1608897
« Int. Phaimacopsychiat. 13: 230-233 (1978)
Therapy of Extrapyramidal Side Effects, with Particular Reference to Persistent Dyskinesia and Lithium Tremor1 W. Pöldinger Kantonale Psychiatrische Klinik, Wil/St. Gallen
Key Words. Persistent dyskinesia • Lithium tremor ■ Amantadine ■ Bromocriptine • Ox prenolol Abstract. In 13 of 27 cases of persistent dyskinesia, treatment with amantadine, in an average dose of 300 mg, brought good to moderate improvement. In 14 patients who showed no response whatever, further treatment, with bromocriptine in doses raised gradu ally to a final daily dosage of 15 mg, was effective in four cases, though the improvement was generally only moderate. In more than 50 percent of the cases of initial tremor induced by lithium therapy, oxprenolol in daily doses of 160-240 mg produced good effects and moderate improvement was noted in a few further cases. In a series of 20 patients with initial tremor due to neuroleptic therapy, on the other hand, the same treatment proved unsuccessful in the majority of cases. This is the converse of the experience gained with the classical antiparkinson agents, which have proved more effective against tremor induced by neuroleptics than against lithium-induced tremor.
Persistent Dyskinesia Persistent dyskinesias occurring during long-term treatment with neuroleptics or upon sudden withdrawal of these agents after their long-term administration are among the most refractory of the extrapyramidal side effects of psycho tropic drugs. Unlike the initial dyskinesias, which respond very well to anti parkinson agents, the persistent dyskinesias are rarely, if at all, amenable to such treatment. Only the persistent dyskinesias, appearing after the sudden with drawal of long-term therapy, can be suppressed by the renewed administration of the neuroleptic.
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1 Presented at the VI World Congress of Psychiatry in Honolulu, Hawaii, August 28-September 3, 1977.
231
Therapy of Persistent Dyskinesia and Lithium Tremor Table I. Treatment of persistent dyskinesia with amantadine (300 mg daily) Good effect
Moderate effect
9
4
2
3
7
N
No effect
Oropharyngoglossal syndrome Athetotic motor restlessness Akathisia
11
2 0
2 3
3 8
Total
27
6
7
14
Downloaded by: King's College London 137.73.144.138 - 1/12/2019 9:01:44 AM
Encouraged by a preliminary report that amantadine had a beneficial effect on persistent dyskinesias of this nature, we treated 27 cases with this preparation (2, 5). Table I shows the results of treatment with an average dose of 100 mg amantadine three times a day. Of nine patients with a typical oropharyngoglossal syndrome, four responded well, two moderately well and three not at all. In seven patients with athetotic motor restlessness affecting the arms and the spinal region, we noted good responses in two and moderate responses in another two. As a rule, the improvement became evident in the second week of treatment. Whereas the preparation clearly had a distinct effect on these forms of hyper kinesia, only 3 of 11 patients who developed akathisia during long-term neuro leptic therapy showed a moderate improvement. Nevertheless, it seems to us significant that even as many as 13 of 27 patients with persistent dyskinesias derived some benefit, considering how very resistant to therapy these persistent dyskinesias are. Amantadine was well tolerated in these cases, though it must be remembered that it is not easy to estimate how well a drug is tolerated by these chronically, severely ill schizophrenic patients, who as a rule tend to be mono syllabic and not very communicative. It should be added that the series com prised 19 men and 8 women, of ages ranging from 36 to 61 years, who had, on the average, been receiving neuroleptic therapy for more than 3 years. One woman who developed galactorrhoea during long-term therapy with chlorpromazine was treated with 7.5 mg bromocriptin daily. This not only stopped the discharge but also resulted in a considerable improvement of the dyskinesia so we gave the patients who had failed to respond to amantadine further treat ment with bromocriptine. We increased the dosage gradually, within six days, to 5 mg three times a day, i.e. a total dose of 15 mg daily. Of the 14 patients in
232
Pöldinger Table II. Treatment of persistent dyskinesia with bromocriptine (15 mg daily) Good effect
Moderate effect
3
1
1
1
3 8
0
1
2
0
1
7
14
1
3
10
N
Oropharyngoglossal syndrome Athetotic motor restlessness Akathisia Total
No effect
whom amantadine had had no effect, four showed an improvement (table II). Within the first two weeks of this treatment a notable improvement was seen in one of the three patients with an oropharyngoglossal syndrome refractory to amantadine and a moderate improvement in another. Only one of the three patients with athetotic motor restlessness and one of the eight with tardive akathisia derived any benefit from treatment with bromocriptine, and in both these cases the effects of the drug were moderate. The therapeutic results were thus much poorer than those obtained with amantadine, though it must be conceded that the cases in question were a negative selection, since treatment with amantadine had already proved unsuc cessful.
Therapy of Tremor with Oxprenolol
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On the basis of preliminary reports indicating that oxprenolol can relieve tremor (1), we carried out a therapeutic trial with this compound in patients receiv ing lithium in maintenance dosages sufficient to keep the serum levels at 0.8 meq/1 and in 20 patients in whom initial tremor had appeared during treat ment with neuroleptics. Oxprenolol was administered in doses of 160 to 240 mg daily. Table III shows the results obtained in 26 male and 14 female patients of ages ranging from 18 to 54 years. In all these cases, tremor had developed for the first time during treatment, that is to say, at the outset of treatment. Whereas good results were observed in more than half of the cases in which tremor had
233
Therapy of Persistent Dyskinesia and Lithium Tremor Table III. Treatment of tremor with oxprenolol (160-240 mg daily)
Induced by lithium Induced by neuroleptics
N
Good effect
Moderate effect
No effect
20
11
20
4
4 5
11
5
appeared during long-term therapy with lithium and only 5 patients failed to respond at all, the treatment was less successful in cases of initial tremor induced by neuroleptics. In this latter series of patients, good effects were obtained in 4 cases and moderate effects in 5; 11 patients showed no response whatever, even at a dose of 240 mg daily. These results seem interesting, considering that the classical antiparkinson agents have scarcely any effect or only a very poor effect on lithium tremor. Beside this study we have also seen good effects on the tremor of alcoholics, as reported before (3, 4).
References 1
2
3 4
5
Brosteanu, ÌÌ., Floru, L., and Kaiser, H.: Double-blind trial with oxprenolol versus placebo in the treatment of lithium-induced tremor; in Kielholz Beta-blockers and the central nervous system; pp. 184-190 (Hans Huber, Bern, Stuttgart, Vienna 1977). Di Moscio, A.; Bernardo, D.L.; Greenblatt, D.J., and Marder, J.E.: A controlled trial of amantadine in drug-induced extrapyramidal disorders. Archs gen. Psychiat. 33: 599-602 (1976). Drew, L.R.H.; Moon, J.R., and Buchanan, F.H.: Inderal (propranolol) in the treatment of alcoholism. Med. J. Aust. 282-285 (1973). Kuhn, R.: Discussion (The use of beta-blockers in the management of withdrawal syndromes); in Kielholz Beta-blockers and the central nervous system; p. 158 (Hans Huber, Bern, Stuttgart, Vienna 1977). Merren, M.D.: Amantadine in tardive dyskinesia (cont.). New Engl. J. Med. 286: 385 (1972).
Downloaded by: King's College London 137.73.144.138 - 1/12/2019 9:01:44 AM
Prof. Dr. W. Pöldinger, Chefarzt, Kantionale Psychiatrische Klinik, CH-9500 Wil/St. Gallen (Switzerland)
« Int. Phaimacopsychiat. 13: 230-233 (1978)
Therapy of Extrapyramidal Side Effects, with Particular Reference to Persistent Dyskinesia and Lithium Tremor1 W. Pöldinger Kantonale Psychiatrische Klinik, Wil/St. Gallen
Key Words. Persistent dyskinesia • Lithium tremor ■ Amantadine ■ Bromocriptine • Ox prenolol Abstract. In 13 of 27 cases of persistent dyskinesia, treatment with amantadine, in an average dose of 300 mg, brought good to moderate improvement. In 14 patients who showed no response whatever, further treatment, with bromocriptine in doses raised gradu ally to a final daily dosage of 15 mg, was effective in four cases, though the improvement was generally only moderate. In more than 50 percent of the cases of initial tremor induced by lithium therapy, oxprenolol in daily doses of 160-240 mg produced good effects and moderate improvement was noted in a few further cases. In a series of 20 patients with initial tremor due to neuroleptic therapy, on the other hand, the same treatment proved unsuccessful in the majority of cases. This is the converse of the experience gained with the classical antiparkinson agents, which have proved more effective against tremor induced by neuroleptics than against lithium-induced tremor.
Persistent Dyskinesia Persistent dyskinesias occurring during long-term treatment with neuroleptics or upon sudden withdrawal of these agents after their long-term administration are among the most refractory of the extrapyramidal side effects of psycho tropic drugs. Unlike the initial dyskinesias, which respond very well to anti parkinson agents, the persistent dyskinesias are rarely, if at all, amenable to such treatment. Only the persistent dyskinesias, appearing after the sudden with drawal of long-term therapy, can be suppressed by the renewed administration of the neuroleptic.
Downloaded by: King's College London 137.73.144.138 - 1/12/2019 9:01:44 AM
1 Presented at the VI World Congress of Psychiatry in Honolulu, Hawaii, August 28-September 3, 1977.
231
Therapy of Persistent Dyskinesia and Lithium Tremor Table I. Treatment of persistent dyskinesia with amantadine (300 mg daily) Good effect
Moderate effect
9
4
2
3
7
N
No effect
Oropharyngoglossal syndrome Athetotic motor restlessness Akathisia
11
2 0
2 3
3 8
Total
27
6
7
14
Downloaded by: King's College London 137.73.144.138 - 1/12/2019 9:01:44 AM
Encouraged by a preliminary report that amantadine had a beneficial effect on persistent dyskinesias of this nature, we treated 27 cases with this preparation (2, 5). Table I shows the results of treatment with an average dose of 100 mg amantadine three times a day. Of nine patients with a typical oropharyngoglossal syndrome, four responded well, two moderately well and three not at all. In seven patients with athetotic motor restlessness affecting the arms and the spinal region, we noted good responses in two and moderate responses in another two. As a rule, the improvement became evident in the second week of treatment. Whereas the preparation clearly had a distinct effect on these forms of hyper kinesia, only 3 of 11 patients who developed akathisia during long-term neuro leptic therapy showed a moderate improvement. Nevertheless, it seems to us significant that even as many as 13 of 27 patients with persistent dyskinesias derived some benefit, considering how very resistant to therapy these persistent dyskinesias are. Amantadine was well tolerated in these cases, though it must be remembered that it is not easy to estimate how well a drug is tolerated by these chronically, severely ill schizophrenic patients, who as a rule tend to be mono syllabic and not very communicative. It should be added that the series com prised 19 men and 8 women, of ages ranging from 36 to 61 years, who had, on the average, been receiving neuroleptic therapy for more than 3 years. One woman who developed galactorrhoea during long-term therapy with chlorpromazine was treated with 7.5 mg bromocriptin daily. This not only stopped the discharge but also resulted in a considerable improvement of the dyskinesia so we gave the patients who had failed to respond to amantadine further treat ment with bromocriptine. We increased the dosage gradually, within six days, to 5 mg three times a day, i.e. a total dose of 15 mg daily. Of the 14 patients in
232
Pöldinger Table II. Treatment of persistent dyskinesia with bromocriptine (15 mg daily) Good effect
Moderate effect
3
1
1
1
3 8
0
1
2
0
1
7
14
1
3
10
N
Oropharyngoglossal syndrome Athetotic motor restlessness Akathisia Total
No effect
whom amantadine had had no effect, four showed an improvement (table II). Within the first two weeks of this treatment a notable improvement was seen in one of the three patients with an oropharyngoglossal syndrome refractory to amantadine and a moderate improvement in another. Only one of the three patients with athetotic motor restlessness and one of the eight with tardive akathisia derived any benefit from treatment with bromocriptine, and in both these cases the effects of the drug were moderate. The therapeutic results were thus much poorer than those obtained with amantadine, though it must be conceded that the cases in question were a negative selection, since treatment with amantadine had already proved unsuc cessful.
Therapy of Tremor with Oxprenolol
Downloaded by: King's College London 137.73.144.138 - 1/12/2019 9:01:44 AM
On the basis of preliminary reports indicating that oxprenolol can relieve tremor (1), we carried out a therapeutic trial with this compound in patients receiv ing lithium in maintenance dosages sufficient to keep the serum levels at 0.8 meq/1 and in 20 patients in whom initial tremor had appeared during treat ment with neuroleptics. Oxprenolol was administered in doses of 160 to 240 mg daily. Table III shows the results obtained in 26 male and 14 female patients of ages ranging from 18 to 54 years. In all these cases, tremor had developed for the first time during treatment, that is to say, at the outset of treatment. Whereas good results were observed in more than half of the cases in which tremor had
233
Therapy of Persistent Dyskinesia and Lithium Tremor Table III. Treatment of tremor with oxprenolol (160-240 mg daily)
Induced by lithium Induced by neuroleptics
N
Good effect
Moderate effect
No effect
20
11
20
4
4 5
11
5
appeared during long-term therapy with lithium and only 5 patients failed to respond at all, the treatment was less successful in cases of initial tremor induced by neuroleptics. In this latter series of patients, good effects were obtained in 4 cases and moderate effects in 5; 11 patients showed no response whatever, even at a dose of 240 mg daily. These results seem interesting, considering that the classical antiparkinson agents have scarcely any effect or only a very poor effect on lithium tremor. Beside this study we have also seen good effects on the tremor of alcoholics, as reported before (3, 4).
References 1
2
3 4
5
Brosteanu, ÌÌ., Floru, L., and Kaiser, H.: Double-blind trial with oxprenolol versus placebo in the treatment of lithium-induced tremor; in Kielholz Beta-blockers and the central nervous system; pp. 184-190 (Hans Huber, Bern, Stuttgart, Vienna 1977). Di Moscio, A.; Bernardo, D.L.; Greenblatt, D.J., and Marder, J.E.: A controlled trial of amantadine in drug-induced extrapyramidal disorders. Archs gen. Psychiat. 33: 599-602 (1976). Drew, L.R.H.; Moon, J.R., and Buchanan, F.H.: Inderal (propranolol) in the treatment of alcoholism. Med. J. Aust. 282-285 (1973). Kuhn, R.: Discussion (The use of beta-blockers in the management of withdrawal syndromes); in Kielholz Beta-blockers and the central nervous system; p. 158 (Hans Huber, Bern, Stuttgart, Vienna 1977). Merren, M.D.: Amantadine in tardive dyskinesia (cont.). New Engl. J. Med. 286: 385 (1972).
Downloaded by: King's College London 137.73.144.138 - 1/12/2019 9:01:44 AM
Prof. Dr. W. Pöldinger, Chefarzt, Kantionale Psychiatrische Klinik, CH-9500 Wil/St. Gallen (Switzerland)
