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Alpha-tocopherol in the treatment of tardive dyskinesia
122 Extrapyramidal side effects (EPSE) occur in a wide number of neuroleptic-treated patients and some data show differences in prevalence between diagnostic subgroups [I]. In a previous study evaluating EPSE occurrence and severity among schizophrenic and non-schizophrenic spectrum neuroleptic treated patients [2], an intriguing finding was a higher EPSE occurrence in subjects with delusional disorders in comparison to schizophrenic ones, despite significantly lower neuroleptic mean dose. In order to study this finding in a wider sample, EPSE occurrence and severity were evaluated in 42 schizophrenic (mean age 33 years& I I .2 sd) and 31 delusional disorder inpatients (mean age 46 years+ I2 sd) of both sexes. Patients, diagnosed according to DSMIIIR criteria and treated with neuroleptics for at least two weeks were studied by means of the Simpson and Angus Rating Scale, the neurological section of UKU scale and the Barnes Akathisia Rating Scale. EPSE occurred more in delusional disorders (87.1%) than in schizophrenics (73.8%) independently from age and sex, despite significantly lower neuroleptic daily doses (ANOVA test, p=O.Ol, mean doses 3.28 vs 5.88 mg). These data, confirming our previous results, underline the need for further study about possible differences in sensitivity to neuroleptic-induced EPSE related to diagnosis. I. Nasrallah 1456. 2. Smeraldi
H.A.
et al. (1988) Am. J. Psychiatry
E. et al. (1991) Schizophr.
145, l455-
Res. 4, 367-368.
V.4 ALCOHOL USE IN SCHIZOPHRENIA: SYMPTOMATOLOGY, RELATIONSHIP WITH TARDIVE DYSKINESIA AND AGE AT ONSET P.J. Duke, C. Pantelis and T.R.E. Barnes Academic Unit, Gordon Hospital, SW1 V 2RH. U.K.
Bloomburg
St, London
Alcohol-related morbidity was assessed using a structured interview in the course of a comprehensive epidemiologically based study of schizophrenia in an inner London borough (the South Westminster Schizophrenia Survey). The responses to a questionnaire on drinking behaviour indicated problem drinking 52 (19.6%) of 265 patients. These index patients had higher ratings for hallucinations on the Manchester Scale (~~0.05) and for hostility, anxiety, depression and neglect of appearance on the Social Behaviour Schedule. The mean number of severe behaviours on the SBS was significantly higher in index patients than in controls (PCO.05). The mean age of onset of schizophrenia was significantly later in index cases (35.1) years than in controls (30.5 years; ~~0.05) matched for age and sex while the mean length of illness was shorter (8.3 and 14.3 years, ~~0.05). Within these patients with problem drinking there was a negative correlation
(- 0.2193; p
V.5 ALPHA-TOCOPHEROL IN THE TREATMENT OF TARDIVE DYSKINESIA D. Junker, P. Steigleider and W.F. Gattaz Central Institute of Mental Health, Unit Neurobiology of Functional Psychoses. P.O. Box 12 21 20. D-6800 Mannheim I, Germany Neuroleptic treatment leads to an increased turnover of catecholamines, especially dopamine, in the brain, which results in an increased production of cytotoxic free radicals. One current hypothesis on the etiology of tardive dyskinesia (TD) postulates that these free radicals may destabilize the neuronal membranes in the basal ganglia by lipid peroxidation. Alphatocopherol as a free radical scavenger might protect cell membranes against this oxidative damage. Two recent studies have shown a significant improvement of tardive dyskinesia after administration of alpha-tocopherol. To replicate these findings we are treating patients with persistent tardive dyskinesia and constant neuroleptic doses over 4 weeks with 1200 mg/day alpha-tocopherol or placebo in a randomized double blind design. Tardive dyskinesia is
123 being assessed by means of the Abnormal Involuntary Movement Scale (AIMS). In a preliminary evaluation we analyzed the data from the first 16 patients that completed the study (6 male, IO female, age S1.6* 18.6 years). We found a significant improvement in older patients (age> 40 years) on alpha-tocopherol as compared to the placebo group (p < 0.05). No therapeutic effects of alphatocopherol were observed in the younger patients (age<40 years). Up to now age is the only valid risk factor which increases vulnerability for TD. Because the content of alpha-tocopherol in the brain is known to decrease with age, it is tempting to speculate that (1) the decrease of brain alpha-tocopherol with age enhances the susceptibility of elder individuals to the damaging effects of free radicals, resulting in increased susceptibility to neuroleptic-induced TD, and that (2) therefore these elder patients might benefit from high-dose alpha-tocopherol therapy, as found in the present study. However, this working hypothesis certainly needs confirmation in a larger sample before any definite conclusion can be drawn.
V.6 REVERSIBILITY AND IRREVERSIBILITY OF TARDIVE DYSKINESIA FOLLOWING NEUROLEPTIC WITHDRAWAL A.C. Lahti’, G.K. Thaker2, C.A. Tamminga2
M. Moran’
and
‘Departmentof Psychiatry, University of Michigan, Ann Arbor, MI, U.S.A. and 2Maryland Psychiatric Research Center, Baltimore, MD, U.S.A. Tardive dyskinesia (TD) is a hyperkinetic motor disorder which is thought to be secondary to neuronal changes following chronic receptor blockade by neuroleptics in the basal ganglia. Recently it has been suggested that the process is reversible if the dopamine (DA) blockade is removed. To further explore this issue we carried out a long term follow up (mean= 13.1 months) of 20 TD patients (mean age 43.7* 16.1 years), who had been withdrawn from their neuroleptic treatment during the follow up period. The study demonstrated that 13 patients (65%) showed a decrease in TD, two (10%) did not demonstrate any change and five (25%) had worsening TD. Overall, there was a significant decrease in TD (paired t-test, p=O.O118). The average reduction of TD was 17.9% k 34.7 overall, but in these 13 patients who improved, the reduction was 37.1% k22.3. Significant predictors of decrease in TD included length of withdrawal period (partial r = 0.63, p <:0.0 I), male gender (r = 0.76, p < O.OOl), and higher baseline TD score (partial r= 0.78, p=O.OOl). The results strongly suggest that TD is reversible, although it is not reversible in all cases. Further, since neuroleptic withdrawal is not always possible, the results emphasize the utility of atypical neuroleptics (e.g. clozapine), which exert low or no DA receptor blockade in the basal ganglia.
V.1 THE INCIDENCE OF NEUROLEPTICINDUCED AKATHISIA H. Oberbauer, C.H. Miller, M. Hummer W.W. Fleischhacker Department Anichstrafle
and
of Psychiatry, University Clinics Innsbruck, 35. A-6020 Innsbruck, Austria
Incidence figures for neuroleptic-induced akathisia (NIA) range from 25 to 75% in the literature. This discrepancy is mainly due to differential diagnostic approaches of the syndrome. All the authors reporting lower incidence figures stress the objective phenomena of NIA, reports that emphasize the subjective component find higher rates. We present a preliminary analysis of an ongoing drug monitoring program of antipsychotic drugs. So far, SS patients have been evaluated using various side effect rating scales including the Hillside Akathisia Scale. 40% of the sample scored higher than two (small amplitude movements, part of the time) or more on the objective part of the scale, a subjective rating of two (subjective symptoms present and easily controlled) or more was found in 54.28%. Assuming that both phenomena are necessary for the valid diagnosis of akathisia we calculated an incidence of 28.6% (95% confidence intervals, 14.6-46.5%). All patients had developed NIA by the third day of antipsychotic treatment. Our results are comparable to those of earlier reports and reemphasize the need of recognition and adequate treatment of this distressing side effect of antipsychotic drugs.
V.8 DISTURBANCES IN MOTOR DEXTERITY PERFORMANCE OF SCHIZOPHRENIC PATIENTS AS PREDICTOR FOR THE MANIFESTATION OF EXTRAPYRAMIDAL SIDE EFFECTS DURING NEUROLEPTTC TREATMENT P. Steigleider
and W.F. Gattaz
Central Institute of Mental Health, Unit Neurobiology of Functional Psychoses, P.O. Box I2 21 20. D-6800 Mannheim I. Germany
The tolerance to neuroleptic therapy with regard to the development of extrapyramidal side-effects (EPS) varies widely among schizophrenic patients. The individual vulnerability threshold to EPS has recently been shown to remain stable over time. A number of studies reported an increased occurrence of EPS in patients with structural brain abnormalities as assessed by computertomography. Similarly, a poorer performance in motor dexterity tests was shown in schizophrenics with abnormal CT findings. These data suggest that poor
H.A.
et al. (1988) Am. J. Psychiatry
E. et al. (1991) Schizophr.
145, l455-
Res. 4, 367-368.
V.4 ALCOHOL USE IN SCHIZOPHRENIA: SYMPTOMATOLOGY, RELATIONSHIP WITH TARDIVE DYSKINESIA AND AGE AT ONSET P.J. Duke, C. Pantelis and T.R.E. Barnes Academic Unit, Gordon Hospital, SW1 V 2RH. U.K.
Bloomburg
St, London
Alcohol-related morbidity was assessed using a structured interview in the course of a comprehensive epidemiologically based study of schizophrenia in an inner London borough (the South Westminster Schizophrenia Survey). The responses to a questionnaire on drinking behaviour indicated problem drinking 52 (19.6%) of 265 patients. These index patients had higher ratings for hallucinations on the Manchester Scale (~~0.05) and for hostility, anxiety, depression and neglect of appearance on the Social Behaviour Schedule. The mean number of severe behaviours on the SBS was significantly higher in index patients than in controls (PCO.05). The mean age of onset of schizophrenia was significantly later in index cases (35.1) years than in controls (30.5 years; ~~0.05) matched for age and sex while the mean length of illness was shorter (8.3 and 14.3 years, ~~0.05). Within these patients with problem drinking there was a negative correlation
(- 0.2193; p
V.5 ALPHA-TOCOPHEROL IN THE TREATMENT OF TARDIVE DYSKINESIA D. Junker, P. Steigleider and W.F. Gattaz Central Institute of Mental Health, Unit Neurobiology of Functional Psychoses. P.O. Box 12 21 20. D-6800 Mannheim I, Germany Neuroleptic treatment leads to an increased turnover of catecholamines, especially dopamine, in the brain, which results in an increased production of cytotoxic free radicals. One current hypothesis on the etiology of tardive dyskinesia (TD) postulates that these free radicals may destabilize the neuronal membranes in the basal ganglia by lipid peroxidation. Alphatocopherol as a free radical scavenger might protect cell membranes against this oxidative damage. Two recent studies have shown a significant improvement of tardive dyskinesia after administration of alpha-tocopherol. To replicate these findings we are treating patients with persistent tardive dyskinesia and constant neuroleptic doses over 4 weeks with 1200 mg/day alpha-tocopherol or placebo in a randomized double blind design. Tardive dyskinesia is
123 being assessed by means of the Abnormal Involuntary Movement Scale (AIMS). In a preliminary evaluation we analyzed the data from the first 16 patients that completed the study (6 male, IO female, age S1.6* 18.6 years). We found a significant improvement in older patients (age> 40 years) on alpha-tocopherol as compared to the placebo group (p < 0.05). No therapeutic effects of alphatocopherol were observed in the younger patients (age<40 years). Up to now age is the only valid risk factor which increases vulnerability for TD. Because the content of alpha-tocopherol in the brain is known to decrease with age, it is tempting to speculate that (1) the decrease of brain alpha-tocopherol with age enhances the susceptibility of elder individuals to the damaging effects of free radicals, resulting in increased susceptibility to neuroleptic-induced TD, and that (2) therefore these elder patients might benefit from high-dose alpha-tocopherol therapy, as found in the present study. However, this working hypothesis certainly needs confirmation in a larger sample before any definite conclusion can be drawn.
V.6 REVERSIBILITY AND IRREVERSIBILITY OF TARDIVE DYSKINESIA FOLLOWING NEUROLEPTIC WITHDRAWAL A.C. Lahti’, G.K. Thaker2, C.A. Tamminga2
M. Moran’
and
‘Departmentof Psychiatry, University of Michigan, Ann Arbor, MI, U.S.A. and 2Maryland Psychiatric Research Center, Baltimore, MD, U.S.A. Tardive dyskinesia (TD) is a hyperkinetic motor disorder which is thought to be secondary to neuronal changes following chronic receptor blockade by neuroleptics in the basal ganglia. Recently it has been suggested that the process is reversible if the dopamine (DA) blockade is removed. To further explore this issue we carried out a long term follow up (mean= 13.1 months) of 20 TD patients (mean age 43.7* 16.1 years), who had been withdrawn from their neuroleptic treatment during the follow up period. The study demonstrated that 13 patients (65%) showed a decrease in TD, two (10%) did not demonstrate any change and five (25%) had worsening TD. Overall, there was a significant decrease in TD (paired t-test, p=O.O118). The average reduction of TD was 17.9% k 34.7 overall, but in these 13 patients who improved, the reduction was 37.1% k22.3. Significant predictors of decrease in TD included length of withdrawal period (partial r = 0.63, p <:0.0 I), male gender (r = 0.76, p < O.OOl), and higher baseline TD score (partial r= 0.78, p=O.OOl). The results strongly suggest that TD is reversible, although it is not reversible in all cases. Further, since neuroleptic withdrawal is not always possible, the results emphasize the utility of atypical neuroleptics (e.g. clozapine), which exert low or no DA receptor blockade in the basal ganglia.
V.1 THE INCIDENCE OF NEUROLEPTICINDUCED AKATHISIA H. Oberbauer, C.H. Miller, M. Hummer W.W. Fleischhacker Department Anichstrafle
and
of Psychiatry, University Clinics Innsbruck, 35. A-6020 Innsbruck, Austria
Incidence figures for neuroleptic-induced akathisia (NIA) range from 25 to 75% in the literature. This discrepancy is mainly due to differential diagnostic approaches of the syndrome. All the authors reporting lower incidence figures stress the objective phenomena of NIA, reports that emphasize the subjective component find higher rates. We present a preliminary analysis of an ongoing drug monitoring program of antipsychotic drugs. So far, SS patients have been evaluated using various side effect rating scales including the Hillside Akathisia Scale. 40% of the sample scored higher than two (small amplitude movements, part of the time) or more on the objective part of the scale, a subjective rating of two (subjective symptoms present and easily controlled) or more was found in 54.28%. Assuming that both phenomena are necessary for the valid diagnosis of akathisia we calculated an incidence of 28.6% (95% confidence intervals, 14.6-46.5%). All patients had developed NIA by the third day of antipsychotic treatment. Our results are comparable to those of earlier reports and reemphasize the need of recognition and adequate treatment of this distressing side effect of antipsychotic drugs.
V.8 DISTURBANCES IN MOTOR DEXTERITY PERFORMANCE OF SCHIZOPHRENIC PATIENTS AS PREDICTOR FOR THE MANIFESTATION OF EXTRAPYRAMIDAL SIDE EFFECTS DURING NEUROLEPTTC TREATMENT P. Steigleider
and W.F. Gattaz
Central Institute of Mental Health, Unit Neurobiology of Functional Psychoses, P.O. Box I2 21 20. D-6800 Mannheim I. Germany
The tolerance to neuroleptic therapy with regard to the development of extrapyramidal side-effects (EPS) varies widely among schizophrenic patients. The individual vulnerability threshold to EPS has recently been shown to remain stable over time. A number of studies reported an increased occurrence of EPS in patients with structural brain abnormalities as assessed by computertomography. Similarly, a poorer performance in motor dexterity tests was shown in schizophrenics with abnormal CT findings. These data suggest that poor