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Alprazolam
 Golongan
: Benzodiazepine (anxiolytic)
 Generik : alprazolam.
 Dagang : Xanax, Atarax, Zypras.

Indikasi :
 Generalized anxiety disorder (IR)
 Panic disorder (IR and XR)
 Gang. Cemas lainnya + insomnia
Ajunctive : Acute mania dan Acute psychosis
 Cara kerja Alprazolam
 Mengikat Bzp rec. pd GABA-A ligand-gated chloride channel
 Meningkatkan efek inhibisi Gaba.
 Meningkatakan aliran chlorida melalui saluran Gaba
 Menghambat aktivitas neuron di Inhibits neuronal activity
presumably in amygdala-centered fear circuits shg menguntungkan
utk terapi gangguan cemas.
 Onset efek :
 Bisa pd pemberian pertama sp beberapa minggu kmd.
Respon Alprazolam (+)
 Th/ cemas singkat (bbrp mgg) : bs distop - sesuai kebutuhan.
 Th/ Gg. Cemas kronis:
 Tujuan : remisi penuh, cegah kambuh.
 Mengurangi/menghilangkan gejala,tp tdk menyembuhkan krn bs
kambuh
 T/ cemas jangka panjang :
 Ganti SSRI atau SNRI utk maintenen.
 Bzp  6 bln ,gejala(-), tapering of
 Kambuh , ganti :
o
SSRI or SNRI;
o
benzodiapine ;
o
kombinasi Bzp dan SSRI or SNRI.
Respon terapi Alprazolam (-)
Pertimbangkan :
 Ganti obat lain atau tambahkan obat augmentasi.
 Psikoterapi (CBT).
 Konkomitan substance abuse
 Alprazolam abuse
Diagnosa lain : ok KMU
Kombinasi dg obat augmentasi pd Partial Response/TreatmentResistance
 Bzp adl augmenting agent(obat penguat efek…): Antipsikotik dan mood
stabilizers. , dipakai utk aumentasi obat:
 SSRIs and SNRIs pd T/ gg. Cemas.
 Tidak rasional jika dikombinasi dg Bzp lain.
 Sbg “anxiolitik” Bzp konkomitan dg sedatif-hipnotik lain utk menidurkan.
Tests periodik
 LFT dan darah lengkap utk px Kejang2 , konkomitan dg KMU/ obat2an lain
KMU dlm jangka panjang.
Efek Samping alprazolam
Mekanisme ES:
 Mekanismanya = efek terapi; ES = respon berlebihan pd rec.Bzp.
 Adaptasi rec.Bzp jangka panjang dependensi, toleransi dan withdrawal
Bzp.
 ES umumnya cepat muncul, sering hilang setelah bbrp lama.
ES yg sering terjadi :
✽ Sedation, fatigue, depression
✽ Dizziness, ataxia, slurred speech, weakness
✽ Forgetfulness, confusion
✽ Hyper-excitability, nervousness
o
Rare hallucinations, mania
o
Rare hypotension
o
Hypersalivation, dry mouth
ES yg berbahaya/menganggu

Depresi pernafasan, tut bila ada over dosis depresan CNS.

Jarang ggn fs hati, ginjal ; blood dyscrasias
 BB naik
 Sedasi :
 Jarang
 Pd awal terapi, dosis naik
 Hilang dg waktu
What To Do About Side Effects
 Tunggu (=observasi),  Tunggu ,  Tunggu
 Turunkan dosis.
 Ganti dg alprazolam XR
 Dosis terbesar diberikan sbl tidur, agar saing tdk ngantuk.
 Ganti obat lain.
 Beri flumazenil jika ES nya berat/membahayakan jiwa.
DOSING AND USE Alprazolam (Alp)
Usual Dosage Range
Anxiety : alprazolam IR: 1–4 mg/day
Panic
: alprazolam IR: 5–6 mg/day
Panic
: alprazolam XR: 3–6 mg/day
Dosage Forms :
Alp. IR tab. 0.25 mg scored ; 0.5 mg , 1 mg ; 2 mg multiscored
Alp IR solution, concentrate 1 mg/mL
Alp XR (extended-release) tab 0.5 mg, 1 mg, 2 mg, 3 mg
How to Dose
 Anxiety, alprazolam IR :
 dimulai
1
/3 x ( 0.75 – 1.5 mg/hr),
 naikkan tiap 3-4 hr ; sp 4 mg/hr.
 Panic, alprazolam IR ;
 dimulai
1
/3 x 1.5 mg/hr),
 naikkan < 1 mg tiap 3-4 hr ; sp 4 10 mg/hr.
 Panic, alprazolam XR :
 dimulai 1 x 0.5–1 mg/hr,
 naikkan 1 mg/hr 10 mg/hr.
Dosing Tips

Bzp -sparing strategy : dosis terendah - lama T / tersingkat.

Ases rutin perlu obat kontinu?

Resiko dependensi naik dg naiknya dosis & lama terapi.

Utk Gejala cemas antar-wkt obat: naikan dosis/dibagi lebih frequent/ ganti
XR/Top Up (ektra)

XR : 1 – 2 kali/hr, jangan diparo.

Dosis Alp + 1/10 dosis Bzp ,
2 kali dosis clonazepam
Overdose
 sedation, confusion, poor
 coordination, diminished reflexes, coma  dead
 Alprazolam saja / + alkohol.
Long-Term Use
 Resiko dependensi : T/ > 12 mgg, tut pd polysubstance abuse.
 Habit Forming
 Alpra. is a Schedule IV drug
 Bisa dependensi dan/ tpleransi.
How to Stop
 Bila mendadak ; riw. Kejang2; dosis > 4 mg  kejang2•
 Tapering : 0.5 mg/3hr
 Kasus sulit: < 0,025 mg / mgg.

Kasus sangat sulit tapering dg 1%/3hr ( tapering lambat + desensitisasi
perilaku

Yakinkan : gejala kambuh/ withdrawal ?•

Bzp-dependent anxiety patients dan insulin-dependent diabetics adalah
tidak addiksi thd obatnya.

Px Bzp-dependent distop obat :

Gejalanya kambuh.

Gejala tambah buruk (rebound),

dan/atau ok gej. withdrawal
Pharmacokinetics
 Dimetabolisir oleh CY P450 3A4
 Metabolitnya tidak aktif.
 T ½ eliminasi=12–15 jam
Drug Interactions
 Alp + CNS depresan efek depresif >
 Inhibitor CY P450 3A4, eg nefa-zodone, fluvoxamine, fluoxetine: jus jeruk 
menurunkan clearance me -naikkan kadar plasma Alp. dan efek sedatif
alp.jd kadr Alp hrs diturunkan,
 Azole antifungal agents ( ketoconazole ,itraconazole), macrolide
antibiotics, protease inhibitors: mening-katkan kadar plasma Alp.
 Inducers of CY P450 3A4 (carbamazepine), menurun-kan clearance dan
kadar Alpefek terapi turun.
Other Warnings/Precautions

Perubahan dosis atas anjuran dokter.

Px Py Paru  kematian (jarang).

Riw Pg Zat / alkohaol  meningkatkan resiko dependensi.

T/ px Depresi  Hypomania ,mania ; mpberat ide2 bunuh diri.

Hati2 pd px “ obstructive sleep apnea “

Menyebabkan gangguan pikiran dan perubahan perilaku .
Do Not Use

Pd px narrow angle-closure glaucoma

Px memakai ketoconazole or itraconazole (azole antifungal)

Riw. allergy to alprazolam atau Bzp lainnya.
Pemakaian Alprazolam pd populasi khusus :
Pada pasien-2 :
•
Px Gg Ginjal  hati2
• Px Gg Hati : mulai dg dosis rendah: (0,5-0,75 mg/hr) , dibagi 2- 3 dosis
• Px Gg Jantung : Bzp telah dipakai utk T/ Cemas ok IMA (infark)
Elderly
• mulai dg dosis rendah : (0,5-0,75 mg/hr) , dibagi 2- 3 dosis , dimonitor ketat.
Children and Adolescents
• Keamanan dan kemanjurannya blm pasti, tp sering dipakai dlm wkt yg singkat
dan dosis rendah.
• Efek jangka panjang blm diketahui.
Sebaiknya dosis rendah, monitor lebih ketat
Pregnancy

Risk Category D [pd janin terbukti beresiko, manfaat terapi (+)
pertimbangkan pemakaiannya.

Terbukti meningkatkan kemungkinan cacad pd janin., shg

Tidak dianjurkan utk T/ cemas pd trimester

Penghentian : tapering of

Pemberian pd trimester III  withdrawal efect pd janin.

Kejang2 yg bisa membahayakan janin.
Breast Feeding

Rekomondasi : stop obat atau pemberian susu botol.

SE pd infant : gang makan, sedasi, weight loss.
THE ART OF PSYCHOPHARMACOLOGY-ALP
Potential Advantages

Onset efeknya cepat.

Sedasinya kurang dp Bzp lainnya.

Ada tablet long acting (XR)
Potential Disadvantages

Efek Euphoria nya bs menyebabkana “abuse”

Abuse pd px sedang/riw  substance abusers
Primary Target Symptoms

Panic attacks

Anxiety
Pearls
Paling populer dikalangan dokter, psikiater.

Bermanfaat ajunctive T/ dg SSRI; SNRI pd Gg Cemas

Tidak efektif sbg monoterapi Psikotik; utk ajunktif : mood stabilizers dan
antipsikotik.

Bisa utk tr depresi ; bs menyebabkan depresi px lainnya.

Stop Alp : Resiko kejang2 pd 3 hr pertama , tut bl ada riw ; kejang , trauma
kepala, atau withdrawal zat pd abuser.

Onset efek klinis bs mendahului plasma half-life (>cepat) ,shg dpt dbrk >
2-3 kali/hr , khususnya utk immediate release alprazolam

Pemberian : fluvoxamine, fluoxetine, atau nefazodone dpt meningkatkan
kadar alprazolam shg pasien sangat ngantuk levels, atau dosis
Alprazolam diturunkan sp ½ nya atau lebih .

Utk tr Insomnia : bs sbg gejala gg jiwa primer atau komorbiditas atau ok
KMU.
✽ Alprazolam XR kurang sedatif dp immediate release alpra.
✽ Alprazolam XR: frekuensi pemberian < I.R ; gej interdose <, dan kurang
“clockwatching” nya pd pasien cemas .

Kenaikan kadar plasma XR > lambat  euphoria & abuse > kecil

Penurunan kadar plasmaXR > lambat  withdrawal > kecil
✽ Alprozolam XR : durasi onset biologisnya > lama dp clonazepam
✽ Clonazepam dianggap “longacting alprazolam-like anxiolytic” ;
Alprazolam XR dianggap”longer-acting clonazepam-like anxiolytic”; dg
keunggulan kurang : euphoria, abuse, dependence, dan withdrawal problems,
RISPERIDONE
Class :
Nama :

Brands :
 Risperdal (oral)
 CONSTA (im)
 Generic: Resperidone

Atypical antipsychotic
 Serotonin-dopami-ne
Antagonist, SDRA;
 Second generation
antipsychotic;

Mood stabilizer
THERAPEUTICS :Commonly Prescribed For (bold for FDA approved)

Schizophrenia
 Terapi : oral/Consta
 Mencegah kambuh : oral

Gang.Psikotik lainnya : oral

Acute mania: oral
 monotherapy and adjunct to lithium or valproate

Bipolar maintenance

Bipolar depression

Gang. Perilaku pada : Demensia ; Anak-2 dan Remaja.

Problema Gang. Kontrol impuls
CONSTA : long-acting microspheres
intramuscularly, deep , gluteal
How The Drug Works
How Long Until It Works
Blokade D2 dopamine Rec. 
menurunkan gejala positif psikosa
,menstabilkan gejala afektif,.
Gejala Psikotik dapat membaik dalam
1 minggu, tapi perlu beberapa
minggu untuk berefek penuh pada
gejala perilaku yaitu sampai
stabilisasi gejala kognitif dan afektif.
Blokade serotonin 2A Rec, 
meningkatan release Dopamin
kemudian menurunkan ES/gejala
motorik dan memperbaiki gejala
kognitif dan afektif.
Interaksi pada receptor2 lain bisa
berperanan pada efikasi resperidon•
Lama efikasi obat dianjurkan
ditunggu :
Umumnya : 4 – 6 mgg bisa sampai
16 – 20 minggu untuk berespon
bagus, terhadap gejala kognitif
✽ eg pd Rec. Alpha 2 antagonist bs
menimbulkan efek antidepresan.
If it doesnt work

Ganti antipsikotik atipikal lainnya (olanzapine, quetiapine, ziprasidone,
aripiprazole, atau amisulpride)

Jika dengan > 2 antipsikotik monoterapi tdk berrespon  pertimbangkan
clozapine

Jika tidak ada antipsikotik atipikal lini pertama yg efektif pertimbangkan :

Terapi dengan dosis tinggi , atau

Augmentasi dengan valproate or lamotrigine

Beberapa pasien perlu antipsikotik konvensional(tipikal)

Pertimbangkan “tidak patuh” (noncompliance) dan
 Ganti antipsikotik yg efek sampingnya lebih rendah. atau
 Anti psikotik long acting (depot injection)

Pertimbangkan segera mulai rehabilitasi dan psikoterapi•

Pertimbangkan adanya concomitant drug abuse
If It Works
 Pada px Skizofrenia :

Menururunkan gejala Positif.

Memperbaiki gejala Negatif : agersivitas, gej kognitif & afektif.

Remisi parsial: menurunkan gejala sp 1/3

Dengan th/ teratur > 1 thn , 5–15% px  perbaikan gej. > 50–60%
(superresponders, “awakeners” ) dpt bekerja,hidup mandiri, dpt
bersosialisasi.

Px Bipoler : Reduksi gej. sp > ½ nya.

Teruskan terapi sp “a plateau of improvement”, teruskan :
 Selama 1 thn (Episode I psikosa)
 Selama mungkin (Episode > II)
 Bahkan pada Ep I , tr/ bisa selamanya

Pada Gg.Bipoler bs mereduksi dan mencegah kambuhnya mania
Best Augmenting Combos for Partial Response or TreatmentResistance

Valproic acid (valproate, divalproex, divalproex ER)
Other mood stabilizing
 Anticonvulsants (carba-mazepine, oxcarbazepine, lamotrigine)
 Lithium

Benzodiazepines
SIDE EFFECTS
 How Drug Causes Side
Efects
 Bloking reseptor :

Alpha 1 adrenergic
dizzines, sedasi,
hipotensi.

Dopamine 2 recs.di :
 Striatum,  ES
motorik , tut dosis
tinggi.
 Pituitary, 
hiperprolaktinemia
 Mekanisma atipikal
antipsikotik thd insiden :
menaikkan BB, DM dan
dislipidemiablm diketahui.
 ✽Dose-related
hyperprolactinemia
 Notable Side Efects
 Dizziness, insomnia,
headache, anxiety, sedation
 Meningkatkan resiko DM &
dyslipidemia
 ✽Dose-dependent
EPS(symptomps)
 Tardive dyskinesia .
 Nausea, constipation,
abdominal pain,weight gain
 Orthostatic hypotension,
 Tachycardia, sexual
dysfunction
 Life Threatening or
 Dangerous Side Effects

Hyperglycemia, dg : ketoacidosis or hyperosmolar ,
coma or death.

Px Lansia dementia :  CVA
; Stroke, TIA, dead.

Meningkatkan kematian
mortalitas pd lansia dg
dementia-related psychosis

Neuroleptic malignant
syndrome

Kejang2


 Weight Gain

Kasus Weight gain : cukup
banyak.

Jadi problema medik

Bisa beda orang
dan/antipsikotiknya.
 Sedation

Kasusnya cukup banyak.

Umumnya hanya
sementara.

Efek sedasi masing2
antipsikotik berbeda


 DOSING AND USE
 Usual Dosage Range

2 - 8 mg/hr – oral utk :
 Psikosa Akut.
 Gangguan Bipolar

0.5 - 2.0 mg/hr – oral utk :
 Anak-2 dan
 Lanjut usia.

25–50 mg depot - im , tiap 2 minggu.
 Dosage Forms

Tablet : 0.25; 0.5; 1, 2, 3; 4 mg,

Orally disintegrating tablets (XR) 0.5 mg, 1 mg, 2 mg

Liquid 1 mg/mL — 30 mL/botol.

Risperidone long-acting depot microspheres formulation for deep
im inj (gluteal). 25 mg; 37.5 mg; 50 mg vial/kit
 How to Dose

Psikosa non-emergensi
 Dimulai: oral 1 mg/hr; dibagi dalam 2 dosis -> hari berikutnya
naikan 1 mg/hr sampai dosis efektif tercapai
 Umum  maks 16 mg/hr .
 Khusus: efek maks 4 - 8 mg/hr
 Dpt diberikan 1 kph / 2 kph.

Long-acting risperidone :
 Harus dicoba oral dulu.
 Deep im, gluteal, tiap 2 minggu

Long-acting risperidone :

Harus dicoba oral dulu.

Inj I Consta + Oral antipsiko-tik  3 minggu oral di stop.

Penyuntik : terlatih.

Dosis : Consta 25 - > 50 mg/ 2mgg .

Interval titrasi > 4 mgg.

Jangan menggabungkan 2 vial Consta, (eg 50 mg/vial , tidak boleh
diganti 2 vial @ 25 mg/ suntikan.
 Dosing Tips – Oral Formulation
 Less may be more: berikan dosis terendah, dg “efikasi
stabil”, tanpa mengurangi efikasinya; oleh karena dapat
menurunkan efek samping, terutama pd dosis > 6 mg/hr;
 ✽ Dosis ter Efektif utk Psikosa ; Gg Bipoler : 2 – 6 mg/hr
( dosis rata2 4,5 mg/hr ). Dosis ini paling murah dp obat lain.

Px Gaduh gelisah drpd menaikkan dosis, pertimbangkan
augmentasi dg : benzodiazepin atau antipsikotik tipikal , oral/im.

Pd partial responders pertimbangkan augmentasi dg : mood
stabilizing anticonvulsant, valproate or lamotrigin.

di Approved sp 16 mg/hr - oral, tp EPS meningkat pd > 6 mg/hr.

Risperidone oral solution : tidak kompatibel dg teh atau Cola.

Anak2 dan Lansia :
 Mulai dg 2 dd  sp dosis maintenen tercapai  1 dd.
 Berikan dosis yg lbh rendah dr dosis umum.

 Dosing Tips –Long-Acting Microsphere Depot Formulation
 Consta inj. : saat inisiasi onset aksi nya bs terlambat 2 minggu.
 ✽Inisiasi Consta: beri antipsikotik oral 3 minggu (lanjutan/inisiasi)
 Steady-state plasma concentrations Consta tercapai setelah
suntikan, bertahan sp 4 - 6 mgg dr suntikan terakhir.
4
 Terlambat inj. Consta > 2 mgg  inj. Re-inisiasi , dilindungi dg 3 mgg
antipsikotik oral. : < 2 mgg , tdk perlu perlindungan oral
 Consta hrs disimpan di refrigerator.
 Harus dibeli dlm paket utuh ok obat tdk dlm btk larutan ( ½ spuit
tidak sama dg ½ dosis).
 Overdose

Lethalitas dg monoterapi
jarang; sedasi, palpitasi,
kejang, TD turun, sesak
nafas.

Rapid oral
discontinuation:
 Long-Term Use


  rebound psychosis
&
Mencegah kambuh
skizofrenia.
 gejala memberat.
Maintenen :Gg Bipoler & Gg
Tingkah Laku
 Habit Forming

Tidak menyebabkan
ketergantungan
 How to Stop

 Pharmacokinetics

Metabilitnya “aktif”

Dimetabolisir : CYP450 2D6

T ½ Risperidon-oral: 20-24
jam.

T ½ Long-acting Risp : 3–6
hr

Eliminasi Consta : + 7–8 .
2
Titrasi turun dg pelan , >
6-8 mgg - oral, tut utk cross
titration.

 Drug Interactions

Meningkatkan efek anti-hipertensi

Sbg: antagonis levodopa, dopamine agonists

Kombinasi “obat” yg meningkat-kan kadar plasma Risperidone (tak
perlu penyesuaian dosis) :
 Clozapine: (menurunkan Clearance)
 Fluoxetine & paroxetine
 Inhibitor CYP4502D6

Pemberian Risp. bsm carbamazepine :  menurunkan kadar
plasma Risp.
 Other Warnings/ Precautions

Hati
2
pd px dg resiko:
 Hipotensif(dehidrasi, kepanasan)
 Pneumonia asprasi, dysphagia

Priapism
 Do Not Use

Riw. alergi risperidone
 SPECIAL POPULATIONS
 Renal Impairment

Initial-oral : 2 x 0.5 mg/hr ; mgg 1st ; 2 x 1 mg ; mgg 2nd

Consta: diberikan ssdh px toleran pd 2 mg/hr – oral.

Consta : 25 mg/2 mgg. (lindungi oral 3 mgg)
 Hepatic Impairment

Initial-oral : 2 x 0.5 mg/hr ; mgg 1st ; 2 x 1 mg ; mgg 2nd

Consta: diberikan ssdh px toleran pd 2 mg/hr – oral

Consta : 25 mg/2 mgg. (lindungi oral 3 mgg)
 Cardiac Impairment

Hati2 resiko orthostatic hypotension
 ✽ Lansia dg atrial fibrillation, menaikan resiko stroke.
 Elderly

Initial-oral : 2 x 0.5 mg ; naikkan dg 2 x 0.5 mg ; mgg; bila > 2 x 1,5
mg/hr – titrasi tiap mgg.

Consta : 25 mg/2 mgg. (lindungi oral 3 mgg)
 Pregnancy

Risk Category C (ada efek buruk pd binatang coba).

Pd kehamilan gej. Psikotik bs tambah berat, shg perlu terapi.

Data awal: infant yg terpapar resperidone dlm uterus tdk nampak
gej. buruk/efek samping.

Risperidone may be preferable to anticonvulsant mood stabilizers if
treatment is required during pregnancy

Efek hyperprolactinemia pd janin blm diketahui.
 Breast Feeding

Tidak diketahui apakah resperidon di sekresi ke asi
 ✽ Rekomendasi : stop obat atau pemberian susu botol.

Ibu menyusui yg minum Resp. harus dimonitor efek sampingnya
 Children and Adolescents

Keamanan dan efektifitasnya blm dpastikan.
 ✽ Reperidon paling sering dipakai .
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Aman utk Gg Tingkah Laku
Perlu kontrol yg lebih ketat.
 THE ART OF PSYCHOPHARMACOLOGY
 Potential Advantages
 Pada kasus Psikosa dan bipoler yg refrakter thd terapi antipsikotik
lain.
 Untuk terapi pasien/kasus:
 ✽ Demensia dg ciri agresif.
 ✽ Gg Tingkah laku pd anak.
 ✽ Non-compliant patients (Costa)
 ✽ Hasil terapi akan baik jika kepatuhan ditingkatkan (Costa)
 Potential Disadvantages
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Pd px dmn efek hiperprolaktinemi tdk diharapkan ,misal pd: ibu
hamil, gadis dg amenore, premenopause tanpa estrogen
replacement terapi)
 Primary Target Symptoms
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Gejala Positif psikosa
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Gejala Negatif psikosa
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Fungsi Kognitif.
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Unstable mood ( depressi dan mania )
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Gejala agresif
 Pearls
 Diterima luas utk terapi:
1) Agitasi & agresi pd demensia
2) Gejala perilaku pd anak & remaja
 Juga dipakai utk kasus2 yg refrakter dan gejala positif bukan skizof.
 Hanya atipikal Hiperprolaktinemia
 Hiperprolaktinemia pd wanita dg estrogen rendahosteoprosis
 Kurang meningkatkan BB
 Kurang efek sedasinya
 Pd dosis terapi  termurah
 Resiko Stroke : pd Lansia dg atrial fibrilasi.
 Resiko DM & dyslipidemia msh kontroversi
 ES motorik lbh kuat dp antipsikotik lain pd lansia dg Parkinson’s
disease or Lewy Body dementia
 Satu2nya antipsikotik atipikal dg formula inj, Long acting
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 SERTRALINE
 Nama :
 Brands : Zoloft ,
Fridep
 Generic: Sertalin
 Class : SSRI
(selective serotonin
reuptake inhibitor);
sering diklasisifikasikan sbg
antidepressant, tp sertralin
bukanlah sekedar anti
depresan
 Indikasi :
1) Major depressive
disorder(MDD)
2) Premenstrual dysphoric
disorder (PMDD)
3) Panic disorder
4) Posttraumatic stress
disorder (PTSD)
5) Social anxiety disorder
(social phobia)
6) Obsessive-compulsive
disorder (OCD)
7) Generalized anxiety
disorder (GAD)

 How The Drug Works
 Memacu Nts serotonin.
 Memblok serotonin reuptake pump (serotonin transporter)
 Desensitisasi serotonin recep-tors, tut serotonin 1A receptors
 Meningkatkan neurotransmisi serotonin.
 ✽ Memblok dopamine reuptake pump (dopamine transporter),
shg meningkatkan neurotrans-misi dopamin dan berkontribusi pd
efek terapinya.
 Berefek mild antagonist actions at sigma receptors
 How Long Until It Works
 ✽ Bbrp px mengalami peningkat-an energi atau keaktifan pd awal
terapi dimulai.
 Onset teurapetiknya: tidak segera, sering terlambat 2 – 4 mgg .
 Jika tidak berefek dlm 6-8 mgg, mungkin perlu naikkan dosis. Atau
obat tdk berefek. •
 Obat bs dilanjutkan selama bbrp tahun utk mencegah kambuhnya
gejala.
 If It Works
 Tujuan terapi: sembuh dr gejala dan mencegah kambuh.
 Terapi sering mengurangi/ menghilangkan gejala, tp tidak
menyembuhkan krn sering kambuh bila obat dihentikan.
 Terapi dilanjutkan sp seluruh gejala hilang/sangat berkurang (e.g.,
OCD, PTSD)
 Sejak gejala hilang, lanjutlan terapi sp 1 thn (pd episode I depresi)
 Utk episede ke II. Dst, obat dilanjutkan utk wkt tak terbatas.
 Pd Gangguan cemas juga bs tak terbatas lamnya pemberian obat
 If It Doesn’t Work
1) Partial response; gej.sisa depresi : (insomnia, fatigue, gangguan
konsentrasi)
2) Nonresponders = treatment-resistant or treatment-refractory
3) “Poop-out” : inisial responnya bagus, kmd kambuh wlp obatnya
diteruskan.
 Pertimbangkan :
1) Obat : naikkan dosis, ganti obat atau tambahkan obat aumentasi.
2) Psikoterapi.
3) Evaluasi : diagnosa lain atau ada komorbiditas dg ( KMU , PgZat dll)
4) Bbrp px nampak obat tidak manjur ok aktivasi dari Ggn Bipoler sbg
ggn latent atau yg mendasarinya. Perlu: antidepresan di stop dan
diganti mood stabilizer

 Best Augmenting Combos for Partial Response or TreatmentResistance
 • Trazodone, especially for insomnia
 • In the U.S., sertraline (Zoloft) is commonly
 augmented with bupropion (Wellbutrin)
 with good results in a combination
 anecdotally called “Well-loft” (use
 combinations of antidepressants with
 caution as this may activate bipolar
 disorder and suicidal ideation)
 Mirtazapine, reboxetine, or atomoxetine
 (add with caution and at lower doses since
 sertraline could theoretically raise
 atomoxetine levels); use combinations of
 antidepressants with caution as this may
 activate bipolar disorder and suicidal
 ideation
 • Modafinil, especially for fatigue, sleepiness,
 and lack of concentration
 • Mood stabilizers or atypical antipsychotics
 for bipolar depression, psychotic
 depression, treatment-resistant depression,
 or treatment-resistant anxiety disorders
 • Benzodiazepines
 • If all else fails for anxiety disorders,
 consider gabapentin or tiagabine
 • Hypnotics for insomnia
 • Classically, lithium, buspirone, or thyroid
 hormone
 SIDE EFFECTS
 How Drug Causes S.E.
 Theoretically due to increases in serotonin
 concentrations at serotonin receptors in
 parts of the brain and body other than
 those that cause therapeutic actions (e.g.,
 unwanted actions of serotonin in sleep
 centers causing insomnia, unwanted
 actions of serotonin in the gut causing
 diarrhea, etc.)
 ✽ Increasing serotonin can cause
 diminished dopamine release and might
 contribute to emotional flattening, cognitive
 slowing, and apathy in some patients,
 although this could theoretically be
 diminished in some patients by sertraline’s
 dopamine reuptake blocking properties
 • Most side efects are immediate but often
 go away with time, in contrast to most
 therapeutic efects which are delayed and
 are enhanced over time
 • Sertraline’s possible dopamine reuptake
 blocking properties could contribute to
 agitation, anxiety, and undesirable
 activation, especially early in dosing
 Notable Side Effects
 Sexual dysfunction (men: delayed
 ejaculation, erectile dysfunction; men andwomen: decreased sexual
desire,
 anorgasmia)
 • Gastrointestinal (decreased appetite,
 nausea, diarrhea, constipation, dry mouth)
 • Mostly central nervous system (insomnia
 but also sedation, agitation, tremors,
 headache, dizziness)
 • Note: patients with diagnosed or
 undiagnosed bipolar or psychotic disorders
 may be more vulnerable to CNS-activating
 actions of SSRIs
 • Autonomic (sweating)
 • Bruising and rare bleeding
 • Rare hyponatremia (mostly in elderly
 patients and generally reversible on
 discontinuation of sertraline)
 • Rare hypotension
 Life Threatening or Dangerous Side Effects
 Rare seizures
 • Rare induction of mania and activation of suicidal ideation
 Weight Gain
 • Reported but not expected
 • Some patients may actually experience weight loss
 Sedation
 • Reported but not expected
 • Possibly activating in some patients
 What To Do About Side Effects
 Wait
 • Wait
 • Wait
 • If sertraline is activating, take in the morning to help reduce
insomnia
 • Reduce dose to 25 mg or even 12.5 mg until side efects abate,
then increase dose as tolerated, usually to at least 50 mg/day
 • In a few weeks, switch or add other drugs
 Best Augmenting Agents for Side Effects
 Often best to try another SSRI or another antidepressant
monotherapy prior toresorting to augmentation strategies to treat
side efects
 • Trazodone or a hypnotic for insomnia
 • Bupropion, sildenafil, vardenafil or tadalafil
 for sexual dysfunction
 • Bupropion for emotional flattening,
 cognitive slowing, or apathy
 • Mirtazapine for insomnia, agitation, and
 gastrointestinal side efects
 • Benzodiazepines for jitteriness and anxiety,
 especially at initiation of treatment and
 especially for anxious patients
 • Many side efects are dose-dependent (i.e.,
 they increase as dose increases, or they
 reemerge until tolerance re-develops)
 • Many side efects are time-dependent (i.e.,
 they start immediately upon dosing and
 upon each dose increase, but go away with
 time)
 • Activation and agitation may represent the
 induction of a bipolar state, especially a
 mixed dysphoric bipolar II condition
 sometimes associated with suicidal
 ideation, and require the addition of
 lithium, a mood stabilizer or an atypical
 antipsychotic, and/or discontinuation of
 sertraline

 DOSING AND USE
 Usual Dosage Range
 • 50–200 mg/day
 Dosage Forms
 • Tablets 25 mg scored, 50 mg scored,
 100 mg
 How to Dose
 • Depression and OCD: initial 50 mg/day;
 usually wait a few weeks to assess drug
 efects before increasing dose, but can
 increase once a week; maximum generally
 200 mg/day; single dose
 • Panic and PTSD: initial 25 mg/day; increase
 to 50 mg/day after 1 week thereafter,
 usually wait a few weeks to assess drug
 efects before increasing dose; maximum
 generally 200 mg/day; single dose
 Dosing Tips
 • All tablets are scored, so to save costs,
 give 50 mg as half of 100 mg tablet, since 100 mg and 50 mg
tablets cost about the
 same in many markets
 • Give once daily, often in the mornings to
 reduce chances of insomnia
 • Many patients ultimately require more than
 50 mg dose per day
 • Some patients are dosed above 200 mg
 • Evidence that some treatment-resistant
 OCD patients may respond safely to doses
 up to 400 mg/day, but this is for experts
 and use with caution
 • The more anxious and agitated the patient,
 the lower the starting dose, the slower the
 titration, and the more likely the need for a
 concomitant agent such as trazodone or a
 benzodiazepine
 • If intolerable anxiety, insomnia, agitation,
 akathisia, or activation occur either upon
 dosing initiation or discontinuation,
 consider the possibility of activated bipolar
 disorder and switch to a mood stabilizer or
 atypical antipsychotic
 • Utilize half a 25 mg tablet (12.5 mg) when
 initiating treatment in patients with a
 history of intolerance to previous
 antidepressants

 DOSING AND USE

How to Stop
 • Taper to avoid withdrawal efects
 (dizziness, nausea, stomach cramps,
 sweating, tingling, dysesthesias)
 • Many patients tolerate 50% dose reduction
 for 3 days, then another 50% reduction for
 3 days, then discontinuation
 • If withdrawal symptoms emerge during
 discontinuation, raise dose to stop
 symptoms and then restart withdrawal
 much more slowly

Pharmacokinetics
 • Parent drug has 22–36 hour half-life
 Metabolite half-life 62–104 hours
 • Inhibits CYP450 2D6 (weakly at low doses)
 • Inhibits CYP450 3A4 (weakly at low doses)

 SPECIAL POPULATIONS
 Renal Impairment
 • No dose adjustment
 • Not removed by hemodialysis
 Hepatic Impairment
 • Lower dose or give less frequently, perhaps
 by half
 Cardiac Impairment
 • Preliminary research suggests that
 sertraline is safe in these patients
 • Treating depression with SSRIs in patients
 with acute angina or following myocardial
 infarction may reduce cardiac events and
 improve survival as well as mood
 Elderly
 • Some patients may tolerate lower doses
 and/or slower titration better •
 Children and Adolescents
 • Use with caution, observing for activation of known or unknown
bipolar disorder and/or suicidal ideation, and strongly consider
informing parents or guardian of this risk so they can help observe
child or adolescent patients
 • Approved for use in OCD
 • Ages 6–12: initial dose 25 mg/day
 • Ages 13 and up: adult dosing
 • Long-term efects, particularly on growth, have not been studied

 Pregnancy
 Risk Category C [some
animal studies
 show adverse efects, no
controlled studies
 in humans]
 • Not generally
recommended for use
during
 pregnancy, especially
during first trimester
 • Nonetheless, continuous
treatment during
 pregnancy may be
necessary and has not
 been proven to be harmful
to the fetus
 • At delivery there may be
more bleeding in
 the mother and transient
irritability or
 sedation in the newborn
 • Must weigh the risk of
treatment (first
 trimester fetal
development, third
trimester
 newborn delivery) to the
child against the
 risk of no treatment
(recurrence of
 depression, maternal
health, infant
 bonding) to the mother and
child
 • For many patients this
may mean
 continuing treatment during
pregnancy
 • Neonates exposed to
SSRIs or SNRIs late
 in the third trimester have
developed
 complications requiring
prolonged
 hospitalization, respiratory
support, and
 tube feeding; reported
symptoms are
 consistent with either a
direct toxic efect
 of SSRIs and SNRIs or,
possibly, a drug
 discontinuation syndrome,
and include
 respiratory distress,
cyanosis, apnea,
 seizures, temperature
instability, feeding
 difficulty, vomiting,
hypoglycemia,
 hypotonia, hypertonia,
hyperreflexia,
 tremor, jitteriness,
irritability, and constant
 crying

 Breast Feeding
 • Some drug is found in
mother’s breast milk
 • Trace amounts may be
present in nursing
 children whose mothers are
on sertraline
 • Sertraline has shown
efficacy in treating
 postpartum depression
 • If child becomes irritable
or sedated, breast
 feeding or drug may need
to be
 discontinued
 • Immediate postpartum
period is a high-risk
 time for depression,
especially in women
 who have had prior
depressive episodes,
 so drug may need to be
reinstituted late in
 the third trimester or shortly
after
 childbirth to prevent a
recurrence during
 the postpartum period
 • Must weigh benefits of
breast feeding with
 risks and benefits of
antidepressant
 treatment versus
nontreatment to both the
 infant and the mother
 • For many patients, this
may mean
 continuing treatment during
breast feeding
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
 THE ART OF PSYCHOPHARMACOLOGY
 Potential Advantages
 • Patients with atypical
depression
 (hypersomnia, increased
appetite)
 • Patients with fatigue and
low energy
 • Patients who wish to avoid
 hyperprolactinemia (e.g.,
pubescent
 • Initiating treatment in
anxious patients with
 some insomnia
 children, girls and women
with
 • Patients with comorbid
irritable bowel
 galactorrhea, girls and
women with
 syndrome
 unexplained amenorrhea,
postmenopausal
 women who are not taking
estrogen
 replacement therapy)
 • Patients who are sensitive
to the prolactinelevating
 properties of other SSRIs
 (sertraline is the one SSRI
that generally
 does not elevate prolactin)
 Potential Disadvantages
 • Can require dosage
titration
 Primary Target
Symptoms
 • Depressed mood
 • Anxiety
 • Sleep disturbance, both
insomnia and
 hypersomnia (eventually,
but may actually
 cause insomnia, especially
short-term)
 • Panic attacks, avoidant
behavior, reexperiencing,
 hyperarousal
