sthal risperidone, alprazolam, sertraline

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 off

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/Treatment-Resistance

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/m en ganggu

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 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 off

Pemberian pd trimester III withdrawal effect 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

Nama :

Brands :

Risperdal (oral)

CONSTA (im)

Generic: Resperidone

Class :

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

Blokade D2 dopamine Rec. menurunkan gejala positif psikosa ,menstabilkan gejala 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•

✽ eg pd Rec. Alpha 2 antagonist bs menimbulkan efek antidepresan.

How Long Until It Works

Gejala Psikotik dapat membaik dalam 1 minggu, tapi perlu beberapa minggu untuk berefek penuh pada gejala perilaku yaitu sampai stabilisasi gejala kognitif dan afektif.

Lama efikasi obat dianjurkan ditunggu :

Umumnya : 4 – 6 mgg bisa sampai

16 – 20 minggu untuk berespon bagus, terhadap gejala kognitif

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 Treatment-Resistance

Valproic acid (valproate, divalproex, divalproex ER)

Other mood stabilizing

Anticonvulsants (carba-mazepine, oxcarbazepine, lamotrigine)

Lithium

Benzodiazepines

SIDE EFFECTS

How Drug Causes Side Effects

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.

Notable Side Effects

Meningkatkan resiko DM & dyslipidemia

✽Dose-dependent EPS(symptomps)

✽Dose-related hyperprolactinemia

Tardive dyskinesia .

Dizziness, insomnia, headache, anxiety, sedation

Nausea, constipation, abdominal pain,weight gain

Orthostatic hypotension,

Tachycardia, sexual dysfunction

Life Threatening o r

Dangerous Side Effects

Hyperglycemia, dg : keto-acidosis 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 4 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 ( ½ spuit tidak sama dg ½ dosis).

Overdose

Lethalitas dg monoterapi jarang; sedasi, palpitasi, kejang, TD turun, sesak nafas.

Long-Term Use

Mencegah kambuh skizofrenia.

Maintenen :Gg Bipoler & Gg Tingkah Laku

Habit Forming

Tidak menyebabkan ketergantungan

How to Stop

Titrasi turun dg pelan2 , > 6-8 mgg - oral, tut utk cross titration.

Rapid oral discontinuation:

rebound psychosis &

gejala memberat.

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 .

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


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.


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


Keamanan dan efektifitasnya blm dpastikan.

✽ Reperidon paling sering dipakai .

Aman utk Gg Tingkah Laku

Perlu kontrol yg lebih ketat.

THE ART OF PSYCHOPHARMACOLOGY


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)


Pd px dmn efek hiperprolaktinemi tdk diharapkan ,misal pd: ibu hamil, gadis dg amenore, premenopause tanpa estrogen replacement terapi)


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 Parkinson’s 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 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 Treatment-Resistance

• 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 effects are immediate but often

go away with time, in contrast to most

therapeutic effects 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 effects 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 effects

• 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 effects

• Benzodiazepines for jitteriness and anxiety,

especially at initiation of treatment and

especially for anxious patients

• Many side effects are dose-dependent (i.e.,

they increase as dose increases, or they

reemerge until tolerance re-develops)

• Many side effects 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

effects 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

effects 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 effects

(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 •


• 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 effects, particularly on growth, have not been studied

Pregnancy

Risk Category C [some animal studies

show adverse effects, 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 effect

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

THE ART OF PSYCHOPHARMACOLOGY


• Patients with atypical depression

(hypersomnia, increased appetite)

• Patients with fatigue and low energy

• Patients who wish to avoid

hyperprolactinemia (e.g., pubescent

children, girls and women with

galactorrhea, girls and women with

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)


• Initiating treatment in anxious patients with

some insomnia

• Patients with comorbid irritable bowel

syndrome

• Can require dosage titration


• Depressed mood

• Anxiety

• Sleep disturbance, both insomnia and

hypersomnia (eventually, but may actually

cause insomnia, especially short-term)

• Panic attacks, avoidant behavior, reexperiencing,

hyperarousal

sthal risperidone, alprazolam, sertraline

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