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Combined electroconvulsive and neuroleptic therapy in schizophrenia refractory to neuroleptics
Schizophrenia Elsevier
SCHIZO
Research,
351
3 (1990) 35 I-354
Short communication
00125
Combined electroconvulsive and neuroleptic therapy in schizophrenia refractory to neuroleptics P. Kiinig and U. Glatter-Giitz Landes-Nervenkrankenhaus (Received
Valduna, Department 18 December
of Psychiarry
1989, accepted
26 March
I, Rankwjeil, Austria 1990)
The results of treatment in 13 schizophrenic patients (nine males, four females) who underwent electroconvulsive therapy (ECT) because of varying degrees of therapy resistance to neuroleptics (therapy failures, renewed and in some cases catatonic exacerbation under neuroleptic therapy, neuroleptic intolerance) are reported. The single treatments,which were carried out on average 12 times (between six and 20 times), led from very good to good remission in a period of between 10 and 7 years in nine patients. Four patients did not respond adequately: the small improvement of psychopathology on discharge correlated with unfavorable outcome. In three of these patients, the asthenic syndrome was found on admission and persisted. In patients with good remission, neuroleptics could be reduced after ECT by over 70%, and over 50% in patients with poor remission. This result confirms corresponding literature data with regard to neuroleptics. The results in this highly selected group also confirm Bleuler’s ‘one third rule’ of remissions, also the fact that global outcome does not correlate with response to neuroleptics, as well as confirming the relevance of the psychopathological state on discharge as an outcome predictor. Key words: Neuroleptic
resistance;
Electroconvulsive
therapy;
A re-evaluation of the use of electroconvulsive therapy (ECT) for treatment of severe psychoses has become necessary after various negative appraisals in recent years. Publications of the APA task force on ECT (Fink, 1979) as well as the statement of the Royal College of Psychiatrists have provided the basis for this. For Austria, we have appraised the value of ECT in a psychiatric hospital (catchment area about 300,000 inhabitants, sole inpatient institution with about 15 independently practising psychiatrists (Kbnig, 1989)). We previously described the frequency, establishment of the indication and in some cases the efficiency of diagnoses in that study. In the present paper the course of treatment and the outcome of 13 patients with schizophrenic
0920.9964/90/$03.50
of neuroleptics;
(Schizophrenia)
diseases will be presented. 7-10 years after treatment.
INTRODUCTION
Correspondence Rankweil, Austria.
Reduction
to:
0
P.
Kiinig,
LNKH
1990 Elsevier
Valduna,
Science Publishers
A-6830
PATIENTS
AND
Data
were
collected
METHODS
This is a retrospective survey of patients of both sexes (nine men, four women) who had been hospitalized on the basis of ICD 9 diagnoses 295.0-295.3. The selection was made from the total group of ECT-treated patients in the study quoted above (Kdnig, 1989). Since they had proved to be refractory to neuroleptic therapy, the patients had undergone ECT treatment despite neuroleptic therapy during hospitalization in the period from 1979 to 1982. Patients with belowaverage intelligence, with schizoaffective psychoses or marked fluctuations in mood in the history of their schizophrenic disease were not included in the otherwise random sample.
B.V. (Biomedical
Division)
352
The relevant data were compiled from case histories, the ECT protocols as well as a telephone interview obtained by U.G.-G. from the previously treated patients, their relatives and managing physicians. In some cases, data on premorbid personality and the type of follow-up therapy could not be obtained. The status on admission and discharge was classified in accordance with the IMPS syndrome score scale (Moller et al., 1982); psychotic excitation (PE), paranoid-hallucinatory syndrome (PHS), depressive-apathetic syndrome (DAS), phobic-anancastic and psycho-organic brain syndrome (POS) (see Table 1). From 1979 to 1982, 13 patients (nine males, four females) with an average age of 34 years (range 15-65) at the time of ECT were treated on average 12 times (range 6-20 ECTs). This was carried out on occasion of the first admission in six patients, of the second admission in three patients, and during a further inpatient treatment in four patients. Six patients were not readmitted during the follow-up period (Table 1). In eight patients the indication was established because of resistance to therapy, in three cases because of renewed exacerbation of catatonic symptoms or highly suicidal tendencies. Neuroleptic intolerance was present in one patient. The neuroleptics administered before and after ECT (Table 2) were mainly haloperidol (in some
TABLE
cases clopenthixol), additionally fluphenazine droperidol were used in the acute phase.
and
RESULTS
The case histories show a poor response to ECT (inadequate improvement on discharge) in four patients. The neuroleptic dosage could nevertheless be lowered by 53% in these four patients (after on average 13.5 ECTs). In the psychopathological findings on admission, these patients showed the factor ‘psychotic excitation’ in only one case, and a ‘paranoid-hallucinatory syndrome’ was more pronounced in another case. This psychopathology also persisted after treatment, even if it was mitigated up to the time of discharge. In two of these patients, a depressive-asthenic syndrome was diagnosed on admission. This also persisted up to discharge and was combined with a psycho-organic brain syndrome or a residual state after treatment. Of the four patients, the first two had been hospitalized eight times at the time of treatment. One patient had been hospitalized four times and one patient was hospitalized for the first time. One patient from this group (comprising four patients) is still hospitalized, one patient was hospitalized three times within 4 years after discharge,
1
Classification
of 13 patienis
treated with EC7
Pat.
mlf
y/ECT
ZCD dg.
no. ECTs
Outc.
Rely
ECTjudm.
Treat.yar
B B D E F G H L M M M s W
52 59 22 25 34 15 20 30 31 23 65 40 29
295.3 295.3 295.0 295.3 295.2 295.3 295.3 295.3 295.3 295.3 295.2 295.0 295.3
14 7 15 14 13 16 12 6 8 13 12 20 11
+ + + + + _ + _ + + _ + +
0 0 0.25 0.6 2 6* 0 0.7 0 0.3 stat. 0+ 0
1
)r f m m f m m m m m m f
2 2 2 1 1 1 4 1 7 8** 8+* 1
1979 1979 1980 1980 1980 1981 1981 1982 1982 1982 1983 1983 1983
Key: Patients; sex; age at recorded ETC; ICD diagnosis; individual number re/y = readmission after years; ECT on admission number; year of treatment; previous admission; O+ died later.
of ECTs necessary; outcome: + = good, - = negative; *moved to Turkey; **ECT already carried out during
353
TABLE
2
Neuroleptics
administered
before and after ECT
Pat.
m/t”
NL before/after
B B D E F G H L M M M s w
m f f m m f m m m m m m f
clo/clo drop/halo clo/thio drop/cl0 fluph/halo halo/cloz fluph/halo halojfluph halo/halo halo/halo halo/cl0 halo/halo fluph/halo
CPZU
bt$ore/after
7021600
I,398176 1 1071275 541 l/409
1,484/282 9691233 1,213/669 6101179 614/188 1,045/500 I ,880/306 1,100/1,106 3,122/618
Indication
Outcome
into]. ther.res. autoaggr. ther.res.C therres. therres. therres. ther.res. ther.res. ther.res. ther.res.C ther.res.C ther.res.
+ + + + + _ + _ + + _ +
Keq’: Patients; sex; neuroleptic used before/after ECT: CPZU (chlorpromazine units) before/after ECT; indication for ECT (into1 = drug intolerance, therres. = therapy-resistant, autoaggr. = autoaggressive, C = catatonia); outcome, (+ = good, - = negative); NL = neuroleptic; clo = clopenthixol; thio = thioperazine; drop = droperidol; halo = haloperidol; cloz = clozapine; fluph = fluphenazine.
one patient died later of carcinoma, one female patient was later discharged abroad (a complete record of follow-up was not obtained in this patient; she was hospitalized once more 6 years after discharge). Good response to treatment (improvement of psychopathology at the time of discharge in the CGI of at least three points) was registered in nine patients. ‘Psychotic excitation’ was recorded on admission in five patients, and there were ‘paranoid-hallucinatory syndromes’ in four patients. The remaining IMPS scores (DAS, POS, PHS) were not diagnosed on admission. On discharge after an average of ten ECTs (and neuroleptic treatment), no psychopathological abnormalities could be diagnosed with the following exceptions: one patient showed a depressive-apathetic syndrome and one patient showed a psycho-organicbrain syndrome. In this group of nine patients, the neuroleptic dose could be reduced by about 72% after ECT. In the further course, four patients had one readmission and one patient had two in the follow-up period; the remaining patients were not hospitalized again.
DISCUSSION
The value of ECT in the treatment of (acute) schizophrenic diseases, especially with ‘positive
symptoms’ appears to be adequately documented in the literature (summary in Bradley and Hirsch, 1986). A good response to ECT in combination with neuroleptic treatment is also to be found in our highly selected group of schizophrenic patients refractory to therapy: more than 60% of the patients responded to combined treatment very well or well, although a satisfactory result of treatment could not be attained with neuroleptics alone before ECT. Conversely, although the number of cases is small, our results also appear to confirm the ‘one third rule of thumb’, an averaging of outcomes introduced in Europe by Bleuler stating that grossly 30% of schizophrenics remit more or less completely. Approximately 30% end up in residual syndromes of various intensities and slightly under 30% show an unfavorable, chronic outcome (Bleuler, 1972). Our results also corresponded to the experience of Kolakowska et al. according to which the global outcome does not correlate with response to neuroleptics. In addition, our results in a small but highly selected group confirm the experience of Miiller et al. (1982) in that psychopathology on admission correlates with the finding on discharge, but was less outcome predictive than the psychopathological status on discharge. Patients who were in good remission on discharge all showed good outcome with regard to recommencement of work, work efficiency and social contacts. The
354
four patients insufficiently improved on discharge also showed an unfavorable outcome throughout. The asthenic syndrome on admission (three patients) was found in patients with inadequate improvement on discharge and showed a tendency to persist. The controlled study of Janakiramaiah et al. (1982) has documented the reduction of neuroleptic medication subsequent to a course of ECT. A comparable effect appears in the group presented here: in patients with good remission, a reduction of neuroleptics by 72% CPZU could be achieved, and even by 53% in patients with poor treatment results. Despite qualitative and quantitative differences, this constitutes a noteworthy therapeutic effect even considering the number of cases. The effect becomes even more evident considering the overall efficiency of treatment, especially as adverse drug effects of neuroleptics may contribute to lack of compliance, and may produce irreversible side effects after prolonged application.
REFERENCES
Bleuler, E. (1972) Lehrbuch der Psychiatric, bearbeitet von M. Bleuler. Springer, Berlin. p. 429. Bradley, P.B. and Hirsch, S.R. (1986) The Psychopharmacology and Treatment of Schizophrenia. Oxford Umversity Press, Oxford. Fink, M. (1979) Convulsive Therapy: Theory and Practice. Raven Press, New York. Guy, W. and Bonato, R.R. (1970) Manula for the ECDEUAssessment Battery 2. revised edn. Chevy Chase, Maryland. Janakiramaiah, N., Channabasavanna, S.M. and Narasimha, N.S. (1982) ECT/chlorpromazine combination versus chlorpromazine alone in acute schizophrenic patients. Acta Psychiatr. Stand. 66, 464-470. Konig, P., Angelberger-Spitaler, H., Conca, A. and Schneider, H.J. (1990) 1st die Electrokrampftherapie obsolet? Wien. Klin. Wochenschr., in press. Moller, H.J., Eilert-Werner, K., Wiischer-Stockheim, M. and Von Zerssen, D. (1982) Relevante Merkmale fur die 5-Jahres-Prognose von Patienten mit schizophrenen und verwandten paranoiden Psychosen. Arch. Psychiatr. Nervenk. 23 1, 305-322. Royal College (1977) The Royal College of Psychiatrists Memorandum on the use of Electroconvulsive Therapy. Br. J. Psychiatry 131, 261-272.
SCHIZO
Research,
351
3 (1990) 35 I-354
Short communication
00125
Combined electroconvulsive and neuroleptic therapy in schizophrenia refractory to neuroleptics P. Kiinig and U. Glatter-Giitz Landes-Nervenkrankenhaus (Received
Valduna, Department 18 December
of Psychiarry
1989, accepted
26 March
I, Rankwjeil, Austria 1990)
The results of treatment in 13 schizophrenic patients (nine males, four females) who underwent electroconvulsive therapy (ECT) because of varying degrees of therapy resistance to neuroleptics (therapy failures, renewed and in some cases catatonic exacerbation under neuroleptic therapy, neuroleptic intolerance) are reported. The single treatments,which were carried out on average 12 times (between six and 20 times), led from very good to good remission in a period of between 10 and 7 years in nine patients. Four patients did not respond adequately: the small improvement of psychopathology on discharge correlated with unfavorable outcome. In three of these patients, the asthenic syndrome was found on admission and persisted. In patients with good remission, neuroleptics could be reduced after ECT by over 70%, and over 50% in patients with poor remission. This result confirms corresponding literature data with regard to neuroleptics. The results in this highly selected group also confirm Bleuler’s ‘one third rule’ of remissions, also the fact that global outcome does not correlate with response to neuroleptics, as well as confirming the relevance of the psychopathological state on discharge as an outcome predictor. Key words: Neuroleptic
resistance;
Electroconvulsive
therapy;
A re-evaluation of the use of electroconvulsive therapy (ECT) for treatment of severe psychoses has become necessary after various negative appraisals in recent years. Publications of the APA task force on ECT (Fink, 1979) as well as the statement of the Royal College of Psychiatrists have provided the basis for this. For Austria, we have appraised the value of ECT in a psychiatric hospital (catchment area about 300,000 inhabitants, sole inpatient institution with about 15 independently practising psychiatrists (Kbnig, 1989)). We previously described the frequency, establishment of the indication and in some cases the efficiency of diagnoses in that study. In the present paper the course of treatment and the outcome of 13 patients with schizophrenic
0920.9964/90/$03.50
of neuroleptics;
(Schizophrenia)
diseases will be presented. 7-10 years after treatment.
INTRODUCTION
Correspondence Rankweil, Austria.
Reduction
to:
0
P.
Kiinig,
LNKH
1990 Elsevier
Valduna,
Science Publishers
A-6830
PATIENTS
AND
Data
were
collected
METHODS
This is a retrospective survey of patients of both sexes (nine men, four women) who had been hospitalized on the basis of ICD 9 diagnoses 295.0-295.3. The selection was made from the total group of ECT-treated patients in the study quoted above (Kdnig, 1989). Since they had proved to be refractory to neuroleptic therapy, the patients had undergone ECT treatment despite neuroleptic therapy during hospitalization in the period from 1979 to 1982. Patients with belowaverage intelligence, with schizoaffective psychoses or marked fluctuations in mood in the history of their schizophrenic disease were not included in the otherwise random sample.
B.V. (Biomedical
Division)
352
The relevant data were compiled from case histories, the ECT protocols as well as a telephone interview obtained by U.G.-G. from the previously treated patients, their relatives and managing physicians. In some cases, data on premorbid personality and the type of follow-up therapy could not be obtained. The status on admission and discharge was classified in accordance with the IMPS syndrome score scale (Moller et al., 1982); psychotic excitation (PE), paranoid-hallucinatory syndrome (PHS), depressive-apathetic syndrome (DAS), phobic-anancastic and psycho-organic brain syndrome (POS) (see Table 1). From 1979 to 1982, 13 patients (nine males, four females) with an average age of 34 years (range 15-65) at the time of ECT were treated on average 12 times (range 6-20 ECTs). This was carried out on occasion of the first admission in six patients, of the second admission in three patients, and during a further inpatient treatment in four patients. Six patients were not readmitted during the follow-up period (Table 1). In eight patients the indication was established because of resistance to therapy, in three cases because of renewed exacerbation of catatonic symptoms or highly suicidal tendencies. Neuroleptic intolerance was present in one patient. The neuroleptics administered before and after ECT (Table 2) were mainly haloperidol (in some
TABLE
cases clopenthixol), additionally fluphenazine droperidol were used in the acute phase.
and
RESULTS
The case histories show a poor response to ECT (inadequate improvement on discharge) in four patients. The neuroleptic dosage could nevertheless be lowered by 53% in these four patients (after on average 13.5 ECTs). In the psychopathological findings on admission, these patients showed the factor ‘psychotic excitation’ in only one case, and a ‘paranoid-hallucinatory syndrome’ was more pronounced in another case. This psychopathology also persisted after treatment, even if it was mitigated up to the time of discharge. In two of these patients, a depressive-asthenic syndrome was diagnosed on admission. This also persisted up to discharge and was combined with a psycho-organic brain syndrome or a residual state after treatment. Of the four patients, the first two had been hospitalized eight times at the time of treatment. One patient had been hospitalized four times and one patient was hospitalized for the first time. One patient from this group (comprising four patients) is still hospitalized, one patient was hospitalized three times within 4 years after discharge,
1
Classification
of 13 patienis
treated with EC7
Pat.
mlf
y/ECT
ZCD dg.
no. ECTs
Outc.
Rely
ECTjudm.
Treat.yar
B B D E F G H L M M M s W
52 59 22 25 34 15 20 30 31 23 65 40 29
295.3 295.3 295.0 295.3 295.2 295.3 295.3 295.3 295.3 295.3 295.2 295.0 295.3
14 7 15 14 13 16 12 6 8 13 12 20 11
+ + + + + _ + _ + + _ + +
0 0 0.25 0.6 2 6* 0 0.7 0 0.3 stat. 0+ 0
1
)r f m m f m m m m m m f
2 2 2 1 1 1 4 1 7 8** 8+* 1
1979 1979 1980 1980 1980 1981 1981 1982 1982 1982 1983 1983 1983
Key: Patients; sex; age at recorded ETC; ICD diagnosis; individual number re/y = readmission after years; ECT on admission number; year of treatment; previous admission; O+ died later.
of ECTs necessary; outcome: + = good, - = negative; *moved to Turkey; **ECT already carried out during
353
TABLE
2
Neuroleptics
administered
before and after ECT
Pat.
m/t”
NL before/after
B B D E F G H L M M M s w
m f f m m f m m m m m m f
clo/clo drop/halo clo/thio drop/cl0 fluph/halo halo/cloz fluph/halo halojfluph halo/halo halo/halo halo/cl0 halo/halo fluph/halo
CPZU
bt$ore/after
7021600
I,398176 1 1071275 541 l/409
1,484/282 9691233 1,213/669 6101179 614/188 1,045/500 I ,880/306 1,100/1,106 3,122/618
Indication
Outcome
into]. ther.res. autoaggr. ther.res.C therres. therres. therres. ther.res. ther.res. ther.res. ther.res.C ther.res.C ther.res.
+ + + + + _ + _ + + _ +
Keq’: Patients; sex; neuroleptic used before/after ECT: CPZU (chlorpromazine units) before/after ECT; indication for ECT (into1 = drug intolerance, therres. = therapy-resistant, autoaggr. = autoaggressive, C = catatonia); outcome, (+ = good, - = negative); NL = neuroleptic; clo = clopenthixol; thio = thioperazine; drop = droperidol; halo = haloperidol; cloz = clozapine; fluph = fluphenazine.
one patient died later of carcinoma, one female patient was later discharged abroad (a complete record of follow-up was not obtained in this patient; she was hospitalized once more 6 years after discharge). Good response to treatment (improvement of psychopathology at the time of discharge in the CGI of at least three points) was registered in nine patients. ‘Psychotic excitation’ was recorded on admission in five patients, and there were ‘paranoid-hallucinatory syndromes’ in four patients. The remaining IMPS scores (DAS, POS, PHS) were not diagnosed on admission. On discharge after an average of ten ECTs (and neuroleptic treatment), no psychopathological abnormalities could be diagnosed with the following exceptions: one patient showed a depressive-apathetic syndrome and one patient showed a psycho-organicbrain syndrome. In this group of nine patients, the neuroleptic dose could be reduced by about 72% after ECT. In the further course, four patients had one readmission and one patient had two in the follow-up period; the remaining patients were not hospitalized again.
DISCUSSION
The value of ECT in the treatment of (acute) schizophrenic diseases, especially with ‘positive
symptoms’ appears to be adequately documented in the literature (summary in Bradley and Hirsch, 1986). A good response to ECT in combination with neuroleptic treatment is also to be found in our highly selected group of schizophrenic patients refractory to therapy: more than 60% of the patients responded to combined treatment very well or well, although a satisfactory result of treatment could not be attained with neuroleptics alone before ECT. Conversely, although the number of cases is small, our results also appear to confirm the ‘one third rule of thumb’, an averaging of outcomes introduced in Europe by Bleuler stating that grossly 30% of schizophrenics remit more or less completely. Approximately 30% end up in residual syndromes of various intensities and slightly under 30% show an unfavorable, chronic outcome (Bleuler, 1972). Our results also corresponded to the experience of Kolakowska et al. according to which the global outcome does not correlate with response to neuroleptics. In addition, our results in a small but highly selected group confirm the experience of Miiller et al. (1982) in that psychopathology on admission correlates with the finding on discharge, but was less outcome predictive than the psychopathological status on discharge. Patients who were in good remission on discharge all showed good outcome with regard to recommencement of work, work efficiency and social contacts. The
354
four patients insufficiently improved on discharge also showed an unfavorable outcome throughout. The asthenic syndrome on admission (three patients) was found in patients with inadequate improvement on discharge and showed a tendency to persist. The controlled study of Janakiramaiah et al. (1982) has documented the reduction of neuroleptic medication subsequent to a course of ECT. A comparable effect appears in the group presented here: in patients with good remission, a reduction of neuroleptics by 72% CPZU could be achieved, and even by 53% in patients with poor treatment results. Despite qualitative and quantitative differences, this constitutes a noteworthy therapeutic effect even considering the number of cases. The effect becomes even more evident considering the overall efficiency of treatment, especially as adverse drug effects of neuroleptics may contribute to lack of compliance, and may produce irreversible side effects after prolonged application.
REFERENCES
Bleuler, E. (1972) Lehrbuch der Psychiatric, bearbeitet von M. Bleuler. Springer, Berlin. p. 429. Bradley, P.B. and Hirsch, S.R. (1986) The Psychopharmacology and Treatment of Schizophrenia. Oxford Umversity Press, Oxford. Fink, M. (1979) Convulsive Therapy: Theory and Practice. Raven Press, New York. Guy, W. and Bonato, R.R. (1970) Manula for the ECDEUAssessment Battery 2. revised edn. Chevy Chase, Maryland. Janakiramaiah, N., Channabasavanna, S.M. and Narasimha, N.S. (1982) ECT/chlorpromazine combination versus chlorpromazine alone in acute schizophrenic patients. Acta Psychiatr. Stand. 66, 464-470. Konig, P., Angelberger-Spitaler, H., Conca, A. and Schneider, H.J. (1990) 1st die Electrokrampftherapie obsolet? Wien. Klin. Wochenschr., in press. Moller, H.J., Eilert-Werner, K., Wiischer-Stockheim, M. and Von Zerssen, D. (1982) Relevante Merkmale fur die 5-Jahres-Prognose von Patienten mit schizophrenen und verwandten paranoiden Psychosen. Arch. Psychiatr. Nervenk. 23 1, 305-322. Royal College (1977) The Royal College of Psychiatrists Memorandum on the use of Electroconvulsive Therapy. Br. J. Psychiatry 131, 261-272.