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
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 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 •
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 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
Potential Advantages
• 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)
Potential Disadvantages
• Initiating treatment in anxious patients with
some insomnia
• Patients with comorbid irritable bowel
syndrome
• 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