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Current Medical Research and Opinion
Vol. 6 , No. 1 , 1979
Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
B. 0. Williams, M.B., Ch.R., M.R.C.P., and
D. Carlyle, M.B., Ch.B. Department of Geriatric Medicine, The Victoria Infirmary, Glasgow, Scotland
Cum. Med. Res. Opin., (1979), 6, 1.
Received : 8th December 1978
Summary A clinical evaluation was carried out in 20 elderly patients with parkinsonism to assess the effectiveness and acceptability of treatment with a combinution preparation of levodopa and benserazide over a period of 9 months. Mean daily maintenance dosage was 612.5 mg levodopa and 140 mg benserazide. The effects of treatment on clinical features and activities of daily living were monitored at monthly intervals. SigniJicant improvement occurred in thefirst month and optimal improvement was usually reached by the end of 3-months’ treatment. Akinesia and rigidity were abolished or improved in the majority ofpatients but the effect on tremor was less satisfactory. Thepreparation was well tolerated and side-effects were not troublesome. Key words: Levodopa - benserazide - drug therapy, combination - parkinsonism
Introduction The efficacy of levodopa in the treatment of parkinsonism has been well demonstrated’ .2 and there has been a resultant significant increase in the life expectancy of patients with this disorder.’ Combination therapy comprising levodopa and a peripheral dopa-decarboxylase inhibitor, carbidopa (1-u-methyldopahydrazine) or benserazide (dl-2-amino-hydroxy-2-2,3,4,4-trihydroxybenzyl propionohydrazide) (‘Madopar’t), have been shown to have greater eficacy and fewer side-effects than levodopa alone.6.8 A combination preparation is now the first choice in those patients in whom levodopa therapy is indicated.’ This paper reports on the therapeutic effects and adverse reactions of the combination preparation of levodopa and benserazide (‘Madopar’) in a group of elderly patients.
Patients and methods Twenty patients were included in the trial, 12 females and 8 males with an age range of 63 to 87 years (mean 79 years). The diagnosis of parkinsonism was made when 2 of the 3 features of akinesia, rigidity and tremor were present. Twelve patients had received no previous antiparkinsonism therapy, 2 patients had been treated with ttrade mark, Roche 1
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Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
anticholinergic drugs, 2 with levodopa, 3 with levodopa and carbidopa, and 1 patient had been receiving levodopa, anticholinergics and amantidine. Only 1 patient had received phenothiazines and these had been stopped for 3 weeks before the trial commenced. Each patient was initially examined and the clinical signs and functional disabilities noted were evaluated and scored as described by the two-part system of McDowell et a1.5 The activities of daily living were assessed by 2 trained occupational therapists. Initial investigations included a full blood count, serum urea, electrolytes and creatinine, liver function tests, full urinalysis, a 12-lead electrocardiogram and chest radiograph, and these tests were repeated at the end of the study. Mental status was assessed using a 16-question test covering orientation, simple calculation, memory for remote and recent events, names of prominent people, dates of important events and ability for short-term recall. Seventeen patients had no evidence of intellectual deficit, while 1 maleand 2 female patients had evidence of mild dementia. Seven patients required initial in-patient management but were later followed up as out-patients. Eight patients were managed at the out-patient department throughout the trial period and 5 patients required continuing hospital care. Each patient was assessed monthly and the disability scores were noted. The percentage improvement achieved was derived from the formula: initial total score - score at maximal improvement x loo. initial score Dosage The 12 previously untreated patients were commenced on 1 capsule (‘Madopar’ 125) containing 100 mg levodopa and 28.5 mg benserazide hydrochloride (equivalent to 25 mg of the base) twice daily and the dosage was increased twice each week until the optimal therapeutic effect was obtained or side-effects supervened. Those patients previously treated with levodopa alone were changed over to the combination. At the time of change-over, 500 mg levodopa was replaced with 1 capsule of the combination and for the first 48 hours of the new regimen, 1 capsule less than the calculated equivalent dosage was used. Thereafter, the dosage was adjusted as already described. All other antiparkinsonism therapy was discontinued. Maintenance dosage of the combined preparation ranged from 1 capsule twice daily to 2 capsules 3-times a day (mean 612.5 mg levodopa and 140 mg benserazide daily). The preparation was well tolerated by the whole group.
Results The 20 patients were followed up for a mean period of 8 months (2 to 11 months) and 15 patients completed more than 6 months of the trial. The results were analyzed by Student’s t-test. Clinicalfeatures The therapeutic effects on the main clinical features of parkinsonism are shown in Tables I, I1 and Figure 1. 2
B. 0. Williams and D. Carlyle
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Table 1. Changes in the main clinical features of patients with parkinsonism during treatment with levodopa and benserazide Clinical feature
Akinesia
Rigidity
Tremor
Abolished Improved A bolished/recurred Transient during therapy No change Worse
11 2 4
13
4
4
3
2
2 1
Total no. patients
19
1
3 1 1
20
13
Table 11. Changes in group mean scores for clinical features over 9 months of treatment: mean (H3.E.M.) scores Clinical feature
Akinesia (max. 10 points) Rigidity (max. 14 points) Tremor (max. 10 points)
Before treatmen t
After treatment
1 month
3 months
6 months
9 months
1 2 . 8 1 1.0
4.3+1.3*
3.7 4-1.1
2.7t1.4
1.31-1.3
7.7+0.5
7.0+0.5
4.1+1.1**
2.311.0
2.611.3
5.4+1.1
5.011 .O
2.9 t l . O
2.1 t 1 . 0
Not scored
Note: significant difference from previous period *p < 0.01, * * p i 0.02 (t-test) Figure 1. Changes in group mean scores for the clinical features of akinesia, rigidity and tremor over 9 months
-
-
Akinesia
0-
- - o Rigidity Tremor
I
1
I
2
1
3
I
4
1
5
6
7
I
8
9
Time (months) 3
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Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
Akinesia was abolished in 11 patients, improved in 2, and temporarily abolished in 4, with no effects in the remaining 2 patients. A significant reduction in akinesia occurred during the first month but there was no further significant change during the trial (Table 11). Rigidity was abolished in 13 patients, temporarily abolished in 4, and worsened in 1 patient. There was no significant change noted in the mean score for rigidity until 3 months of therapy had elapsed (Table 11) and there was no further significant change during the trial. Tremor was abolished in 4 patients, improved in 1 patient, and temporarily abolished in 3 patients. This feature occurred transiently during therapy in 3 patients and became worse in the male patient with vascular dementia. There was no significant reduction in the mean score for tremor during the trial until 9 months but at this time the number of patients remaining with tremor was too small to be considered significant. Activities ojduily living The group mean total scores for activities of daily living are shown in Table I11 and Figure 2. There was a significant reduction in disability in terms of activities of daily living during the first month of therapy but no significant change occurred thereafter in the trial. Table 111. Changes in group mean scores for total scores for clinical features, activities of daily living, and both combined, over 9 months of treatment: mean (&S.E.M.) scores Assessment
Clinical features (max. 88 points) Activities of daily living (max. 132 points) Score for disability (max. 220 points)
Before treatment
After treatment month 3 months
6 months
9 months
32.1*2.3
20.8*2.1*
15.7k2.7
11.9*2.2
11.353.8
65.717.3
42.2*4.9**
38.0*6.8
42.4+13.1
46.6*12.9
97.8+8.3
63.0&5.9*
53.718.9
54.3*12.7
57.9*15.8
Note: significant differences from previous period *p< 0.01, **p < 0.02 (t-test)
0verull scores The changes in overall scores are shown in Tables 111, IV and Figure 2. In the first month of therapy, 18 patients had improved their overall scores by a mean of 40 % (range 14 % to 71 %). Two patients deteriorated in the first few weeks and one of these, a man of 63 years with vascular dementia, continued to deteriorate until his death after 8 months in the trial. The other, a woman of 67 years, appeared to improve after her initial deterioration. Optimal improvement was reached by half of the group by the end of the first 3 months of therapy. Nineteen patients improved during the trial with a mean improvement of 67 % (range 35 % to 100%) and, overall, 15 patients improved by more than 50 %. The significant change in the mean total points score for the group was noted during the first month of therapy (Table 111) and there was no significant change thereafter. 4
B.0. Williams and D. Carlyle
Figure 2. Changes in group mean scores for total scores for clinical features, activities of daily living, and both combined, over 9 months
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0-
1
I
1
1
3
-
Clinical features Activities of daily living Total disability
-0
4
I
I
6
5
I
7
I
8
i
9
Time (months) Table IV. Percentage improvement in total scores for clinical features and activities of daily living in patients with parkinsonism after treatment
% improvement 85 to 100 50 to 75 25 to 50 0 to 25
No. patients 6 9 4 1
Adverse effects Details of the adverse effects reported during the trial are given in Table V. Table V. Side-effects of levodopa and benserazide reported during trial Side-effect Nausea Nightmares/confusion Involuntary movements On/off effect Asymptomatic postural hypotension Symptomatic postural hypotension
No. patients 4 1 2 2 4 2
5
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Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
Seven patients had one or more side-effects but all of these problems were controlled by adjustment of the individual patient’s drug regimen. Nausea was reported by 4 patients and 2 of these suffered from this symptom only during ambulance journeys. One patient experienced nocturnal confusion and nightmares and involuntary movements were observed in 2 patients. Three patients had a slight reduction in the supine blood pressure and 6 patients had demonstrable postural hypotension (systolic blood pressure drop of 30 mmHg or more), 2 of these with associated symptoms. There were no abnormalities detected in the haematological or biochemical investigations apart from a slight rise in the blood urea in 9 patients. The initial electrocardiogram was normal in 9 patients, 2 tracings showed evidence of previous acute myocardial infarction, 6 were ischaemic in character, and the remaining 3 showed evidence of conduction defects. The tracings were repeated at the end of the trial period and there were no changes noted.
Discussion In the management of parkinsonism there appears to be little difference between the therapeutic effects and side-effects of levodopa with benserazide and levodopa with carbidopa’3~~ but side-effects with either combination are considerably fewer than with levodopa alone. Pakkenberg et al.9 reported fewer side-effects with the levodopalbenserazide preparation in acomparative study of the two combination preparations but this was most likely due to a higher dosage of levodopa administered as levodopalcarbidopa during the trial and side-effects appear to depend on the total daily dosage of levodopa.3 In this study, the combination preparation of levodopa and benserazide (‘Madopar’) proved effective in improving the clinical features of parkinsonism in a group of elderly patients. The preparation was easily swallowed, well tolerated and sideeffects were not troublesome. Gastro-intestinal upset (20 %) and involuntary movements (10%) were less common than have been reported el~ewhere.~,’ O The combination preparation proved effective and was well tolerated in 5 patients who had developed unacceptable gastro-intestinal side-effects with levodopa alone or with levodopa/carbidopa therapy. All of the patients improved during this trial, except 1 man, with a diagnosis of vascular dementia and extrapyramidal signs, whose condition deteriorated until his death. Significant improvement occurred in the first month and optimal improvement was usually reached by the end of 3-months’ treatment. Akinesia and rigidity were abolished or improved in the majority of patients, but the effect on tremor was less satisfactory and less sustained. In conclusion, levodopa and benserazide (‘Madopar’) appear to be a safe and effective combination in the treatment of elderly patients with parkinsonism. 6
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B. 0. Williams and D. Carlyle
References 1. Broe, G. A., and Caird. F. I., (1973). Levodopa for parkinsonism in elderly and demented patients. Med. J. Aust., 1, 630-635. 2. Cotzias, G. C., Papavasiliou, P. S.,and Gellene, R., (1969). Modification of parkinsonism chronic treatment with L-dopa. N . Engl. J. Med., 280,337-345. 3. Greenacre, J. K., Coxon, A., Petrie, A., and Reid, J. L., (1976). Comparison of levodopa with carbidopa or benserazide in parkinsonism. Lancet, 2,381-384. 4. Korten, J. J., Keyser, A., Joosten, E. M. G., and Gabreels, F. J. M., (1975). Madopar versus Sinemet: a clinical study on their effectiveness. Eur. Neurol., 13,65-71. 5 . McDowell, F., Lee, J. E., Swift, T., Sweet, R. D., Ogsbury, J. S.,and Kessler, J. T.,(1970). Treatment of Parkinson’s syndrome with I-dihydroxyphenylalanine(levodopa). Ann. Intern. Med., 72,29-35. 6. Markham, C. H., Diamond, S. G., and Treciokas, L. J., (1974). Carbidopa in Parkinson’s disease and in nausea and vomiting of levodopa. Arch. Neurol., 31,128-133. 7. Marsden, C. D., (1976). Advances in the management of Parkinson’s disease. Scott. Med. J.. 21, 139-148. 8. Miller, E. M., and Wiener, L.,(1974). RO4-4602and levodopa in the treatment of parkinsonism. Neurology, 24,482-486. 9. Pakkenberg, H., Birket-Smith, E., Dupont, E., Hansen, E., Mikkelsen, B., Presthus, J., Rautakorpi, I., Riman, E., and Rinne, U. K., (1976). Parkinson’s disease treated with Sinemet or Madopar: a controlled multicentre trial. Acta Neurol. Scand., 53,376-385. 10. Rinne, U. K., Birket-Smith, E., Dupont, E., Hansen, E., Hyyppa, M., Marttila, R., Mikkelsen, B., Pakkenberg, H., and Presthus, J., (1975). Levodopa alone and in combination with a peripheral
decarboxylase inhibitor benserazide (Madopar) in the treatment of Parkinson’s disease: a controlled clinical trial. J . Neurol., 211, 1-9. 11. Sweet, R. D., and McDowell, F. H., (1975). Five years’ treatment of Parkinson’s disease with levodopa. Therapeutic results and survival of 100 patients. Ann. Intern. Med., 83,456-463.
7
Current Medical Research and Opinion
Vol. 6 , No. 1 , 1979
Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
B. 0. Williams, M.B., Ch.R., M.R.C.P., and
D. Carlyle, M.B., Ch.B. Department of Geriatric Medicine, The Victoria Infirmary, Glasgow, Scotland
Cum. Med. Res. Opin., (1979), 6, 1.
Received : 8th December 1978
Summary A clinical evaluation was carried out in 20 elderly patients with parkinsonism to assess the effectiveness and acceptability of treatment with a combinution preparation of levodopa and benserazide over a period of 9 months. Mean daily maintenance dosage was 612.5 mg levodopa and 140 mg benserazide. The effects of treatment on clinical features and activities of daily living were monitored at monthly intervals. SigniJicant improvement occurred in thefirst month and optimal improvement was usually reached by the end of 3-months’ treatment. Akinesia and rigidity were abolished or improved in the majority ofpatients but the effect on tremor was less satisfactory. Thepreparation was well tolerated and side-effects were not troublesome. Key words: Levodopa - benserazide - drug therapy, combination - parkinsonism
Introduction The efficacy of levodopa in the treatment of parkinsonism has been well demonstrated’ .2 and there has been a resultant significant increase in the life expectancy of patients with this disorder.’ Combination therapy comprising levodopa and a peripheral dopa-decarboxylase inhibitor, carbidopa (1-u-methyldopahydrazine) or benserazide (dl-2-amino-hydroxy-2-2,3,4,4-trihydroxybenzyl propionohydrazide) (‘Madopar’t), have been shown to have greater eficacy and fewer side-effects than levodopa alone.6.8 A combination preparation is now the first choice in those patients in whom levodopa therapy is indicated.’ This paper reports on the therapeutic effects and adverse reactions of the combination preparation of levodopa and benserazide (‘Madopar’) in a group of elderly patients.
Patients and methods Twenty patients were included in the trial, 12 females and 8 males with an age range of 63 to 87 years (mean 79 years). The diagnosis of parkinsonism was made when 2 of the 3 features of akinesia, rigidity and tremor were present. Twelve patients had received no previous antiparkinsonism therapy, 2 patients had been treated with ttrade mark, Roche 1
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Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
anticholinergic drugs, 2 with levodopa, 3 with levodopa and carbidopa, and 1 patient had been receiving levodopa, anticholinergics and amantidine. Only 1 patient had received phenothiazines and these had been stopped for 3 weeks before the trial commenced. Each patient was initially examined and the clinical signs and functional disabilities noted were evaluated and scored as described by the two-part system of McDowell et a1.5 The activities of daily living were assessed by 2 trained occupational therapists. Initial investigations included a full blood count, serum urea, electrolytes and creatinine, liver function tests, full urinalysis, a 12-lead electrocardiogram and chest radiograph, and these tests were repeated at the end of the study. Mental status was assessed using a 16-question test covering orientation, simple calculation, memory for remote and recent events, names of prominent people, dates of important events and ability for short-term recall. Seventeen patients had no evidence of intellectual deficit, while 1 maleand 2 female patients had evidence of mild dementia. Seven patients required initial in-patient management but were later followed up as out-patients. Eight patients were managed at the out-patient department throughout the trial period and 5 patients required continuing hospital care. Each patient was assessed monthly and the disability scores were noted. The percentage improvement achieved was derived from the formula: initial total score - score at maximal improvement x loo. initial score Dosage The 12 previously untreated patients were commenced on 1 capsule (‘Madopar’ 125) containing 100 mg levodopa and 28.5 mg benserazide hydrochloride (equivalent to 25 mg of the base) twice daily and the dosage was increased twice each week until the optimal therapeutic effect was obtained or side-effects supervened. Those patients previously treated with levodopa alone were changed over to the combination. At the time of change-over, 500 mg levodopa was replaced with 1 capsule of the combination and for the first 48 hours of the new regimen, 1 capsule less than the calculated equivalent dosage was used. Thereafter, the dosage was adjusted as already described. All other antiparkinsonism therapy was discontinued. Maintenance dosage of the combined preparation ranged from 1 capsule twice daily to 2 capsules 3-times a day (mean 612.5 mg levodopa and 140 mg benserazide daily). The preparation was well tolerated by the whole group.
Results The 20 patients were followed up for a mean period of 8 months (2 to 11 months) and 15 patients completed more than 6 months of the trial. The results were analyzed by Student’s t-test. Clinicalfeatures The therapeutic effects on the main clinical features of parkinsonism are shown in Tables I, I1 and Figure 1. 2
B. 0. Williams and D. Carlyle
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Table 1. Changes in the main clinical features of patients with parkinsonism during treatment with levodopa and benserazide Clinical feature
Akinesia
Rigidity
Tremor
Abolished Improved A bolished/recurred Transient during therapy No change Worse
11 2 4
13
4
4
3
2
2 1
Total no. patients
19
1
3 1 1
20
13
Table 11. Changes in group mean scores for clinical features over 9 months of treatment: mean (H3.E.M.) scores Clinical feature
Akinesia (max. 10 points) Rigidity (max. 14 points) Tremor (max. 10 points)
Before treatmen t
After treatment
1 month
3 months
6 months
9 months
1 2 . 8 1 1.0
4.3+1.3*
3.7 4-1.1
2.7t1.4
1.31-1.3
7.7+0.5
7.0+0.5
4.1+1.1**
2.311.0
2.611.3
5.4+1.1
5.011 .O
2.9 t l . O
2.1 t 1 . 0
Not scored
Note: significant difference from previous period *p < 0.01, * * p i 0.02 (t-test) Figure 1. Changes in group mean scores for the clinical features of akinesia, rigidity and tremor over 9 months
-
-
Akinesia
0-
- - o Rigidity Tremor
I
1
I
2
1
3
I
4
1
5
6
7
I
8
9
Time (months) 3
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Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
Akinesia was abolished in 11 patients, improved in 2, and temporarily abolished in 4, with no effects in the remaining 2 patients. A significant reduction in akinesia occurred during the first month but there was no further significant change during the trial (Table 11). Rigidity was abolished in 13 patients, temporarily abolished in 4, and worsened in 1 patient. There was no significant change noted in the mean score for rigidity until 3 months of therapy had elapsed (Table 11) and there was no further significant change during the trial. Tremor was abolished in 4 patients, improved in 1 patient, and temporarily abolished in 3 patients. This feature occurred transiently during therapy in 3 patients and became worse in the male patient with vascular dementia. There was no significant reduction in the mean score for tremor during the trial until 9 months but at this time the number of patients remaining with tremor was too small to be considered significant. Activities ojduily living The group mean total scores for activities of daily living are shown in Table I11 and Figure 2. There was a significant reduction in disability in terms of activities of daily living during the first month of therapy but no significant change occurred thereafter in the trial. Table 111. Changes in group mean scores for total scores for clinical features, activities of daily living, and both combined, over 9 months of treatment: mean (&S.E.M.) scores Assessment
Clinical features (max. 88 points) Activities of daily living (max. 132 points) Score for disability (max. 220 points)
Before treatment
After treatment month 3 months
6 months
9 months
32.1*2.3
20.8*2.1*
15.7k2.7
11.9*2.2
11.353.8
65.717.3
42.2*4.9**
38.0*6.8
42.4+13.1
46.6*12.9
97.8+8.3
63.0&5.9*
53.718.9
54.3*12.7
57.9*15.8
Note: significant differences from previous period *p< 0.01, **p < 0.02 (t-test)
0verull scores The changes in overall scores are shown in Tables 111, IV and Figure 2. In the first month of therapy, 18 patients had improved their overall scores by a mean of 40 % (range 14 % to 71 %). Two patients deteriorated in the first few weeks and one of these, a man of 63 years with vascular dementia, continued to deteriorate until his death after 8 months in the trial. The other, a woman of 67 years, appeared to improve after her initial deterioration. Optimal improvement was reached by half of the group by the end of the first 3 months of therapy. Nineteen patients improved during the trial with a mean improvement of 67 % (range 35 % to 100%) and, overall, 15 patients improved by more than 50 %. The significant change in the mean total points score for the group was noted during the first month of therapy (Table 111) and there was no significant change thereafter. 4
B.0. Williams and D. Carlyle
Figure 2. Changes in group mean scores for total scores for clinical features, activities of daily living, and both combined, over 9 months
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0-
1
I
1
1
3
-
Clinical features Activities of daily living Total disability
-0
4
I
I
6
5
I
7
I
8
i
9
Time (months) Table IV. Percentage improvement in total scores for clinical features and activities of daily living in patients with parkinsonism after treatment
% improvement 85 to 100 50 to 75 25 to 50 0 to 25
No. patients 6 9 4 1
Adverse effects Details of the adverse effects reported during the trial are given in Table V. Table V. Side-effects of levodopa and benserazide reported during trial Side-effect Nausea Nightmares/confusion Involuntary movements On/off effect Asymptomatic postural hypotension Symptomatic postural hypotension
No. patients 4 1 2 2 4 2
5
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Levodopa/benserazide (‘Madopar’) combination therapy in elderly patients with parkinsonism
Seven patients had one or more side-effects but all of these problems were controlled by adjustment of the individual patient’s drug regimen. Nausea was reported by 4 patients and 2 of these suffered from this symptom only during ambulance journeys. One patient experienced nocturnal confusion and nightmares and involuntary movements were observed in 2 patients. Three patients had a slight reduction in the supine blood pressure and 6 patients had demonstrable postural hypotension (systolic blood pressure drop of 30 mmHg or more), 2 of these with associated symptoms. There were no abnormalities detected in the haematological or biochemical investigations apart from a slight rise in the blood urea in 9 patients. The initial electrocardiogram was normal in 9 patients, 2 tracings showed evidence of previous acute myocardial infarction, 6 were ischaemic in character, and the remaining 3 showed evidence of conduction defects. The tracings were repeated at the end of the trial period and there were no changes noted.
Discussion In the management of parkinsonism there appears to be little difference between the therapeutic effects and side-effects of levodopa with benserazide and levodopa with carbidopa’3~~ but side-effects with either combination are considerably fewer than with levodopa alone. Pakkenberg et al.9 reported fewer side-effects with the levodopalbenserazide preparation in acomparative study of the two combination preparations but this was most likely due to a higher dosage of levodopa administered as levodopalcarbidopa during the trial and side-effects appear to depend on the total daily dosage of levodopa.3 In this study, the combination preparation of levodopa and benserazide (‘Madopar’) proved effective in improving the clinical features of parkinsonism in a group of elderly patients. The preparation was easily swallowed, well tolerated and sideeffects were not troublesome. Gastro-intestinal upset (20 %) and involuntary movements (10%) were less common than have been reported el~ewhere.~,’ O The combination preparation proved effective and was well tolerated in 5 patients who had developed unacceptable gastro-intestinal side-effects with levodopa alone or with levodopa/carbidopa therapy. All of the patients improved during this trial, except 1 man, with a diagnosis of vascular dementia and extrapyramidal signs, whose condition deteriorated until his death. Significant improvement occurred in the first month and optimal improvement was usually reached by the end of 3-months’ treatment. Akinesia and rigidity were abolished or improved in the majority of patients, but the effect on tremor was less satisfactory and less sustained. In conclusion, levodopa and benserazide (‘Madopar’) appear to be a safe and effective combination in the treatment of elderly patients with parkinsonism. 6
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B. 0. Williams and D. Carlyle
References 1. Broe, G. A., and Caird. F. I., (1973). Levodopa for parkinsonism in elderly and demented patients. Med. J. Aust., 1, 630-635. 2. Cotzias, G. C., Papavasiliou, P. S.,and Gellene, R., (1969). Modification of parkinsonism chronic treatment with L-dopa. N . Engl. J. Med., 280,337-345. 3. Greenacre, J. K., Coxon, A., Petrie, A., and Reid, J. L., (1976). Comparison of levodopa with carbidopa or benserazide in parkinsonism. Lancet, 2,381-384. 4. Korten, J. J., Keyser, A., Joosten, E. M. G., and Gabreels, F. J. M., (1975). Madopar versus Sinemet: a clinical study on their effectiveness. Eur. Neurol., 13,65-71. 5 . McDowell, F., Lee, J. E., Swift, T., Sweet, R. D., Ogsbury, J. S.,and Kessler, J. T.,(1970). Treatment of Parkinson’s syndrome with I-dihydroxyphenylalanine(levodopa). Ann. Intern. Med., 72,29-35. 6. Markham, C. H., Diamond, S. G., and Treciokas, L. J., (1974). Carbidopa in Parkinson’s disease and in nausea and vomiting of levodopa. Arch. Neurol., 31,128-133. 7. Marsden, C. D., (1976). Advances in the management of Parkinson’s disease. Scott. Med. J.. 21, 139-148. 8. Miller, E. M., and Wiener, L.,(1974). RO4-4602and levodopa in the treatment of parkinsonism. Neurology, 24,482-486. 9. Pakkenberg, H., Birket-Smith, E., Dupont, E., Hansen, E., Mikkelsen, B., Presthus, J., Rautakorpi, I., Riman, E., and Rinne, U. K., (1976). Parkinson’s disease treated with Sinemet or Madopar: a controlled multicentre trial. Acta Neurol. Scand., 53,376-385. 10. Rinne, U. K., Birket-Smith, E., Dupont, E., Hansen, E., Hyyppa, M., Marttila, R., Mikkelsen, B., Pakkenberg, H., and Presthus, J., (1975). Levodopa alone and in combination with a peripheral
decarboxylase inhibitor benserazide (Madopar) in the treatment of Parkinson’s disease: a controlled clinical trial. J . Neurol., 211, 1-9. 11. Sweet, R. D., and McDowell, F. H., (1975). Five years’ treatment of Parkinson’s disease with levodopa. Therapeutic results and survival of 100 patients. Ann. Intern. Med., 83,456-463.
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