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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (5): 495-502.doi: 10.3736/jcim20110506

Special Issue: Traditional Chinese Medicine

• Study Protocol • Previous Articles     Next Articles

Treatment effects of traditional Chinese medicines Suoquan Pill and Wuling Powder on clozapine-induced hypersalivation in patients with schizophrenia: Study protocol of a randomized, placebo-controlled trial

Chia-Chun Hung1, Pin-Kuei Fu1, Hsyn-Yi Wang2, Chin-Hong Chan1, Tsuo-Hung Lan1,3,4()   

  1. 1. Psychiatry Department, Taichung Veterans General Hospital, Taichung, Taiwan, China
    2. Nuclear Medicine Department, Taichung Veterans General Hospital, Taichung, Taiwan, China
    3. Institute of Genome Science, National Yang-Ming University, Taipei, Taiwan, China
    4. Division of Mental Health and Substance Abuse Research, National Health Research Institute, Miaoli County, Taiwan, China
  • Received:2011-02-11 Accepted:2011-03-29 Online:2011-05-20 Published:2011-05-15
  • Contact: Lan Tsuo-Hung E-mail:thlan@ym.edu.tw

Background: It is reported that 30% to 80% schizophrenia patients suffered from hypersalivation when taking clozapine. Some investigations of the use of formulas of traditional Chinese medicine (TCM) to treat clozapine-induced hypersalivation suggested their potential treatment effects. In these formulas, Suoquan Pill (SQP) and Wuling Powder (WLP) were suggested to have therapeutic effects in improving clozapine-induced hypersalivation.
Methods and design: A prospective, double-blind, randomized, placebo-controlled study will be conducted to test the therapeutic effects of SQP and WLP in relieving hypersalivation in patients taking clozapine. A total of 45 patients will be enrolled into this study with 15 in each treatment group. Patients will receive medication according to their assigned group. Either SQP 10 g per oral dose twice daily, WLP 10 g per oral dose twice daily or placebo powder 10 g per oral dose twice daily will be prescribed to the patients for 8 weeks. The Drooling Severity Scale, Nocturnal Hypersalivation Rating Scale and sialoscintigraphy will be used as the primary outcome measures; the Clinical Global Impressions Severity, the Positive and Negative Syndrome Scale, the Abnormal Involuntary Movement Scale, the Simpson-Angus Scale and the TCM constitutional scale will be used as the secondary outcome measures
Discussion: It is hypothesized that SQP and WLP will have a beneficial effect in controlling clozapine-induced hypersalivation symptoms. It may also improve the life quality of psychotic patients by improving their mental status.

Key words: clozapine, schizophrenia, sialorrhea, therapeutic methods,traditional Chinese medicine, Suoquan Pill, Wuling Powder, study protocol

[1] Miller DD . Review and management of clozapine side effects[J].J Clin Psychiatry, 2000, 61(Suppl 8):14-17;discussion 18-19
doi: 10.1076/1380-3395(200010)22:5;1-9;FT702 pmid: 10811238
[2] Cree A, Mir S, Fahy T . A review of the treatment options for clozapine-induced hypersalivation[J]. Psychiatr Bull, 2001,25(3):114-116
doi: 10.1192/pb.25.3.114
[3] Praharaj SK, Arora M, Gandotra S . Clozapine-induced sialorrhea: pathophysiology and management strategies[J]. Psychopharmacology (Berl), 2006,185(3):265-273
doi: 10.1007/s00213-005-0248-4 pmid: 16514524
[4] Rogers DP, Shramko JK . Therapeutic options in the treatment of clozapine-induced sialorrhea[J]. Pharmacotherapy, 2000,20(9):1092-1095
doi: 10.1592/phco.20.13.1092.35036 pmid: 10999502
[5] Freudenreich O, Beebe M, Goff DC . Clozapine-induced sialorrhea treated with sublingual ipratropium spray: a case series[J]. J Clin Psychopharmacol, 2004,24(1):98-100
doi: 10.1097/01.jcp.0000106228.36344.2e pmid: 14709958
[6] Reinstein MJ, Sirotovskaya LA, Chasanov MA, Jones LE, Mohan S . Comparative efficacy and tolerability of benzatropine and terazosin in the treatment of hypersalivation secondary to clozapine[J]. Clin Drug Investig, 1999,17(2):97-102
doi: 10.2165/00044011-199917020-00003
[7] Lieberman JA, Safferman AZ . Clinical profile of clozapine: adverse reactions and agranulocytosis[J]. Psychiatr Q, 1992,63(1):51-70
doi: 10.1007/BF01064682 pmid: 1438605
[8] Safferman A, Liberman JA, Kane JM, Szymanski S, Kinon B . Update on the clinical efficacy and side effects of clozapine[J]. Schizophr Bull, 1991,17(2):247-261
doi: 10.1093/schbul/17.2.247 pmid: 1882209
[9] Boyce HW, Bakheet MR . Sialorrhea: a review of a vexing, often unrecognized sign of oropharyngeal and esophageal disease[J]. J Clin Gastroenterol, 2005,39(2):89-97
[10] Robinson D, Fenn H, Yesavage J . Possible association of parotitis with clozapine[J]. Am J Psychiatry, 1995,152(2):297-298
doi: 10.1176/ajp.152.2.297 pmid: 7840372
[11] Brodkin ES, Pelton GH, Price LH . Treatment of clozapine-induced parotid gland swelling[J]. Am J Psychiatry, 1996,153(3):445
[12] Drug-induced sialorrhoea and excessive saliva accumulation[J]. Prescrire Int, 2009,18(101):119-121
pmid: 19637431
[13] Hinkes R, Quesada TV, Currier MB, Gonzalez-Blanco M . Aspiration pneumonia possibly secondary to clozapine-induced sialorrhea[J]. J Clin Psychopharmacol, 1996,16(6):462-463
doi: 10.3371/CSRP.SAFI.061213 pmid: 8959476
[14] Pearlman C . Clozapine, nocturnal sialorrhea, and choking[J]. J Clin Psychopharmacol, 1994,14(4):283
doi: 10.1097/00004714-199408000-00013 pmid: 7962689
[15] Berlan M, Montastruc JL, Lafontan M . Pharmacological prospects for α2-adrenoceptor antagonist therapy[J]. Trends Pharmacol Sci, 1992,13(7):277-282
doi: 10.1016/0165-6147(92)90085-K
[16] Mandel ID, Zengo A, Katz R, Wotman S . Effect of adrenergic agents on salivary composition[J]. J Dent Res, 1975,54(Spec No B):B27-B33
doi: 10.1177/00220345750540022001 pmid: 237019
[17] Davydov L, Botts SR . Clozapine-induced hypersalivation[J]. Ann Pharmacother, 2000,34(5):662-665
doi: 10.1002/ppul.10457 pmid: 9328507
[18] Zorn SH, Jones SB, Ward KM, Liston DR . Clozapine is a potent and selective muscarinic M4 receptor agonist[J]. Eur J Pharmacol, 1994,269(3):R1-R2
doi: 10.1016/0922-4106(94)90047-7 pmid: 7895765
[19] Rabinowitz T, Frankenburg FR, Centorrino F, Kando J . The effect of clozapine on saliva flow rate: a pilot study[J]. Biol Psychiatry, 1996,40(11):1132-1134
doi: 10.1016/S0006-3223(96)89255-9 pmid: 8931916
[20] Grabowski J . Clonidine treatment of clozapine-induced hypersalivation[J]. J Clin Psychopharmacol, 1992,12(1):69-70
doi: 10.1097/00001573-199202000-00028 pmid: 1552044
[21] Praharaj SK, Verma P, Roy D, Singh A . Is clonidine useful for treatment of clozapine-induced sialorrhea?[J]. J Psychopharmacol, 2005,19(4):426-428
doi: 10.1177/0269881105053311 pmid: 15983000
[22] Corrigan FM, MacDonald S, Reynolds GP .Clozapine-induced hypersalivation and the alpha 2 adrenoceptor[J]. Br J Psychiatry, 1995,167(3):412
doi: 10.1192/bjp.169.3.380b pmid: 8879729
[23] Webber MA, Szwast SJ, Steadman TM, Frazer A, Malloy FW, Lightfoot JD, Shekhar A . Guanfacine treatment of clozapine-induced sialorrhea[J]. J Clin Psychopharmacol, 2004,24(6):675-676
doi: 10.1097/01.jcp.0000145348.06783.1d pmid: 15538136
[24] Bai YM, Lin CC, Chen JY, Liu WC . Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: a randomized, double-blind, placebo-controlled, cross-over study[J]. J Clin Psychopharmacol, 2001,21(6):608-611
doi: 10.1097/00004714-200112000-00012
[25] Fritze J, Elliger T . Pirenzepine for clozapine-induced hypersalivation[J]. Lancet, 1995,346(8981):1034
doi: 10.1016/S0140-6736(95)91713-6 pmid: 7475564
[26] Schneider B, Weigmann H, Hiemke C, Weber B, Fritze J . Reduction of clozapine-induced hypersalivation by pirenzepine is safe[J]. Pharmacopsychiatry, 2004,37(2):43-45
doi: 10.1055/s-2004-815523 pmid: 15048609
[27] Antonello C, Tessier P . Clozapine and sialorrhea: a new intervention for this bothersome and potentially dangerous side effect[J]. J Psychiatry Neurosci, 1999,24(3):250
[28] Comley C, Galletly C, Ash D . Use of atropine eye drops for clozapine induced hypersalivation[J]. Aust N Z J Psychiatry, 2000,34(6):1033-1034
doi: 10.1046/j.1440-1614.2000.0840f.x pmid: 11127617
[29] Sharma A, Ramaswamy S, Dahl E, Dewan V . Intraoral application of atropine sulfate ophthalmic solution for clozapine-induced sialorrhea[J]. Ann Pharmacother, 2004,38(9):1538
doi: 10.1345/aph.1E077 pmid: 15252196
[30] Aggarwal A, Garg A, Jiloha RC . Trihexyphenidyl(benzhexol) in clozapine-induced nocturnal enuresis and sialorrhea[J]. Indian J Med Sci, 2009,63(10):470-471
doi: 10.4103/0019-5359.57642 pmid: 19901488
[31] Poyurovsky M, Modai I, Weizman A . Trihexyphenidyl as a possible therapeutic option in clozapine-induced nocturnal enuresis[J]. Int Clin Psychopharmacol, 1996,11(1):61-63
doi: 10.1097/00004850-199603000-00010 pmid: 8732317
[32] Praharaj SK, Sarkhel S, Khanande RV, Sinha VK . Complete resolution of clozapine-induced sialorrhea with low dose trihexyphenidyl[J]. Psychopharmacol Bull, 2010,43(4):73-75
doi: 10.1007/s00213-009-1699-9 pmid: 21240153
[33] Spivak B, Adlersberg S, Rosen L, Gonen N, Mester R, Weizman A . Trihexyphenidyl treatment of clozapine-induced hypersalivation[J]. Int Clin Psychopharmacol, 1997,12(4):213-215
doi: 10.1097/00004850-199707000-00005 pmid: 9347382
[34] Richardson C, Kelly DL, Conley RR . Biperiden for excessive sweating from clozapine[J]. Am J Psychiatry, 2001,158(8):1329-1330
doi: 10.1176/appi.ajp.158.8.1329 pmid: 11481175
[35] Calderon J, Rubin E, Sobota WL . Potential use of ipatropium bromide for the treatment of clozapine-induced hypersalivation: a preliminary report[J]. Int Clin Psychopharmacol, 2000,15(1):49-52
doi: 10.1097/00004850-200015010-00008
[36] Sockalingam S, Shammi C, Remington G . Treatment of clozapine-induced hypersalivation with ipratropium bromide: a randomized, double-blind, placebo-controlled crossover study[J]. J Clin Psychiatry, 2009,70(8):1114-1119
doi: 10.4088/JCP.08m04495
[37] Duggal HS . Glycopyrrolate for clozapine-induced sialorrhea[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2007,31(7):1546-1547
doi: 10.1016/j.pnpbp.2007.06.013 pmid: 17614181
[38] Liang CS, Ho PS, Shen LJ, Lee WK, Yang FW, Chiang KT . Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study[J]. Schizophr Res, 2010,119(1-3):138-144
doi: 10.1016/j.schres.2010.02.1060
[39] Robb AS, Lee RH, Cooper EB, Siedel JV, Nusrat N . Glycopyrrolate for treatment of clozapine-induced sialorrhea in three adolescents[J]. J Child Adolesc Psychopharmacol, 2008,18(1):99-107
doi: 10.1089/cap.2007.0037 pmid: 18294092
[40] Gaftanyuk O, Trestman RL . Scolpolamine patch for clozapine-induced sialorrhea[J]. Psychiatr Serv, 2004,55(3):318
doi: 10.1176/appi.ps.55.3.318 pmid: 15001737
[41] Croissant B, Hermann D, Olbrich R . Reduction of side effects by combining clozapine with amisulpride: case report and short review of clozapine-induced hypersalivation – a case report[J]. Pharmacopsychiatry, 2005,38(1):38-39
doi: 10.1055/s-2005-837771
[42] Kreinin A, Epshtein S, Sheinkman A, Tell E . Sulpiride addition for the treatment of clozapine-induced hypersalivation: preliminary study[J]. Isr J Psychiatry Relat Sci, 2005,42(1):61-63
doi: 10.1017/S1041610205001948 pmid: 16134408
[43] Kreinin A, Novitski D, Weizman A . Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study[J]. Int Clin Psychopharmacol, 2006,21(2):99-103
doi: 10.1097/01.yic.0000188216.92408.69
[44] Praharaj SK, Ray P, Gandotra S .Amisulpride improved debilitating clozapine-induced sialorrhea[J].Am J Ther, 2010: Epub ahead of print
doi: 10.1097/MJT.0b013e3181c84bbd pmid: 20068443
[45] Praharaj SK, Sarkar S, Sinha VK . Amisulpride treatment for clozapine-induced sialorrhea[J]. J Clin Psychopharmacol, 2009,29(2):189-190
doi: 10.1097/JCP.0b013e318199f264 pmid: 19512987
[46] Copp PJ, Lament R, Tennent TG . Amitriptyline in clozapine-induced sialorrhoea[J]. Br J Psychiatry, 1991,159:166
doi: 10.1192/bjp.159.1.166a pmid: 1888974
[47] Kreinin A, Miodownik C, Libov I, Shestakova D, Lerner V . Moclobemide treatment of clozapine-induced hypersalivation: pilot open study[J]. Clin Neuropharmacol, 2009,32(3):151-153
doi: 10.1097/WNF.0b013e31818f1111
[48] Praharaj SK, Arora M . Amitriptyline for clozapine-induced nocturnal enuresis and sialorrhoea[J]. Br J Clin Pharmacol, 2007,63(1):128-129
doi: 10.1111/j.1365-2125.2006.02748.x pmid: 2000705
[49] Syed R, Au K, Cahill C, Duggan L, He Y, Udu V, Xia J .Pharmacological interventions for clozapine-induced hypersalivation[J].Cochrane Database Syst Rev, 2008,( 3):CD005579
doi: 10.1093/schbul/sbn043 pmid: 2632459
[50] Kahl KG, Hagenah J, Zapf S, Trillenberg P, Klein C, Lencer R . Botulinum toxin as an effective treatment of clozapine-induced hypersalivation[J]. Psychopharmacology (Berl), 2004,173(1-2):229-230
doi: 10.1007/s00213-004-1803-0 pmid: 14747903
[51] Steinlechner S, Klein C, Moser A, Lencer R, Hagenah J . Botulinum toxin B as an effective and safe treatment for neuroleptic-induced sialorrhea[J]. Psychopharmacology (Berl), 2010,207(4):593-597
doi: 10.1007/s00213-009-1689-y pmid: 19823807
[52] Conry A, Siris SG, Bermanzohn PC . Improvement of clozapine-induced sialorrhea after septoplasty[J]. Am J Psychiatry, 1996,153(3):444
doi: 10.1176/ajp.153.3.444 pmid: 8610844
[53] Sockalingam S, Remington G . Review: insufficient evidence to guide use of drugs for clozapine induced hypersalivation[J]. Evid Based Ment Health, 2009,12(1):12
doi: 10.1136/ebmh.12.1.12 pmid: 19176771
[54] Syed Sheriff RJ, Au K, Cahill C, Duggan L, He Y, Udu V, Xia J . Pharmacological interventions for clozapine-induced hypersalivation[J]. Schizophr Bull, 2008,34(4):611-612
doi: 10.1093/schbul/sbn043 pmid: 2632459
[55] Kang B, Liu YC, Zhang YP, Han Y, Fan LZ, Zhou J . Effects of Suoquan Pill for reducing clozapine-induced salivation[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1993,13(6):347-348
康冰, 刘玉成, 张雅萍, 韩玉, 樊禄珍, 周军 . 缩泉丸治疗氯氮平所致流涎的临床观察[J]. 中国中西医结合杂志, 1993,13(6):347-348
[56] American Psychiatric Association . Diagnostic and statistical manual of mental disorders (DSM-Ⅳ-TR). Text revision. 4th ed. Washington DC: American Psychiatric Association. 2000
[57] Suskind DL, Tilton A . Clinical study of botulinum-A toxin in the treatment of sialorrhea in children with cerebral palsy[J]. Laryngoscope, 2002,112(1):73-81
doi: 10.1097/00005537-200201000-00014
[58] Jongerius PH, van Limbeek J, Rotteveel JJ . Assessment of salivary flow rate: biologic variation and measure error[J]. Laryngoscope, 2004,114(10):1801-1804
doi: 10.1097/00005537-200410000-00023 pmid: 15454775
[59] Kohn WG, Ship JA, Atkinson JC, Patton LL, Fox PC . Salivary gland 99mTc-scintigraphy: a grading scale and correlation with major salivary gland flow rates[J]. J Oral Pathol Med, 1992,21(2):70-74
doi: 10.1111/jop.1992.21.issue-2
[60] Umehara I, Yamada I, Murata Y, Takahashi Y, Okada N, Shibuya H . Quantitative evaluation of salivary gland scintigraphy in Sjorgen's syndrome[J]. J Nucl Med, 1999,40(1):64-69
[61] Vigh L, Carlsen O, Hartling OJ . Uptake index and stimulated salivary gland response in 99Tcm-pertechnetate salivary gland scintigraphy in normal subjects[J]. Nucl Med Commun, 1997,18(4):363-366
doi: 10.1097/00006231-199704000-00177
[62] Bohuslavizki KH, Brenner W, Tinnemeyer S, Wolf H, Sippel C, Tonshoff G, Karde P, Stauch C, Clausen M, Henze E . Normal data base for quantitative salivary gland scintigraphy[J]. Radiol Oncol, 1995,29(4):297-305
[63] Guy W , National Institute of Mental Health (U.S.), Psychopharmacology Research Branch; Early Clinical Drug Evaluation Program. ECDEU assessment manual for psychopharmacology. Revised ed. Rockville: U. S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs. 1976.
[64] Kay SR, Fiszbein A, Opler LA . The positive and negative syndrome scale(PANSS) for schizophrenia[J]. Schizophr Bull, 1987,13(2):261-276
doi: 10.1093/schbul/13.2.261
[65] Munetz MR, Benjamin S . How to examine patients using the abnormal involuntary movement scale[J]. Hosp Community Psychiatry, 1988,39(11):1172-1177
[66] Simpson GM, Angus JW . A rating scale for extrapyramidal side effects[J]. Acta Psychiatr Scand Suppl, 1970,212:11-19
[67] China Association of Chinese Medicine. ZYYXH/T157-2009 Classification and determination of constitution in TCM[M]. Beijing: China Press of Traditional Chinese Medicine, 2009
中华中医药学会. ZYYXH/T157-2009中医体质分类与判定[M]. 北京: 中国中医药出版社, 2009
[68] World Health Organization . WHO launches the first global strategy on traditional and alternative medicine.
[69] Farde L, Nordstrom AL . PET analysis indicates atypical central dopamine receptor occupancy in clozapine-treated patients[J]. Br J Psychiatry Suppl, 1992,( 17):30-33
[70] Farde L, Nordstrom AL, Nyberg S, Halldin C, Sedvall G . D1-, D2-, and 5-HT2-receptor occupancy in clozapine-treated patients[J]. J Clin Psychiatry, 1994,55(Suppl B):67-69
pmid: 7961577
[71] Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G . 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[J]. Arch Gen Psychiatry, 1992,49(7):538-544
doi: 10.1001/archpsyc.1992.01820070032005
[72] Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B . Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials[J]. Am J Psychiatry, 2001,158(4):518-526
doi: 10.1176/appi.ajp.158.4.518
[73] Solanki RK, Singh P, Swami MK . Clozapine: current perspective[J]. Indian J Psychiatry, 2007,49(4):271-276
doi: 10.4103/0019-5545.37668
[74] Taylor DM , Duncan-McConnell D.Refractory schizophrenia and atypical antipsychotics[J]. J Psychopharmacol, 2000,14(4):409-418
doi: 10.1177/026988110001400411 pmid: 11198061
[75] Tuunainen A, Wahlbeck K, Gilbody S . Newer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials[J]. Schizophr Res, 2002,56(1-2):1-10
doi: 10.1016/S0920-9964(01)00212-2
[76] Wahlbeck K, Cheine M, Essali A, Adams C . Evidence of clozapine’s effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials[J]. Am J Psychiatry, 1999,156(7):990-999
[77] Calabrese JR, Kimmel SE, Woyshville MJ, Rapport DJ, Faust CJ, Thompson PA, Meltzer HY . Clozapine for treatment-refractory mania[J]. Am J Psychiatry, 1996,156(6):759-764
doi: 10.1176/ajp.153.6.759 pmid: 8633686
[78] Ciapparelli A , Dell’Osso L, Bandettini di Poggio A, Carmassi C, Cecconi D, Fenzi M, Chiavacci MC, Bottai M, Ramacciotti CE, Cassano GB.Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study[J]. J Clin Psychiatry, 2003,64(4):451-458
doi: 10.4088/JCP.v64n0416
[79] Fehr BS, Ozcan ME, Suppes T . Low doses of clozapine may stabilize treatment-resistant bipolar patients[J]. Eur Arch Psychiatry Clin Neurosci, 2005,255(1):10-14
doi: 10.1007/s00406-004-0528-8 pmid: 15538596
[80] Kimmel SE, Calabrese JR, Woyshville MJ, Meltzer HY . Clozapine in treatment-refractory mood disorders[J]. J Clin Psychiatry, 1994,55(Suppl B):91-93
doi: 10.1207/s15374424jccp2303_10 pmid: 7961583
[81] Mahmood T, Devlin M, Silverstone T . Clozapine in the management of bipolar and schizoaffective manic episodes resistant to standard treatment[J]. Aust N Z J Psychiatry, 1997,31(3):424-426
doi: 10.3109/00048679709073854
[82] McElroy SL, Dessain EC, Pope HG Jr, Cole JO, Keck PE Jr, Frankenberg FR, Aizley HG, O’Brien S . Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia[J]. J Clin Psychiatry, 1991,52(10):411-414
[83] Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J .11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study(FIN11 study)[J]. Lancet, 2009,374(9690):620-627
doi: 10.1016/S0140-6736(09)60742-X
[84] Greene P, Cote L, Fahn S .Treatment of drug-induced psychosis in Parkinson’s disease with clozapine[J].Adv Neurol, 1993, 60: 703-706
pmid: 8420214
[85] Rosenthal SH, Fenton ML, Harnett DS . Clozapine for the treatment of levodopa-induced psychosis in Parkinson's disease[J]. Gen Hosp Psychiatry, 1992,14(4):285-286
doi: 10.1016/0163-8343(92)90100-O pmid: 1505751
[86] Kane JM, Honigfeld G, Singer J, Meltzer H, the Clozapine Collaborative Study Group .Clozapine for the treatment-resistant schizophrenic: results of a US multicenter trial[J]. Psychopharmacology (Berl), 1989,99(Suppl 1):S60-S63
doi: 10.1007/BF00442561
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