SKRIPSI

NUVERA ARGIANTI

STUDI PENGGUNAAN KLORPROMAZIN

PADA PASIEN SKIZOFRENIA

(Penelitian Dilakukan di RSJ Dr. Radjiman

Wediodiningrat Lawang)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2018

ii

iii

iv

KATA PENGANTAR

Assalamualaikum Wr. Wb.

Puji syukur ke hadirat Allah SWT yang telah melimpahkan berkah, rahmat,

karunia dan hidayah ke hamba-Nya, karena dengan pertolongan-Nya skripsi yang

berjudul Studi Penggunaan Klorpromazin pada Pasien Skizofrenia

(Penelitian dilakukan pada Rumah Sakit Jiwa Dr. Radjiman Wediodiningrat

Lawang) dapat diselesaikan tepat waktu dan dengan sebaik-baiknya. Selanjutnya

penulis ingin mengucapkan terima kasih yang tidak terhingga kepada:

1. Orang tua Ibu Bahagia dan Bapak Muhammad Akhyar serta saudara Anisa

Lestari, Muhammad Habil Sauri Yahya, dan Muthia Latifah Cahyani yang

telah memberi motivasi dan doa terbesar saya untuk segera menyelesaikan

skripsi ini

2. Bapak Faqih Ruhyanudin, M. Kep., Sp. Kep. MB selaku dekan Fakultas Ilmu

Kesehatan Universitas Muhammadiyah Malang

3. Direktur dan staf Rumah Sakit Jiwa Dr. Radjiman Wediodingrat Lawang

yang telah membantu kelancaran penilitian skripsi hingga akhir.

4. Bapak Drs. Didik Hasmono, Apt., MS slaku pembimbing I yang telah banyak

meluangkan waktu untuk membimbing, mengarahkan, dan memberi

semangat, motivasi, serta menginspirasi penulis selama menempuh pendidikan

sampai terselesaikannya tugas akhir ini, semoga Allah selalu melimpahkan

kesehatan.

5. Ibu Dra. Lilik Yusetyani, Apt., Sp. FRS selaku Pembimbing II yang selalu

bersedia mengorbankan waktu untuk membimbing dan memberikan motivasi

serta selalu sabar dalam mengarahkan hingga tugas akhir ini dapat

diselesaikan dengan baik dan tepat waktu, semoga Allah selalu melimpahkan

kesehatan.

6. Ibu Hidajah Rachmawati, S.Si., Apt., Sp. FRS dan Ibu Ika Ratna Hidayati, S.

Farm., M. Sc., Apt selaku penguji I dan II yang telah banyak memberikan

kritikan dan saran demi terselesaikannya tugas akhir ini dengan sebaik-

baiknya, semoga Allah selalu melimpahkan kesehatan.

v

7. Seluruh jajaran prodi, dosen dan staf tata usaha Farmasi yang telah

memberikan dedikasi yang besar kepada penulis.

8. Kepada Santri Ningthias, Dwi Ridha Novianty, Winda Khairun Nasicha, Putri

Astutik, Rima Dwi Cahyani, Pangastutik Santikrama, Aldiala Apriliawati,

Muhammad Rivaldy Risnanda, Gading, Noval Yusup, dan teman-teman

lainnya yang tidak bisa saya sebutkan semuanya yang selalu memotivasi dan

sangat membantu dalam menyusun skiripsi ini.

9. Teman satu kelompok skripsi yang bertema Skizofrenia: Ririantika Dwi

Jiansari, Arina Rahayu, Noor Izzatil Faizah, Rahmat Akbar dan sesama

pejuang klinis lainnya yang telah berjuang bersama.

10. Terakhir, Seluruh teman-teman jurusan Farmasi angkatan 2014 yang telah

berjuang bersama penulis untuk menyelesaikan pendidikan di Program Studi

Farmasi.

Akhir kata, penulis mohon maaf atas kekurangan dan ketidaksempurnaan

penulisan skripsi dan dengan senang hati menerima kritik dan saran yang

membangun. Semoga skripsi ini bermanfaat dalam mengembangkan ilmu

pengetahuan bidang farmasi klinis bagi penulis maupun pembaca.

Wassalamualaikum Wr. Wb.

Malang, 6 Juni 2018

Nuvera Argianti

ix

DAFTAR ISI

KATA PENGANTAR .......................................................................................... iv

RINGKASAN ....................................................................................................... vi

ABSTRAK ........................................................................................................... vii

DAFTAR ISI ......................................................................................................... ix

DAFTAR GAMBAR .......................................................................................... xiv

DAFTAR TABEL................................................................................................ xv

DAFTAR LAMPIRAN ...................................................................................... xvi

DAFTAR SINGKATAN ................................................................................... xvii

BAB I PENDAHULUAN ...................................................................................... 1

1.1 Latar Belakang.......................................................................................... 1

1.2 Rumusan Masalah .................................................................................... 4

1.3 Tujuan Penelitian ...................................................................................... 4

1.4 Manfaat Penelitian .................................................................................... 4

BAB II TINJAUAN PUSTAKA ........................................................................... 5

2.1 Skizofrenia ................................................................................................ 5

2.1.1 Definisi .............................................................................................. 5

2.1.2 Epidemiologi ..................................................................................... 5

2.1.3 Etiologi .............................................................................................. 7

2.1.3.1 Faktor Genetik ............................................................................... 8

2.1.3.2 Faktor Lingkungan ........................................................................ 9

2.1.3.3 Perubahan Neuroanatomis ............................................................. 9

2.1.3.4 Perubahan Sirkuit Fungsional pada Skizofrenia............................ 9

2.1.3.5 Gangguan Transmisi Sinaptik Pada Skizofrenia ........................... 9

2.1.3.6 Sitokin pada Skizofrenia.............................................................. 10

2.1.3.7 Hipotesis Serotonin Terhadap Skiofrenia .................................... 10

2.1.3.8 Hipotesis Dopamin Terhadap Skizofrenia................................... 10

2.1.4 Klasifikasi Skizofrenia .................................................................... 11

2.1.4.1 Skizofrenia Tipe Paranoid ........................................................... 11

2.1.4.2 Skizofrenia Tipe Tidak Terorganisir (Hebefrenik)...................... 12

2.1.4.3 Skizofrenia Tipe Katatonik.......................................................... 12

x

2.1.4.4 Skizofrenia Tipe Tidak Berdiferensiasi ....................................... 12

2.1.4.5 Skizofrenia Tipe Residual ........................................................... 12

2.1.5 Patofisiologi Skizofrenia ................................................................. 13

2.1.6 Gejala dan Gambaran Klinis ........................................................... 16

2.1.6.1 Gejala Positif ............................................................................... 16

2.1.6.2 Gejala Negatif .............................................................................. 16

2.1.6.3 Gejala Kognitif ............................................................................ 17

2.1.7 Diagnosis ......................................................................................... 17

2.1.7.1 Kriteria A ..................................................................................... 18

2.1.7.2 Kriteria B ..................................................................................... 18

2.1.7.3 Kriteria C ..................................................................................... 18

2.1.7.4 Kriteria D ..................................................................................... 18

2.1.7.5 Kriteria E ..................................................................................... 19

2.1.7.6 Kriteria F ..................................................................................... 19

2.2 Terapi Skizofrenia .................................................................................. 19

2.2.1 Tujuan Terapi Skizofrenia............................................................... 19

2.2.2 Prinsip Umum Terapi Skizofrenia .................................................. 19

2.2.2.1 Terapi Awal ................................................................................. 19

2.2.2.2 Terapi Stabilisasi ......................................................................... 20

2.2.2.3 Terapi Pemeliharaan .................................................................... 20

2.2.3 Terapi Non Farmakologi ................................................................ 20

2.2.3.1 Terapi ECT (Electroconvulsive).................................................. 21

2.2.3.2 Terapi Perilaku Kognitif untuk Orang dengan Skizofrenia ......... 22

2.2.3.3 Pendekatan Berbasis Keluarga untuk Pasien Skizofrenia ........... 22

2.2.3.4 Rehabilitasi dalam skizofrenia .................................................... 23

2.2.4 Terapi Farmakologi ......................................................................... 24

2.2.4.1 Algoritma dan Guidline terapi ..................................................... 24

2.2.4.2 Antipsikotik ................................................................................. 25

2.2.4.2.1 Klorpromazin ......................................................................... 28

2.2.4.2.2 Flufenazin .............................................................................. 28

2.2.4.2.3 Haloperidol ............................................................................ 28

2.2.4.2.4 Perfenazin .............................................................................. 29

xi

2.2.4.2.5 Aripiprazole ........................................................................... 29

2.2.4.2.6 Asenapin ................................................................................ 29

2.2.4.2.7 Klozapin ................................................................................. 29

2.2.4.2.8 Olanzapin ............................................................................... 30

2.2.4.2.9 Risperidon .............................................................................. 30

2.2.4.2.10 Quetiapin .............................................................................. 30

2.2.4.3 Penstabil Mood (mood stabilizer) ............................................... 31

2.2.4.3.1 Lithium ................................................................................... 32

2.2.4.3.2 Karbamazepin ........................................................................ 32

2.2.4.3.3 Divalproex Na ........................................................................ 32

2.2.4.3.4 Asam Valproat ....................................................................... 32

2.2.4.3.5 Lamotrigine ............................................................................ 33

2.2.4.4 Antidepresan ................................................................................ 33

2.2.4.4.1 Antidepresan SSRI ................................................................. 36

2.2.4.4.2 Antidepresan SNRI ................................................................ 37

2.2.4.4.3 Antidepresan 5-HT Receptor Modulators .............................. 37

2.2.4.4.4 Antidepresan Trisiklik ........................................................... 37

2.2.4.4.5 Antidepresan Monoamine Oxidase Inhibitors (MAOi) ......... 37

2.2.4.5 Antianxietas ................................................................................. 38

2.2.4.5.1 Alprazolam ............................................................................. 39

2.2.4.5.2 Diazepam ............................................................................... 39

2.2.4.5.3 Lorazepam.............................................................................. 39

2.2.4.5.4 Nitrazepam ............................................................................. 39

2.2.4.5.5 Midazolam ............................................................................. 39

2.3 Tinjauan Klorpromazin .......................................................................... 40

2.3.1 Efek Farmakologis .......................................................................... 40

2.3.2 Mekanisme Kerja ............................................................................ 40

2.3.3 Farmakokinetik ............................................................................... 47

2.3.4 Dosis ................................................................................................ 48

2.3.5 Efek Samping .................................................................................. 48

2.3.6 Interaksi ........................................................................................... 48

2.3.7 Sediaan Klorpromazin di Indonesia ................................................ 48

xii

BAB III KERANGKA KONSEPTUAL ............................................................ 49

3.1 Kerangka Konseptual ............................................................................. 49

3.2 Kerangka Operasional ............................................................................ 50

BAB IV METODE PENELITIAN .................................................................... 51

4.1 Rancangan Penelitian ............................................................................. 51

4.2 Populasi dan Sampel............................................................................... 51

4.3 Bahan Penelitian ..................................................................................... 51

4.4 Instrumen Penelitian ............................................................................... 52

4.5 Tempat dan Waktu Penelitian ................................................................ 52

4.6 Definisi Operasional ............................................................................... 52

4.7 Metode Pengumpulan Data .................................................................... 53

4.8 Analisis Data .......................................................................................... 53

BAB V HASIL PENELITIAN ........................................................................... 54

5.1 Data Demografi ...................................................................................... 54

5.1.1 Distribusi Berdasarkan Jenis Kelamin Pasien ................................. 54

5.1.2 Distribusi Berdasarkan Usia Pasien ................................................ 55

5.1.3 Distribusi Berdasarkan Berat Badan Pasien .................................... 55

5.1.4 Distribusi Berdasarkan Status Pasien .............................................. 56

5.2 Diagnosis Jenis Skizofrenia .................................................................... 56

5.3 Pola Penggunaan Terapi Pada Pasien Skizofrenia ................................. 57

5.4 Pola Penggunaan Terapi Pada Pasien ..................................................... 59

5.4.1 Pola Penggunaan Terapi Tunggal Pasien Rawat Jalan ................... 59

5.4.2 Pola Penggunaan Terapi 2 Kombinsi Pasien Rawat Jalan .............. 59

5.4.3 Pola Penggunaan Terapi 3 Kombinsi Pasien Rawat Jalan .............. 61

5.4.4 Pola Penggunaan Terapi 4 Kombinsi Pasien Rawat Jalan .............. 64

5.4.5 Pola Penggunaan Terapi 2 Kombinsi Pasien Rawat Inap ............... 66

5.4.6 Pola Penggunaan Terapi 4 Kombinsi Pasien Rawat Inap ............... 67

5.5 Pola Pergantian Terapi Klorpromazin pada Pasien Skizofrenia............. 68

5.5.1 Pola Pergantian Terapi Klorpromazin Pasien Rawat Jalan ............. 68

5.5.2 Pola Pergantian Terapi Klorpromazin Pasien Rawat Inap .............. 73

5.6 Lama Pemberian Terapi Obat Klorpromazin ......................................... 75

5.6.1 Lama pemberian Terapi Obat Klorpromazin Rawat Jalan .............. 75

xiii

5.6.2 Lama pemberian Terapi Obat Klorpromazin Rawat Inap ............... 75

BAB VI PEMBAHASAN .................................................................................... 76

BAB VII KESIMPULAN DAN SARAN ........................................................... 87

7.1 Kesimpulan ............................................................................................. 87

7.2 Saran ....................................................................................................... 87

DAFTAR PUSTAKA .......................................................................................... 88

LAMPIRAN ......................................................................................................... 95

xiv

DAFTAR GAMBAR

Gambar 2.1. DALY Skizofrenia menurut WHO ................................................... 6

Gambar 2.2. Jalur dopaminergik pada otak manusia ........................................... 13

Gambar 2.3. Aktivitas Hiperdopaminergik di Jalur Mesolimbik ......................... 14

Gambar2.4. Aktivitas Hipodopaminergik di jalur Mesokorteks ......................... 15

Gambar 2.5. Algoritma penggunaan obat Antipsikosis pada Skizofrenia ........... 24

Gambar 2.6. Struktur kimia antipsikosis generasi pertama.................................. 26

Gambar 2.7. Struktur kimia antipsikosis generasi kedua ..................................... 26

Gambar 2.8. Mekanisme Kerja Klorpromazin ..................................................... 40

Gambar 2.9. Mekanisme Klorpromazin Pada Jalur Mesolimbik ......................... 41

Gambar 2.10.Mekanisme Klorpromazin Pada Jalur Mesokorteks........................ 42

Gambar 2.11.Mekanisme Klorpromazin Pada Jalur Nigrostriatal ........................ 43

Gambar 2.12.Mekanisme Klorpromazin menyebabkan Tardive dyskinesia ........ 44

Gambar 2.13.Mekanisme Klorpromazin Pada Jalur Tuberoinfundibular ............. 44

Gambar 2.14.Klorpromazin Pada Berbagai Reseptor ........................................... 45

Gambar 2.15.Mekanisme Klorpromazin Pada Reseptor Kolinergik ................... 45

Gambar 2.16.Hubungan timbal balik dopamin dan asetilkolin............................. 46

Gambar 2.17.Dopamin, asetilkolin, dan antagonis D2 ......................................... 46

Gambar 2.18 Antagonis D2 dan agen antikolinergik ............................................ 47

Gambar 3.1. Skema Kerangka Konseptual ........................................................... 49

Gambar 3.2 Skema Kerangka Operasional .......................................................... 50

xv

DAFTAR TABEL

Tabel II.1. Prevalensi Gangguan Jiwa Berat Menurut Provinsi Indonesia 2013 .... 7

Tabel II.2.Obat-obat Antipsikotik berdasar golongan/kelas dan dosisnya ........... 25

Tabel II.3. Farmakokinetik obat antipsikotik FGA dan SGA ............................... 27

Tabel II.4. Efek samping obat antipsikotik FGA dan SGA .................................. 27

Tabel II.5. Dosis dan pemakaian klinik mood stabilizer ....................................... 31

Tabel II.6.Golongan obat Antidepresan dan dosis pemakaiannya ........................ 33

Tabel II.7.Profil Farmakokinetik Antidepresan .................................................... 35

Tabel II.8.Golongan obat Antiansietas (Benzodiazepin) ...................................... 38

Tabel II.9.Farmakokinetik agen Antiansietas Benzodiazepin ............................... 38

Tabel V.1 Distribusi Jenis Kelamin Pasien ........................................................... 54

Tabel V.2 Distribusi Berdasarkan Usia Pasien ..................................................... 55

Tabel V.3 Berat Badan Pasien Skizofrenia dengan Terapi Klorpromazin ............ 55

Tabel V.5 Distribusi Berdasarkan Status Pasien ................................................... 56

Tabel V.6 Distribusi Diagnosa Skizofrenia .......................................................... 56

Tabel V.7 Pola Penggunaan Terapi Pada Pasien Rawat Jalan Skizofrenia ........... 57

Tabel V.8 Persen Pola Penggunaan Terapi Pasien Rawat Jalan Skizofrenia ........ 57

Tabel V.9 Pola Penggunaan Terapi Pasien Rawat Inap Skizofrenia .................... 58

Tabel V.10 Persen Pola Penggunaan Terapi Pasien Rawat Jalan Skizofrenia ...... 59

Tabel V.11 Pola Penggunaan Terapi Tunggal Pasien Rawat Jalan ...................... 59

Tabel V.12 Pola Penggunaan Terapi 2 Kombinasi Pasien Rawat Jalan ............... 59

Tabel V.13 Pola Penggunaan Terapi 3 Kombinasi Pasien Rawat Jalan ............... 61

Tabel V.14 Pola Penggunaan Terapi 4 Kombinasi Pasien Rawat Jalan ............... 64

Tabel V.15 Pola Penggunaan Terapi 2 Kombinasi Pasien Rawat Inap ................ 66

Tabel V.16 Pola Penggunaan Terapi 4 Kombinasi Pasien Rawat Inap ................ 67

Tabel V.17 Pola Pergantian Terapi Klorpromazin Pasien Rawat Jalan ................ 68

Tabel V.18 Pola Pergantian Terapi Klorpromazin Pasien Rawat Inap ................. 73

Tabel V.19 Lama Pemberian Terapi Klorpromazin pada Saat Rawat Jalan ......... 75

Tabel V.20 Lama Pemberian Terapi Klorpromazin pada Saat Rawat Inap .......... 75

xvi

DAFTAR LAMPIRAN

Lampiran 1: Daftar Riwayat Hidup....................................................................... 95

Lampiran 2: Surat Tugas ....................................................................................... 96

Lampiran 3: Surat Keterangan Selesai Penelitian ................................................. 97

Lampiran 4: Surat Ethical Clearence .................................................................... 98

Lampiran 5: Surat Hasil Plagiasi Naskah.............................................................. 99

Lampiran 6: Surat Pernyataan ............................................................................. 102

xvii

DAFTAR SINGKATAN

5-HT : Serotonin

ADL : Activities of Daily Living

ALT : Alanine Transminase

AST : Aspartate Transaminase

Ca2+

: Kalsium

CBT : Cognitive Behavioural Therapy

CT Scan : Computerized Tomographic Scan

DA : Dopamin

DSM : Diagnostic and Statistical Manual

ECT : Electro Convulsive Therapy

EPSP : Excitatory Postsynaptic Potential

GABA : Gamma Aminobutyric Acid

K+ : Kalium

LPD : Lembar Pengumpul Data

LSD : Lysergic Acid Diethylamide

mg : miligram

MRI : Magnetic Resonance Imaging

MRS : Magnetic Resonance Spectroscopy

NMDA : N-metil-d-aspartat

PFC : Pre Frontal Cortex

Riskesdas : Riset Kesehatan Dasar

RMK : Rekam Medik Kesehatan

RSJ : Rumah Sakit Jiwa

RTA : Reality Testing Ability

SNRI : Selective Norepinephrine Reuptake Inhibitor

SSP : Sistem Saraf Pusat

SSRI :Selective Serotonin Reuptake Inhibitor

TCA : Tricyclic Antidepressants

WHO : World Health Organization

88

DAFTAR PUSTAKA

Abouzaid, Sofiya., Haijun Tian., Huanxue Zhou., Kristijan H. Kahler., Michelle

Harris., and Edward Kim. 2012. Economic Burden Associated with

Extrapyramidal Symptoms in a Medicaid Population with

Schizophrenia. Community Ment Health J 50:51–58.

Albert, Jeffrey S., and Michael W. Wood. 2012. Targets and emerging

therapies for schizophrenia. USA: John Wiley & Sons, Inc.

Amelia, Diny Rezki., dan Zainul Anwar. 2013. Relaps pada pasien skizofrenia.

JIPT: Vol. 01. No:01

Badan Pengawas Obat dan Makanan Republik Indonesia. 2017. Informatorium

Obat Nasional Indonesia. Jakarta: Koperpom.

Benson, Kathleen L. 2012. Therapy in Sleep Medicine. United States: Elsevier

Inc

Bhandari, Smitha. 2016. Schizophrenia. WebMD medical Reference.

Carruthers, Sean. P., Caroline T. Gurvich., and Susan L. Rossel. 2015. The

Muscarinic System, Cognition, and Schizophrenia. Neuroscience and

Biobehavioral Volume 55: Page 393-402

Castle, David, and Peter Buckley. 2015. Schizophrenia 2nd

ED. USA: Oxford

University Press.

Chong, Siow-Ann., Perminder Sachdev., Rathi Mahendran., and Hong-Choon

Chua. 2000. Neuroleptic and anticholinergic drug use in Chinese

patients with schizophrenia resident in a state psychiatric hospital in

Singapore. Australian and New Zealand Journal of Psychiatry: 34:988–

991.

Dipiro, T. J., Robert L. T., Garry C. Y., Garry R. M., Barbara, G. w., and L.

Michael P. 2014. Pharmacotherapy a Patophysiologic approach. USA:

McGraw-Hill Education.

Dold, Markus., Myrto T Samara., Chunbo Li., Magdolna Tardy., and Stefan

Leucht. 2015. Haloperidol versus first-generation antipsychotics for

the treatment of schizophrenia and other psychotic disorders.

Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD009831.

89

Dong, Haiman., Qian Wang., Dexiao Zhu., Fei Gao., Hui Wang., Lihua Bao., Jing

Zhang., Yanlai Hu., Zhaoxi Ding., and Jinhao Sun. 2016. Paliperidone

increases spontaneous and evoked firing of mesocortical dopaminergic

neurons by activating a hyperpolarization-activated inward current.

Schizophrenia Research 176 (2016) 252–258.

Dudley, Katharine., Xiaomeng Liu., and Saskia De Haan. 2017. Chlorpromazine

dose for people with schizophrenia. Cochrane Database of Systematic

Reviews, Issue 4. Art. No.: CD007778.

Ellenbroek Bart A. and Andrea M. Cesura. 2015. Small Molecule Therapeutics

for Schizophrenia. New York: Springer International Publishing

Switzerland.

Farooq, Saeed., and Surendra P Singh. 2014. Fixed dose-combination products

in psychiatry: Systematic review and meta-analysis. Journal of

Psychopharmacology: Vol. 29(5) 556 –564.

Fleischhacker, W. W., and Ian, P. S. 2011. Encyclopedia of Schizophrenia. UK:

Springer Healthcare Limited.

Gillies, Donna., Stephanie Sampson., Alison Beck., and John Rathbone. 2013.

Benzodiazepines for psychosis-induced aggression or agitation.

CochraneDatabase of Systematic Reviews, Issue 4. Art. No: CD003079.

Goodwin, Guy., Wolfgang Fleischhacker., Celso Arango., Pierre Baumann.,

Michael Davidson., Marc de Hert., Peter Falkai., Shitij Kapur., Stefan

leucht., Rasmus Licht., Dieter Naber., Veronica O’Keane., George

Papakostas., Eduard Vieta., and Joseph Zohar. 2008. Advantages and

disadvantages of combination treatment with antipsychotic. European

Neuropsychopharmacology: 19, 520-532.

Haleem, Darakhshan J. 2015. 5-HT1A receptor-dependent control of

nigrostriatal dopamine neurotransmission in the pharmacotherapy of

Parkinson’s disease and schizophrenia. Behavioural Pharmacology

26:45–58.

Henderson, David C., Brenda Vincenzi., Nicolas V Andrea., Melissa Ulloa., and

Paul M Copeland. 2015. Pathophysiological mechanisms of increased

cardiometabolic risk in people with schizophrenia and other severe

mental illnesses. Lancet Psychiatry: 2: 452–64

Huang, Si-Sheng., Yi-Cheng Liao., Yen-Yuh Hsieh., Chin-Yi Huang., Nan-Ying

Chiu., Yen-Kuang Yang., and Winston W. Shen. 2006. Combination

antipsychotic therapy in psychiatric outpatient clinics in Taiwan.

Comprehensive Psychiatry: 47, 421-425.

90

Huang, Yu-Chi., Chi-Fa Yung., Pao-Yen Lin., Yu Lee., Chih-Ching Wu., Su-Ting

Shu., Chien-Chih Chen., Mian-Yoon Chong., Chieh-Hsin Lin., and Liang-

Jen Wang. 2017. Gender differences in susceptibility to schizophrenia:

potential implication of neurosteroids. Psychoneuroendocrinology:

S0306-4530(17)30413-4

Ikatan Apoteker Indonesia.2017. Informasi Spesialite Obat Indonesia. Jakarta:

ISFI Penerbitan Jakarta.

Iorizzo, Carrie. 2014. Schizophrenia and other psychotic disorders. Kanada:

Crabtree Publishing Company.

Ito C, Kubota Y, and Sato M. A. 1999. Prospective survey on drug choice for

prescriptions for admitted patients with schizophrenia. Psychiatry Clin

Neurosci. 53 (Suppl 1): S35–40.

Jose, Jancy., H. Nandeesha., Shivanand Kattimani., Kavitha Meiyappan.,

Siddharth Sarkar., and Devanarayanan Sivasankar. 2015. Association

Between Prolactin and Thyroid Hormones with Severity of

Psychopathology and Suicide Risk in Drug Free Male Schizophrenia.

Clinica Chimita Acta 444: 78-80.

Katona, Cornelius., Claudia Cooper., and Mary Robertson. 2015. Psychiatry at a

glance. UK: John Wiley & Sons Ltd

Katzung & Trevor, B. G, and Anthony T. J. 2013. Basic and clinical

pharmacology 13th Ed. USA: McGraw-Hill Education.

KB, Saha., Bo L., Zhao S., Xia J., Sampson S., and Zaman Ru. 2016.

Chlorpromazine versus atypical antipsychotic drugs for

schizophrenia. The Cochraine Collaboration: John Wiley & Sons, Ltd.

Kelly Deanna L., Elaine Weiner, and Heidi J. Wehring. 2013. Pharmacotherapy

Principles & Practice. Third Edition. United States: McGraw-Hill

Education.

Koch, Kai., Kamel Mansi., Euan Haynes., Clive E Adams., Stephanie Sampson.,

and Vivek A Furtado. 2014. Trifluoperazine versus placebo for

schizophrenia. Cochrane Database of Systematic Reviews, Issue 1. Art.

No.: CD010226.

Lacy, Charles F., Lora L. Amstrong., Morton P. Goldman., and Leonard L. Lance.

Drug Information Handbook. 17th

Edition. United States: American

Pharmacist Association.

Lauriello, John., and Stefano Pallanti. Clinical Manual For Treatment of

Schizophrenia. USA: American Psychiatric Association.

91

Lerner, Paul P., Chanoch Miodownik., and Vladimir Lerner. 2015. Tardive

dyskinesia (syndrome): a current concept and modern approaches to

its management. Israel: Bar-Ilan University

Lerner, Vladimir., Chanoch Miodownik., Alexander Kaptsan., Yuly Bersudsky.,

Igor Libov., Ben-Ami Sela., and Eliezer Witztum. 2007. Vitamin

B6 Treatment for Tardive Dyskinesia: A Randomized, Double-Blind,

Placebo-Controlled, Crossover Study. J Clin Psychiatry; 68 (11) : 1648-

1654.

Leucht, Claudia., Maria Kitzmantel., John Kane., Stefan Leucht., and Wan Lian

LC Chua. 2008. Haloperidol versus chlorpromazine for schizophrenia.

Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD004278.

Lieberman, Jeffrey A., T. Scott Stroup., and Diana O. Perkins. 2012. Essentials of

schizophrenia. USA: American Psychiatric Publishing, Inc.

Lin, Ching-Hua., Fu-Chiang Wang., Shih-Chi Lin., Yu-Hui Huang., and Cheng-

Chung Chen. 2017. A randomized, double blind, comparison of the

efficacy and safety of low-dose olanzapine and low-dose

trifluoperazine versus full-dose olanzapine in acute treatment of

schizophrenia. SCHRES-07109; Number of pages 08.

Lipina, Tatjana V., and John C. Roder. 2015. Drug Discovery For

Schizophrenia. UK: The Royal Society of Chemistry.

Mamakou, V., Thanopoulou A., Goniakis F., Tentolouris N., and Kontaxakis V.

2018. Schizophrenia and type 2 diabetes mellitus. Psychiatriki; 1: 64-73

Marcsisin, Michael J., Jason B. Rosenstock., and Jessica M. Gannon.

Schizophrenia and Related Disorder. UK: Oxford University Press.

McGregor, Claire., Alexander Riordan., and Janice Thornton. 2017. Estrogens

and the cognitive symptoms of schizophrenia: possible

neuroprotective mechanisms. Frontiers in Neuroendocrinology: S0091-

3022(17)30034-1

Meng, Qingli., Feng Hou.,and Qiulan Zhang. 2008. Effects of chlorpromazine

on sleep quality, clinical and emotional measures among patients with

schizophrenia. Clinical Neurology and Neurosurgery: S0303-

8467(18)30009-X

MIMS. 2017. Referensi Obat Informasi Ringkas Produk Obat. Jakarta:

Bhuana Ilmu Populer (Kelompok Gramedia).

Multani, Pushpinder Kaur., Nitin Saini., Ravneet Kaur., and Praveen Sharma.

2014. Biomarkers in Toxicology. United States: Elsevier Inc.

92

Neal, M. J., 2016. Medical Pharmacology at a Glance. UK: John Wiley & Sons,

Ltd.

Nielsen, J., P. Damkier., H. Lublin., and D. Taylor. 2011. Optimizing clozapine

treatment. Acta Psychiatrica Scandinavica: 123: 411–422.

Parks, Peggy. J. 2011. Schiozphrenia Disease and Disorder. USA:

ReferencePoint Press, Inc.

Petrides, Georgios., Chitra Malur., Raphael J. Braga., Samuel H. Bailine., Nina R.

Schooler., Anil K. Malhotra., John M. Kane., Sohag Sanghani., Terry E.

Goldberg., Majnu John., and Alan Mendelowitz. 2015. Electroconvulsive

Therapy Augmentation in Clozapine-Resistant Schizophrenia: A

Prospective, Randomized Study. American Journal Psychiatry: 1-7.

Pratt, Carlos W., Kenneth J. Gill., Norra M. Barrett., and Melissa M. Roberts.

2014. Psychiatric Rehabilitation. Third Edition. United States: Elsevier

Inc.

Roder, Volker., and Alice Medalia. 2010. Neurocognition and Social Cognition

in Schizophrenia Patients. Key Issues in Mental Health: vol 177, pp 1–

22.

S. Nur., and Adam CE. 2016. Chlorpromazine versus reserpine for

schizophrenia. The Cochraine Collaboration: John Wiley & Sons, Ltd.

Sachdev, P. S., and Matcheri, S. K. 2010. Secondary schizophrenia. New York:

Cambridge University Press.

Shean, Glenn D. 2010. Recovery from Schizophrenia Etiological Models and

Evidence-Based Treatments. New York: Hindawi Publishing

Corporation.

Sim, Kang., Alex Su, Senta Fujii., Shu-yu Yang., Mian-Yoon Chong., Gabor S.

Ungvari., Tianmei Si., Eun K. Chung., Hin-Yeung Tsang., Yiong H.

Chan., Stephan Heckers., Naotaka Shinfuku., and Chay H. Tan. 2004.

Antipsychotic polypharmacy in patients with schizophrenia: a

multicentre comparative study in East Asia. British Journal of Clinical

Pharmacology, 58:2.

Solismaa, Anssi., Olli Kampman., Leo-Pekka lyytikäinen., Niko Seppälä., Merja

Viikki., Nina Mononen., Terho Lehtimäki., and Esa Leinonen. 2017.

Histaminergic gene polymorphism associated with sedation in

clozapine-treated patients. European Neuropsychopharmacology:

Volume 27, Issue 5, Pages 442–449.

93

Stahl, M. Stephen. 2013. Stahl’s Essential Psychopharmacology. Fourth

Edition. United States: Cambridge University Press.

Stroup, T. Scott., and Jeffrey A. Lieberman. 2010. Antipsychotic Trials in

Schizophrenia. USA: Cambridge University Press.

Takita, Yukika., Yoshikazu Takaesu., Kotaro Ono., Kunihiro Futenma., Akiyoshi

Shimura., Akiko Murakoshi., Yoko Komada., Yuichi Inoue., and Takeshi

Inoue. 2016. Association between the high-dose use of benzodiazepines

and rehospitalization in patients with schizophrenia: a 2-year

naturalistic study. Neuropsychiatric Disease and Treatment: 12 3243–

3247.

Tani, Masayuki., Norihisa Akashi., Koji Hori., Kimiko Konishi., Yuka Kitajima.,

Hiroi Tomioka., Atsuko Inamoto., Akihito Hirata., Akisa Tomita., Taishi

Koganemaru., Akari Takahashi., and Mitsugu Hachisu. 2015.

Anticholinergic Activity and Schizophrenia. Neurodegener Dis ;

15:168–174.

Tardy, Magdolna., Markus Dold., Rolf R Engel., and Stefan Leucht. 2014.

Trifluoperazine versus low-potency first-generation antipsychotic

drugs for schizophrenia. Cochrane Database of Systematic Reviews

2014, Issue 7. Art. No.: CD009396.

Tateyama, Masato., Ikuo Kudo., Motohide Hashimoto., Yasuyuki Abe., Akira

Kainuma., Kimio Yoshimura., Masahiro Asai., Mathias Bartels., and

Siegfried Kasper. 1999. Is Paranoid Schizophrenia the Most Common

Subtype?. Psychopathology; 32:98–106

Tomioka, Yukiko., Shusuke Numata., Makoto Kinoshita., Hidehiro Umehara.,

Shin-ya Watanabe., Masahito Nakataki., Yoshimi Iwayama., Tomoko

Toyota., Masashi Ikeda., Hidenaga Yamamori., Shinji Shimodera., Atsushi

Tajima., Ryota Hashimoto., Nakao Iwata., Takeo Yoshikawa., and Tetsuro

Ohmori. 2018. Decreased serum pyridoxal levels in schizophrenia:

meta-analysis and Mendelian randomization analysis. J Psychiatry

Neurosci;43(3).

Tsuang, M. T., Stephen V. Faraone, and Stephen J. Glatt. 2011. Schizophrenia.

New York: Oxford University Press.

Wang, Yijun., Jun Xia., Bartosz Helfer., Chunbo Li., and Stefan Leucht. 2016.

Valproate for schizophrenia. Cochrane Database of Systematic Reviews,

Issue 11. Art. No.: CD004028.

Weinberger, D. R, and Paul J. Harrison. 2011. Schizophrenia. UK: Blackwell

Publishing Ltd.

94

Wells, B. G., Joseph T. Dipiro., Terry L. S., and Cecily P. D. 2015.

Pharmacotherapy Handbook 9th

ED. USA: McGraw-Hill Education.

World Health Organization. Shizophrenia.

http://www.who.int/mediacentre/factsheets/fs397/en/. Diakses pada

tanggal: 10 Agustus 2017.