- Email: [email protected]
Quetiapine successfully treating oculogyric crisis induced by antipsychotic drugs
396
Case reports / Journal of Clinical Neuroscience 14 (2007) 396–398
Regarding the differential diagnosis of hydatid cysts, arachnoid cysts and epidermoids are common in the cerebellopontine cisterns.7 Cystic astrocytomas, porencephalic cysts and pyogenic or fungal abscesses are other lesions to be differentiated.2 Epidermoid cysts, being the third most common cerebellopontine angle tumor, usually have slightly hyperintense signal intensity on proton density MRI. These lesions usually surround neighboring nerves and vessels, whereas arachnoid and hydatid cysts displace adjacent structures.8 The differential diagnosis of meningioma, hemangioma, glomus tumor, cystic astrocytomas and abscesses may be confirmed by the absence of a mural nodule, perifocal edema and contrast enhancement. Arachnoid cysts and porencephalic cysts do not show contrast enhancement as much as hydatid cysts. On the other hand, diffusion MRI is not very useful because both hydatid and arachnoid cysts show increased diffusion.1,2 The treatment of choice for supratentorial cerebral hydatid cyst is cautious surgical removal without rupture. This is more difficult when the hydatid cyst is located in the cerebellopontine cisterns, as the cranial nerves and vascular structures in this region are tightly adhered to the hydatid cyst membrane and if cyst is removed without microdissection, it may result in neural and vascular harm as well as unexpected rupture. In conclusion, MRI is a valuable diagnostic technique to visualize cisternal hydatid cysts and to differentiate them from other cystic lesions and tumors. MRI can precisely define the relationship of the cyst with the vascular and neural
structures, as well as the jugular foramen and the internal acoustic canal which is important in pre-operative planning. References 1. Abbassion K, Amirjamshidi A. Diagnosis and management of hydatid cyst of the central nervous system: Part 1: General considerations and hydatid disease of the brain. Neurosurg Q 2001;11:1–9. 2. Ersahin Y, Mutluer S, Gu¨zelbag E. Intracranial hydatid cyst in children. Neurosurgery 1993;33:219–25. 3. Tistouridis J, Dimitriadis AS, Kazana E. MR in cisternal hydatid cysts. AJNR Am J Neuroradiol 1997;18:1586–7. 4. Altıno¨rs N, Bavbek M, Caner HC, et al. Central nervous system hydatidosis in Turkey: a cooperative study and literature survey analysis of 458 cases. J Neurosurg 2000;93:1–8. 5. Villarejo F, Blazquez MG, Arcas J, et al. Hydatid cyst of the posterior fossa: case report. Neurosurgery 1983;12:228–9. 6. Akdemir G, Ergu¨n R, Gezici AR, et al. Multiple hydatid cyst of aqueduct of Sylvius. Case report with MR Imaging study. Turk Neurosurg 2000;10:142–4. 7. Mascalchi M. Pontine hydatid cyst in association with an acoustic neurinoma. MR appearance in an unusual case. AJNR Am J Neuroradiol 1991;12:190–3. 8. Vaquero J, Jimenez C, Martinez R. Growth of hydatid cysts evaluated by CT scanning after presumed cerebral hydatid embolism. J Neurosurg 1982;75:837–8. 9. Rumboldt Z, Jednacak H, Talan-Hranilovic J, et al. Unusual appearance of a cisternal hydatid cyst. AJNR Am J Neuroradiol 2003;24: 112–4. 10. Von Sinner WN, Strake TEL, Clark D, et al. MR imaging in hydatid disease. AJR Am J Roentgenol 1991;157:741–5. 11. Tien RD, Macfall J, Heinz ER. Evaluation of complex cystic masses of the brain: value of steady-state free-precession MR imaging. AJR Am J Roentgenol 1992;159:1049–55.
doi:10.1016/j.jocn.2006.04.007
Quetiapine successfully treating oculogyric crisis induced by antipsychotic drugs Philippos Gourzis a b
a,*
, Panagiotis Polychronopoulos b, Andreas A. Argyriou b, Elisabeth Chroni b, Stavroula Beratis a
Department of Psychiatry, University of Patras Medical School, Rion-Patras, Greece Department of Neurology, University of Patras Medical School, Rion-Patras, Greece Received 14 November 2005; accepted 22 April 2006
Abstract We report two patients who developed persistent oculogyric crisis, obsessional thoughts and psychiatric symptoms after prolonged treatment with typical and atypical antipsychotics. Both our patients did not improve after withdrawal of these antipsychotics, but rather after quetiapine was administered. 2006 Elsevier Ltd. All rights reserved. *
Corresponding author. Tel.: +30 2610 999 728; fax: +30 260 994 534. E-mail address: [email protected] (P. Gourzis).
Case reports / Journal of Clinical Neuroscience 14 (2007) 396–398
397
Keywords: Oculogyric crisis; Quetiapine; Antipsychotics; Extrapyramidal side effects; Tardive dystonia
1. Introduction Oculogyric dystonic reaction or oculogyric crisis (OGC), affecting the extra-ocular muscles, is an infrequent sideeffect of neuroleptic therapy. Although it occurs acutely, several reports suggested that OGC may be a manifestation of tardive dystonia (TD).1,2 We report two patients who developed persistent OGC, obsessional thoughts and psychiatric symptoms after prolonged treatment with typical and atypical antipsychotics. Symptomatology has subsided completely following quetiapine administration. 2. Presentation of cases The first patient, a 35-year-old man was admitted to the psychiatric wards due to a relapse of schizophrenic psychosis. The patient was rated as ‘above average’ in the total score of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia.3 Paranoid schizophrenia was diagnosed at the age of 23. He received haloperidol (15 mg/day) and biperiden (6 mg/day) for 7 years. Subsequently, he was treated with sertindole (16 mg/day) alone for 2 years and with olanzapine (15 mg/day) alone for the next 3 years. Four months before admission he discontinued his treatment, resulting in a psychotic relapse. During hospitalization he was treated with risperidone (8 mg/ day) and biperiden (6 mg/day). Six months after the initiation of haloperidol, he developed episodes of eye deviation combined with anxiety, restlessness and mood abnormalities, during which consciousness was unimpaired. The episodes appeared once or twice, every 1–2 days and lasted for 20–30 min. The eye movements with concomitant depressive or anxious mood disturbances were maintained during the entire period of treatment with the four antipsychotics, including the 4-month drug-free period. Seven months after discharge from hospital the patient continued to manifest OGC, while being treated with risperidone (8 mg/day) and biperiden (6 mg/day). At that time, risperidone was gradually substituted with quetiapine at a final dose of 800 mg/day. During the next month, the time needed for complete switch to quetiapine, OGC had gradually subsided. Eighteen months later the patient remains free of dystonic symptoms, while his psychiatric symptoms are satisfactorily controlled. The second patient, a 29-year-old man with paranoid schizophrenia started treatment with haloperidol (10 mg/ day) and biperiden (6 mg/day) 4 years previously (‘above average’ in the total PANSS score3 at the time of first diagnosis). After discharge from hospital he continued on the same medication with adequately management of psychosis. The patient was then re-admitted because of conjugate upward eye deviations concomitant with obsessional
thoughts, persecutory delusions and anxiety. The symptoms had a regular time-pattern, appearing in the late afternoon, every 4–6 days, with a duration of 45–60 min. Assuming that the above-described symptomatology was possibly related to the antipsychotic treatment, haloperidol was gradually withdrawn and quetiapine was added, starting with at a dose of 50 mg/day. During the transitional period, the above described crises gradually subsided both in duration and frequency. When quetiapine was administered at a final dose of 600 mg/day and haloperidol was withdrawn, and the crises completely disappeared. Now, 14 months later, the patient remains asymptomatic. Neither patient had personal or family histories of movement disorders or exhibited other extrapyramidal manifestations. General biochemistry, blood counts and levels of serum ceruloplasmin and vitamin B12 were either normal or negative. There was neither exposure to heavy metals or toxins nor exposure to dopamine receptor blocking agents, including antiemetics. Brain MRI and EEG were normal for both patients. 3. Discussion We have previously published two cases with atypical antipsychotic-induced focal TD, successfully treated with quetiapine without loss of psychotic symptom control.4 The cases in this report clearly differ from the previous publication, as these are cases of OGC induction after exposure to antipsychotics. Unlike TD, OGC is rare and often difficult to diagnose as an extrapyramidal side effect of antipsychotics. To our knowledge, there are no published data regarding the use of quetiapine on OGC. Based on previous reports supporting the beneficial effects of clozapine on TD,5 we treated our patients with quetiapine, which is an atypical antipsychotic with close pharmacological resemblance to clozapine. The atypical antipsychotics result in fewer extrapyramidal symptoms and are associated with lower binding to D2 receptors.4,6 Clozapine and quetiapine have a lower D2 occupancy as well as a greater affinity for serotonin 5-HT2 receptors than dopamine D2 receptors compared to typical and other atypical antipsychotics.7–9 The less frequent occurrence of extrapyramidal symptoms and prolactin elevation following exposure to clozapine and quetiapine may be attributed to the property of both drugs to induce a low response with D2 occupancy.9 Additionally, both drugs share another important characteristic, that is, the rapid release from D2 receptors in less than 60 seconds.10 This rapid release of quetiapine from D2 receptors by endogenous dopamine may also contribute to low D2 receptor occupancy, thus to less occurrence of extrapyramidal symptoms.10
398
Case reports / Journal of Clinical Neuroscience 14 (2007) 396–398
Drugs with faster dissociation from D2 receptors are more responsive to phasic bursts of dopamine transmission. Phasic transmission is essential for dopamine to exert its physiologic effects; thus, drugs with faster dissociation should attenuate dopamine transmission with a lesser distortion of the phasic physiologic signaling.11 According to the above evidence and the notion of fast dissociation of atypical antipsychotics,12 we may hypothesize that the rapid release of quetiapine from D2 receptors leads to a better phasic transmission of dopamine which is essential for it to exert its physiological effects,11 and the resultant decline of OGC. Clozapine and quetiapine share several pharmacological similarities; however, we have chosen to treat our patients with quetiapine, due to its excellent safety profile. Of all the antipsychotic drugs, quetiapine may have the least potential for causing extrapyramidal symptoms and other serious adverse events.13 On the contrary, clozapine use is limited mainly because of the potential induction of serious adverse events, such as agranulocytosis, weight gain and diabetes mellitus.13 Summarizing, our reports showed that the administration of quetiapine eliminated the three components of OGC, that is, eye deviation, thought disorder and depressive, anxious mood disturbance. In both our patients, OGC did not subside after withdrawal of the conventional antipsychotics, but only when quetiapine was administered. Being treated with quetiapine, they remained free of neuroleptic-induced side-effects as well as of psychotic relapses for 18 and 14 months, respectively. However, since two patients are a small number of cases upon which to draw any definite conclusions, further study is warranted in order to confirm our findings. doi:10.1016/j.jocn.2006.04.006
References 1. FitzGerald PM, Jaknovic J. Tardive oculogyric crises. Neurology 1989;39:1434–7. 2. Nasrallah HA, Pappas NJ, Crowe RR. Oculogyric dystonia in tardive dyskinesia. Am J Psychiatry 1980;137:850–1. 3. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–76. 4. Gourzis P, Polychronopoulos P, Papapetropoulos S, et al. Quetiapine in the treatment of focal tardive dystonia induced by other atypical antipsychotics: a report of 2 cases. Clin Neuropharmacol 2005;28: 195–6. 5. Adityanjee, Estera A. Successful treatment of tardive dystonia with clozapine. Biol Psychiatry 1996;39:1064–5. 6. Farde L, Nordstrom Al, Wiesel FA, et al. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Arch Gen Psychiatry 1992;49:538–44. 7. Saller CF, Salama AI. Seroquel: biochemical profile of a potential atypical antipsychotic. Psychopharmacology (Berl) 1993;112:285–92. 8. Kasper S, Tauscher J, Heiden A. Quetiapine: efficacy and tolerability in schizophrenia. Eur Neuropsychopharmacol 2001;11 (Suppl.4):S405–13. 9. Kapur S, Zipursky RB, Remington G. Clinical and theoretical implications of 5HT2A and D2 receptor occupancy of clozapine, risperidone and olanzapine in schizophrenia. Am J Psychiatry 1999;156:286–93. 10. Seeman P, Tallerico T. Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry 1999;156:876–84. 11. Kapur S, Remington G. Dopamine D2 receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biolog Psychiatry 2001;50:873–83. 12. Kapur S, Seeman P. Does fast dissociation from the dopamine D2 receptors explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001;158:360–9. 13. Nasrallah HA, Mulvihill T. Iatrogenic disorders associated with conventional vs atypical antipsychotics. Ann Clin Psychiatry 2001;13: 215–27.
Case reports / Journal of Clinical Neuroscience 14 (2007) 396–398
Regarding the differential diagnosis of hydatid cysts, arachnoid cysts and epidermoids are common in the cerebellopontine cisterns.7 Cystic astrocytomas, porencephalic cysts and pyogenic or fungal abscesses are other lesions to be differentiated.2 Epidermoid cysts, being the third most common cerebellopontine angle tumor, usually have slightly hyperintense signal intensity on proton density MRI. These lesions usually surround neighboring nerves and vessels, whereas arachnoid and hydatid cysts displace adjacent structures.8 The differential diagnosis of meningioma, hemangioma, glomus tumor, cystic astrocytomas and abscesses may be confirmed by the absence of a mural nodule, perifocal edema and contrast enhancement. Arachnoid cysts and porencephalic cysts do not show contrast enhancement as much as hydatid cysts. On the other hand, diffusion MRI is not very useful because both hydatid and arachnoid cysts show increased diffusion.1,2 The treatment of choice for supratentorial cerebral hydatid cyst is cautious surgical removal without rupture. This is more difficult when the hydatid cyst is located in the cerebellopontine cisterns, as the cranial nerves and vascular structures in this region are tightly adhered to the hydatid cyst membrane and if cyst is removed without microdissection, it may result in neural and vascular harm as well as unexpected rupture. In conclusion, MRI is a valuable diagnostic technique to visualize cisternal hydatid cysts and to differentiate them from other cystic lesions and tumors. MRI can precisely define the relationship of the cyst with the vascular and neural
structures, as well as the jugular foramen and the internal acoustic canal which is important in pre-operative planning. References 1. Abbassion K, Amirjamshidi A. Diagnosis and management of hydatid cyst of the central nervous system: Part 1: General considerations and hydatid disease of the brain. Neurosurg Q 2001;11:1–9. 2. Ersahin Y, Mutluer S, Gu¨zelbag E. Intracranial hydatid cyst in children. Neurosurgery 1993;33:219–25. 3. Tistouridis J, Dimitriadis AS, Kazana E. MR in cisternal hydatid cysts. AJNR Am J Neuroradiol 1997;18:1586–7. 4. Altıno¨rs N, Bavbek M, Caner HC, et al. Central nervous system hydatidosis in Turkey: a cooperative study and literature survey analysis of 458 cases. J Neurosurg 2000;93:1–8. 5. Villarejo F, Blazquez MG, Arcas J, et al. Hydatid cyst of the posterior fossa: case report. Neurosurgery 1983;12:228–9. 6. Akdemir G, Ergu¨n R, Gezici AR, et al. Multiple hydatid cyst of aqueduct of Sylvius. Case report with MR Imaging study. Turk Neurosurg 2000;10:142–4. 7. Mascalchi M. Pontine hydatid cyst in association with an acoustic neurinoma. MR appearance in an unusual case. AJNR Am J Neuroradiol 1991;12:190–3. 8. Vaquero J, Jimenez C, Martinez R. Growth of hydatid cysts evaluated by CT scanning after presumed cerebral hydatid embolism. J Neurosurg 1982;75:837–8. 9. Rumboldt Z, Jednacak H, Talan-Hranilovic J, et al. Unusual appearance of a cisternal hydatid cyst. AJNR Am J Neuroradiol 2003;24: 112–4. 10. Von Sinner WN, Strake TEL, Clark D, et al. MR imaging in hydatid disease. AJR Am J Roentgenol 1991;157:741–5. 11. Tien RD, Macfall J, Heinz ER. Evaluation of complex cystic masses of the brain: value of steady-state free-precession MR imaging. AJR Am J Roentgenol 1992;159:1049–55.
doi:10.1016/j.jocn.2006.04.007
Quetiapine successfully treating oculogyric crisis induced by antipsychotic drugs Philippos Gourzis a b
a,*
, Panagiotis Polychronopoulos b, Andreas A. Argyriou b, Elisabeth Chroni b, Stavroula Beratis a
Department of Psychiatry, University of Patras Medical School, Rion-Patras, Greece Department of Neurology, University of Patras Medical School, Rion-Patras, Greece Received 14 November 2005; accepted 22 April 2006
Abstract We report two patients who developed persistent oculogyric crisis, obsessional thoughts and psychiatric symptoms after prolonged treatment with typical and atypical antipsychotics. Both our patients did not improve after withdrawal of these antipsychotics, but rather after quetiapine was administered. 2006 Elsevier Ltd. All rights reserved. *
Corresponding author. Tel.: +30 2610 999 728; fax: +30 260 994 534. E-mail address: [email protected] (P. Gourzis).
Case reports / Journal of Clinical Neuroscience 14 (2007) 396–398
397
Keywords: Oculogyric crisis; Quetiapine; Antipsychotics; Extrapyramidal side effects; Tardive dystonia
1. Introduction Oculogyric dystonic reaction or oculogyric crisis (OGC), affecting the extra-ocular muscles, is an infrequent sideeffect of neuroleptic therapy. Although it occurs acutely, several reports suggested that OGC may be a manifestation of tardive dystonia (TD).1,2 We report two patients who developed persistent OGC, obsessional thoughts and psychiatric symptoms after prolonged treatment with typical and atypical antipsychotics. Symptomatology has subsided completely following quetiapine administration. 2. Presentation of cases The first patient, a 35-year-old man was admitted to the psychiatric wards due to a relapse of schizophrenic psychosis. The patient was rated as ‘above average’ in the total score of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia.3 Paranoid schizophrenia was diagnosed at the age of 23. He received haloperidol (15 mg/day) and biperiden (6 mg/day) for 7 years. Subsequently, he was treated with sertindole (16 mg/day) alone for 2 years and with olanzapine (15 mg/day) alone for the next 3 years. Four months before admission he discontinued his treatment, resulting in a psychotic relapse. During hospitalization he was treated with risperidone (8 mg/ day) and biperiden (6 mg/day). Six months after the initiation of haloperidol, he developed episodes of eye deviation combined with anxiety, restlessness and mood abnormalities, during which consciousness was unimpaired. The episodes appeared once or twice, every 1–2 days and lasted for 20–30 min. The eye movements with concomitant depressive or anxious mood disturbances were maintained during the entire period of treatment with the four antipsychotics, including the 4-month drug-free period. Seven months after discharge from hospital the patient continued to manifest OGC, while being treated with risperidone (8 mg/day) and biperiden (6 mg/day). At that time, risperidone was gradually substituted with quetiapine at a final dose of 800 mg/day. During the next month, the time needed for complete switch to quetiapine, OGC had gradually subsided. Eighteen months later the patient remains free of dystonic symptoms, while his psychiatric symptoms are satisfactorily controlled. The second patient, a 29-year-old man with paranoid schizophrenia started treatment with haloperidol (10 mg/ day) and biperiden (6 mg/day) 4 years previously (‘above average’ in the total PANSS score3 at the time of first diagnosis). After discharge from hospital he continued on the same medication with adequately management of psychosis. The patient was then re-admitted because of conjugate upward eye deviations concomitant with obsessional
thoughts, persecutory delusions and anxiety. The symptoms had a regular time-pattern, appearing in the late afternoon, every 4–6 days, with a duration of 45–60 min. Assuming that the above-described symptomatology was possibly related to the antipsychotic treatment, haloperidol was gradually withdrawn and quetiapine was added, starting with at a dose of 50 mg/day. During the transitional period, the above described crises gradually subsided both in duration and frequency. When quetiapine was administered at a final dose of 600 mg/day and haloperidol was withdrawn, and the crises completely disappeared. Now, 14 months later, the patient remains asymptomatic. Neither patient had personal or family histories of movement disorders or exhibited other extrapyramidal manifestations. General biochemistry, blood counts and levels of serum ceruloplasmin and vitamin B12 were either normal or negative. There was neither exposure to heavy metals or toxins nor exposure to dopamine receptor blocking agents, including antiemetics. Brain MRI and EEG were normal for both patients. 3. Discussion We have previously published two cases with atypical antipsychotic-induced focal TD, successfully treated with quetiapine without loss of psychotic symptom control.4 The cases in this report clearly differ from the previous publication, as these are cases of OGC induction after exposure to antipsychotics. Unlike TD, OGC is rare and often difficult to diagnose as an extrapyramidal side effect of antipsychotics. To our knowledge, there are no published data regarding the use of quetiapine on OGC. Based on previous reports supporting the beneficial effects of clozapine on TD,5 we treated our patients with quetiapine, which is an atypical antipsychotic with close pharmacological resemblance to clozapine. The atypical antipsychotics result in fewer extrapyramidal symptoms and are associated with lower binding to D2 receptors.4,6 Clozapine and quetiapine have a lower D2 occupancy as well as a greater affinity for serotonin 5-HT2 receptors than dopamine D2 receptors compared to typical and other atypical antipsychotics.7–9 The less frequent occurrence of extrapyramidal symptoms and prolactin elevation following exposure to clozapine and quetiapine may be attributed to the property of both drugs to induce a low response with D2 occupancy.9 Additionally, both drugs share another important characteristic, that is, the rapid release from D2 receptors in less than 60 seconds.10 This rapid release of quetiapine from D2 receptors by endogenous dopamine may also contribute to low D2 receptor occupancy, thus to less occurrence of extrapyramidal symptoms.10
398
Case reports / Journal of Clinical Neuroscience 14 (2007) 396–398
Drugs with faster dissociation from D2 receptors are more responsive to phasic bursts of dopamine transmission. Phasic transmission is essential for dopamine to exert its physiologic effects; thus, drugs with faster dissociation should attenuate dopamine transmission with a lesser distortion of the phasic physiologic signaling.11 According to the above evidence and the notion of fast dissociation of atypical antipsychotics,12 we may hypothesize that the rapid release of quetiapine from D2 receptors leads to a better phasic transmission of dopamine which is essential for it to exert its physiological effects,11 and the resultant decline of OGC. Clozapine and quetiapine share several pharmacological similarities; however, we have chosen to treat our patients with quetiapine, due to its excellent safety profile. Of all the antipsychotic drugs, quetiapine may have the least potential for causing extrapyramidal symptoms and other serious adverse events.13 On the contrary, clozapine use is limited mainly because of the potential induction of serious adverse events, such as agranulocytosis, weight gain and diabetes mellitus.13 Summarizing, our reports showed that the administration of quetiapine eliminated the three components of OGC, that is, eye deviation, thought disorder and depressive, anxious mood disturbance. In both our patients, OGC did not subside after withdrawal of the conventional antipsychotics, but only when quetiapine was administered. Being treated with quetiapine, they remained free of neuroleptic-induced side-effects as well as of psychotic relapses for 18 and 14 months, respectively. However, since two patients are a small number of cases upon which to draw any definite conclusions, further study is warranted in order to confirm our findings. doi:10.1016/j.jocn.2006.04.006
References 1. FitzGerald PM, Jaknovic J. Tardive oculogyric crises. Neurology 1989;39:1434–7. 2. Nasrallah HA, Pappas NJ, Crowe RR. Oculogyric dystonia in tardive dyskinesia. Am J Psychiatry 1980;137:850–1. 3. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–76. 4. Gourzis P, Polychronopoulos P, Papapetropoulos S, et al. Quetiapine in the treatment of focal tardive dystonia induced by other atypical antipsychotics: a report of 2 cases. Clin Neuropharmacol 2005;28: 195–6. 5. Adityanjee, Estera A. Successful treatment of tardive dystonia with clozapine. Biol Psychiatry 1996;39:1064–5. 6. Farde L, Nordstrom Al, Wiesel FA, et al. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Arch Gen Psychiatry 1992;49:538–44. 7. Saller CF, Salama AI. Seroquel: biochemical profile of a potential atypical antipsychotic. Psychopharmacology (Berl) 1993;112:285–92. 8. Kasper S, Tauscher J, Heiden A. Quetiapine: efficacy and tolerability in schizophrenia. Eur Neuropsychopharmacol 2001;11 (Suppl.4):S405–13. 9. Kapur S, Zipursky RB, Remington G. Clinical and theoretical implications of 5HT2A and D2 receptor occupancy of clozapine, risperidone and olanzapine in schizophrenia. Am J Psychiatry 1999;156:286–93. 10. Seeman P, Tallerico T. Rapid release of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry 1999;156:876–84. 11. Kapur S, Remington G. Dopamine D2 receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biolog Psychiatry 2001;50:873–83. 12. Kapur S, Seeman P. Does fast dissociation from the dopamine D2 receptors explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001;158:360–9. 13. Nasrallah HA, Mulvihill T. Iatrogenic disorders associated with conventional vs atypical antipsychotics. Ann Clin Psychiatry 2001;13: 215–27.