in men. Atherosclerosis, 1983; 48: 167.
4. Bennett, J.L., and Hamilton, C.D. Effects of chlorpromazine in combination with activating drugs on thyroid function tests. J. Neuropsy­chiatiy,1961;3 :118.
5. Sasald, J. , Kumagae, G., Sata, T., Kuramitsu, M. and Arakawa, K. Decreased concentration of high density lipoprotein cholesterol in schizo­phrenic patients treated with phenothiazines. Atherosclerosis, 1984; 5:163.
6. Simpson, G.M. and Cooper, T.B. The effect of three butyrophenones on serum cholesterol levels. Curr. Ther. Res., 1966; 8:249.
7. Sasaki, J., Funakoshi, M. and Arakawa, K. Lipids and apolipoproteins in patients treated with major tranquilizers. Clin. Pharmacol., Ther., 1985; 37: 684.
8. Zaidi, M.H.,Tareen, I.A.K., Tayyab,M. and Khan H. Biochemical profile of schizophrenics. Pakistani. Med. Res., 1986; 25:14.
9. Zoilner, N. and Kirsch, K. Zeitsçhiift fur, die, Gasamat. Experimentelle medizin, 1962; 135: 545.
10. Watson, D. Simple method for the determination of serum cholesterol. Clin. Chim. Acta, 1960; 5:637.
11. Gieqel, J.L., Ham, A.B, and Clema, W. Manual and semi-automated procedure for measurements of triglycerides in serum. Clin. Chem., 1975; 21: 1575.
12. Lopes-Virella, M.F., Stone, P., Ellis, S. and Coiweil, LA. Cholesterol determination in high-density lipoproteins separated by three different methods, Clin. Chem., 1977; 23 : 882.
13. Burstein, M. and Samaille, J. Colorimetric methods for the determination of low density lipoproteins. La Press Med., 1958; 66 : 974.
14. Wilson, P.F.W., Zech, L.A. and Gregg, R.E. Estimation of VLDL— cholesterol in hyperli­pidemia. Clin. Chem. Acta, 1979; 18: 499.
15. Goodman, L.S., and Gilman, A. The pharmacolo­gical basis of therapeutics. 4th ed. New York, Macmillan, 1970, p. 155.
16. Hussar, A.E. Coronary heart disease in chronic schizophrenic patients. A clinicopathologic study. Circulation, 1965; 31: 919.

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