Session 111. Patterns of drug utilization Sources of information on drug usage in Sweden Based on sales statistics, prescription habits and figures, interviews, and, in certain instances, on determinations of drug plasma levels, various aspects of drug usage in Sweden are examined. The working of the drug regulatory agency in Sweden is elucidated against the background of the above sources from which drug usage information is obtained.
Barbro Westerho1m, M.D. Stockholm, Sweden
National Corporation of Swedish Pharmacies
In planning my discussion for this meeting I thought that perhaps one way to do it was to outline the various sources of information on drug usage in Sweden, and show examples from some of the investigations performed. The sourees used are: sales statisties, preseriptions, interview studies, and determinations of drug plasma levels. Sales statistics
The erudest way of obtaining an impression of the use of drugs is via sales statisties. By analyzing sales data one ean aequire information on what preparations are used, ehanges of use over a time period, and a rough estimate of the amount of use. Comparisons ean also be made with other eountries from whieh sales data are available. Ta make meaningful eomparisons between sales, one has to transform the data into units which take into aeeount that drugs are used in different dosages and at different strengths. A Reprint requests to: Dr. Barbro Westerho1m, National Corporation of Swedish Pharmacies, S 10514, Stockholm, Sweden.
644
working party on studies on drug utilization" supported by funds from WHO has, therefore, established an "agreed daily dose." unit for a number of drugs, among them psyehotropie agents. A eomparison of sales data for psyehotropic drugs from Sweden (obtained from Läkemedelsstatistik AB) and Norway (obtained from Norsk Medisinaldepot) from the period 1970 to 1972 reveals that the number of agreed daily doses per 1,000 inhabitants per day is higher in Sweden than in Norway" (Table I). However, if one looks into individual groups of drugs the situation varies. For minor tranquilizers (mainly benzodiazepines) the Norwegian sales figures are higher than the Swedish. This may be due to the fact that a reeommendation was issued in Sweden that phenothiazine derivatives (mainly antihistamines with sedative effect) should be used instead of barbiturates and minor tranquilizers in certain cases to diminish the risk of misuse. Another example is a comparison made on the use of antidiabetic agents in Norway, Northern Ireland, and Sweden.! It was found
Valurne 19 Number 5, Part 2
that the consumption of insulin was similar in Norway and Northem Ireland (3.5 and 3.9 agreed daily doses per 1,000 inhabitants per day) but almost twice as high in Sweden (6.9). The variation in the consumption of oral antidiabetic drugs was even more marked. The figure for Sweden was 15.8, for Norway 7.3, and for Northem Ireland as low as 4.3 agreed daily doses per 1,000 inhabitants per day. In part, but not wholly, the differences can be explained by different incidence rates of diabetes in the three countries . Thus in-depth studies are motivated to reveal the underlying causes. Regional differences can also be observed within countries. For Sweden it could, for instance, be shown that the sale of insulin was evenly spread over the country whereas the oral diabetic agents were sold to a lesser extent in the area of Stockholm and the south of Sweden as compared to the rest of the country (Fig. 1). Sales statistics can also be used to measure the effect of information on the prescribing habits of the doctor. Two examples can be mentioned. Fig. 2 shows the drop in the sales of drugs containing metamizol (dipyrone) after three warnings to the medical profession from the Swedish Adverse Drug Reaction Committee in 19676 about the risk of agranulocytosis. Fig. 3 gives a picture of the development in sales of psychotropic drugs during the 1970s. Because of the discussions on the risk of misuse the National Board of Health and Welfare published booklets and papers on hypnotics, sedatives, and minor tranquilizers in 1971 and 1972. A letter was also issued to all doctors recommending the prescribing of packages as small as possible and of stating the time interval between refills on repeat prescriptions. At the same time information was given to the public via the pharmacies and to mass media on the drugs. The activity resulted in numbers of articles in the lay press discussing the need of the benzodiazepines, especially. A decline in the sales figures has occurred since the information campaign started. Although sales data do not answer the questions raised above, they serve as an indication as to what one should look for in greater detail.
Drug usage in Sweden
645
Fig. 1. No. of agreed daily doses of oral antidiabetic agents per 1,000 inhabitants per day sold in seven hospital regions in Sweden during the second quarter of 1971.
Hospital data
Since 1970 information on the drugs distributed to the majority of hospitals in Sweden has been obtainable from the National Corporation of Pharmacies in Sweden.? It is also possible to obtain information on the drugs used by individual departments within the hospital. Comparisons can thus be made conceming the use of a particular group of drugs in one hospital or department and that in another. It could, for instance, be shown that the mean number of agreed daily doses of hypnotics,
646
Clinieal Pharmacology and Therapeuties
Westerholm
MILLION OF TABLETS (n· 103 )
~""'od'__''''
7 6
__x-x x
5
~PhenothiaZines
4
3
2
~,Cb?f~§'~gse~ o ranu ocosis 15 10 5
x-
- - - - - - - - - - . . Comb.sedativesanalgesics x_X-x
o 1965 1966 1967 1968 1969 1970 1971 Year
Fig. 2. Sales of metamizol (dipyrone) in Sweden following warnings to the medical profession and number of reported cases of agranulocytosis. (From Böttiger, L. E., and Westerho1m, H.: Drug-induced blood dyscrasias in Sweden, Br. Med. J. 3:339-343, 1973.)
sedatives, and minor tranquilizers per treatment day delivered to the departments of medicine and gynecology was about the same in the two specialties but a wide variation was noted between hospitals (Table 11). The delivery to psychiatrie departments so far has been analyzed in only two hospitals. In one the number of delivered daily doses per treatment day was 1.55, in the other it was 0.83. It is not yet known whether the high figure in the former hospital is due to the use of higher daily doses or whether there is some sort of wastage of the drugs. It is also possible to look at the number of different drugs being used in each pharmacologic group. In most of our hospitals there are drug committees which try to cut down the number of different drugs used. The number of hypnotics, sedatives, and minor tranquilizers used in the different hospital departments varied a good deal (Table III). The hospitals with very active drugcommittees tend to have the lowest number ofdrugs within each group. Judging from the profile of drugs being used in the various departments it appears that some prefer
0---0---....0---... Tricyclic antidepressants
_ _ _ _ _ _ Barbiturates ---..
1970
1971
-
1972
-Central stimulants
1973
YEAR
Fig. 3. Sales of psychotropic drugs in Sweden from 1970 through 1973.
barbiturates and others nitrazepam as sleeping pills. At present the information from the hospital delivery statistics can serve as an alert as to what to look for in depth. Whatever the answers, the data seem to be useful for the drug committees in the various hospitals. Prescription data
From the information on the prescription one can obtain data of age and sex distribution of the users, drugs prescribed, with dosage and amount, and specialty of the physician. Since December, 1973, the Swedish National Corporation of Pharmacies has analyzed a 1:288 sample of the prescriptions collected from pharmacies. Tables IV, V, and VI give a picture of the type of information which can be obtained. As in other investigations, it could be shown that more women than men use psychotropic drugs and that the use increases with age. From this type of data it is, however, not possible to judge to what extent overuse exists since it is not known why the drugs have been prescribed and how they are taken. It is gratifying to see that in this sample there were no prescriptions of chloramphenicol, which in Sweden is promoted only for typhoid and
Volume /9 Number 5. Part 2
Drug usage in Sweden
647
Table I. Yearly sale of psychotropic drugs in Sweden and Norway, 1970-1972 No. of agreed daily doseslJ ,000 inhabitantslday
ISweden
1972
1971
1970
ISweden
ISweden
1972 ratio
NorwaylSweden (%)
Group of drugs
Norway
Sedatives and hypnotics Minor tranquilizers Major tranquilizers Antidepressants
26 41 6 5
40 32 8 8
23 39 6 5
38 32 8 8
23 36 6 5
32 32 9 8
72 113 67 63
Total
78
88
73
86
70
81
86
Norway
Table 11. Deliveries 0/ hypnotics, sedatives, and minor tranquilizers to medical and gynecologic (including obstetric) departments, 1973 No. of agreed daily doses per treatment day Type of hospital and department
No,
University: Interna! medicine Gynecology and obstetries
6 6
County: Internal medicine Gynecology and obstetries
21 21
Mean
0,47 0,42
0.56 0,42
I Range 0.32-0.71 0.24-0.61
0.28-0.85 0.15-0.77
paratyphoid, and when the drug has been shown to be superior to other drugs by bacteriologic tests or possibly when treating fulminant pyrexia without a clear bacteriologic diagnosis in hospital. Another study of interest going on in the county of Jämtland in Sweden is the continuous registration of individual purchases of drugs on prescription. The registration started March, 1968, in the town of Östersund. 3 Initially one fifteenth of the population in Östersund was monitored; in 1970 two fifteenths of the population in the whole county of Jämtland where Östersund is the main town was included in the investigation. The purchases of sedatives, hypnotics, and
Norway
Table 111. No. 0/ different hypnotics, sedatives, and minor tranquilizers delivered to medical and gynecologic (including obstetric) departments, 1973 Type of hospital and department University: Internal medicine Gynecology and obstetries County: Internal medicine Gynecology and obstetries
No. of specialties No.
Mean
I Range
5
25
21-36
6
18
13-27
21
20
11-29
21
13
7-21
minor tranquilizers in Östersund during the period from March, 1968, to June, 1969, were analyzed by Bergström and Westerholm." Almost half of the patients (46%) obtained only one such prescription during the 16-mo period studied and 9% had eight or more. These two groups, called Group Sand R, respectively, were compared with regard to other drugs used and numbers of tablets per prescription. Since there has been much concern about the use and overuse of hypnotics, sedatives, and minor tranquilizers, it was thought of interest to follow these patients and study their prescription drug purchases 5 yr later, that is, in 1973.5 The material from 1968-1969 comprised 417 patients in Group Sand 76 in Group R. The number of patients no longer living in the county is the same in the two groups percentagewise, namely, 17%. Of those remaining in
648
Westerholm
Clinical Pharmacology and Therapeutics
Table IV. NHS prescriptions, March, 1974: Psychotropic drugs, sample 1: 288
0/ prescriptions per age
No.
0-14 Drug Hypnotics, sedatives, minor tranquilizers Major tranquilizers Antidepressants Central stimulants Total
15-44
MI F
group (yr)
45-64
MI
F
MI
65F
MI
Total
F
MI
F
14
7
86
161
176
260
113
252
389
680
3 3 0
7 0 0
40 12 2
43 31 12
61 32 7
78 40 17
31 2 6
68 26 11
135 49 15
196 97 40
20
14
140
247
276
395
152
357
588
1,013
Table V. NHS prescriptions, March, 1974: Hypnotics, sedatives. and minor tranquilizers, sample 1 : 288 No.
15-44
0-14
Drug Barbiturates Piperidinedione derivatives Propanediols Benzodiazepines Alcohols, aldehydes Antihistamines Bromides Others (combinations, etc.) Total
M
1 1 0 0 0 11
14
0/ prescriptions per
IF
1 0 0 0 0 5
7
age group (yr)
45-64
65-
MI
F
MI
F
7 3 1 51 1 6
14 3 2 105 2 6
21 6 1 105 5 7
17 5 4 158 3 11
17
29
31
86
161
176
the county 247 (59%) in Group S and 48 (63%) in Group R lived in the area of the town of Östersund, the others farther outside but still within the border of the county of Jämtland. The reasons for no longer living in the county are death (43 cases) and movement to other areas (42). Of the diseased patients, four committed suicide, two belonged to Group S, and two to Group R. Of the patients stillliving in the county, 23 % in Group S bought hypnotics, sedatives, and minor tranquilizers in 1973. The corresponding figure in Group S is 87%. A decrease in the number of prescriptions was noticed in Group R in 1973 as compared to 1968 to 1969. There was also a decrease of the number of tablets per individual per month and a change from larger to smaller amounts of drugs per prescription.
I
I
F
M
12 0 4 69 2 3
42 1 4 143 3 13
41 10 6 225 8 27
62
23
46
72
138
260
113
252
389
680
-0-
M
Total F
74 9 10 406 8 35
The benzodiazepines dominated both groups both in 1968-1969 and 1973, followed by barbiturates. Percentagewise there was a shift from the latter to the former in 1973. From information about the number of tablets prescribed and the dosage, it could be estimated when the patient should return for refill. In Group S there was only one patient showing a tendency to shorten the intervals between refills. This patient was using nitrazepam. Without knowledge of the patient's medical history and the reason for the prescription it is not possible to judge whether there was an overuse or not. In Group R three individuals have reduced the purchase intervals or increased the amounts obtained in 1973 as compared with 1968-1969. In two the increase is insignificant and does not cause a suspicion
Drug usage in Sweden
Volume 19 Number 5, Part 2
649
Tahle VI. NHS preseriptions, March, 1974: Chemotherapeutic agents, sample 1 :288 No.
0/ prescriptions per age group (yr) 15-44
0-14
Drug
MI
F
M
Sulfonamides Penicillins Tetracyclines Streptomycin Ch1oramphenico1 Erythromycin Anti-TB Bactrim group Others
1 100 0 0 0 20 1 0 5
9 92 2 1 0 9 0 2 5
9 95 36 0 0 10 0 0
Total
127
120
I
65-
45-64
MI
F 23 128 48 0 0
F
MI
11
13 32 20 0 0 4
10
0 7 24
5 0 17
22 47 23 1 0 9 1 4 22
160
241
91
129
of overuse. The third patient was known already in 1968 as a drug abuser and is under the supervision of one psychiatrist who prescribes the drugs for 1- or 2-wk periods at a time. The findings in this study indicate that at least in a rural population the risk of developing misuse of sedatives in a 5-yr period is not very large. However, only partial conclusions should be drawn from this study since it is not known why the drugs have been prescribed and how the patients actually have taken them. Prescription data combined with interviews
The Department of Drugs of Sweden (corresponding to the FDA in the United States) has to follow the prescribing and use of drugs and to take necessary steps in case anything unsatisfactory is revealed. Because of the criticism of the prescribing of hypnotics and sedatives, prescriptions including these drugs were analyzed in various ways. During a 6-mo period repeat prescriptions, on which patients had obtained the drugs at least twice as quickly as could be expected from the amount and dosage, were sent to the Department of Drugs by all pharmacies in Sweden on a voluntary basis." The number of prescriptions received was 2,218 and the number of drug orders was 2,419. Of these prescriptions 1,311 (59%) were intended for women. The most common drugs were barbiturates and benzodiazepines.
Total
I
F
F
M
13 18 12 0 0 2 0 0 8
21 32 0 0 5 2 5 20
36 245 68 0 0 36 6 0 40
75 299 84 2 0 34 3 18 71
53
96
431
586
11
The total number of doctors responsible for the prescriptions was 907, most of whom had written only a few such prescriptions. For 716 doctors information was obtained conceming age, specialty, and place of work. Fifty-five per cent were 50 yr of age and above. The youngest doctors were between 30 and 40 yr of age. Doctors with no specialty head the list, followed by internists and general practitioners. If the repeat prescriptions had been issued with extremely short intervals, or if one doctor had very many such patients, a letter was sent asking why the drug was prescribed. Altogether this part of the study comprised 121 doctors and 736 patients. The symptoms for which the drugs were prescribed were mainly insomnia and psychotic disorders. For 224 patients (30%) no information was obtained about the period during which the doctor had been in charge of the patient; 45 (6%) were new, 42 (6%) had been known by the doctor for 1-2 yr, and 388 (54%) for at least 3 yr. A total of 115 patients had received psychiatrie treatment earlier; 20 were now in hornes for the aged. In 240 cases (33%) the doctor had suspected too high a consumption, in 132 acceptable reasons were presented for the quick refill, e.g., holiday trip, pharmacy far away. Seventy-seven patients had given some of the tablets to relatives. Ninety-one patients had been recommended on the phone by the doctor to use a higher dosage than the one written on the prescription.
650
Westerholm
This repeat-prescription investigation may be criticized because one does not know to what extent pharmacies did not send in prescriptions. However, it gives some information on who prescribes hypnotics, sedatives, and minor tranquilizers on repeat prescriptions and to whom and for what. Plasma level determinations
The crucial point in the discussion on drug usage, however, is information on to what extent the patients have actually consumed the drugs sold and whether they obtained the drugs over the counter or on prescription. The most objective method to measure the consumption is by means of plasma determinations. Such determinations are performed for certain drugs and mainly in hospitals with a clinical pharmacologic laboratory . It is usually inpatients who are examined but there has been one outpatient study which is of particular interest here. A comparison between digoxin-treated patients in Funäsdalen (outpatient care) and Huddinge Hospital has shown considerable differences in plasma concentrations at the same prescribed doses. In the hospitalized patients about 20% (174) had levels about 2 ng/ml, whereas in outpatients (66) 3% were above this level. A possible subtherapeutic concentration (~0.5 ng/ml) was found in 20% of the outpatients as compared to 11% among the hospitalized individuals. When the outpatients had been informed about the importance of taking the prescribed dose, a significant increase of the plasma levels was seen in eight patients. In some patients low digoxin levels could be attributed to too low a dose prescribed in relation to the body weight.
Clinical Pharmacology
and Therapeutics
Final re marks
We have far from a complete picture concerning the extent to which, why, and how drugs are being used. Overconsumption of drugs has been the subject of several papers and discussions while the problem of underconsumption has been more or less overlooked. Thus further efforts are needed to elucidate how optimal drug therapy can be reached. References 1. Bergman, U., Elmes, P., Halse, M., Lunde, P. K. M., Sjöqvist, F., and Westerho1m, B.: The measurement of drug consumption, Eur. J. Clin. Pharmaco!. 8:83-89, 1975. 2. Bergman, U., Sjöqvist, F., and Söderhjelm, L.: Utilization of digoxin in a low-density population area in Sweden. In press, Eur. J. Clin. Pharmaco!. 3. Bergström, 1., Carmstad, A., Elwin, C-E., Heedman, P-A., Källström, B., Moell, B., Swaren, U., Westerho1m, B., and Wiman, F.: Läkemedelsregistrering i Jämtlands län. Kliniska erfarenheter fran förstudie 1968, Läkartidningen 67 (Supp!. 3):91-99, 1970. 4. Bergström, K., and Westerho1m, B.: Ueköp av sedativa, hypnotika och ataraktika i Östersundsomradet, Läkartidningen 69:1366-1370, 1972. 5. Boethius, G., and Westerho1m, B.: Is the use of hypnotics, sedatives and minor tranquilizers a major health problem? In press, Acta Med. Scand. 6. Böttiger, L. E., and Westerho1m, B.: Druginduced blood dyscrasias in Sweden, Br. Med. J. 3:339-343, 1973. 7. Carmstad, A., Davidson, B., Holmberg, B., and Ström, S.: Central data-behandling av läkemedelsleveranser till sjukhus, Sven. Farm. Tidskr. 74:809-916, 1970. 8. Halvorsen, I. K., Halse, M., and Lunde, P. K. M.: Sammenligning av legemiddelforbruk (salg), Norden, Nord. Med. 89:84-88, 1974. 9. Westerho1m, B.: Minskad försäljning av psykofarmaka efter informationskampanj, Socialnytt. Nr. 4, 1974.
Barbro Westerho1m, M.D. Stockholm, Sweden
National Corporation of Swedish Pharmacies
In planning my discussion for this meeting I thought that perhaps one way to do it was to outline the various sources of information on drug usage in Sweden, and show examples from some of the investigations performed. The sourees used are: sales statisties, preseriptions, interview studies, and determinations of drug plasma levels. Sales statistics
The erudest way of obtaining an impression of the use of drugs is via sales statisties. By analyzing sales data one ean aequire information on what preparations are used, ehanges of use over a time period, and a rough estimate of the amount of use. Comparisons ean also be made with other eountries from whieh sales data are available. Ta make meaningful eomparisons between sales, one has to transform the data into units which take into aeeount that drugs are used in different dosages and at different strengths. A Reprint requests to: Dr. Barbro Westerho1m, National Corporation of Swedish Pharmacies, S 10514, Stockholm, Sweden.
644
working party on studies on drug utilization" supported by funds from WHO has, therefore, established an "agreed daily dose." unit for a number of drugs, among them psyehotropie agents. A eomparison of sales data for psyehotropic drugs from Sweden (obtained from Läkemedelsstatistik AB) and Norway (obtained from Norsk Medisinaldepot) from the period 1970 to 1972 reveals that the number of agreed daily doses per 1,000 inhabitants per day is higher in Sweden than in Norway" (Table I). However, if one looks into individual groups of drugs the situation varies. For minor tranquilizers (mainly benzodiazepines) the Norwegian sales figures are higher than the Swedish. This may be due to the fact that a reeommendation was issued in Sweden that phenothiazine derivatives (mainly antihistamines with sedative effect) should be used instead of barbiturates and minor tranquilizers in certain cases to diminish the risk of misuse. Another example is a comparison made on the use of antidiabetic agents in Norway, Northern Ireland, and Sweden.! It was found
Valurne 19 Number 5, Part 2
that the consumption of insulin was similar in Norway and Northem Ireland (3.5 and 3.9 agreed daily doses per 1,000 inhabitants per day) but almost twice as high in Sweden (6.9). The variation in the consumption of oral antidiabetic drugs was even more marked. The figure for Sweden was 15.8, for Norway 7.3, and for Northem Ireland as low as 4.3 agreed daily doses per 1,000 inhabitants per day. In part, but not wholly, the differences can be explained by different incidence rates of diabetes in the three countries . Thus in-depth studies are motivated to reveal the underlying causes. Regional differences can also be observed within countries. For Sweden it could, for instance, be shown that the sale of insulin was evenly spread over the country whereas the oral diabetic agents were sold to a lesser extent in the area of Stockholm and the south of Sweden as compared to the rest of the country (Fig. 1). Sales statistics can also be used to measure the effect of information on the prescribing habits of the doctor. Two examples can be mentioned. Fig. 2 shows the drop in the sales of drugs containing metamizol (dipyrone) after three warnings to the medical profession from the Swedish Adverse Drug Reaction Committee in 19676 about the risk of agranulocytosis. Fig. 3 gives a picture of the development in sales of psychotropic drugs during the 1970s. Because of the discussions on the risk of misuse the National Board of Health and Welfare published booklets and papers on hypnotics, sedatives, and minor tranquilizers in 1971 and 1972. A letter was also issued to all doctors recommending the prescribing of packages as small as possible and of stating the time interval between refills on repeat prescriptions. At the same time information was given to the public via the pharmacies and to mass media on the drugs. The activity resulted in numbers of articles in the lay press discussing the need of the benzodiazepines, especially. A decline in the sales figures has occurred since the information campaign started. Although sales data do not answer the questions raised above, they serve as an indication as to what one should look for in greater detail.
Drug usage in Sweden
645
Fig. 1. No. of agreed daily doses of oral antidiabetic agents per 1,000 inhabitants per day sold in seven hospital regions in Sweden during the second quarter of 1971.
Hospital data
Since 1970 information on the drugs distributed to the majority of hospitals in Sweden has been obtainable from the National Corporation of Pharmacies in Sweden.? It is also possible to obtain information on the drugs used by individual departments within the hospital. Comparisons can thus be made conceming the use of a particular group of drugs in one hospital or department and that in another. It could, for instance, be shown that the mean number of agreed daily doses of hypnotics,
646
Clinieal Pharmacology and Therapeuties
Westerholm
MILLION OF TABLETS (n· 103 )
~""'od'__''''
7 6
__x-x x
5
~PhenothiaZines
4
3
2
~,Cb?f~§'~gse~ o ranu ocosis 15 10 5
x-
- - - - - - - - - - . . Comb.sedativesanalgesics x_X-x
o 1965 1966 1967 1968 1969 1970 1971 Year
Fig. 2. Sales of metamizol (dipyrone) in Sweden following warnings to the medical profession and number of reported cases of agranulocytosis. (From Böttiger, L. E., and Westerho1m, H.: Drug-induced blood dyscrasias in Sweden, Br. Med. J. 3:339-343, 1973.)
sedatives, and minor tranquilizers per treatment day delivered to the departments of medicine and gynecology was about the same in the two specialties but a wide variation was noted between hospitals (Table 11). The delivery to psychiatrie departments so far has been analyzed in only two hospitals. In one the number of delivered daily doses per treatment day was 1.55, in the other it was 0.83. It is not yet known whether the high figure in the former hospital is due to the use of higher daily doses or whether there is some sort of wastage of the drugs. It is also possible to look at the number of different drugs being used in each pharmacologic group. In most of our hospitals there are drug committees which try to cut down the number of different drugs used. The number of hypnotics, sedatives, and minor tranquilizers used in the different hospital departments varied a good deal (Table III). The hospitals with very active drugcommittees tend to have the lowest number ofdrugs within each group. Judging from the profile of drugs being used in the various departments it appears that some prefer
0---0---....0---... Tricyclic antidepressants
_ _ _ _ _ _ Barbiturates ---..
1970
1971
-
1972
-Central stimulants
1973
YEAR
Fig. 3. Sales of psychotropic drugs in Sweden from 1970 through 1973.
barbiturates and others nitrazepam as sleeping pills. At present the information from the hospital delivery statistics can serve as an alert as to what to look for in depth. Whatever the answers, the data seem to be useful for the drug committees in the various hospitals. Prescription data
From the information on the prescription one can obtain data of age and sex distribution of the users, drugs prescribed, with dosage and amount, and specialty of the physician. Since December, 1973, the Swedish National Corporation of Pharmacies has analyzed a 1:288 sample of the prescriptions collected from pharmacies. Tables IV, V, and VI give a picture of the type of information which can be obtained. As in other investigations, it could be shown that more women than men use psychotropic drugs and that the use increases with age. From this type of data it is, however, not possible to judge to what extent overuse exists since it is not known why the drugs have been prescribed and how they are taken. It is gratifying to see that in this sample there were no prescriptions of chloramphenicol, which in Sweden is promoted only for typhoid and
Volume /9 Number 5. Part 2
Drug usage in Sweden
647
Table I. Yearly sale of psychotropic drugs in Sweden and Norway, 1970-1972 No. of agreed daily doseslJ ,000 inhabitantslday
ISweden
1972
1971
1970
ISweden
ISweden
1972 ratio
NorwaylSweden (%)
Group of drugs
Norway
Sedatives and hypnotics Minor tranquilizers Major tranquilizers Antidepressants
26 41 6 5
40 32 8 8
23 39 6 5
38 32 8 8
23 36 6 5
32 32 9 8
72 113 67 63
Total
78
88
73
86
70
81
86
Norway
Table 11. Deliveries 0/ hypnotics, sedatives, and minor tranquilizers to medical and gynecologic (including obstetric) departments, 1973 No. of agreed daily doses per treatment day Type of hospital and department
No,
University: Interna! medicine Gynecology and obstetries
6 6
County: Internal medicine Gynecology and obstetries
21 21
Mean
0,47 0,42
0.56 0,42
I Range 0.32-0.71 0.24-0.61
0.28-0.85 0.15-0.77
paratyphoid, and when the drug has been shown to be superior to other drugs by bacteriologic tests or possibly when treating fulminant pyrexia without a clear bacteriologic diagnosis in hospital. Another study of interest going on in the county of Jämtland in Sweden is the continuous registration of individual purchases of drugs on prescription. The registration started March, 1968, in the town of Östersund. 3 Initially one fifteenth of the population in Östersund was monitored; in 1970 two fifteenths of the population in the whole county of Jämtland where Östersund is the main town was included in the investigation. The purchases of sedatives, hypnotics, and
Norway
Table 111. No. 0/ different hypnotics, sedatives, and minor tranquilizers delivered to medical and gynecologic (including obstetric) departments, 1973 Type of hospital and department University: Internal medicine Gynecology and obstetries County: Internal medicine Gynecology and obstetries
No. of specialties No.
Mean
I Range
5
25
21-36
6
18
13-27
21
20
11-29
21
13
7-21
minor tranquilizers in Östersund during the period from March, 1968, to June, 1969, were analyzed by Bergström and Westerholm." Almost half of the patients (46%) obtained only one such prescription during the 16-mo period studied and 9% had eight or more. These two groups, called Group Sand R, respectively, were compared with regard to other drugs used and numbers of tablets per prescription. Since there has been much concern about the use and overuse of hypnotics, sedatives, and minor tranquilizers, it was thought of interest to follow these patients and study their prescription drug purchases 5 yr later, that is, in 1973.5 The material from 1968-1969 comprised 417 patients in Group Sand 76 in Group R. The number of patients no longer living in the county is the same in the two groups percentagewise, namely, 17%. Of those remaining in
648
Westerholm
Clinical Pharmacology and Therapeutics
Table IV. NHS prescriptions, March, 1974: Psychotropic drugs, sample 1: 288
0/ prescriptions per age
No.
0-14 Drug Hypnotics, sedatives, minor tranquilizers Major tranquilizers Antidepressants Central stimulants Total
15-44
MI F
group (yr)
45-64
MI
F
MI
65F
MI
Total
F
MI
F
14
7
86
161
176
260
113
252
389
680
3 3 0
7 0 0
40 12 2
43 31 12
61 32 7
78 40 17
31 2 6
68 26 11
135 49 15
196 97 40
20
14
140
247
276
395
152
357
588
1,013
Table V. NHS prescriptions, March, 1974: Hypnotics, sedatives. and minor tranquilizers, sample 1 : 288 No.
15-44
0-14
Drug Barbiturates Piperidinedione derivatives Propanediols Benzodiazepines Alcohols, aldehydes Antihistamines Bromides Others (combinations, etc.) Total
M
1 1 0 0 0 11
14
0/ prescriptions per
IF
1 0 0 0 0 5
7
age group (yr)
45-64
65-
MI
F
MI
F
7 3 1 51 1 6
14 3 2 105 2 6
21 6 1 105 5 7
17 5 4 158 3 11
17
29
31
86
161
176
the county 247 (59%) in Group S and 48 (63%) in Group R lived in the area of the town of Östersund, the others farther outside but still within the border of the county of Jämtland. The reasons for no longer living in the county are death (43 cases) and movement to other areas (42). Of the diseased patients, four committed suicide, two belonged to Group S, and two to Group R. Of the patients stillliving in the county, 23 % in Group S bought hypnotics, sedatives, and minor tranquilizers in 1973. The corresponding figure in Group S is 87%. A decrease in the number of prescriptions was noticed in Group R in 1973 as compared to 1968 to 1969. There was also a decrease of the number of tablets per individual per month and a change from larger to smaller amounts of drugs per prescription.
I
I
F
M
12 0 4 69 2 3
42 1 4 143 3 13
41 10 6 225 8 27
62
23
46
72
138
260
113
252
389
680
-0-
M
Total F
74 9 10 406 8 35
The benzodiazepines dominated both groups both in 1968-1969 and 1973, followed by barbiturates. Percentagewise there was a shift from the latter to the former in 1973. From information about the number of tablets prescribed and the dosage, it could be estimated when the patient should return for refill. In Group S there was only one patient showing a tendency to shorten the intervals between refills. This patient was using nitrazepam. Without knowledge of the patient's medical history and the reason for the prescription it is not possible to judge whether there was an overuse or not. In Group R three individuals have reduced the purchase intervals or increased the amounts obtained in 1973 as compared with 1968-1969. In two the increase is insignificant and does not cause a suspicion
Drug usage in Sweden
Volume 19 Number 5, Part 2
649
Tahle VI. NHS preseriptions, March, 1974: Chemotherapeutic agents, sample 1 :288 No.
0/ prescriptions per age group (yr) 15-44
0-14
Drug
MI
F
M
Sulfonamides Penicillins Tetracyclines Streptomycin Ch1oramphenico1 Erythromycin Anti-TB Bactrim group Others
1 100 0 0 0 20 1 0 5
9 92 2 1 0 9 0 2 5
9 95 36 0 0 10 0 0
Total
127
120
I
65-
45-64
MI
F 23 128 48 0 0
F
MI
11
13 32 20 0 0 4
10
0 7 24
5 0 17
22 47 23 1 0 9 1 4 22
160
241
91
129
of overuse. The third patient was known already in 1968 as a drug abuser and is under the supervision of one psychiatrist who prescribes the drugs for 1- or 2-wk periods at a time. The findings in this study indicate that at least in a rural population the risk of developing misuse of sedatives in a 5-yr period is not very large. However, only partial conclusions should be drawn from this study since it is not known why the drugs have been prescribed and how the patients actually have taken them. Prescription data combined with interviews
The Department of Drugs of Sweden (corresponding to the FDA in the United States) has to follow the prescribing and use of drugs and to take necessary steps in case anything unsatisfactory is revealed. Because of the criticism of the prescribing of hypnotics and sedatives, prescriptions including these drugs were analyzed in various ways. During a 6-mo period repeat prescriptions, on which patients had obtained the drugs at least twice as quickly as could be expected from the amount and dosage, were sent to the Department of Drugs by all pharmacies in Sweden on a voluntary basis." The number of prescriptions received was 2,218 and the number of drug orders was 2,419. Of these prescriptions 1,311 (59%) were intended for women. The most common drugs were barbiturates and benzodiazepines.
Total
I
F
F
M
13 18 12 0 0 2 0 0 8
21 32 0 0 5 2 5 20
36 245 68 0 0 36 6 0 40
75 299 84 2 0 34 3 18 71
53
96
431
586
11
The total number of doctors responsible for the prescriptions was 907, most of whom had written only a few such prescriptions. For 716 doctors information was obtained conceming age, specialty, and place of work. Fifty-five per cent were 50 yr of age and above. The youngest doctors were between 30 and 40 yr of age. Doctors with no specialty head the list, followed by internists and general practitioners. If the repeat prescriptions had been issued with extremely short intervals, or if one doctor had very many such patients, a letter was sent asking why the drug was prescribed. Altogether this part of the study comprised 121 doctors and 736 patients. The symptoms for which the drugs were prescribed were mainly insomnia and psychotic disorders. For 224 patients (30%) no information was obtained about the period during which the doctor had been in charge of the patient; 45 (6%) were new, 42 (6%) had been known by the doctor for 1-2 yr, and 388 (54%) for at least 3 yr. A total of 115 patients had received psychiatrie treatment earlier; 20 were now in hornes for the aged. In 240 cases (33%) the doctor had suspected too high a consumption, in 132 acceptable reasons were presented for the quick refill, e.g., holiday trip, pharmacy far away. Seventy-seven patients had given some of the tablets to relatives. Ninety-one patients had been recommended on the phone by the doctor to use a higher dosage than the one written on the prescription.
650
Westerholm
This repeat-prescription investigation may be criticized because one does not know to what extent pharmacies did not send in prescriptions. However, it gives some information on who prescribes hypnotics, sedatives, and minor tranquilizers on repeat prescriptions and to whom and for what. Plasma level determinations
The crucial point in the discussion on drug usage, however, is information on to what extent the patients have actually consumed the drugs sold and whether they obtained the drugs over the counter or on prescription. The most objective method to measure the consumption is by means of plasma determinations. Such determinations are performed for certain drugs and mainly in hospitals with a clinical pharmacologic laboratory . It is usually inpatients who are examined but there has been one outpatient study which is of particular interest here. A comparison between digoxin-treated patients in Funäsdalen (outpatient care) and Huddinge Hospital has shown considerable differences in plasma concentrations at the same prescribed doses. In the hospitalized patients about 20% (174) had levels about 2 ng/ml, whereas in outpatients (66) 3% were above this level. A possible subtherapeutic concentration (~0.5 ng/ml) was found in 20% of the outpatients as compared to 11% among the hospitalized individuals. When the outpatients had been informed about the importance of taking the prescribed dose, a significant increase of the plasma levels was seen in eight patients. In some patients low digoxin levels could be attributed to too low a dose prescribed in relation to the body weight.
Clinical Pharmacology
and Therapeutics
Final re marks
We have far from a complete picture concerning the extent to which, why, and how drugs are being used. Overconsumption of drugs has been the subject of several papers and discussions while the problem of underconsumption has been more or less overlooked. Thus further efforts are needed to elucidate how optimal drug therapy can be reached. References 1. Bergman, U., Elmes, P., Halse, M., Lunde, P. K. M., Sjöqvist, F., and Westerho1m, B.: The measurement of drug consumption, Eur. J. Clin. Pharmaco!. 8:83-89, 1975. 2. Bergman, U., Sjöqvist, F., and Söderhjelm, L.: Utilization of digoxin in a low-density population area in Sweden. In press, Eur. J. Clin. Pharmaco!. 3. Bergström, 1., Carmstad, A., Elwin, C-E., Heedman, P-A., Källström, B., Moell, B., Swaren, U., Westerho1m, B., and Wiman, F.: Läkemedelsregistrering i Jämtlands län. Kliniska erfarenheter fran förstudie 1968, Läkartidningen 67 (Supp!. 3):91-99, 1970. 4. Bergström, K., and Westerho1m, B.: Ueköp av sedativa, hypnotika och ataraktika i Östersundsomradet, Läkartidningen 69:1366-1370, 1972. 5. Boethius, G., and Westerho1m, B.: Is the use of hypnotics, sedatives and minor tranquilizers a major health problem? In press, Acta Med. Scand. 6. Böttiger, L. E., and Westerho1m, B.: Druginduced blood dyscrasias in Sweden, Br. Med. J. 3:339-343, 1973. 7. Carmstad, A., Davidson, B., Holmberg, B., and Ström, S.: Central data-behandling av läkemedelsleveranser till sjukhus, Sven. Farm. Tidskr. 74:809-916, 1970. 8. Halvorsen, I. K., Halse, M., and Lunde, P. K. M.: Sammenligning av legemiddelforbruk (salg), Norden, Nord. Med. 89:84-88, 1974. 9. Westerho1m, B.: Minskad försäljning av psykofarmaka efter informationskampanj, Socialnytt. Nr. 4, 1974.
