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Differing time course of emergence of psychotic symptoms and dyskinesia after neuroleptic withdrawal
Schizophrenru Rrseur~h,3(1990)78~83
78
Elsevier
X.A.l. x.
TARDIVE
MOVEMENT
DISORDERS
DYSKINESIA
-
AND
A. Clinical
studies
COGNITIVE
FUNCTIONS
IN SCHIZOPHRENIA
SD Soni and D Neil1 Prestwich
and Hope
Hospituls,
Manchester
M25
7BL,
U.K.
The treatment of schizophrenia is at present limited to a single class of drugs known as neuroleptics. These drugs are potent agents and are quite effective in the control of the active symptoms of the illness but have a high incidence of seriously disabling side effects some of which, like tardive dyskinesia (TD), may be irreversible. It is known that TD affects the more chronic patients who also show evidence of cognitive function abnormalities but the nature of these has not been investigated in any detail. In particular, it is unclear whether any regional or focal abnormalities of psychological functioning in the brain have a relationship to the eventual emergence of TD. This study was undertaken to investigate the specific issue of cerebral dysfunction in schizophrenic patients with TD. METHODS AND RESULTS: 22 patients with clinical evidence of TD were matched with 22 patients without TD for age, sex, diagnosis and neuroleptic treatment. Both groups were assessed on various clinical rating scales for schizophrenia and neuroleptic side effects (including TD) and subjected to a neuropsychological battery to assess regional cortex dysfunction. The battery was fully computerized and took about 90 min to administer to each patient. The clinical rating scales included DSM-III-R, Manchester Scale (KGV), Brief Psychiatric Rating Scale (BPRS). Scale for Assessment of negative symptoms (SANS). Extrapyramidal rating scale (EPS) and abnormal involuntary movement scale (AIMS). The results show that there were no difference between the two groups with respect to the several tests for cognitive functions used in the study. The schizophrenics, as a group. however, did show marked impairment which was more severe in some of the tests.
X.A.2.
DIFFERING TIME COURSE OF EMERGENCE AFTER NEUROLEFTIC WITHDRAWAL
L Dixon, G Thakar,
N Cascella.
Maryland
Research
Psychiatric
M Yablonski
Center,
PO Box
OF PSYCHOTIC
SYMPTOMS
AND
DYSKINESIA
and C Tamminga 21247,
Baltimore,
Muryland
21228,
U.S.A
The course of re-emergence of psychotic symptoms and movement disorders following abrupt neuroleptic withdrawal has helped understand the mechanism of neuroleptic action and pathophysiology of psychosis and tardive dyskinesia (TD). 15 chronic DSM-III schizophrenic inpatients were withdrawn abruptly from neuroleptics in a double-blind, placebo controlled design. They received weekly ratings of mental status (BPRS). TD (Smith, Doppler and videotaping), plasma prolactin and HVA for at least 5 weeks post-neuroleptic withdrawal. The BPRS psychosis factor score at baseline was 8.9 k 4.2, decreased to a low of 8.2 + 4.2 at week 3 and then increased precipitously at week 5 to 10.0-t 3.9. Withdrawal factor scores, increased steadily over each week from 6.7 f 2.3 to 7.8 + 2.0. Anxiety and depression factor scores decreased gradually from 4.5 f 1.9 to 3.9 f 1.5 and 6.6 _t 2.3 to 5.5 f 2.0, respectively. TD, in contrast to psychotic symptoms, increased steadily within 2 weeks of discontinuation in almost every body area 0920-9964/90/$03.50
0 1990 Elsevier Science Publishers
B.V. (Biomedical
Division)
79 assessed (lips, fingers, eyes, neck, knees, and legs). The presentation will include analysis of prolactin, HVA values, and patient subgroups. The early emergence of TD and later emergence of psychotic symptoms may indicate different dopaminergic mechanisms or different interactions with other neurotransmitter systems underlying the two clinical phenomena. The significance of these findings with respect to the dopamine supersensitivity hypothesis of dyskinesia and depolarization blockade model of psychosis will be discussed.
X.A.3.
AKATHISIA WITH
VARIANTS:
CHRONIC
PREVALENCE
AND
IRON
STATUS
IN AN INPATIENT
POPULATION
SCHIZOPHRENIA
TRE Barnes, SM Halstead and P Little Department of Psychiatry, Charing Cross and Westminster
Medical School, London W6 8Rp,
U.K.
In a sample of 120 long-stay inpatients (mean age 52.9, SD 9.43) fulfilling DSM-III-R criteria for schizophrenia the prevalence of chronic akathisia was 24% while for pseudoakathisia, where the characteristic subjective experience of restlessness is not reported, the figure was 18%. These results are similar to those obtained in a younger population of 82 outpatients with schizophrenia (mean age 44.3 years, SD 12.6) previously studied, in which the corresponding figures were 28% and 12% (Barnes and Braude, 1985). In the inpatient sample, the patients with chronic akathisia were significantly younger and receiving significantly higher doses of antipsychotic medication than those without akathisia. Male patients appeared to be at an increased risk of pseudoakathisia. No significant correlation was found between serum iron concentration and severity of akathisia. There as no significant difference in serum iron levels between patients with chronic akathisia and those without akathisia. However, serum iron and percentage saturation were significantly elevated in the subgroup of patients with pseudoakathisia when compared with patients with chronic akathisia but not with those without akathisia. These findings are in contrast to the association between low serum iron and akathisia reported by Brown et al. (1987).
REFERENCES: BARNES TRE AND BRAUDE WM. AKATHISIA VARIANTS AND TARDIVE DYSKINESIA. ARCHIVES OF GENERAL PSYCHIATRY 1985; 42: 874-878. BROWN KW, GLEN SE AND WHITE T. Low
SERUM IRON STATUS AND AKATHISIA. LANCET 1987; 1:1234-1236.
X.B.l. x. MOVEMENT DISORDERS - B. Biochemical
DOPAMINERGIC NEUROLEPTIC
BEHAVIORAL TREATMENT
studies
HYPERSENSITIVITY
IN MONKEYS
RECEIVING
LONG
TERM
DE Casey Psychiatv Service, VA Medical Center, Portland, OR 97207, U.S.A. Dopamine receptor hypersensitivity is the purported pathophysiology of tardive dyskinesia (TD). To study this, the long term effects of haloperidol (HAL) treatment were evaluated in cebus monkeys. 11 male monkeys, 21-24 years old, received oral HAL 0.25 mg/kg daily for 2 months. This was followed by 2 months (1 month during and 1 month after HAL) of periodic dopamine agonist tests (apomorphine (APO),
78
Elsevier
X.A.l. x.
TARDIVE
MOVEMENT
DISORDERS
DYSKINESIA
-
AND
A. Clinical
studies
COGNITIVE
FUNCTIONS
IN SCHIZOPHRENIA
SD Soni and D Neil1 Prestwich
and Hope
Hospituls,
Manchester
M25
7BL,
U.K.
The treatment of schizophrenia is at present limited to a single class of drugs known as neuroleptics. These drugs are potent agents and are quite effective in the control of the active symptoms of the illness but have a high incidence of seriously disabling side effects some of which, like tardive dyskinesia (TD), may be irreversible. It is known that TD affects the more chronic patients who also show evidence of cognitive function abnormalities but the nature of these has not been investigated in any detail. In particular, it is unclear whether any regional or focal abnormalities of psychological functioning in the brain have a relationship to the eventual emergence of TD. This study was undertaken to investigate the specific issue of cerebral dysfunction in schizophrenic patients with TD. METHODS AND RESULTS: 22 patients with clinical evidence of TD were matched with 22 patients without TD for age, sex, diagnosis and neuroleptic treatment. Both groups were assessed on various clinical rating scales for schizophrenia and neuroleptic side effects (including TD) and subjected to a neuropsychological battery to assess regional cortex dysfunction. The battery was fully computerized and took about 90 min to administer to each patient. The clinical rating scales included DSM-III-R, Manchester Scale (KGV), Brief Psychiatric Rating Scale (BPRS). Scale for Assessment of negative symptoms (SANS). Extrapyramidal rating scale (EPS) and abnormal involuntary movement scale (AIMS). The results show that there were no difference between the two groups with respect to the several tests for cognitive functions used in the study. The schizophrenics, as a group. however, did show marked impairment which was more severe in some of the tests.
X.A.2.
DIFFERING TIME COURSE OF EMERGENCE AFTER NEUROLEFTIC WITHDRAWAL
L Dixon, G Thakar,
N Cascella.
Maryland
Research
Psychiatric
M Yablonski
Center,
PO Box
OF PSYCHOTIC
SYMPTOMS
AND
DYSKINESIA
and C Tamminga 21247,
Baltimore,
Muryland
21228,
U.S.A
The course of re-emergence of psychotic symptoms and movement disorders following abrupt neuroleptic withdrawal has helped understand the mechanism of neuroleptic action and pathophysiology of psychosis and tardive dyskinesia (TD). 15 chronic DSM-III schizophrenic inpatients were withdrawn abruptly from neuroleptics in a double-blind, placebo controlled design. They received weekly ratings of mental status (BPRS). TD (Smith, Doppler and videotaping), plasma prolactin and HVA for at least 5 weeks post-neuroleptic withdrawal. The BPRS psychosis factor score at baseline was 8.9 k 4.2, decreased to a low of 8.2 + 4.2 at week 3 and then increased precipitously at week 5 to 10.0-t 3.9. Withdrawal factor scores, increased steadily over each week from 6.7 f 2.3 to 7.8 + 2.0. Anxiety and depression factor scores decreased gradually from 4.5 f 1.9 to 3.9 f 1.5 and 6.6 _t 2.3 to 5.5 f 2.0, respectively. TD, in contrast to psychotic symptoms, increased steadily within 2 weeks of discontinuation in almost every body area 0920-9964/90/$03.50
0 1990 Elsevier Science Publishers
B.V. (Biomedical
Division)
79 assessed (lips, fingers, eyes, neck, knees, and legs). The presentation will include analysis of prolactin, HVA values, and patient subgroups. The early emergence of TD and later emergence of psychotic symptoms may indicate different dopaminergic mechanisms or different interactions with other neurotransmitter systems underlying the two clinical phenomena. The significance of these findings with respect to the dopamine supersensitivity hypothesis of dyskinesia and depolarization blockade model of psychosis will be discussed.
X.A.3.
AKATHISIA WITH
VARIANTS:
CHRONIC
PREVALENCE
AND
IRON
STATUS
IN AN INPATIENT
POPULATION
SCHIZOPHRENIA
TRE Barnes, SM Halstead and P Little Department of Psychiatry, Charing Cross and Westminster
Medical School, London W6 8Rp,
U.K.
In a sample of 120 long-stay inpatients (mean age 52.9, SD 9.43) fulfilling DSM-III-R criteria for schizophrenia the prevalence of chronic akathisia was 24% while for pseudoakathisia, where the characteristic subjective experience of restlessness is not reported, the figure was 18%. These results are similar to those obtained in a younger population of 82 outpatients with schizophrenia (mean age 44.3 years, SD 12.6) previously studied, in which the corresponding figures were 28% and 12% (Barnes and Braude, 1985). In the inpatient sample, the patients with chronic akathisia were significantly younger and receiving significantly higher doses of antipsychotic medication than those without akathisia. Male patients appeared to be at an increased risk of pseudoakathisia. No significant correlation was found between serum iron concentration and severity of akathisia. There as no significant difference in serum iron levels between patients with chronic akathisia and those without akathisia. However, serum iron and percentage saturation were significantly elevated in the subgroup of patients with pseudoakathisia when compared with patients with chronic akathisia but not with those without akathisia. These findings are in contrast to the association between low serum iron and akathisia reported by Brown et al. (1987).
REFERENCES: BARNES TRE AND BRAUDE WM. AKATHISIA VARIANTS AND TARDIVE DYSKINESIA. ARCHIVES OF GENERAL PSYCHIATRY 1985; 42: 874-878. BROWN KW, GLEN SE AND WHITE T. Low
SERUM IRON STATUS AND AKATHISIA. LANCET 1987; 1:1234-1236.
X.B.l. x. MOVEMENT DISORDERS - B. Biochemical
DOPAMINERGIC NEUROLEPTIC
BEHAVIORAL TREATMENT
studies
HYPERSENSITIVITY
IN MONKEYS
RECEIVING
LONG
TERM
DE Casey Psychiatv Service, VA Medical Center, Portland, OR 97207, U.S.A. Dopamine receptor hypersensitivity is the purported pathophysiology of tardive dyskinesia (TD). To study this, the long term effects of haloperidol (HAL) treatment were evaluated in cebus monkeys. 11 male monkeys, 21-24 years old, received oral HAL 0.25 mg/kg daily for 2 months. This was followed by 2 months (1 month during and 1 month after HAL) of periodic dopamine agonist tests (apomorphine (APO),