#
2002 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2002 Volume 6 Pages 175 ± 177
175
Quetiapine in tardive dyskinesia SURESH CHARI,1 AK JAINER,2 ANDREW ASHLEY-SMITH1 AND MAXINE CLEAVER1 1
2
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/07/14 For personal use only.
Caludon Centre, Coventry and St Michael’s Hospital, Warwick, UK
Correspondence Address Dr AK Jainer, MD, MRCPsych, Specialist Registrar in Psychiatry, St. Michael’s Hospital, St. Michael’s Road, Warwick CV34 5QW
Received 1 September 2001; accepted for publication 7 February 2002
Tardive dyskinesia (TD) is a potentially irreversible side-effect of antipsychotic medication. Some atypical antipsychotics, by virtue of their better side-effect profile, seem to have an ability to reverse TD. The importance of trying to treat TD has become more urgent in view of the medico-legal implications of Article 3 of the Human Rights Act, 1998 which states that ``no one shall be subjected to inhuman or degrading treatment or punishment’’: interpretation of this article was successfully used to win a large out-of-court settlement for a patient with TD in our region. Though clozapine has been used in cases with TD, its role is limited, due to the risk of agranulocytosis. We write about three cases with TD who responded 1 well to quetiapine (Seroquel , AstraZeneca), and suggest that more robust research be carried out to investigate the initial promise. (Int J Psych Clin Pract 2002; 6: 175 ± 177) Keywords tardive dyskinesia quetiapine
INTRODUCTION
T
ardive dyskinesia (TD) is described as a syndrome of potentially irreversible hyperkinetic dyskinesias and is classed as a type of extrapyramidal syndrome (EPS). It was probably first recognized by Sigwald and colleagues in 1959 and later clearly defined by Uhrbrand 1 and Faurbye in 1960. TD manifests as involuntary, purposeless, repetitive movement, which can affect any part of the body, but is more often seen around the mouth ± the Bucco Linguo [=mouth & tongue] Masticatory (BLM) type. It is increased by anxiety and reduces during drowsiness and often disappears during sleep.2 Patients suffering from TD are often not aware of it, but it is a wellrecognized cause of distress and embarrassment to carers and contributes to the stigma of mental illness. Though it is often seen in the background of long-term antipsychotic prescribing, it can occur in the natural course of untreated mental illnesses. Jeste and Caliguri found that elderly women with a diagnosis of an affective disorder and 3 diffuse brain pathology are more likely to suffer from TD. The minimum period of exposure seems to be 3-6 months, and there is a marked incidence after the age of 45; the incidence rapidly went up from 26% at 1 year to 60% in the 4 3rd year in elderly subjects. Prevalence rates vary according to the population samples studied, but figures of 20 ± 40% of patients with schizophrenia treated with long-term antipsychotic drugs have been identified. Risk factors include exposure to ECT, leucotomy, evidence of
atypical antipsychotics Seroquel
cognitive dysfunction,5 negative symptoms in schizophrenia and diabetes mellitus. A history of acute extrapyramidal syndromes is probably related to an increased risk of tardive dyskinesia. Lengthy drug-free intervals are also a risk factor: more than two interruptions increase the risk of tardive dyskinesia by more than three times.6 Carlsson proposed that it may be due to receptor upregulation and supersensitivity to dopamine resulting from prolonged dopaminergic blockade in the nigrostriatal 7 dopamine pathway. Other hypotheses put forward have been free radical neurotoxicity, GABA insufficiency and noradrenergic dysfunction models.
CASE HISTORIES CASE 1 Our first case is a 42-year-old divorced caucasian woman who was first diagnosed as having schizophrenia at the age of 17. Since then she has had 17 admissions to psychiatric units over the last 23 years and has received a number of antipsychotics: conventional antipsychotics, depot antipsychotics and atypicals. She was first noticed to have TD in 1990, and quantified using the Abnormal Involuntary Movement Scale.8 She scored 8 on this occasion, and this worsened significantly in 2000 to reach a total score of 22 with severe oro-facial symptoms. In April 2000 she was commenced on quetiapine, a dibenzothiazepin atypical
176
S Chari et al
antipsychotic, after which her tardive dyskinesia markedly improved. Her AIMS score has been progressively dropping and when rated on the last occasion, a few months ago, she did not score on the scale, and her level of social functioning is now reasonable, though she continues to suffer from positive psychotic symptoms, on 600 mg per day of quetiapine.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/07/14 For personal use only.
CASE 2 The next case in our small series is a 63-year-old caucasian woman with a 30-year history of schizoaffective disorder who rarely complies with medication of any sort. Given the severity of her presentation, she has been treated with electroconvulsive therapy (ECT), oral antipsychotics and depot preparations of different types on a number of occasions. The main difficulty in her management was the disabling manifestation of TD, and this made further treatment with long-acting antipsychotic injections untenable. She was started on quetiapine while in hospital and over a period of a year her AIMS score dropped from 19 to 3. Now out of hospital, she has adhered to quetiapine over the past 3 months, and it is hoped that this will continue.
CASE 3 The final case in our series is a 52-year-old Asian woman with a 5-year history of a psychotic illness, which came to light following the death of her husband. She was treated with oral antipsychotics, but this had to be changed to a flupentixol decanoate depot due to non-compliance, resulting in extreme self-neglect. Unfortunately this resulted in severe TD symptoms, and she scored 17 on the AIMS. This then decreased to a score of 10 after she began quetiapine and maintained it for 24 weeks, and it is hoped that a further improvement will be achieved.
DISCUSSION Why is it that some atypicals seem to have a beneficial effect on symptoms like TD? The four major dopamine pathways in the brain ± the mesolimbic, mesocortical, nigrostriatal and tubero-infundibular ± contain differing levels of other receptors like serotonin. Usually, a homeostasis is maintained, and this balance is upset by antipsychotics in general. Many of the side-effects like EPS and the negative symptoms in psychotic illnesses could be attributed to the blanket blockade of the major dopamine pathways. However, the newer atypicals have different levels of dopamine blockade and serotonin facilitation in the major dopamine pathways and this allows treatment of the
positive symptoms like delusions and hallucinations, without bringing on EPS and related side-effects. Clozapine has been reported to improve dyskinetic 9 movements in 43% of patients. Quetiapine, a newer atypical antipsychotic, has a chemical structure closely similar to that of clozapine. It also acts on 5HT2 receptors, and these interactions between serotonin and dopamine in the basal ganglia may be responsible for the benefit seen; some case reports have been published about its use in 1 0 ,1 1 treating TD. Quetiapine is particularly useful in treating psychosis associated with Parkinsonian symptoms, because of its virtual lack of EPS. There have been some case reports published about the efficacy of olanzapine,1 2 ,1 3 and fewer reports about the role of risperidone,1 4 ,1 5 in the management of established TD. It is possible that these atypical antipsychotics also have a similar mechanism of action. The three patients in our sample fulfilled the criteria for persistent TD. The appearance of TD was assessed using the Glazer-Morgenstern (G-M) criteria,1 6 which specify a total AIMS score 5 3 and at least one AIMS score 5 2. Persistent TD incidence was defined as meeting the G-M criteria at two consecutive visits.
CONCLUSIONS If our report is substantiated by others, it will have important implications for the treatment of those who have, or who are at risk of developing, tardive dyskinesia. Small case series have definite methodological constraints, and it is not advisable to generalize the findings without the benefit of further, more robust, randomized double-blind studies. However, given the potential irreversibility of TD, any treatment that shows promise should be evaluated more thoroughly, and this small series indicates that quetiapine may be one such option.
KEY POINTS . Tardive dyskinesia is a potentially irreversible side-effect associated with antipsychotic medication . TD may possibly be reversed by atypical antipsychotics, and quetiapine initially shows promise . The successful interpretation of Article 3 of the Human Rights Act, 1998, with respect to TD may open the floodgates to more medico-legal issues . More robust research is needed to confirm the findings of this small case series
Quetiapine in tardive dysk inesia
177
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/07/14 For personal use only.
REFERENCES 1. Uhrbrand L, Faurbye A (1960) Reversible and irreversible dyskinesia after treatment with perphenazine, chlorpromazine, reserpine and ECT. Psychopharmacologia 1: 408 ± 18. 2. Bazire S (2000) Psychotropic Drug Directory 2000: A professionals’ pocket handbook and aide memoire. Mark Allen Publishing, Dinton, 82. 3. Jeste DV, Caliguri MP, Paulsen JS et al (1993) Tardive dyskinesia. Schizophrenia Bull 19: 305 ± 15. 4. Jeste DV, Caliguri MP, Paulsen JS et al (1995) Risk of tardive dyskinesia in older patients. A prospective longitudinal study of 266 outpatients. Arch Gen Psychiatry 52: 756 ± 65. 5. American Psychiatric Association (1992) Tardive Dyskinesia: A Task Force Report of the American Psychiatric Association. APA, Washington, DC. 6. van Harten PN, Hoek HW Matroos GE et al (1998) Intermittent neuroleptic treatment and risk for tardive dyskinesia: The CuracËao extrapyramidal syndrome study. III. Am J Psychiatry 155: 565 ± 7. 7. Carlsson A (1970) Biochemical implications of dopa-induced actions on the central nervous system with particular reference to abnormal movements. In: L-Dopa and Parkinsonism (eds A Barbeau & FH McDowell). Davis, Philadelphia. 8. Guy W (1976) Assessment Manual for Psychopharmacology (revised). Washington DC: Department of Health, Education, and Welfare. Early Clinical Drug Evaluation Unit.
9. Lieberman JA, Saltz BL, Johns CA et al (1991) The effects of clozapine on tardive dyskinesia. Br J Psychiatry 158: 503 ± 10. 10. Farah A (2001) Reduction of tardive dyskinesia with quetiapine. Schizophrenia Res 47: 309 ± 10. 11. Vesely C, Kufferle B, Brucke T et al (2000) Remission of severe tardive dyskinesia in a schizophrenic patient treated with the atypical antipsychotic substance quetiapine. Int Clin Psychopharmacol 15: 57 ± 60. 12. Almeida OP (1998) Olanzapine for the treatment of tardive dyskinesia. J Clin Psychiatry 59: 380 ± 1. 13. O’Brien J, Barber R (1998) Marked improvement in tardive dyskinesia following treatment with olanzapine in an elderly subject. Br J Psychiatry 172: 186 ± 9. 14. Rangwani SR, Gupta S, Burke WJ et al (1996) Improvement of debilitating tardive dyskinesia with risperidone. Ann Clin Psychiatry 8: 27 ± 9. 15. Kooptiwoot S, Settachan T (2000) Improvement of tardive dyskinesia with risperidone. A case report. J Med Assoc Thailand 83: 1430 ± 2. 16. Morgenstern H, Glazer WM (1993) Identifying risk factors for tardive dyskinesia among long term outpatients maintained with neuroleptic medications. Results of the Yale tardive dyskinesia study. Arch Gen Psychiatry 50: 723 ± 33.
2002 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2002 Volume 6 Pages 175 ± 177
175
Quetiapine in tardive dyskinesia SURESH CHARI,1 AK JAINER,2 ANDREW ASHLEY-SMITH1 AND MAXINE CLEAVER1 1
2
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/07/14 For personal use only.
Caludon Centre, Coventry and St Michael’s Hospital, Warwick, UK
Correspondence Address Dr AK Jainer, MD, MRCPsych, Specialist Registrar in Psychiatry, St. Michael’s Hospital, St. Michael’s Road, Warwick CV34 5QW
Received 1 September 2001; accepted for publication 7 February 2002
Tardive dyskinesia (TD) is a potentially irreversible side-effect of antipsychotic medication. Some atypical antipsychotics, by virtue of their better side-effect profile, seem to have an ability to reverse TD. The importance of trying to treat TD has become more urgent in view of the medico-legal implications of Article 3 of the Human Rights Act, 1998 which states that ``no one shall be subjected to inhuman or degrading treatment or punishment’’: interpretation of this article was successfully used to win a large out-of-court settlement for a patient with TD in our region. Though clozapine has been used in cases with TD, its role is limited, due to the risk of agranulocytosis. We write about three cases with TD who responded 1 well to quetiapine (Seroquel , AstraZeneca), and suggest that more robust research be carried out to investigate the initial promise. (Int J Psych Clin Pract 2002; 6: 175 ± 177) Keywords tardive dyskinesia quetiapine
INTRODUCTION
T
ardive dyskinesia (TD) is described as a syndrome of potentially irreversible hyperkinetic dyskinesias and is classed as a type of extrapyramidal syndrome (EPS). It was probably first recognized by Sigwald and colleagues in 1959 and later clearly defined by Uhrbrand 1 and Faurbye in 1960. TD manifests as involuntary, purposeless, repetitive movement, which can affect any part of the body, but is more often seen around the mouth ± the Bucco Linguo [=mouth & tongue] Masticatory (BLM) type. It is increased by anxiety and reduces during drowsiness and often disappears during sleep.2 Patients suffering from TD are often not aware of it, but it is a wellrecognized cause of distress and embarrassment to carers and contributes to the stigma of mental illness. Though it is often seen in the background of long-term antipsychotic prescribing, it can occur in the natural course of untreated mental illnesses. Jeste and Caliguri found that elderly women with a diagnosis of an affective disorder and 3 diffuse brain pathology are more likely to suffer from TD. The minimum period of exposure seems to be 3-6 months, and there is a marked incidence after the age of 45; the incidence rapidly went up from 26% at 1 year to 60% in the 4 3rd year in elderly subjects. Prevalence rates vary according to the population samples studied, but figures of 20 ± 40% of patients with schizophrenia treated with long-term antipsychotic drugs have been identified. Risk factors include exposure to ECT, leucotomy, evidence of
atypical antipsychotics Seroquel
cognitive dysfunction,5 negative symptoms in schizophrenia and diabetes mellitus. A history of acute extrapyramidal syndromes is probably related to an increased risk of tardive dyskinesia. Lengthy drug-free intervals are also a risk factor: more than two interruptions increase the risk of tardive dyskinesia by more than three times.6 Carlsson proposed that it may be due to receptor upregulation and supersensitivity to dopamine resulting from prolonged dopaminergic blockade in the nigrostriatal 7 dopamine pathway. Other hypotheses put forward have been free radical neurotoxicity, GABA insufficiency and noradrenergic dysfunction models.
CASE HISTORIES CASE 1 Our first case is a 42-year-old divorced caucasian woman who was first diagnosed as having schizophrenia at the age of 17. Since then she has had 17 admissions to psychiatric units over the last 23 years and has received a number of antipsychotics: conventional antipsychotics, depot antipsychotics and atypicals. She was first noticed to have TD in 1990, and quantified using the Abnormal Involuntary Movement Scale.8 She scored 8 on this occasion, and this worsened significantly in 2000 to reach a total score of 22 with severe oro-facial symptoms. In April 2000 she was commenced on quetiapine, a dibenzothiazepin atypical
176
S Chari et al
antipsychotic, after which her tardive dyskinesia markedly improved. Her AIMS score has been progressively dropping and when rated on the last occasion, a few months ago, she did not score on the scale, and her level of social functioning is now reasonable, though she continues to suffer from positive psychotic symptoms, on 600 mg per day of quetiapine.
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/07/14 For personal use only.
CASE 2 The next case in our small series is a 63-year-old caucasian woman with a 30-year history of schizoaffective disorder who rarely complies with medication of any sort. Given the severity of her presentation, she has been treated with electroconvulsive therapy (ECT), oral antipsychotics and depot preparations of different types on a number of occasions. The main difficulty in her management was the disabling manifestation of TD, and this made further treatment with long-acting antipsychotic injections untenable. She was started on quetiapine while in hospital and over a period of a year her AIMS score dropped from 19 to 3. Now out of hospital, she has adhered to quetiapine over the past 3 months, and it is hoped that this will continue.
CASE 3 The final case in our series is a 52-year-old Asian woman with a 5-year history of a psychotic illness, which came to light following the death of her husband. She was treated with oral antipsychotics, but this had to be changed to a flupentixol decanoate depot due to non-compliance, resulting in extreme self-neglect. Unfortunately this resulted in severe TD symptoms, and she scored 17 on the AIMS. This then decreased to a score of 10 after she began quetiapine and maintained it for 24 weeks, and it is hoped that a further improvement will be achieved.
DISCUSSION Why is it that some atypicals seem to have a beneficial effect on symptoms like TD? The four major dopamine pathways in the brain ± the mesolimbic, mesocortical, nigrostriatal and tubero-infundibular ± contain differing levels of other receptors like serotonin. Usually, a homeostasis is maintained, and this balance is upset by antipsychotics in general. Many of the side-effects like EPS and the negative symptoms in psychotic illnesses could be attributed to the blanket blockade of the major dopamine pathways. However, the newer atypicals have different levels of dopamine blockade and serotonin facilitation in the major dopamine pathways and this allows treatment of the
positive symptoms like delusions and hallucinations, without bringing on EPS and related side-effects. Clozapine has been reported to improve dyskinetic 9 movements in 43% of patients. Quetiapine, a newer atypical antipsychotic, has a chemical structure closely similar to that of clozapine. It also acts on 5HT2 receptors, and these interactions between serotonin and dopamine in the basal ganglia may be responsible for the benefit seen; some case reports have been published about its use in 1 0 ,1 1 treating TD. Quetiapine is particularly useful in treating psychosis associated with Parkinsonian symptoms, because of its virtual lack of EPS. There have been some case reports published about the efficacy of olanzapine,1 2 ,1 3 and fewer reports about the role of risperidone,1 4 ,1 5 in the management of established TD. It is possible that these atypical antipsychotics also have a similar mechanism of action. The three patients in our sample fulfilled the criteria for persistent TD. The appearance of TD was assessed using the Glazer-Morgenstern (G-M) criteria,1 6 which specify a total AIMS score 5 3 and at least one AIMS score 5 2. Persistent TD incidence was defined as meeting the G-M criteria at two consecutive visits.
CONCLUSIONS If our report is substantiated by others, it will have important implications for the treatment of those who have, or who are at risk of developing, tardive dyskinesia. Small case series have definite methodological constraints, and it is not advisable to generalize the findings without the benefit of further, more robust, randomized double-blind studies. However, given the potential irreversibility of TD, any treatment that shows promise should be evaluated more thoroughly, and this small series indicates that quetiapine may be one such option.
KEY POINTS . Tardive dyskinesia is a potentially irreversible side-effect associated with antipsychotic medication . TD may possibly be reversed by atypical antipsychotics, and quetiapine initially shows promise . The successful interpretation of Article 3 of the Human Rights Act, 1998, with respect to TD may open the floodgates to more medico-legal issues . More robust research is needed to confirm the findings of this small case series
Quetiapine in tardive dysk inesia
177
Int J Psych Clin Pract Downloaded from informahealthcare.com by University of California Irvine on 11/07/14 For personal use only.
REFERENCES 1. Uhrbrand L, Faurbye A (1960) Reversible and irreversible dyskinesia after treatment with perphenazine, chlorpromazine, reserpine and ECT. Psychopharmacologia 1: 408 ± 18. 2. Bazire S (2000) Psychotropic Drug Directory 2000: A professionals’ pocket handbook and aide memoire. Mark Allen Publishing, Dinton, 82. 3. Jeste DV, Caliguri MP, Paulsen JS et al (1993) Tardive dyskinesia. Schizophrenia Bull 19: 305 ± 15. 4. Jeste DV, Caliguri MP, Paulsen JS et al (1995) Risk of tardive dyskinesia in older patients. A prospective longitudinal study of 266 outpatients. Arch Gen Psychiatry 52: 756 ± 65. 5. American Psychiatric Association (1992) Tardive Dyskinesia: A Task Force Report of the American Psychiatric Association. APA, Washington, DC. 6. van Harten PN, Hoek HW Matroos GE et al (1998) Intermittent neuroleptic treatment and risk for tardive dyskinesia: The CuracËao extrapyramidal syndrome study. III. Am J Psychiatry 155: 565 ± 7. 7. Carlsson A (1970) Biochemical implications of dopa-induced actions on the central nervous system with particular reference to abnormal movements. In: L-Dopa and Parkinsonism (eds A Barbeau & FH McDowell). Davis, Philadelphia. 8. Guy W (1976) Assessment Manual for Psychopharmacology (revised). Washington DC: Department of Health, Education, and Welfare. Early Clinical Drug Evaluation Unit.
9. Lieberman JA, Saltz BL, Johns CA et al (1991) The effects of clozapine on tardive dyskinesia. Br J Psychiatry 158: 503 ± 10. 10. Farah A (2001) Reduction of tardive dyskinesia with quetiapine. Schizophrenia Res 47: 309 ± 10. 11. Vesely C, Kufferle B, Brucke T et al (2000) Remission of severe tardive dyskinesia in a schizophrenic patient treated with the atypical antipsychotic substance quetiapine. Int Clin Psychopharmacol 15: 57 ± 60. 12. Almeida OP (1998) Olanzapine for the treatment of tardive dyskinesia. J Clin Psychiatry 59: 380 ± 1. 13. O’Brien J, Barber R (1998) Marked improvement in tardive dyskinesia following treatment with olanzapine in an elderly subject. Br J Psychiatry 172: 186 ± 9. 14. Rangwani SR, Gupta S, Burke WJ et al (1996) Improvement of debilitating tardive dyskinesia with risperidone. Ann Clin Psychiatry 8: 27 ± 9. 15. Kooptiwoot S, Settachan T (2000) Improvement of tardive dyskinesia with risperidone. A case report. J Med Assoc Thailand 83: 1430 ± 2. 16. Morgenstern H, Glazer WM (1993) Identifying risk factors for tardive dyskinesia among long term outpatients maintained with neuroleptic medications. Results of the Yale tardive dyskinesia study. Arch Gen Psychiatry 50: 723 ± 33.
