- Email: [email protected]
Computer-aided assessment of medication induced parkinsonism in first episode psychoses
176
Results." 114 different types of interventions were used in 360 clinical trials over the last 40 years. 70 clinical trials were included in at least one of the metanalyses the others were excluded because they were either not randomized or had no data suitable for this meta-analyses. Four treatments were found to be potentially beneficial for the treatment of TD: vitamin E (NNT=4), tiapride (NNT=2), oxypertine (NNT= 4), and insulin (NNT=3). Lithium and THIP were found to be potentially harmful and neuroleptic cessation and/or reduction were associated with a marked increased in relapse of psychosis. No significant effects could be detected in the other interventions. Conclusion. None of the 114 interventions can be unequivocally recommended as standard treatments for TD. There was robust evidence to suggest that the intervention often proposed as first line-treatment for TD, neuroleptic dose reduction and/or cessation, is hazardous. No RCT-derived data were currently available to support the efficacy of atypical antipsychotics as treatments for TD.
W H A T IS T H E D I F F E R E N T I A L TARDIVE
DYSKINESIA
ANTIPSYCHOTIC
RISK OF
WITH THE NOVEL
OLANZAPINE?
R.N. Tamura, C.M. Beasley, M.A. Dellva, W.M. Glazer, H. Morgenstern, G.D. Tollefson
Lilly Research Laboratories, Eli Lilly and Company. Lilly Corporate Center, Indianapolis, Indiana, 46285 Objective: The incidence of tardive dyskinesia was evaluated in 1714 patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine or haloperidol for a period of up to 2.6 years in three randomized, doubleblind, multicenter studies. It was hypothesized that olanzapine would be associated with a lower incidence of tardive dyskinesia than haloperidol. Methods'." Baseline tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS) and the Schooler-Kane Research Diagnostic Criteria for Tardive Dyskinesia (RD-TD) as modified by Glazer and Morgenstern. Kaplan-Meier survival analysis was used to estimate the risk of tardive dyskinesia for each treatment group at various time points during double-blind therapy. Incidence rates of tardive dyskinesia as well as rate ratios were also estimated during follow-up. Results: The estimated risk remained higher with haloperidol than with olanzapine throughout the follow-up period (p<0.001). The estimated rate ratio for haloperidol compared with olanzapine was 3.69 (95% CI=2.10, 6.50). Based on data following the initial 6 weeks of observation, the estimated 1-year risk of TD was 0.52% with olanzapine and 7.45% with haloperidol. The estimated risk with haloperidol was higher than with olanzapine throughout the followup period (p=0.002). The estimated rate ratio was 11.86 (95% CI =2.30, 61.14). Conclusion. Results of multiple assessments of the incidence of TD indicated a substantially lower risk of TD with olanzapine than with haloperidol.
B. Extra-Pyramidal and Other Side-Effects NEUROCOGNITIVE
DEFICITS,
SYMPTOMS, NEUROLEPTIC AND QUALITY OF LIFE IN
SIDE-EFFECTS
SCHIZOPHRENIA A.G. Awad*, R.J. Heslegrave, L.N.P. Voruganti
The (Tarke hlstitute of Psyehiato', University of Toronto, 250 College Street, Toronto. Ontario, Canada M5T 9R8 The purpose of the study was to examine the relationship between neurocognitive deficits, clinical and treatment parameters and QOL of schizophrenic patients. Sixty outpatients with chronic schizophrenia were assessed for neurocognitive deficits using a computerized test battery (COGLAB). Psychopathology was assessed using the PANSS, neuroleptic side-effects were evaluated using the Hillside Akathisia Scale, AIMS; neuroleptic dysphoria using the DAI. QOL across several domains was assessed using the modified Sickness Impact Profile. Self-rated assessment revealed compromised QOL, both in the global and multidimensional profiles. Neurocognitive assessment revealed significant deficits particularly with respect to impaired iconic memory, reaction time and concept attainment and modulation in the Wisconsin card sorting tasks. Despite the neurocognitive deficits, the correlations between such deficits and QOL were largely weak and not significant. On the other hand symptom expression, particularly general psychopathology as well as the positive and negative symptoms were significantly correlated with QOL. Although no correlation was observed between neuroleptic dosage and QOL, few neuroleptic side-effects, particularly akathisia and neuroleptic dysphoria were significantly related to QOL. Our results suggest that QOL may be more closely related to the severity of symptoms, particularly general psychopathology and negative symptoms, than to neurocognitive deficits. Our data supports emerging literature pointing to the importance of adequate symptom and side-effect control in facilitating and enhancing benefits from psychosocial interventions. From a conceptual viewpoint, the differential impact of symptoms and neurocognitive deficits on the functional status and QOL of schizophrenic patients raises the question whether neurocognitive deficits are independent of clinical symptoms.
COMPUTER-AIDED ASSESSMENT OF MEDICATION INDUCED PARKINSONISM IN FIRST EPISODE PSYCHOSES G. Berger, H. Hofer, M.C.G. Merlo
Universi O' PaTchiatric Services Bern. Bolligenstrasse 111, CH-3000 Bern 60, Switzerland First-episode psychotic patients were successively recruited for testing extrapyramidal side effects during antipsychotic
177
treatment. In order to measure subtle drug induced parkinsonism we applied a computer aided device (Schuhfried). The following measurements were standardized by Ttransformation: tremor, precision of movement, rapidity of movement of arm and hand, and rapidity of movement of wrist and finger. These measures were compared with the haloperidol equivalent. Interestingly, we found no linear relation between dosages and fine motor dysfunctions. After dichotomization of the group in those patients with less than 4 mg haloperidol equivalents and those with higher logistic regression yielded highly significant values (p<0.01) for all parameters but the rapidity of arm and hand. This cutoff point corresponds to the value that McEvoy and collaborator ( 1991 ) have found in their subgroup of first-episode patients. These results are discussed in the context of low-dose regimens in the treatment of firstepisode psychosis.
SIX YEAR FOLLOW-UP CHRONIC
AKATHISIA
SCHIZOPHRENIC
STUDY OF IN A
INPATIENT
POPULATION S.M. Halstead, +T.R.E. Barnes, R.E. Hennessy, U. G o s w a m i
?hnperial College School ~t[ Medicine, London W6 8RP, UK Akathisia and tardive dyskinesia were assessed in 120 longstay schizophrenic patients (Halstead et al.). The group was reassessed after median periods of 22 and 72 months. A total of 76 patients (63%) underwent all three assessments and are reported here. The prevalence of chronic akathisia at baseline was 26% and rose to 36% at final follow-up whereas that of pseudoakathisia fell from 20% to 14% over the same period (ns). Along with the increased prevalence of chronic akathisia, the global severity of akathisia increased over the follow-up period ( T = - 2 . 2 9 8 p=0.024). There was a non-significant trend for chronic akathisia patients to be younger than others at baseline, though this disappeared over the follow-up period. The median age for patients with pseudoakathisia was consistently, but not significantly, greater than that for patients with akathisia, or those not exhibiting either condition at the three assessment times. Diagnosis of pseudoakathisia was not stable and there was no evidence that this condition represented an 'end-stage' of akathisia. The patients with persistent chronic akathisia at all three ratings were receiving doses of antipsychotic medication at the lower end of the therapeutic range as were those with the most severe symptoms of akathisia.
Rq~'rence Halstead S.M. et al. (1994) British Journal of Psychiatry 164, 177 183.
THE SPECTRUM OF NEUROLEPTICINDUCED MOVEMENT DISORDERS EXTRAPYRAMIDAL SIDE EFFECTS CHILDHOOD-ONSET
AND IN
SCHIZOPHRENIA
S. Kumra, L.K. Jacobsen, J.L. R a p o p o r t
Child Psychiat O' Branch, National hlstitute ~[' Mental Health. Big. 10, Rm. 6N240 Bethesda, Mao,land20892. USA In this paper, we present a preliminary examination of the incidence of withdrawal dyskinesias (WD), tardive dyskinesia (TD), and extrapyramidal side effects in patients with childhoodonset schizophrenia. 34 COS patients (mean age + SD, 14.2_+2.1 years) were examined for TD using the Abnormal Involuntary Movements Scale and for extrapyramidal side effects using the Simpson-Angus Neurologic Rating Scale, after a 14 to 28 day drug-free period (n=33), at week 6 of treatment and 2 to 4 years after completion of the study (n= 14). The mean (±SD) number of months of prior neuroleptic exposure for the group was 22.4 (15.0) months. 17 of 34 (50%) of patients were noted to have either WD/TD at some point during their participation in our studies. The majority of patients experienced WD that were mainly in the orofacial region, transient in nature, and suppressed by haloperidol and clozapine. Patients with TD/WD had greater levels of premorbid impairment ( p = 0.02 ), increased severity of positive symptoms of schizophrenia (p<0.01) and a trend toward greater months of neuroleptic exposure (p = 0.10. one-tailed). A high proportion of COS patients were found to have TD/WD. The majority of these abnormal movements were not severe and generally improved over time. TD/WD in COS appears to be associated with greater premorbid impairment and severity of illness.
GATES: A NEW INSTRUMENT FOR THE CLINICAL AND RESEARCH ASSESSMENT OF NEUROLEPTIC-INDUCED
MOVEMENT
DISORDERS T.J.R. Lambert
UniversiO' ~/ Western Australia. Dept ¢~['Psychiatrv, Perth, Australia The GATES (General Akathisia Tardive Phenomena And Extrapyramidal Scale) has been developed to meet the need of clinicians and researchers requiring a composite instrument for the detection and quantification of neuroleptic-induced movement disorders. It has been designed with a major commitment towards providing utility for research assistants and junior staff. There are three components--Demographics, Subjective and Objective. The Objective instrument, the focus of this paper, makes extensive use of operationally defined terms and procedures so as to maximise reliability. Only brief physical signs training is required as many items are observationally-based. The instrument has had broad piloting in mixed populations with some emphasis on those receiving newer atypical neuroleptics and those with first psychosis. The instrument is able to produce scores for rigidity, akinesia,
Results." 114 different types of interventions were used in 360 clinical trials over the last 40 years. 70 clinical trials were included in at least one of the metanalyses the others were excluded because they were either not randomized or had no data suitable for this meta-analyses. Four treatments were found to be potentially beneficial for the treatment of TD: vitamin E (NNT=4), tiapride (NNT=2), oxypertine (NNT= 4), and insulin (NNT=3). Lithium and THIP were found to be potentially harmful and neuroleptic cessation and/or reduction were associated with a marked increased in relapse of psychosis. No significant effects could be detected in the other interventions. Conclusion. None of the 114 interventions can be unequivocally recommended as standard treatments for TD. There was robust evidence to suggest that the intervention often proposed as first line-treatment for TD, neuroleptic dose reduction and/or cessation, is hazardous. No RCT-derived data were currently available to support the efficacy of atypical antipsychotics as treatments for TD.
W H A T IS T H E D I F F E R E N T I A L TARDIVE
DYSKINESIA
ANTIPSYCHOTIC
RISK OF
WITH THE NOVEL
OLANZAPINE?
R.N. Tamura, C.M. Beasley, M.A. Dellva, W.M. Glazer, H. Morgenstern, G.D. Tollefson
Lilly Research Laboratories, Eli Lilly and Company. Lilly Corporate Center, Indianapolis, Indiana, 46285 Objective: The incidence of tardive dyskinesia was evaluated in 1714 patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine or haloperidol for a period of up to 2.6 years in three randomized, doubleblind, multicenter studies. It was hypothesized that olanzapine would be associated with a lower incidence of tardive dyskinesia than haloperidol. Methods'." Baseline tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS) and the Schooler-Kane Research Diagnostic Criteria for Tardive Dyskinesia (RD-TD) as modified by Glazer and Morgenstern. Kaplan-Meier survival analysis was used to estimate the risk of tardive dyskinesia for each treatment group at various time points during double-blind therapy. Incidence rates of tardive dyskinesia as well as rate ratios were also estimated during follow-up. Results: The estimated risk remained higher with haloperidol than with olanzapine throughout the follow-up period (p<0.001). The estimated rate ratio for haloperidol compared with olanzapine was 3.69 (95% CI=2.10, 6.50). Based on data following the initial 6 weeks of observation, the estimated 1-year risk of TD was 0.52% with olanzapine and 7.45% with haloperidol. The estimated risk with haloperidol was higher than with olanzapine throughout the followup period (p=0.002). The estimated rate ratio was 11.86 (95% CI =2.30, 61.14). Conclusion. Results of multiple assessments of the incidence of TD indicated a substantially lower risk of TD with olanzapine than with haloperidol.
B. Extra-Pyramidal and Other Side-Effects NEUROCOGNITIVE
DEFICITS,
SYMPTOMS, NEUROLEPTIC AND QUALITY OF LIFE IN
SIDE-EFFECTS
SCHIZOPHRENIA A.G. Awad*, R.J. Heslegrave, L.N.P. Voruganti
The (Tarke hlstitute of Psyehiato', University of Toronto, 250 College Street, Toronto. Ontario, Canada M5T 9R8 The purpose of the study was to examine the relationship between neurocognitive deficits, clinical and treatment parameters and QOL of schizophrenic patients. Sixty outpatients with chronic schizophrenia were assessed for neurocognitive deficits using a computerized test battery (COGLAB). Psychopathology was assessed using the PANSS, neuroleptic side-effects were evaluated using the Hillside Akathisia Scale, AIMS; neuroleptic dysphoria using the DAI. QOL across several domains was assessed using the modified Sickness Impact Profile. Self-rated assessment revealed compromised QOL, both in the global and multidimensional profiles. Neurocognitive assessment revealed significant deficits particularly with respect to impaired iconic memory, reaction time and concept attainment and modulation in the Wisconsin card sorting tasks. Despite the neurocognitive deficits, the correlations between such deficits and QOL were largely weak and not significant. On the other hand symptom expression, particularly general psychopathology as well as the positive and negative symptoms were significantly correlated with QOL. Although no correlation was observed between neuroleptic dosage and QOL, few neuroleptic side-effects, particularly akathisia and neuroleptic dysphoria were significantly related to QOL. Our results suggest that QOL may be more closely related to the severity of symptoms, particularly general psychopathology and negative symptoms, than to neurocognitive deficits. Our data supports emerging literature pointing to the importance of adequate symptom and side-effect control in facilitating and enhancing benefits from psychosocial interventions. From a conceptual viewpoint, the differential impact of symptoms and neurocognitive deficits on the functional status and QOL of schizophrenic patients raises the question whether neurocognitive deficits are independent of clinical symptoms.
COMPUTER-AIDED ASSESSMENT OF MEDICATION INDUCED PARKINSONISM IN FIRST EPISODE PSYCHOSES G. Berger, H. Hofer, M.C.G. Merlo
Universi O' PaTchiatric Services Bern. Bolligenstrasse 111, CH-3000 Bern 60, Switzerland First-episode psychotic patients were successively recruited for testing extrapyramidal side effects during antipsychotic
177
treatment. In order to measure subtle drug induced parkinsonism we applied a computer aided device (Schuhfried). The following measurements were standardized by Ttransformation: tremor, precision of movement, rapidity of movement of arm and hand, and rapidity of movement of wrist and finger. These measures were compared with the haloperidol equivalent. Interestingly, we found no linear relation between dosages and fine motor dysfunctions. After dichotomization of the group in those patients with less than 4 mg haloperidol equivalents and those with higher logistic regression yielded highly significant values (p<0.01) for all parameters but the rapidity of arm and hand. This cutoff point corresponds to the value that McEvoy and collaborator ( 1991 ) have found in their subgroup of first-episode patients. These results are discussed in the context of low-dose regimens in the treatment of firstepisode psychosis.
SIX YEAR FOLLOW-UP CHRONIC
AKATHISIA
SCHIZOPHRENIC
STUDY OF IN A
INPATIENT
POPULATION S.M. Halstead, +T.R.E. Barnes, R.E. Hennessy, U. G o s w a m i
?hnperial College School ~t[ Medicine, London W6 8RP, UK Akathisia and tardive dyskinesia were assessed in 120 longstay schizophrenic patients (Halstead et al.). The group was reassessed after median periods of 22 and 72 months. A total of 76 patients (63%) underwent all three assessments and are reported here. The prevalence of chronic akathisia at baseline was 26% and rose to 36% at final follow-up whereas that of pseudoakathisia fell from 20% to 14% over the same period (ns). Along with the increased prevalence of chronic akathisia, the global severity of akathisia increased over the follow-up period ( T = - 2 . 2 9 8 p=0.024). There was a non-significant trend for chronic akathisia patients to be younger than others at baseline, though this disappeared over the follow-up period. The median age for patients with pseudoakathisia was consistently, but not significantly, greater than that for patients with akathisia, or those not exhibiting either condition at the three assessment times. Diagnosis of pseudoakathisia was not stable and there was no evidence that this condition represented an 'end-stage' of akathisia. The patients with persistent chronic akathisia at all three ratings were receiving doses of antipsychotic medication at the lower end of the therapeutic range as were those with the most severe symptoms of akathisia.
Rq~'rence Halstead S.M. et al. (1994) British Journal of Psychiatry 164, 177 183.
THE SPECTRUM OF NEUROLEPTICINDUCED MOVEMENT DISORDERS EXTRAPYRAMIDAL SIDE EFFECTS CHILDHOOD-ONSET
AND IN
SCHIZOPHRENIA
S. Kumra, L.K. Jacobsen, J.L. R a p o p o r t
Child Psychiat O' Branch, National hlstitute ~[' Mental Health. Big. 10, Rm. 6N240 Bethesda, Mao,land20892. USA In this paper, we present a preliminary examination of the incidence of withdrawal dyskinesias (WD), tardive dyskinesia (TD), and extrapyramidal side effects in patients with childhoodonset schizophrenia. 34 COS patients (mean age + SD, 14.2_+2.1 years) were examined for TD using the Abnormal Involuntary Movements Scale and for extrapyramidal side effects using the Simpson-Angus Neurologic Rating Scale, after a 14 to 28 day drug-free period (n=33), at week 6 of treatment and 2 to 4 years after completion of the study (n= 14). The mean (±SD) number of months of prior neuroleptic exposure for the group was 22.4 (15.0) months. 17 of 34 (50%) of patients were noted to have either WD/TD at some point during their participation in our studies. The majority of patients experienced WD that were mainly in the orofacial region, transient in nature, and suppressed by haloperidol and clozapine. Patients with TD/WD had greater levels of premorbid impairment ( p = 0.02 ), increased severity of positive symptoms of schizophrenia (p<0.01) and a trend toward greater months of neuroleptic exposure (p = 0.10. one-tailed). A high proportion of COS patients were found to have TD/WD. The majority of these abnormal movements were not severe and generally improved over time. TD/WD in COS appears to be associated with greater premorbid impairment and severity of illness.
GATES: A NEW INSTRUMENT FOR THE CLINICAL AND RESEARCH ASSESSMENT OF NEUROLEPTIC-INDUCED
MOVEMENT
DISORDERS T.J.R. Lambert
UniversiO' ~/ Western Australia. Dept ¢~['Psychiatrv, Perth, Australia The GATES (General Akathisia Tardive Phenomena And Extrapyramidal Scale) has been developed to meet the need of clinicians and researchers requiring a composite instrument for the detection and quantification of neuroleptic-induced movement disorders. It has been designed with a major commitment towards providing utility for research assistants and junior staff. There are three components--Demographics, Subjective and Objective. The Objective instrument, the focus of this paper, makes extensive use of operationally defined terms and procedures so as to maximise reliability. Only brief physical signs training is required as many items are observationally-based. The instrument has had broad piloting in mixed populations with some emphasis on those receiving newer atypical neuroleptics and those with first psychosis. The instrument is able to produce scores for rigidity, akinesia,