ISP

1* 2* 1 1 3 4 3 1 2 1 100191 2 200030 3 410008 4 215008 1 2011 12 R971 C 1003-3734 2014 12-1410 - 08 Clinical guidelines of paliperidone palmitate ZHANG Hong-yan 1 HUANG Ji-zhong 2 SI Tian-mei 1 SHU Liang 1 HAO Wei 3 MEI Qi-yi 4 ZHAO Jing-ping 3 YU Xin 1 ZHANG Ming-yuan 2 1 Peking University Sixth Hospital Peking University Institute of Mental Health Key Laboratory of Mental Health Ministry of Health Peking University Beijing 100191 China 2 Shanghai Mental Health Center Shanghai 200030 China 3 Institute of Mental Health Xiangya No. 2 Hospital of Central South University Changsha 410008 China 4 Suzhou Guangji Hospital Suzhou 215008 China Abstract Paliperidone palmitate is an atypical long acting antipsychotics which can fast onset in acute phase and continuously improve the symptoms in maintenance phase. It has the solid efficacy and convenient administration which offer a new option for schizophrenia treatment and will help patients to adhere the treatment and prevent relapse. As the sole long acting antipsychotics with monthly injection it was approved by CFDA in 2011 and indicated for the acute and maintenance treatment of schizophrenia. Based on the published manuscripts and clinical experience CSCG China Schizophrenia Coordination Group organized the experts to write this paper which will discuss the characteristic of paliperidone palmitate on pharmacology applicable patients dosage information and adverse reaction. We hope this clinical usage guideline of paliperidone palmitate could provide the useful suggestion for clinical practice and make more patients get benefits. Key words paliperidone palmitate long acting antipsychotics schizophrenia relapse clinical guideline paliperidone palmitate2 010 82801984 E-mail sally_zhy@ sina. com 021 64387250 E-mail junghjz@ sina. cn * 1410 2014 23 12

12 1 1. 1 10 1 1 2-3 13 4 14 4-5 15 6-7 8 9 10-11 1. 3 9 2 ISP 12 1. 2 2012 1411 2014 23 12

9- CYP 2D6 16 9 1 14 2 D 2 5-2A 5-HT 2A K d 1. 6 1. 1 17 7. 5 ng ml - 1 65% ~ 80% D 2 14 NE α 2 K i 3. 9 17 2 NE 5-HT α 2 NE 5-HT 5-HT NE D 3 13 2. 1 9-RS -3-2- 4-6- -1 2- -3-yl -1-yl -2- -4- -6 7 8 9-5-HT 7-4H- 1 2-a -9-yl- K i 2. 8 17 5-HT 7 D 2 DA D 2 13 α 1 H 1 17 39 78 117 156 234 mg 25 50 75 100 150 mg 14 2. 3 1 d 1 d 126 d 13 14 d 8 10 ng ml - 1 2. 2 65% ~ 80% D 2 1412 2014 23 12 K i 3. 5 17 D 3

28% 14 5 3 18 - AUC 25 ~ 150 mg C max 100 mg 1. 8 2. 2 14 3. 2 59% 25% 20 P450 CYP 21 10% CYP 14 CYP450 2D6 19 CYP450 3A4 /5 14 25 ~ 150 mg 25 ~ 49 d 14 3. 3 14 25 kg m - 2 < 25 kg m - 2 15 22 P- 9 14 3 1 3. 1 1413 2014 23 12

3. 4 4. 2. 4 1 EPS 22 2 3 4. 3 3 ~ 6 4 4 ~ 6 4. 1 3 2 3 150 mg d 8 100 mg 75 ~ 150 mg eq 13 3 4. 3. 1 1 6 2 150 mg 4. 2 150 mg 1 4. 2. 1 3 4 4. 3. 2 4. 2. 2 4. 4 4. 2. 3 4. 4. 1 1 2 4. 4. 2 6 1414 2014 23 12

/ 150 mg 100 mg 100 mg 75 mg 5 1 2 ~ 4 4. 4. 3 2 4. 5 4. 5. 1 100 mg 35. 6% 1 150 mg 39. 2% 2 2 d 1 150 mg d 8 100 mg 4. 5. 2 1 2 /mg /mg /mg 2 3 ~ 4 5 ~ 6 ~ 8 6 9 12 ~ 15 75 100 150 10 15 20 ~ 30 400 ~ 600 600 ~ 800 > 800 10 ~ 15 20 ~ 25 > 30 80 ~ 120 120 ~ 160 > 160 15 4. 6 2 2 1 d 8 2 d d 6 d 10 2 2 1 1 7 d 4 ~ 6 2 1 /mg 2 /mg 25 50 ~ 75 mg eq. > 6 < 6 37. 5 75 ~ 100mg eq. 2 50 100 ~ 150 mg eq. 2 1 2 150 mg2 4. 5. 3 100 mg 1 1 6 3 d d 1 150 mg d 8 100 mg 4. 7 1 1 ~ 2 1415 2014 23 12

2 4. 9. 4 18 4. 9. 5 65 3 4 14 23% QTc 450 ms 4. 8 4. 8. 1 90 kg 4. 8. 2 1 QTc 1. 5 22 QTc 470 ms QTc 450 ms < 90 kg 1 23 2 3 1. 5 EPS 22 4. 9 4. 9. 1 15 50 ml min - 1 < 80 ml min - 1 d 1 100 mg 1 75 mg 50 mg < 50 ml min - 1 4. 9. 2 4. 9. 3 1. EB/OL. 2014-05 - ar-5wwnvogtweszgz2x6bta06gkcnfxdlucm_wvlq. 1416 2014 23 12 15 4. 10 01. http / /wenku. baidu. com /link url = YvKGG14YTQ0RQL 5z20oT6u8D4Gqtql6srxAnFQwqeG4cPyQXRs-lfdDjFAQGxvKZc_ 2 LIEBERMAN JA KOREEN AR CHAKOS M et al. Factors influencing treatment response and outcome of first-episode schiz-

ophrenia implications for understanding the pathophysiology of schizophrenia J. J Clin Psychiatry 1996 57 Suppl 9 5-9. 3 SHEITMAN BB LIEBERMAN JA. The natural history and pathophysiology of treatment resistant schizophrenia J. J Psychiatr Res 1998 32 3-4 143-150. 4 LIEBERMAN JA. Atypical antipsychotic drugs as a first-line treatment of schizophrenia a rationale and hypothesis J. J Clin Psychiatry 1996 57 Suppl 11 68-71. 5 BIRCHWOOD M TODD P JACKSON C. Early intervention in psychosis. The critical period hypothesis J. Br J Psychiatry Suppl 1998 172 33 53-59. 6 CIUDAD A SAN L BERNARDO M et al. Relapse and therapeutic interventions in a 1-year observational cohort study of nonadherent outpatients with schizophrenia J. Prog Neuropsychopharmacol Biol Psychiatry 2012 36 2 245-250. 7 DEVYLDER JE LUKENS EP. Family history of schizophrenia as a risk factor for axis I psychiatric conditions J. J Psychiatr Res 2013 47 2 181-187. 8 ASCHER-SVANUM H ZHU B FARIES DE et al. The cost of relapse and the predictors of relapse in the treatment of schizophrenia J. BMC Psychiatry 2010 10 2. 9 ROBINSON D WOERNER MG ALVIR JM et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder J. Arch Gen Psychiatry 1999 56 3 241-247. 10 CHIEN WT CHAN S MORRISSEY J et al. Effectiveness of a mutual support group for families of patients with schizophrenia J. J Adv Nurs 2005 51 6 595-608. 11 MAROM S MUNITZ H JONES PB et al. Familial expressed emotion outcome and course of Israeli patients with schizophrenia J. Schizophr Bull 2002 28 4 731-743. 12 DRURY VM ROBINSON EJ BIRCHWOOD M. Theory of mind skills during an acute episode of psychosis and following recovery J. Psychol Med 1998 28 5 1101-1112. 13 OWEN RT. Paliperidone palmitate injection Its efficacy safety and tolerability in schizophrenia J. Drugs Today Barc 2010 46 7 463-471. Chinese Journal of New Drugs 2014 23 12 14 HOY SM SCOTT LJ KEATING GM. Intramuscular paliperidone palmitate J. CNS Drugs 2010 24 3 227-244. 15 GOPAL S GASSMANN-MAYER C PALUMBO J et al. Practical guidance for dosing and switching paliperidone palmitate treatment in patients with schizophrenia J. Curr Med Res Opin 2010 26 2 377-387. 16 FAKHOURY WK WHITE I PRIEBE S. Be good to your patient how the therapeutic relationship in the treatment of patients admitted to assertive outreach affects rehospitalization J. J Nerv Ment Dis 2007 195 9 789-791. 17 GRAY JA ROTH BL. The pipeline and future of drug development in schizophrenia J. Mol Psychiatry 2007 12 10 904-922. 18 EMSLEY R MEDORI R KOEN L et al. Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis a preliminary study J. J Clin Psychopharmacol 2008 28 2 210-213. 19 PRIKRYL R PRIKRYLOVA KH VRZALOVA M et al. Role of long-acting injectable second-generation antipsychotics in the treatment of first-episode schizophrenia a clinical perspective J. Schizophr Res Treatment 2012 2012 764769. 20 PANDINA GJ LINDENMAYER JP LULL J et al. A randomized placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia J. J Clin Psychopharmacol 2010 30 3 235-244. 21 PANDINA G LANE R GOPAL S et al. A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia J. Prog Neuropsychopharmacol Biol Psychiatry 2011 35 1 218-226. 22 HOUGH D GOPAL S VIJAPURKAR U et al. Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia a randomized double-blind placebo-controlled study J. Schizophr Res 2010 116 2-3 107-117. / 2014-05 - 26 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 櫃 1370 2014-04 - 01. http / /www. sfda. gov. cn. 7 CFDA. 13 CFDA. EB /OL. 2005 2014-04 - 01. http / /www. sfda. gov. cn. EB /OL. 2013 2014-04 - 01. ht- 8 CFDA. tp / /www. cde. org. cn. EB /OL. 2013 2014-04 - 01. http / /www. sfda. 14 CDE. EB /OL. 2012 gov. cn. 2014-04 - 01. http / /www. www. cde. org. cn. 9 CFDA. EB /OL. 15 CFDA. 2012 2014-04 - 01. http / / www. sfda. gov. cn. EB /OL. 2005 2014-04 - 01. http / /www. cde. org. cn. 10 CFDA. EB / 16 CFDA. OL. 2013 2014-04 - 01. http / /www. cde. org. cn. EB /OL. 2011 2014-04 - 01. http / /www. sfda. gov. cn. 11 CFDA. EB /OL. 2013 2014-04 - 01. http / /www. cde. org. cn. 12 CFDA. Ⅰ EB /OL. 2011 / 2014-04 - 21 1417 2014 23 12