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 :

SSRI or SNRI;

benzodiapine ;

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

Rare hypotension

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: 14 mg/day
Panic

: alprazolam IR: 56 mg/day

Panic

: alprazolam XR: 36 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

/3 x ( 0.75 1.5 mg/hr),

naikkan tiap 3-4 hr ; sp 4 mg/hr.

Panic, alprazolam IR ;
dimulai

/3 x 1.5 mg/hr),

naikkan < 1 mg tiap 3-4 hr ; sp 4 10 mg/hr.

Panic, alprazolam XR :
dimulai 1 x 0.51 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 eliminasi=1215 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 Alpefek 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 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 dianggaplonger-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 , 515% px perbaikan gej. > 5060%
(superresponders, awakeners ) dpt bekerja,hidup mandiri, dpt
bersosialisasi.

Px Bipoler : Reduksi gej. sp > 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
dislipidemiablm 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.

2550 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.

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 ( spuit
tidak sama dg 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 Risperidon-oral: 20-24
jam.

T Long-acting Risp : 36
hr

Eliminasi Consta : + 78 .

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

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 .

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

Pd px dmn efek hiperprolaktinemi tdk diharapkan ,misal pd: ibu

hamil, gadis dg amenore, premenopause tanpa estrogen
replacement terapi)

Primary Target Symptoms

Gejala Positif psikosa

Gejala Negatif psikosa

Fungsi Kognitif.

Unstable mood ( depressi dan mania )

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 rendahosteoprosis
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 Parkinsons
disease or Lewy Body dementia
Satu2nya antipsikotik atipikal dg formula inj, Long acting

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 Doesnt 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 sertralines
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
Sertralines 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
50200 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 2236 hour half-life

Metabolite half-life 62104 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 612: 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
mothers 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

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