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Pisa syndrome during aripiprazole treatment: A case report
Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 286 – 287 www.elsevier.com/locate/pnpbp
Short communication
Pisa syndrome during aripiprazole treatment: A case report Eugenia Rota ⁎, Giovanni Bergesio, Elisabetta Dettoni, Claudio M. Demicheli Neurology, Psychiatry and Internal Medicine Unit, Casa di Cura Città di Bra, Bra (CN), Italy Received 18 March 2006; received in revised form 16 May 2006; accepted 13 June 2006 Available online 17 July 2006
Abstract Pisa syndrome (or pleurothotonus), consisting of a tonic flexion of the trunk, has been recently reported also in association with atypical antipsychotics. We describe the first case of Pisa syndrome during aripiprazole treatment in an elderly (77-year-old) woman, admitted to hospital for behavioural and psychological symptoms of dementia. The ongoing treatment with quetiapine was rapidly tapered and stopped, and a switch to aripiprazole (15 mg/die) was attempted the subsequent day. Six days later, an acute tonic flexion of trunk and head towards the right was observed. Aripiprazole was discontinued and the Pisa syndrome completely disappeared within 3 days, without any adjunctive treatment. © 2006 Elsevier Inc. All rights reserved. Keywords: Aripiprazole; Atypical antipsychotics; Dystonia; Extrapyramidal side effects; Pisa syndrome
1. Introduction
2. Case report
Pisa syndrome (or pleurothotonus) is an axial dystonia, characterized by tonic lateral flexion and slight rotation of the trunk. Although most commonly subsequent to prolonged exposure to conventional antipsychotics, this syndrome has been recently reported also in association with atypical antipsychotics, cholinesterase inhibitors and in patients affected by neurodegenerative disorders (Suzuki and Matsuzaka, 2002; Duggal et al., 2004). Aripiprazole is a novel antipsychotic, acting as partial agonist at dopamine D2 and serotonin 5-HT1A receptors and as antagonist at 5-HT2A (Yokoi et al., 2002), which shows a profile for extrapyramidal side effects similar to placebo in clinical trials (Goodnick and Jerry, 2002). We describe the first case of Pisa syndrome during aripiprazole treatment in an elderly, demented woman; the dystonia rapidly disappeared after the withdrawal of the drug.
A 77-year-old woman was admitted to our Unit in March 2004 for behavioural and psychological symptoms of dementia. Since the diagnosis of probable mixed dementia, according to ICD-10 criteria (Wetterling et al., 1994), in May 2002, she had been treated with quetiapine, titrated up to 100 × 3 mg/die in the last year. She was concomitantly being administered antiplatelet treatment (aspirin 160 mg/die) and benzodiazepines (clonazepam, 0.5 mg/die). On admission, the physical examination revealed non-focal deficits, while MRI imaging detected a cerebrovascular disease, involving also the basal ganglia, and atrophy, more severe at the temporal lobes; the MMSE score was 13. Because of the inadequate control of behavioural and psychological symptoms and the difficult compliance, quetiapine was tapered and stopped within 3 days, and a switch to aripiprazole (15 mg/die) was attempted, although off-label, under strict cardiovascular monitoring. Six days later, an acute dystonic reaction (tonic flexion of trunk and head toward right) was observed. The remaining physical examination was unchanged, as well as the mental status (including the MMSE score), the MRI control did not show any variation. Aripiprazole was discontinued and the Pisa syndrome completely disappeared within 3 days, without any adjunctive treatment.
⁎ Corresponding author. Str. Gariglio 14, 12042 Bra (CN), Italy. Tel.: +39 0172 44922; fax: +39 0172 472514. E-mail address: [email protected] (E. Rota). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.06.009
E. Rota et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 286–287
3. Discussion The case reported suggests that aripiprazole may be implicated in the onset of the Pisa syndrome. The role of partial dopamine D2 receptor partial agonist and serotonin 5-HT2A receptor antagonist renders aripiprazole profile for extrapyramidal side effects similar to placebo in clinical trials (Goodnick and Jerry, 2002). A patient experiencing acute dystonic reaction (including truncal dystonia) with most of other, typical and atypical, antipsychotics but aripiprazole has been recently described (Coffey et al., 2005). Nevertheless, a case of parkinsonism during treatment with aripiprazole (Sharma and Sorrell, 2006) and a few cases of motor worsening in parkinsonian patients treated with aripiprazole for drug-induced psychosis (Fernandez et al., 2004) have been reported. This evidence suggests that also the novel antipsychotic aripiprazole may be responsible of extrapyramidal side-effects, exerting an antagonistic action for dopamine receptors. Particularly, aripiprazole may somehow alter the dopaminergic–cholinergic balance, which is supposed to be the main underlying pathogenetic factor in Pisa syndrome (Suzuki and Matsuzaka, 2002; Villarejo et al., 2003; Duggal et al., 2004). Then, aripiprazole activity at serotonin 5-HT1A and 5-HT2A receptors may also affect those interactions between serotoninergic and dopaminergic system, which are involved in the regulation of extrapyramidal symptoms (Suzuki and Matsuzaka, 2002). However, we cannot rule out that the onset of this dystonia was related to the discontinuation of quetiapine and to the addition of aripiprazole. In fact, some cases of Pisa syndrome have been described after withdrawal of an atypical antipsychotic, maybe in relation with dopaminergic–cholinergic imbalance (Stubner et al., 2000; Suzuki and Matsuzaka, 2002; Villarejo et al., 2003; Duggal et al., 2004). Furthermore, in the case reported, some of these factors were associated, such as old age, female gender, brain damage (cerebrovascular disease and atrophy), and previous combined pharmacological treatments, which seem to represent risk factors for Pisa syndrome (Stubner et al., 2000; Suzuki and Matsuzaka, 2002; Duggal et al., 2004). In fact, from epidemiological data, the Pisa syndrome, different from other types of dystonic reactions, appears to be more prevalent in young and elderly females with organic brain disorders (Suzuki and Matsuzaka, 2002). However, since Pisa syndrome has also been described in two patients affected by neurodegenerative disorders, who were not receiving antipsychotic drugs (Patel et al., 1991; Colosimo, 1998), this syndrome seems to be a multifactorial disorder, whose pathophysiology may involve an asymmetry in neurochemical functioning, associated with cerebral lesions and influenced by jatrogenic factors (Suzuki and Matsuzaka, 2002). A new pathophysiological hypothesis of acute axial dystonias has been recently suggested by Coffey et al. (2005), based
287
on their aforementioned patient, characterized by extreme sensitivity to atypical antipsychotics but aripiprazole, who experienced, in the absence of antipsychotic treatment, after anticonvulsant withdrawal, a dramatic increase in the truncal dystonia as well as in facial dyskinesias, in the context of complex partial seizures. In fact, it has been supposed that this complicated history of truncal dystonia (associated with facial dyskinesias) could be consistent with prodromal signs of frontal or temporal lobe epilepsy; ion channel defects (identified in familial epilepsies as well as in some paroxysmal movement disorders) may be a putative common underlying pathophysiological factor (Coffey et al., 2005), along with (at least in our opinion) organic brain disorders. However, further clinical evidence is required to support this novel hypothesis. 4. Conclusion This report suggests that the occurrence of a Pisa syndrome should be taken into account, when switching from one atypical antipsychotic to another, also to aripiprazole; therefore, caution is required, above all in patients with the abovementioned risk factors. References Coffey GL, Botts SR, de Leon J. High vulnerability to acute dystonic reactions: a case of antipsychotic exposure and uncontrolled seizure activity. Prog Neuropharmacol Biol Psychiatry 2005;29(5):770–4. Colosimo C. Pisa syndrome in a patient with multiple system atrophy. Mov Disord 1998;13:607–9. Duggal HS, Sivamony S, Umapathy C. Pisa syndrome and atypical antipsychotics [letter]. Am J Psychiatry 2004;161(2):373. Fernandez HH, Trieschmann ME, Friedman JH. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol 2004;27(1):4–5. Goodnick PJ, Jerry JM. Aripiprazole: profile on efficacy and safety. Expert Opin Pharmacother 2002;3:1773–81. Patel S, Tariot PN, Hamill RW. Pisa syndrome without neuroleptic exposure in a patient with dementia of the Alzheimer type. J Geriatr Psychiatry Neurol 1991;4:48–51. Sharma A, Sorrell JH. Aripiprazole-induced parkinsonism. Int Clin Psychopharmacol 2006;21(2):127–9. Stubner S, Padberg F, Grohmann R, Hampel H, Hollweg M, Hippius H, et al. Pisa syndrome (pleurothotonus): report of a multicenter drug safety surveillance project. J Clin Psychiatry 2000;61:569–74. Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus). Epidemiology and management. CNS Drugs 2002;16(3):165–74. Villarejo A, Camacho A, Garcia-Ramos R, Moreno T, Penas M, Juntas R, et al. Cholinergic–dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol 2003;26:119–21. Wetterling T, Kanitz RD, Borgis KJ. The ICD-10 criteria for vascular dementia. Dementia 1994;5(3–4):185–8. Yokoi F, Grunder G, Biziere K, Stephane M, Dogan AS, Dannals RF, et al. Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11 C]raclopride. Neuropsychopharmacol 2002;27:248–59.
Short communication
Pisa syndrome during aripiprazole treatment: A case report Eugenia Rota ⁎, Giovanni Bergesio, Elisabetta Dettoni, Claudio M. Demicheli Neurology, Psychiatry and Internal Medicine Unit, Casa di Cura Città di Bra, Bra (CN), Italy Received 18 March 2006; received in revised form 16 May 2006; accepted 13 June 2006 Available online 17 July 2006
Abstract Pisa syndrome (or pleurothotonus), consisting of a tonic flexion of the trunk, has been recently reported also in association with atypical antipsychotics. We describe the first case of Pisa syndrome during aripiprazole treatment in an elderly (77-year-old) woman, admitted to hospital for behavioural and psychological symptoms of dementia. The ongoing treatment with quetiapine was rapidly tapered and stopped, and a switch to aripiprazole (15 mg/die) was attempted the subsequent day. Six days later, an acute tonic flexion of trunk and head towards the right was observed. Aripiprazole was discontinued and the Pisa syndrome completely disappeared within 3 days, without any adjunctive treatment. © 2006 Elsevier Inc. All rights reserved. Keywords: Aripiprazole; Atypical antipsychotics; Dystonia; Extrapyramidal side effects; Pisa syndrome
1. Introduction
2. Case report
Pisa syndrome (or pleurothotonus) is an axial dystonia, characterized by tonic lateral flexion and slight rotation of the trunk. Although most commonly subsequent to prolonged exposure to conventional antipsychotics, this syndrome has been recently reported also in association with atypical antipsychotics, cholinesterase inhibitors and in patients affected by neurodegenerative disorders (Suzuki and Matsuzaka, 2002; Duggal et al., 2004). Aripiprazole is a novel antipsychotic, acting as partial agonist at dopamine D2 and serotonin 5-HT1A receptors and as antagonist at 5-HT2A (Yokoi et al., 2002), which shows a profile for extrapyramidal side effects similar to placebo in clinical trials (Goodnick and Jerry, 2002). We describe the first case of Pisa syndrome during aripiprazole treatment in an elderly, demented woman; the dystonia rapidly disappeared after the withdrawal of the drug.
A 77-year-old woman was admitted to our Unit in March 2004 for behavioural and psychological symptoms of dementia. Since the diagnosis of probable mixed dementia, according to ICD-10 criteria (Wetterling et al., 1994), in May 2002, she had been treated with quetiapine, titrated up to 100 × 3 mg/die in the last year. She was concomitantly being administered antiplatelet treatment (aspirin 160 mg/die) and benzodiazepines (clonazepam, 0.5 mg/die). On admission, the physical examination revealed non-focal deficits, while MRI imaging detected a cerebrovascular disease, involving also the basal ganglia, and atrophy, more severe at the temporal lobes; the MMSE score was 13. Because of the inadequate control of behavioural and psychological symptoms and the difficult compliance, quetiapine was tapered and stopped within 3 days, and a switch to aripiprazole (15 mg/die) was attempted, although off-label, under strict cardiovascular monitoring. Six days later, an acute dystonic reaction (tonic flexion of trunk and head toward right) was observed. The remaining physical examination was unchanged, as well as the mental status (including the MMSE score), the MRI control did not show any variation. Aripiprazole was discontinued and the Pisa syndrome completely disappeared within 3 days, without any adjunctive treatment.
⁎ Corresponding author. Str. Gariglio 14, 12042 Bra (CN), Italy. Tel.: +39 0172 44922; fax: +39 0172 472514. E-mail address: [email protected] (E. Rota). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.06.009
E. Rota et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 286–287
3. Discussion The case reported suggests that aripiprazole may be implicated in the onset of the Pisa syndrome. The role of partial dopamine D2 receptor partial agonist and serotonin 5-HT2A receptor antagonist renders aripiprazole profile for extrapyramidal side effects similar to placebo in clinical trials (Goodnick and Jerry, 2002). A patient experiencing acute dystonic reaction (including truncal dystonia) with most of other, typical and atypical, antipsychotics but aripiprazole has been recently described (Coffey et al., 2005). Nevertheless, a case of parkinsonism during treatment with aripiprazole (Sharma and Sorrell, 2006) and a few cases of motor worsening in parkinsonian patients treated with aripiprazole for drug-induced psychosis (Fernandez et al., 2004) have been reported. This evidence suggests that also the novel antipsychotic aripiprazole may be responsible of extrapyramidal side-effects, exerting an antagonistic action for dopamine receptors. Particularly, aripiprazole may somehow alter the dopaminergic–cholinergic balance, which is supposed to be the main underlying pathogenetic factor in Pisa syndrome (Suzuki and Matsuzaka, 2002; Villarejo et al., 2003; Duggal et al., 2004). Then, aripiprazole activity at serotonin 5-HT1A and 5-HT2A receptors may also affect those interactions between serotoninergic and dopaminergic system, which are involved in the regulation of extrapyramidal symptoms (Suzuki and Matsuzaka, 2002). However, we cannot rule out that the onset of this dystonia was related to the discontinuation of quetiapine and to the addition of aripiprazole. In fact, some cases of Pisa syndrome have been described after withdrawal of an atypical antipsychotic, maybe in relation with dopaminergic–cholinergic imbalance (Stubner et al., 2000; Suzuki and Matsuzaka, 2002; Villarejo et al., 2003; Duggal et al., 2004). Furthermore, in the case reported, some of these factors were associated, such as old age, female gender, brain damage (cerebrovascular disease and atrophy), and previous combined pharmacological treatments, which seem to represent risk factors for Pisa syndrome (Stubner et al., 2000; Suzuki and Matsuzaka, 2002; Duggal et al., 2004). In fact, from epidemiological data, the Pisa syndrome, different from other types of dystonic reactions, appears to be more prevalent in young and elderly females with organic brain disorders (Suzuki and Matsuzaka, 2002). However, since Pisa syndrome has also been described in two patients affected by neurodegenerative disorders, who were not receiving antipsychotic drugs (Patel et al., 1991; Colosimo, 1998), this syndrome seems to be a multifactorial disorder, whose pathophysiology may involve an asymmetry in neurochemical functioning, associated with cerebral lesions and influenced by jatrogenic factors (Suzuki and Matsuzaka, 2002). A new pathophysiological hypothesis of acute axial dystonias has been recently suggested by Coffey et al. (2005), based
287
on their aforementioned patient, characterized by extreme sensitivity to atypical antipsychotics but aripiprazole, who experienced, in the absence of antipsychotic treatment, after anticonvulsant withdrawal, a dramatic increase in the truncal dystonia as well as in facial dyskinesias, in the context of complex partial seizures. In fact, it has been supposed that this complicated history of truncal dystonia (associated with facial dyskinesias) could be consistent with prodromal signs of frontal or temporal lobe epilepsy; ion channel defects (identified in familial epilepsies as well as in some paroxysmal movement disorders) may be a putative common underlying pathophysiological factor (Coffey et al., 2005), along with (at least in our opinion) organic brain disorders. However, further clinical evidence is required to support this novel hypothesis. 4. Conclusion This report suggests that the occurrence of a Pisa syndrome should be taken into account, when switching from one atypical antipsychotic to another, also to aripiprazole; therefore, caution is required, above all in patients with the abovementioned risk factors. References Coffey GL, Botts SR, de Leon J. High vulnerability to acute dystonic reactions: a case of antipsychotic exposure and uncontrolled seizure activity. Prog Neuropharmacol Biol Psychiatry 2005;29(5):770–4. Colosimo C. Pisa syndrome in a patient with multiple system atrophy. Mov Disord 1998;13:607–9. Duggal HS, Sivamony S, Umapathy C. Pisa syndrome and atypical antipsychotics [letter]. Am J Psychiatry 2004;161(2):373. Fernandez HH, Trieschmann ME, Friedman JH. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol 2004;27(1):4–5. Goodnick PJ, Jerry JM. Aripiprazole: profile on efficacy and safety. Expert Opin Pharmacother 2002;3:1773–81. Patel S, Tariot PN, Hamill RW. Pisa syndrome without neuroleptic exposure in a patient with dementia of the Alzheimer type. J Geriatr Psychiatry Neurol 1991;4:48–51. Sharma A, Sorrell JH. Aripiprazole-induced parkinsonism. Int Clin Psychopharmacol 2006;21(2):127–9. Stubner S, Padberg F, Grohmann R, Hampel H, Hollweg M, Hippius H, et al. Pisa syndrome (pleurothotonus): report of a multicenter drug safety surveillance project. J Clin Psychiatry 2000;61:569–74. Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus). Epidemiology and management. CNS Drugs 2002;16(3):165–74. Villarejo A, Camacho A, Garcia-Ramos R, Moreno T, Penas M, Juntas R, et al. Cholinergic–dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol 2003;26:119–21. Wetterling T, Kanitz RD, Borgis KJ. The ICD-10 criteria for vascular dementia. Dementia 1994;5(3–4):185–8. Yokoi F, Grunder G, Biziere K, Stephane M, Dogan AS, Dannals RF, et al. Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11 C]raclopride. Neuropsychopharmacol 2002;27:248–59.