Acta psychiat. scand. (1979) 60, 477-482 School of Pharmacy (Head: A. Kreiser), Hebrew University of Jerusalem, Jerusalem, Israel
Prescribing patterns in psychiatric hospitals in Israel S. YOSSELSON-SUPERSTINE, D. STERNXK AND D. LIEBENZON A survey conducted by pharmacists working in four psychiatric hospitals in Israel to assess the prescribing of psychotropic drugs revealed that polypharmacy was common: patients were receiving up to 11 different drugs and up to six different psychotropic drugs. The average number of psychotropic drugs per patient was two. The most popular combinations of drugs used were; one containing an antipsychotic drug(s) and an antiparkinson drug@)and the other was a combination of more than one antipsychotic agent. Up to 30 doses per day were taken orally by one patient. Drugs that could have easily been administered on a once-a-day time schedule were often administered several times a day. Differences in prescribing patterns in the various hospitals and often times on different wards of the same institution could more easily be attributed to different educational backgrounds, habits and personal beliefs and perhaps the physician’s experience as well, rather than to the types of patients treated. Key words: Antiparkinson drugs - antipsychotics- drug prescribing patterns - psychotropic drugs - survey.
Overuse and misuse of psychotropic medication have been the subject of recent communications initiated by pharmacists as well as by physicians or public health scientists. An extensive review of US. hospital surveys of prescribing practices with psychotropic drugs (Prien et al. (1978)), although criticizing the conclusions, reveals that approximately one third of the patients were treated with polypharmacy, about 30 % were receiving frequent daily doses, antiparkinson drugs were overused, dosage was too low or too high and only a very few patients were on drug holidays. A study conducted among psychiatric patients in Helsinki (Hemminki (1977)) disclosed that 69 7% of the patients received more than one psychotropic drug with an average of 2.1 different psychotropic drugs per patient. An assessment of prescribing of psychotropic drugs by general practitioners in England (Tyrer (1978)) pinpointed prolonged duration of treatment, incorrect dosage and pointless polypharmacy as well. In the United States, where the practice of Clinical Pharmacy has been well established, psychiatric wards and institutions are among the fist to benefit from drug consultations given by the pharmacists who specialize in the pharmacology and the pharmacokinetics of psychotropic drugs. It has been shown (Ellenor (1977), Chien et al. (1978)) that this kind of consultation significantly reduced irrational psychopharmacotherapy. 0001-690X/79/100477-06$02.50/0@ 1979 Munksgaard, Copenhagen
478
Table 1. Demographic and diagnostic information Hospital No. of patients
A 109
% female
B 158
C 76
D 222
38.6
17.6
44.3
44.5 (16-79)
34.8 (14-73)
45.5 (16-89)
62 13.9 1.9 4.4 3.2 5.1 1.9 3.8 2.5 1.3
53.9 19.7 5.3 5.3 4 10.5
50 ~~~~
Mean age (years) (range)
44 (16-90)
Diagnoses (%)
Schizophrenia Affective disorders Paranoid states Organic psychoses Neuroses Personality disorders Epilepsy Mental retardation Other mental disturbances No diagnosis
65 9.2 0.9 2.8
-
8.3 4.6 1.8 6.4 0.9
-
1.3
76.1 2.3 3.6 6.3 1.35 3.6 2.3 3.1 1.35
-
In order to decide if and how clinical pharmacists can contribute to better care in our psychiatric hospitals, we decided to conduct a survey to study the physician prescribing patterns in these institutions. MATERIAL AND METHODS The patients of four psychiatric hospitals, who represented as much as possible the different wards in the hospitals, formed the population of this study. Of the four hospitals, hospital A has 160 beds and is a private hospital, hospital B has 255 beds and is run by the government, hospital C has 216 beds and is run by the workers’ sick fund, and hospital D has 335 beds and is run by the government as well. The characteristics of these patients are described in Table 1. This information as well as the information on all drugs administered to the patients on the day before the visit (including p.r.n. or S.O.S. given on that day) was recorded by the hospital pharmacists. The t h e of their visit to the ward was not known in advance by the physicians or the nurses of that particular ward. Data was gathered from the patients’ charts and the medication charts. The pharmacists recorded the name of the drug, its daily dosage, times of administration, route, duration of treatment (when recorded) and the name of the prescribing physician. RESULTS The total number of the different drugs prescribed in each hospital and of the psychotropic drugs specifically, as well as the range and the mean drug per patient are given in Table 2. Antiparkinson and anticonvulsant agents were not included in the category of psychotropic drugs. Table 3 describes the distribu-
479 Table 2. Number of drugs and mean drug per patient Hospital Mean(range)
n
C
B
A
D
-
n
Mean(range)
4
Mean (range)
n
Mean(range)
Totaldrugs
278
2.5 (0-7)
412
2.6 (0-8)
234
3.0 (0-11)
916
4.1 (1-9)
Psychotropic drugs
210
1.9 (0-4)
261
1.6 (0-5)
162
2.1 (0-5)
500
2.3 (0-6)
~~
~~~
~
Table 3. Distribution of patients by type of drug combination Hospital A
C
B
D
n
%
n
%
n
%
n
%
5
4.6
23
14.6
2
2.6
3
1.4
27
24.8
83
52.5
24
31.6
43
19.4
+ + +
43
39.4
52
32.9
37
48.7
149
67.1
53
48.6
76
48.1
35
46.1
190
85.6
9
8.3
3
1.9
2
2.6
55
24.8
+ +
17
15.6
8
5.1
2
2.6
24
10.8
6
5.5
30
19.0
24
31.6
20
9.0
4
3.7
7
4.4
7
9.2
8
3.6
1 5
0.9 4.6
-
-
2.6 6.6
-
5.1
2 5
-
8
8
3.6
1. N o psychotropic drug 2. Only one psychotropic drug 3. More than one antipsychotic drug 4. Antipsychotic(s) antiparkinson drug(s) 5. Antipsychotic(s) other neurologic drug($ 6. Antipsychotic(s) antianxiety drug(s) 7. Antipsychotic(s) h ypnotic(s) 8. Antipsychotic(s) antidepressant($ 9. Antianxiety(s) antidepressant(s) 10. Other combinations
+
Table 4. Distribution of patients according to number of antipsychotic drugs and the percentage of patients receiving antiparkinson drugs in relation to the number of antipsychotic drugs (phenothiazines and/or butyrophenones) Hosuital B
A
One antipsychotic drug More than one antipsychotic drug Total Per cent of all patients
%
C
D
n
% % *
n
50
53.8 44
87
66.9 51.7 43
63.2 53.5 67
32.1 88.1
43
46.2 74.4 43
33.1 83.7 25
36.8 60
142
67.9 92.2
100 55.9 209 89.5
100 85.6 94.1
93
100 58 85.3
130
* Percent receiving antiparkinson drugs.
% * n
100 62.3 68 82.3
%
% * n
%
%*
480
Table 5. Distribution of patients according to daily number of doses (given per
0s)
Hospital ~~
No. of doses
0-3 4-7 8-
A
B
C
D
% patients
% patients
% patients
% patients
41.3 41.3 17.4
39.2 43.7 17.1
30.3 38.1 31.6
12.2 31.1 56.7
tion of patients by type of drug combination, and Table 4 describes the relationship between the number of antipsychotic drugs (phenothiazines and butyrophenones) and the administration of antiparkinson drugs. In Table 5 the distribution of patients according to the daily number of doses (given per 0s) is summarized. We then studied the frequency of daily dosing of those drugs which could be given once a day, based mainly on kinetic considerations (VeZla (1975)). Chlorpromazine in a daily dose of up to 600 mg can be given once a day without loss of effect or a significant increase in side effects (Roberts (1961), Hrushka et al. (1966)), yet 80 % of the patients in this study received it in up to four divided doses per day. Tricyclic antidepressants, which have, as well as their active metabolites, a long half life (Pukes (1974)), were given once a day in only 22.6 % of the patients who received them. Such was the case with diazepam (MandeIZi et aZ. (1978)) - only 25 % of the patients on this drug received it in a single dose. Phenytoin was administered in two or three divided doses to 94.4 % of the patients who were treated with the drug while the advantages of its administration in a single dose is very well documented (Cocks et al. (1973, Robinson et al. (1975)). Even phenobarbitone, given as an anticonvulsant, was taken by only 50 % of the patients in a single dose. DISCUSSION After a thorough observation of the data collected in this survey the picture revealed is that much of the prescribing practice is based on habits and personal feelings or beliefs rather than on clinical trials and knowledge of pharmacological action and properties of the drugs commonly used in psychiatric practice. In this respect the picture is not much different from the one described by other surveys. No correlation could be drawn in many cases between types of patients or their diagnosis and the drugs which they had received. Hospital D had more schizophrenic patients and hospital C had the least, yet hospital C followed D in the percentage of patients receiving antipsychotic drugs (phenuthiazines and butyrophenones). Polypharmacy was common in this study; patients were receiving up to 11 different drugs and up to six different psychotropic drugs with an average of two psychotropic drugs per patient. Less than 15 % of the patients received no psychotropic drug. Approximately one third of the patients (in hospital B) to two
481 thirds of the patients (in hospital D) received more than one antipsychotic drug (see Table 3). While for some of these patients it meant a combination of a neuroleptic drug with lithium carbonate, which is recommended in some cases; in most of them it involved a combination of two or up to five different neuroleptics (see Table 4). A review of the literature does not support this kind of therapy (Hemminki (1977), Davis & Casper (1977)). Table 4 also supports the known fact that polypharmacy leads to polypharmacy. This is more pronounced in hospitals A and B, where the percentage of patients on more than one antipsychotic drug who also received an antiparkinson drug was higher than the percentage of patients on only one antipsychotic drug also receiving an antiparkinson drug. In hospital D, as we can see from both Tables 3 and 4, the usage of antiparkinson drugs is a common practice. Out of 222 patients, 190 (85.6 %) received protection against extrapyramidal reactions. Of these patients, 20.5 % received more than one antiparkinson agent (up to three drugs per patient). It should be pointed out that only two of these patients had parkinsonism as an official diagnosis in their charts. Fifty-two patients in this hospital received carbamazepine although only five had the official diagnosis of epilepsy clearly indicated in their charts. This was detected especially in one department - an obvious reflection of the personal belief and perhaps experience of the ward physician. Hospital C had more patients with affective disorders and hence used more antidepressants. The difference in the usage of hypnotics among the hospitals could be attributed to the difference in awareness of the corresponding physicians to the sedating effect of some of the antipsychotic drugs. This effect could allow deleting an extra drug from the patients’ drug regimen. Hospital D also stood out with the overwhelming number of doses given to a patient per day - a maximum of 30 doses. Up to 16 doses were given to a patient in hospital C in which approximately one third of the patients received more than eight oral doses per day. CONCLUSION We agree with Prien et al. (1978) that the criticism that this kind of a survey draws could sometimes be unjustified without a comprehensive evaluation of each case. However, a general prescribing pattern can be determined from such a survey and a tendency toward polypharmacy, if it exists, can be shown. It is recommended that the pharmacists in each psychiatric hospital assess the drug treatment in their hospital and compare it to prescribing patterns in other hospitals, so deviations and irrational prescribing habits can be avoided and corrected if necessary. This should be their first action to bettering patient care. ACKNOWLEDGEMENTS
We would like to thank the hospitals that kindly allowed us to collect the data and are especially grateful to Mrs. H . Pressman and Mrs. 1. Cohen, the hospital pharmacists.
482 REFERENCES Chien, C. P., K . Solomon & T. E. Platek (1978): Macro-monitoring: A step toward rationaI psychopharmacotherapy. h e r . I. Hosp. Pharm. 35, 397-402. Cocks, D. A., E. M . R . Critchely, H . W .Hayward, V . Owen, G . E. Mawer & B. G . Woodcock (1975): Control of epilepsy with a single daily dose of phenytoin sodium. Brit. J. clin. Pharmacol. 2, 449-453. Davis,J . M., & R . C a p e r (1977): Antipsychotic drugs: Clinical pharmacology and therapeutic use. Drugs 14, 260-282. Ellenor, G . L. (1977): Reducing irrational antipsychotic polypharmacy prescribing. H a p . Pharm. 12, 369-376. Hemminki, E. (1977): Polypharmacy among psychiatric patients. Acta psychiat. scand. 56, 347-356. Hrushka,M., M.Bruck & J . J.Hsu (1966): Therapeutic effects of different modes of chlorpromazine administration. Dis. nerv. Syst. 27, 522-527. Mandelli, M., G. Tognoni & S. Garattini (1978): Clinical pharmacokinetics of diazepam. Clin. Pharmacokinet. 3, 72-91. Pukes, G . E. (1974): Choice and use of tricyclic antidepressants. Clin. Pharm. Rev., issue No. 4. Prien, R . F., M . B. Balter & E. M . Cafley (1978): Hospital surveys of prescribing practices with psychotherapeutic drugs. Arch. gen. Psychiat. 35, 1271-1275. Roberts, F. J . (1961): Single daily dose treatment of psychiatric patients with phenothiazine derivatives. J. ment. Sci. 107, 104-108. Robinson, 1. D., B. A . Morris, G . W . Aherne & V . Marks (1975): Pharmacokinetics of a single dose of phenytoin in man measured by radioimmunoassay. Brit. J. clin. Pharmacol. 2, 345-349. Tyrer, P. (1978): Drug treatment of psychiatric patients in general practice. Brit. med. J. 2, 1008-1010. Vella,R. (1975): Single daily dosing of some drugs usually given in divided doses. Hosp. Pharm. 10, 514-515. Received June 11, 1979
Shimona Yosselson-Superstine, Pharm.D. Department of Pharmacy School of Pharmacy Hebrew University Jerusalem Israel
Prescribing patterns in psychiatric hospitals in Israel S. YOSSELSON-SUPERSTINE, D. STERNXK AND D. LIEBENZON A survey conducted by pharmacists working in four psychiatric hospitals in Israel to assess the prescribing of psychotropic drugs revealed that polypharmacy was common: patients were receiving up to 11 different drugs and up to six different psychotropic drugs. The average number of psychotropic drugs per patient was two. The most popular combinations of drugs used were; one containing an antipsychotic drug(s) and an antiparkinson drug@)and the other was a combination of more than one antipsychotic agent. Up to 30 doses per day were taken orally by one patient. Drugs that could have easily been administered on a once-a-day time schedule were often administered several times a day. Differences in prescribing patterns in the various hospitals and often times on different wards of the same institution could more easily be attributed to different educational backgrounds, habits and personal beliefs and perhaps the physician’s experience as well, rather than to the types of patients treated. Key words: Antiparkinson drugs - antipsychotics- drug prescribing patterns - psychotropic drugs - survey.
Overuse and misuse of psychotropic medication have been the subject of recent communications initiated by pharmacists as well as by physicians or public health scientists. An extensive review of US. hospital surveys of prescribing practices with psychotropic drugs (Prien et al. (1978)), although criticizing the conclusions, reveals that approximately one third of the patients were treated with polypharmacy, about 30 % were receiving frequent daily doses, antiparkinson drugs were overused, dosage was too low or too high and only a very few patients were on drug holidays. A study conducted among psychiatric patients in Helsinki (Hemminki (1977)) disclosed that 69 7% of the patients received more than one psychotropic drug with an average of 2.1 different psychotropic drugs per patient. An assessment of prescribing of psychotropic drugs by general practitioners in England (Tyrer (1978)) pinpointed prolonged duration of treatment, incorrect dosage and pointless polypharmacy as well. In the United States, where the practice of Clinical Pharmacy has been well established, psychiatric wards and institutions are among the fist to benefit from drug consultations given by the pharmacists who specialize in the pharmacology and the pharmacokinetics of psychotropic drugs. It has been shown (Ellenor (1977), Chien et al. (1978)) that this kind of consultation significantly reduced irrational psychopharmacotherapy. 0001-690X/79/100477-06$02.50/0@ 1979 Munksgaard, Copenhagen
478
Table 1. Demographic and diagnostic information Hospital No. of patients
A 109
% female
B 158
C 76
D 222
38.6
17.6
44.3
44.5 (16-79)
34.8 (14-73)
45.5 (16-89)
62 13.9 1.9 4.4 3.2 5.1 1.9 3.8 2.5 1.3
53.9 19.7 5.3 5.3 4 10.5
50 ~~~~
Mean age (years) (range)
44 (16-90)
Diagnoses (%)
Schizophrenia Affective disorders Paranoid states Organic psychoses Neuroses Personality disorders Epilepsy Mental retardation Other mental disturbances No diagnosis
65 9.2 0.9 2.8
-
8.3 4.6 1.8 6.4 0.9
-
1.3
76.1 2.3 3.6 6.3 1.35 3.6 2.3 3.1 1.35
-
In order to decide if and how clinical pharmacists can contribute to better care in our psychiatric hospitals, we decided to conduct a survey to study the physician prescribing patterns in these institutions. MATERIAL AND METHODS The patients of four psychiatric hospitals, who represented as much as possible the different wards in the hospitals, formed the population of this study. Of the four hospitals, hospital A has 160 beds and is a private hospital, hospital B has 255 beds and is run by the government, hospital C has 216 beds and is run by the workers’ sick fund, and hospital D has 335 beds and is run by the government as well. The characteristics of these patients are described in Table 1. This information as well as the information on all drugs administered to the patients on the day before the visit (including p.r.n. or S.O.S. given on that day) was recorded by the hospital pharmacists. The t h e of their visit to the ward was not known in advance by the physicians or the nurses of that particular ward. Data was gathered from the patients’ charts and the medication charts. The pharmacists recorded the name of the drug, its daily dosage, times of administration, route, duration of treatment (when recorded) and the name of the prescribing physician. RESULTS The total number of the different drugs prescribed in each hospital and of the psychotropic drugs specifically, as well as the range and the mean drug per patient are given in Table 2. Antiparkinson and anticonvulsant agents were not included in the category of psychotropic drugs. Table 3 describes the distribu-
479 Table 2. Number of drugs and mean drug per patient Hospital Mean(range)
n
C
B
A
D
-
n
Mean(range)
4
Mean (range)
n
Mean(range)
Totaldrugs
278
2.5 (0-7)
412
2.6 (0-8)
234
3.0 (0-11)
916
4.1 (1-9)
Psychotropic drugs
210
1.9 (0-4)
261
1.6 (0-5)
162
2.1 (0-5)
500
2.3 (0-6)
~~
~~~
~
Table 3. Distribution of patients by type of drug combination Hospital A
C
B
D
n
%
n
%
n
%
n
%
5
4.6
23
14.6
2
2.6
3
1.4
27
24.8
83
52.5
24
31.6
43
19.4
+ + +
43
39.4
52
32.9
37
48.7
149
67.1
53
48.6
76
48.1
35
46.1
190
85.6
9
8.3
3
1.9
2
2.6
55
24.8
+ +
17
15.6
8
5.1
2
2.6
24
10.8
6
5.5
30
19.0
24
31.6
20
9.0
4
3.7
7
4.4
7
9.2
8
3.6
1 5
0.9 4.6
-
-
2.6 6.6
-
5.1
2 5
-
8
8
3.6
1. N o psychotropic drug 2. Only one psychotropic drug 3. More than one antipsychotic drug 4. Antipsychotic(s) antiparkinson drug(s) 5. Antipsychotic(s) other neurologic drug($ 6. Antipsychotic(s) antianxiety drug(s) 7. Antipsychotic(s) h ypnotic(s) 8. Antipsychotic(s) antidepressant($ 9. Antianxiety(s) antidepressant(s) 10. Other combinations
+
Table 4. Distribution of patients according to number of antipsychotic drugs and the percentage of patients receiving antiparkinson drugs in relation to the number of antipsychotic drugs (phenothiazines and/or butyrophenones) Hosuital B
A
One antipsychotic drug More than one antipsychotic drug Total Per cent of all patients
%
C
D
n
% % *
n
50
53.8 44
87
66.9 51.7 43
63.2 53.5 67
32.1 88.1
43
46.2 74.4 43
33.1 83.7 25
36.8 60
142
67.9 92.2
100 55.9 209 89.5
100 85.6 94.1
93
100 58 85.3
130
* Percent receiving antiparkinson drugs.
% * n
100 62.3 68 82.3
%
% * n
%
%*
480
Table 5. Distribution of patients according to daily number of doses (given per
0s)
Hospital ~~
No. of doses
0-3 4-7 8-
A
B
C
D
% patients
% patients
% patients
% patients
41.3 41.3 17.4
39.2 43.7 17.1
30.3 38.1 31.6
12.2 31.1 56.7
tion of patients by type of drug combination, and Table 4 describes the relationship between the number of antipsychotic drugs (phenothiazines and butyrophenones) and the administration of antiparkinson drugs. In Table 5 the distribution of patients according to the daily number of doses (given per 0s) is summarized. We then studied the frequency of daily dosing of those drugs which could be given once a day, based mainly on kinetic considerations (VeZla (1975)). Chlorpromazine in a daily dose of up to 600 mg can be given once a day without loss of effect or a significant increase in side effects (Roberts (1961), Hrushka et al. (1966)), yet 80 % of the patients in this study received it in up to four divided doses per day. Tricyclic antidepressants, which have, as well as their active metabolites, a long half life (Pukes (1974)), were given once a day in only 22.6 % of the patients who received them. Such was the case with diazepam (MandeIZi et aZ. (1978)) - only 25 % of the patients on this drug received it in a single dose. Phenytoin was administered in two or three divided doses to 94.4 % of the patients who were treated with the drug while the advantages of its administration in a single dose is very well documented (Cocks et al. (1973, Robinson et al. (1975)). Even phenobarbitone, given as an anticonvulsant, was taken by only 50 % of the patients in a single dose. DISCUSSION After a thorough observation of the data collected in this survey the picture revealed is that much of the prescribing practice is based on habits and personal feelings or beliefs rather than on clinical trials and knowledge of pharmacological action and properties of the drugs commonly used in psychiatric practice. In this respect the picture is not much different from the one described by other surveys. No correlation could be drawn in many cases between types of patients or their diagnosis and the drugs which they had received. Hospital D had more schizophrenic patients and hospital C had the least, yet hospital C followed D in the percentage of patients receiving antipsychotic drugs (phenuthiazines and butyrophenones). Polypharmacy was common in this study; patients were receiving up to 11 different drugs and up to six different psychotropic drugs with an average of two psychotropic drugs per patient. Less than 15 % of the patients received no psychotropic drug. Approximately one third of the patients (in hospital B) to two
481 thirds of the patients (in hospital D) received more than one antipsychotic drug (see Table 3). While for some of these patients it meant a combination of a neuroleptic drug with lithium carbonate, which is recommended in some cases; in most of them it involved a combination of two or up to five different neuroleptics (see Table 4). A review of the literature does not support this kind of therapy (Hemminki (1977), Davis & Casper (1977)). Table 4 also supports the known fact that polypharmacy leads to polypharmacy. This is more pronounced in hospitals A and B, where the percentage of patients on more than one antipsychotic drug who also received an antiparkinson drug was higher than the percentage of patients on only one antipsychotic drug also receiving an antiparkinson drug. In hospital D, as we can see from both Tables 3 and 4, the usage of antiparkinson drugs is a common practice. Out of 222 patients, 190 (85.6 %) received protection against extrapyramidal reactions. Of these patients, 20.5 % received more than one antiparkinson agent (up to three drugs per patient). It should be pointed out that only two of these patients had parkinsonism as an official diagnosis in their charts. Fifty-two patients in this hospital received carbamazepine although only five had the official diagnosis of epilepsy clearly indicated in their charts. This was detected especially in one department - an obvious reflection of the personal belief and perhaps experience of the ward physician. Hospital C had more patients with affective disorders and hence used more antidepressants. The difference in the usage of hypnotics among the hospitals could be attributed to the difference in awareness of the corresponding physicians to the sedating effect of some of the antipsychotic drugs. This effect could allow deleting an extra drug from the patients’ drug regimen. Hospital D also stood out with the overwhelming number of doses given to a patient per day - a maximum of 30 doses. Up to 16 doses were given to a patient in hospital C in which approximately one third of the patients received more than eight oral doses per day. CONCLUSION We agree with Prien et al. (1978) that the criticism that this kind of a survey draws could sometimes be unjustified without a comprehensive evaluation of each case. However, a general prescribing pattern can be determined from such a survey and a tendency toward polypharmacy, if it exists, can be shown. It is recommended that the pharmacists in each psychiatric hospital assess the drug treatment in their hospital and compare it to prescribing patterns in other hospitals, so deviations and irrational prescribing habits can be avoided and corrected if necessary. This should be their first action to bettering patient care. ACKNOWLEDGEMENTS
We would like to thank the hospitals that kindly allowed us to collect the data and are especially grateful to Mrs. H . Pressman and Mrs. 1. Cohen, the hospital pharmacists.
482 REFERENCES Chien, C. P., K . Solomon & T. E. Platek (1978): Macro-monitoring: A step toward rationaI psychopharmacotherapy. h e r . I. Hosp. Pharm. 35, 397-402. Cocks, D. A., E. M . R . Critchely, H . W .Hayward, V . Owen, G . E. Mawer & B. G . Woodcock (1975): Control of epilepsy with a single daily dose of phenytoin sodium. Brit. J. clin. Pharmacol. 2, 449-453. Davis,J . M., & R . C a p e r (1977): Antipsychotic drugs: Clinical pharmacology and therapeutic use. Drugs 14, 260-282. Ellenor, G . L. (1977): Reducing irrational antipsychotic polypharmacy prescribing. H a p . Pharm. 12, 369-376. Hemminki, E. (1977): Polypharmacy among psychiatric patients. Acta psychiat. scand. 56, 347-356. Hrushka,M., M.Bruck & J . J.Hsu (1966): Therapeutic effects of different modes of chlorpromazine administration. Dis. nerv. Syst. 27, 522-527. Mandelli, M., G. Tognoni & S. Garattini (1978): Clinical pharmacokinetics of diazepam. Clin. Pharmacokinet. 3, 72-91. Pukes, G . E. (1974): Choice and use of tricyclic antidepressants. Clin. Pharm. Rev., issue No. 4. Prien, R . F., M . B. Balter & E. M . Cafley (1978): Hospital surveys of prescribing practices with psychotherapeutic drugs. Arch. gen. Psychiat. 35, 1271-1275. Roberts, F. J . (1961): Single daily dose treatment of psychiatric patients with phenothiazine derivatives. J. ment. Sci. 107, 104-108. Robinson, 1. D., B. A . Morris, G . W . Aherne & V . Marks (1975): Pharmacokinetics of a single dose of phenytoin in man measured by radioimmunoassay. Brit. J. clin. Pharmacol. 2, 345-349. Tyrer, P. (1978): Drug treatment of psychiatric patients in general practice. Brit. med. J. 2, 1008-1010. Vella,R. (1975): Single daily dosing of some drugs usually given in divided doses. Hosp. Pharm. 10, 514-515. Received June 11, 1979
Shimona Yosselson-Superstine, Pharm.D. Department of Pharmacy School of Pharmacy Hebrew University Jerusalem Israel
