Anxiety Disorders

Anxiety Disorders
 Pengarang: William Andrea R, MD, MS; Pemimpin Redaksi: Soreff Stephen, MD lagi ...
 Ikhtisar
 Presentasi
 DDx
 Hasil pemeriksaan
 Pengobatan
 Obat
Diperbarui: Apr 19, 2011
Latar belakang
gangguan kecemasan adalah gangguan kejiwaan umum. Banyak pasien dengan gangguan kecemasan
mengalami gejala fisik yang berkaitan dengan kecemasan dan kemudian mengunjungi penyedia utama
mereka peduli. Meskipun tingkat prevalensi tinggi kecemasan gangguan ini, mereka sering adalah masalah
klinis underrecognized dan undertreated. The Manual Diagnostik dan Statistik Gangguan Mental, Edisi
Keempat, Teks Revisi (DSM-IV-TR) mengklasifikasikan gangguan kecemasan ke dalam kategori berikut:
 akibat kondisi medis umum Kecemasan
 Zat-akibat gangguan kecemasan
 Generalized gangguan kecemasan
 Panic disorder
 Gangguan stres akut
 Posttraumatic stress disorder (PTSD)
 Penyesuaian gangguan dengan fitur cemas
 Obsesif-kompulsif (OCD)
 fobia sosial , juga disebut kecemasan gangguan sosial
 fobia spesifik, juga disebut sebagai fobia sederhana - fobia tertentu telah lebih jauh lagi oleh DSM-
IV-TR untuk memasukkan jenis hewan, seperti takut anjing (cynophobia), kucing (ailurophobia),
lebah (apiphobia), laba-laba ( Arachnofobia), ular (ophidiophobia); jenis lingkungan alam, seperti
takut ketinggian (acrophobia), air (penyakit anjing gila), atau badai (astraphobia); injeksi darah /
jenis cedera, seperti takut sakit (algophobia) atau dipukuli (rhabdophobia); situasional jenis, seperti
takut terbang (pteromerhanophobia), lift, atau ruang tertutup, dan jenis lainnya
gangguan Kegelisahan tampaknya disebabkan oleh interaksi faktor biopsikososial, termasuk kerentanan
genetik, yang berinteraksi dengan situasi, stres, atau trauma untuk menghasilkan sindrom klinis yang
signifikan. (Lihat Patofisiologi dan Etiologi.)
Gejala bervariasi tergantung pada gangguan kecemasan tertentu. (Lihat Presentasi Klinis.)
1
Pengobatan biasanya terdiri dari kombinasi farmakoterapi (lihat Obat) dan / atau psikoterapi. (Lihat Strategi
Pengobatan dan Manajemen.)
Anatomi
sirkuit Otak dan daerah yang terkait dengan gangguan kecemasan mulai dipahami dengan pengembangan
pencitraan fungsional dan struktural. Amigdala otak muncul kunci dalam modulasi ketakutan dan
kecemasan. Pasien dengan gangguan kecemasan sering menunjukkan meningkat respon amigdala terhadap
isyarat kecemasan. Amigdala dan struktur sistem limbik dihubungkan ke daerah korteks prefrontal.
Hyperresponsiveness dari amigdala mungkin berhubungan dengan ambang aktivasi berkurang ketika
menanggapi ancaman sosial dirasakan. [1, 2] limbik aktivasi kelainan-prefrontal telah terbukti terbalik dengan
respon klinis atau psikologi intervensi farmakologis.
Patofisiologi
Dalam sistem saraf pusat (SSP), para mediator utama dari gejala gangguan kecemasan tampaknya
norepinephrine, serotonin, dopamin, dan asam gamma-aminobutyric (GABA). neurotransmitter dan peptida
lainnya, seperti corticotropin-faktor merilis, mungkin terlibat. Perifer, sistem saraf otonom, terutama sistem
saraf simpatik, menengahi banyak gejala. [3]
Positron emisi tomografi (PET) scanning telah menunjukkan peningkatan aliran di wilayah parahippocampal
yang tepat dan jenis reseptor serotonin berkurang 1A mengikat dalam anterior dan posterior cingulate dan
raphe pasien dengan gangguan panik. [4] MRI telah menunjukkan volume lobus temporal kecil walaupun
normal hippocampal volume pada pasien ini. [5] The CSF dalam studi pada manusia menunjukkan
peningkatan kadar orexin, juga dikenal sebagai hypocretin, yang berpikir untuk memainkan peran penting
dalam patogenesis panik dalam model tikus. [6]
Penelitian dan uji coba pengobatan menunjukkan bahwa kelainan pada neurotransmisi serotonin di otak
yang bermakna terlibat dalam gangguan obsesif-kompulsif (OCD). Hal ini sangat didukung oleh
keberhasilan inhibitor reuptake serotonin dalam pengobatan OCD. [7, 8]
Bukti-bukti juga menunjukkan kelainan pada transmisi dopaminergik di setidaknya beberapa kasus OCD.
Dalam beberapa kohort, gangguan Tourette (juga dikenal sebagai sindrom Tourette) dan tics kronis genetik
co-bervariasi dengan OCD dalam pola autosom dominan. gejala OCD di grup ini pasien menunjukkan
respons khusus terhadap kombinasi inhibitor reuptake serotonin selektif (SSRI) dan antipsikotik. [9]
pencitraan fungsional dalam OCD telah menunjukkan beberapa pola reproducible kelainan. Secara khusus,
Magnetic Resonance Imaging (MRI) dan PET pemindaian menunjukkan peningkatan aliran darah dan
aktivitas metabolik pada korteks orbitofrontal, struktur limbik, berekor, dan talamus, dengan kecenderungan
dominasi sisi kanan. Dalam beberapa penelitian, wilayah tersebut overactivity telah ditunjukkan untuk
menormalkan setelah pengobatan berhasil dengan baik SSRI atau terapi perilaku-kognitif (CBT). [10]
2
Temuan tersebut menunjukkan bahwa hipotesis bahwa gejala OCD didorong oleh penghambatan
intracortical gangguan sirkuit orbitofrontal-subkortikal spesifik yang menengahi emosi yang kuat dan respon
otonom kepada mereka emosi. (Kelainan serupa dari hambatan yang diamati dalam gangguan Tourette,
dengan modulasi abnormal mendalilkan aktivasi ganglia basal.) Cingulotomy, intervensi bedah saraf
kadang-kadang digunakan untuk OCD parah dan pengobatan-tahan, memotong sirkuit ini (lihat Treatment).
Baru-baru ini, perhatian difokuskan pada kelainan glutamatergic di OCD. [11] Walaupun dimodulasi oleh
serotonin dan neurotransmitter lain, sinapsis di-striato-thalamo-cortical sirkuit cortico dianggap pusat
terlibat dalam patologi OCD terutama mempekerjakan neurotransmitter glutamat dan GABA.
Fakta bahwa gejala obsesif-kompulsif tampaknya sering mengambil bentuk yang sangat stereotypic telah
membuat beberapa hipotesa bahwa gangguan patologis dapat menyebabkan OCD disinhibiting dan
membesar-besarkan beberapa built-in potensi perilaku yang kita miliki, yang dalam keadaan lain mungkin
memiliki fungsi adaptif ( misalnya, ritual perawatan primata).
Etiologi
Kecemasan gangguan pada umumnya
Pertimbangan pertama adalah kemungkinan bahwa kecemasan disebabkan oleh kondisi medis yang dikenal
atau tidak dikenal. Zat-induced gangguan kecemasan (obat over-the-counter, obat herbal, zat
penyalahgunaan) adalah diagnosis yang sering tidak terjawab.
Faktor genetik berpengaruh secara signifikan terhadap risiko untuk gangguan kecemasan banyak. Faktor
lingkungan seperti trauma anak usia dini dapat juga berkontribusi terhadap risiko gangguan kecemasan
nanti. Perdebatan apakah gen atau lingkungan yang utama dalam gangguan kecemasan telah berkembang
pemahaman yang lebih baik tentang peran penting dari interaksi antara gen dan lingkungan. [12] Beberapa
orang tampak tahan terhadap stres, sementara yang lain rentan terhadap stres, yang presipitat kecemasan
gangguan.
Sebagian besar menyajikan gangguan kecemasan gangguan kejiwaan fungsional. Teori Psikologis berkisar
dari menjelaskan kecemasan sebagai perpindahan dari suatu konflik intrapsikis (model psikodinamik) untuk
pengkondisian (belajar) paradigma (model kognitif-perilaku). Banyak dari teori ini mengambil bagian dari
kekacauan.
Teori psikodinamik telah dijelaskan kecemasan sebagai konflik antara id dan ego. Agresif dan impulsif drive
mungkin dialami sebagai tidak dapat diterima mengakibatkan represi. Drive ini bisa pecah ditekan melalui
represi, menghasilkan kecemasan otomatis. Perlakuan menggunakan eksplorasi dengan tujuan memahami
konflik yang mendasari. teori kognitif telah menjelaskan kecemasan sebagai kecenderungan untuk melebih-
lebihkan potensi bahaya. Pasien dengan gangguan kecemasan cenderung untuk membayangkan skenario
terburuk dan menghindari situasi yang menurut mereka lebih berbahaya, seperti orang banyak, ketinggian,
atau interaksi sosial.
3
Panic disorder
gangguan Panic tampaknya merupakan neurokimia disfungsi mewarisi genetik yang mungkin melibatkan
ketidakseimbangan otonom, turun-ergic nada GABA [13] ; polimorfisme alelik dari O--methyltransferase
katekol (COMT) gen; fungsi reseptor adenosin meningkat; meningkat kortisol [14] ; berkurang fungsi
reseptor Benzodiazepine, dan gangguan dalam serotonin, [15] serotonin transporter (5-HTTLPR) [16] dan
promotor (SLC6A4) gen, [17] norepinefrin, dopamin, cholecystokinin, dan interleukin-1-beta. [18] Beberapa
berteori bahwa gangguan panik mungkin merupakan keadaan hiperventilasi kronis dan karbon dioksida
hipersensitivitas reseptor. [7] Beberapa pasien epilepsi memiliki panik sebagai manifestasi dari serangan
mereka. penelitian genetik menunjukkan bahwa daerah kromosom 13q, 14q, 22q, 4q31-q34, dan mungkin
9q31 mungkin berhubungan dengan gangguan fenotip heritabilitas panik. [19]
Teori kognitif mengenai panik adalah bahwa pasien dengan gangguan panik memiliki kepekaan yang
meningkat terhadap isyarat otonom internal (misalnya, takikardia).
Memicu kepanikan dapat mencakup hal berikut:
 Cedera (misalnya, kecelakaan, operasi)
 Penyakit
 Interpersonal konflik atau kerugian
 Penggunaan ganja (dapat dikaitkan dengan serangan panik, mungkin karena nafas-holding) [20]
 Penggunaan stimulan, seperti kafein, dekongestan, kokain, dan simpatomimetik (misalnya, amfetamin,
MDMA ["ekstasi"]) [21]
 Pengaturan tertentu, seperti toko dan kendaraan umum (terutama pada pasien dengan agoraphobia)
 Sertraline dapat menimbulkan kepanikan dalam sebelumnya pasien tanpa gejala. [22]
 Sindrom penghentian SSRI dapat menyebabkan gejala yang mirip dengan yang dialami oleh pasien panik.
Dalam pengaturan eksperimental, gejala dapat diperoleh pada orang dengan gangguan panik oleh
hiperventilasi, menghirup karbon dioksida, konsumsi kafein, atau infus natrium laktat hipertonik atau salin
hipertonik, [23] cholecystokinin, isoproterenol, flumazenil [24] , atau naltrexone. [25] Karbon dioksida
Tantangan inhalasi terutama provokatif gejala panik pada perokok. [26]
Posttraumatic stres gangguan
PTSD disebabkan oleh mengalami, menyaksikan, atau dihadapkan dengan sebuah acara yang melibatkan
cedera serius, kematian, atau ancaman terhadap integritas fisik individu, bersama dengan respon tidak
berdaya melibatkan dan / atau takut intens atau horor. Trauma lebih parah dan semakin intens gejala stres
akut, semakin tinggi risiko untuk PTSD. Ketika peristiwa ini melibatkan seorang individu dengan
kerentanan fisiologis berdasarkan genetik (warisan) kontribusi dan karakteristik pribadi lainnya, PTSD hasil.
Para peneliti telah mengidentifikasi faktor-faktor yang berinteraksi mempengaruhi kerentanan terhadap
mengembangkan PTSD. [27] [28] Faktor-faktor ini meliputi:
 Karakteristik dari paparan trauma itu sendiri, seperti kedekatannya dengan, keparahan, dan durasi paparan
trauma
4
 Karakteristik individu, seperti paparan sebelum trauma, kesulitan masa kanak-kanak (misalnya, pemisahan
dari orang tua), kecemasan sudah ada sebelumnya atau depresi, dan jenis kelamin (perempuan mempunyai
risiko lebih besar untuk banyak trauma tegas paling umum)
 Posttrauma faktor, seperti ketersediaan dukungan sosial, munculnya menghindari atau mati rasa,
hyperarousal, dan gejala reexperiencing (untuk reexperiencing gejala khusus, monozygotal studi
menunjukkan kembar pilot bahwa pasien dengan PTSD memiliki gangguan kepunahan dari novel rangsangan
takut AC [29] )
Obsesif-kompulsif
Penyebab OCD belum diketahui, namun faktor genetik, infeksi, kondisi neurologik lain, stres, dan hubungan
interpersonal semuanya telah terbukti relevan.
studi Twin telah mendukung heritabilitas kuat untuk OCD, dengan pengaruh genetik 45-65% dalam studi
pada anak-anak, dan 27-47% pada orang dewasa. [30] kembar monozigot dapat mencolok sesuai untuk OCD
(80-87%), dibandingkan dengan 47-50% konkordansi pada anak kembar dizigotik. [31] Beberapa penelitian
genetik telah mendukung hubungan dengan berbagai, dopaminergik, dan glutamatergic gen serotonergik. [32,
33, 34, 35, 36]
gen lain putatively terkait dengan OCD telah memasukkan mereka coding untuk katekol-
methyltransferase O-(COMT), monoamine oxidase-A (MAO-A), faktor neurotropik yang diturunkan dari
otak (BDNF), myelin glikoprotein oligodendrocyte (Mog), GABA-reseptor tipe B-1, dan mu yang opioid
reseptor, tetapi ini harus dianggap asosiasi sementara pada saat ini. Dalam beberapa kohort, OCD, attention
deficit hyperactivity disorder (ADHD) dan Tourette gangguan / tic gangguan co-bervariasi dalam mode
dominan autosom dengan penetrasi variabel.
Kasus laporan telah dipublikasikan OCD dengan dan tanpa tics yang timbul pada anak dan dewasa muda
berikut kelompok akut A infeksi streptokokus. Kurang laporan mengutip herpes simplex virus sebagai event
menular jelas pengendapan. Telah dihipotesiskan bahwa infeksi ini memicu respons SSP autoimun yang
mengakibatkan gejala neuropsikiatri (pediatrik neuropsikiatrik gangguan autoimun terkait dengan infeksi
streptokokus [panda]). Sejumlah kasus telah dilaporkan membaik poststreptococcal pengobatan berikut
dengan antibiotik.
Langka ada laporan dari OCD menyajikan sebagai manifestasi penghinaan neurologis seperti trauma otak,
penyalahgunaan stimulan, dan keracunan karbon monoksida.
gejala OCD dapat memperburuk dengan stres, namun, stres tampaknya tidak menjadi faktor etiologi.
gejala OCD dapat berinteraksi negatif dengan hubungan interpersonal, dan keluarga dapat menjadi terlibat
dengan penyakit dengan cara kontraproduktif (misalnya, seorang pasien dengan obsesi meragukan berat
terus-menerus dapat meminta jaminan untuk ketakutan irasional dari anggota keluarga atau orang lain yang
signifikan; terus memberikan ini dapat menghambat pasien dari melakukan upaya untuk bekerja pada
gangguan perilaku mereka). Parenting gaya atau didikan tidak muncul menjadi faktor penyebab OCD.
5
Sosial fobia (gangguan kecemasan sosial)
Faktor genetik tampaknya berperan dalam fobia sosial. Berdasarkan studi dan kembar keluarga, risiko untuk
fobia sosial tampaknya cukup diwariskan. [37, 38]
Sosial fobia dapat dimulai dengan pengalaman sosial traumatis (misalnya, malu) atau dengan defisit
keterampilan sosial yang memproduksi berulang pengalaman negatif. Sebuah hipersensitif terhadap
penolakan, mungkin terkait dengan disfungsi serotonergik atau dopaminergik, hadir. kini berpikir bahwa
fobia sosial tampaknya merupakan interaksi antara faktor biologis dan genetik dan acara lingkungan.
Seorang psikoanalis kemungkinan akan konsep kecemasan sosial sebagai gejala yang lebih dalam konflik-
misalnya, rendah diri atau konflik yang belum diselesaikan dengan objek internal. behavioris A akan melihat
fobia sebagai respons, belajar AC yang dihasilkan dari hubungan masa lalu dengan situasi dengan valensi
emosional negatif pada saat asosiasi (misalnya, situasi sosial dihindari karena kecemasan yang intens pada
awalnya berpengalaman dalam setting itu). Bahkan jika tidak ada bahaya yang ditimbulkan dalam
pertemuan sosial yang paling, respon penghindaran telah dikaitkan dengan situasi ini. Perawatan dari
perspektif ini bertujuan untuk melemahkan dan akhirnya memisahkan penanganan khusus dari rangsangan.
Spesifik (sederhana) fobia
Faktor genetik tampaknya berperan dalam fobia tertentu juga (misalnya, di-cedera fobia darah), dan resiko
untuk fobia tersebut tampaknya juga akan cukup diwariskan. [37] Di samping itu, fobia spesifik dapat
diperoleh dengan pengkondisian, pemodelan , pengalaman atau trauma.
Agoraphobia mungkin hasil dari ulang, serangan panik yang tidak terduga, yang, pada gilirannya, dapat
dikaitkan dengan distorsi kognitif, respon dikondisikan, dan / atau kelainan pada neurotransmisi
noradrenergik, serotonergik, atau GABA-terkait.
Epidemiologi
Amerika Serikat statistik
fobia sosial adalah gangguan kecemasan yang paling umum, tetapi memiliki usia awal-awal umur 11 tahun
di sekitar 50% dan pada usia 20 tahun di sekitar 80% dari individu yang memiliki diagnosis-dan itu adalah
faktor risiko depresi berikutnya penyakit dan penyalahgunaan zat. [39]
Setelah diyakini langka, OCD ditemukan memiliki prevalensi seumur hidup pada kisaran 1,7-4%. Penemuan
pengobatan yang efektif dan pendidikan pasien dan penyedia layanan kesehatan telah meningkat secara
signifikan identifikasi individu dengan OCD selama dekade terakhir.
Menurut 2 studi besar di Amerika Serikat-the Epidemiological DAS (ECA) studi [40] dan National
komorbiditas Survey (NCS) studi [41] -dalam hubungannya dengan penelitian lain, prevalensi seumur hidup
taksiran tingkat gangguan kecemasan individu 2,3-2,7% untuk gangguan panik, 4,1-6,6% untuk gangguan
kecemasan umum, 2,3-2,6% untuk OCD, 1-9,3% untuk PTSD, dan 2,6-13,3% untuk fobia sosial.
6
Lebih lanjut, NCS melaporkan seumur hidup berikut (dan 30-hari) memperkirakan prevalensi: 6,7% (dan
2,3%) untuk agoraphobia, 11,3% (dan 5,5%) untuk sederhana (yaitu, spesifik) fobia, dan 13,3% (dan 4,5% )
untuk fobia sosial. [42, 43]
Internasional statistik
Prevalensi gangguan kecemasan spesifik yang bervariasi antara negara dan budaya. Sebuah studi lintas-
nasional prevalensi gangguan panik menemukan tingkat prevalensi seumur hidup berkisar dari 0,4% di
Taiwan menjadi 2,9% di Italia. Sebuah studi lintas-budaya dari prevalensi OCD menemukan tingkat
prevalensi seumur hidup berkisar dari 0,7% di Taiwan menjadi 2,5% di Puerto Rico.
Dalam beberapa budaya Timur Jauh, orang dengan fobia sosial dapat mengembangkan kekhawatiran yang
menyinggung orang lain daripada ketakutan menjadi malu.
Prevalensi gangguan kecemasan oleh ras

Studi ECA tidak menemukan perbedaan dalam tingkat gangguan panik antara putih, Afrika Amerika, atau
populasi Hispanik di Amerika Serikat. Beberapa studi telah menemukan tingkat yang lebih tinggi PTSD
pada populasi minoritas. Beberapa asosiasi ini mungkin disebabkan tingginya tingkat peristiwa traumatik
tertentu (misalnya, penyerangan) pada populasi minoritas.
Sex rasio untuk gangguan kecemasan

Rasio perempuan-ke-laki-laki untuk setiap gangguan kecemasan seumur hidup adalah 3:2 (lihat gambar di
bawah).
Kecemasan. Bagan yang menunjukkan ke-laki-laki sex ratio-perempuan

untuk gangguan kecemasan. Diadaptasi dari Kessler et al, 1994.
Umur distribusi untuk gangguan kecemasan

gangguan kecemasan Kebanyakan dimulai pada masa kanak-kanak, remaja, dan dewasa awal (lihat gambar
di bawah). Separation anxiety adalah suatu gangguan kecemasan masa kanak-kanak yang sering termasuk
7
kecemasan yang berhubungan dengan pergi ke sekolah. Gangguan ini dapat menjadi pelopor untuk
gangguan kecemasan dewasa.
Kecemasan. Age of onset untuk gangguan kecemasan berdasarkan jenis

gangguan kecemasan tertentu.
gangguan Panic menunjukkan usia bimodal onset dalam studi NCS pada kelompok usia 15-24 tahun dan 45-
54 tahun. Usia onset untuk OCD tampaknya pertengahan tahun 20-an sampai 30-an awal.
fobia sosial Kebanyakan dimulai sebelum usia 20 tahun (median usia saat onset penyakit, 16 tahun. [42] )
Agoraphobia biasanya dimulai di akhir masa remaja sampai dewasa awal (umur rata-rata saat onset
penyakit, 29 tahun. [42] )
Secara umum, phobia khusus muncul lebih awal dari fobia sosial atau agoraphobia. Usia onset tergantung
pada fobia tertentu. Misalnya, fobia hewan yang paling umum di tingkat sekolah dasar dan muncul pada usia
rata-rata 7 tahun; fobia darah muncul pada usia rata-rata 9 tahun; fobia gigi muncul pada usia rata-rata 12
tahun, dan claustrophobia muncul di rata-rata usia 20 tahun. Paling sederhana (spesifik) fobia berkembang
selama masa kanak-kanak (median usia saat onset penyakit, 15 y). [42] ) dan akhirnya menghilang. Mereka
yang bertahan sampai dewasa jarang hilang sendiri tanpa pengobatan.
gejala kecemasan Baru-onset pada dewasa yang lebih tua harus segera mencari suatu kondisi medis yang
belum diakui secara umum, gangguan penyalahgunaan zat, atau depresi berat dengan gejala kecemasan
sekunder.
Prognosa
gangguan Kegelisahan memiliki tingkat tinggi komorbiditas dengan depresi besar dan alkohol dan
penyalahgunaan narkoba. Beberapa peningkatan morbiditas dan mortalitas yang terkait dengan gangguan
kecemasan mungkin terkait dengan ini tingginya tingkat komorbiditas. gangguan Kecemasan dapat
menyebabkan morbiditas dan kematian melalui mekanisme neuroendokrin dan neuroimmune atau dengan
stimulasi saraf langsung, (misalnya, hipertensi atau aritmia jantung). Kecemasan kronis mungkin terkait
dengan peningkatan risiko morbiditas dan mortalitas kardiovaskular.
Banyak bukti yang menunjukkan bahwa fobia sosial (gangguan kecemasan sosial) menyebabkan gangguan
fungsional yang signifikan dan penurunan kualitas hidup. [44, 45]
gangguan kecemasan berat mungkin rumit oleh bunuh diri, dengan atau tanpa gangguan mood sekunder
(misalnya, depresi). The Epidemiologi DAS Area studi menemukan bahwa gangguan panik dikaitkan
dengan upaya bunuh diri (rasio odds = 18 dibandingkan dengan populasi tanpa gangguan kejiwaan). Berapa
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banyak asosiasi gangguan panik dengan bunuh diri dimediasi melalui asosiasi gangguan panik dengan
gangguan penyalahgunaan zat mood dan tidak jelas. stres akut mungkin memainkan peran dalam
memproduksi perilaku bunuh diri. Kehadiran dari setiap gangguan kecemasan, fobia termasuk, dalam
kombinasi dengan gangguan mood tampaknya meningkatkan kemungkinan upaya bunuh diri dibandingkan
dengan gangguan mood saja. [46] Bunuh Diri upaya dapat diendapkan oleh peristiwa kehidupan yang
merugikan seperti perceraian atau bencana keuangan. Efek stres akut dalam memproduksi perilaku bunuh
diri yang meningkat pada mereka dengan suasana hati yang mendasari, kecemasan, dan masalah
penyalahgunaan zat.
Fobia sangat komorbid. Kebanyakan fobia sederhana (spesifik) dan sosial komorbid adalah temporal utama,
sementara agoraphobia paling komorbid adalah temporal sekunder. fobia komorbid umumnya lebih parah
daripada fobia murni. Fobia sosial juga sering komorbiditas dengan gangguan depresi mayor dan depresi
atipikal, yang menyebabkan cacat meningkat. [45, 47] Meskipun bukti kerusakan, hanya sebagian kecil
individu dengan sederhana (spesifik) fobia pernah mencari perawatan profesional.
Menariknya, dalam sampel klinis, lebih dari 95% pasien melaporkan agoraphobia juga hadir dengan
gangguan panik , sedangkan pada sampel epidemiologi, agoraphobia sederhana tampaknya lebih menonjol
dari gangguan panik dengan agoraphobia. [48]
Pendidikan Pasien
Pendidikan dapat diperoleh melalui buku, newsletter, kelompok pendukung, dan internet. Beberapa situs
Web yang berguna adalah sebagai berikut:
 Institut Nasional Kesehatan Mental, Gangguan Kecemasan
 SAMHSA's Mental Pusat Informasi Kesehatan Nasional, Gangguan Kecemasan
 MentalHelp.net
 eMedicineHealth, Kesehatan Mental dan Perilaku Pusat dan Kecemasan Pusat
 eMedicineHealth, Stres , Kegelisahan , Panic Attacks , dan Hiperventilasi
Anggota keluarga harus menerima informasi tentang pengaruh gangguan kecemasan pada suasana hati,
perilaku, dan hubungan. Anggota keluarga dapat membantu dalam perawatan dengan memperkuat
kebutuhan untuk perawatan medis dan pengawasan. Anggota keluarga juga dapat membantu dengan
menyediakan sumber daya kolaboratif untuk memantau tingkat keparahan gejala-gejala kecemasan pasien
dan respon terhadap intervensi pengobatan.
Anxiety Disorders
9
 Author: William R Yates, MD, MS; Chief Editor: Stephen Soreff, MD more...
 Overview
 Presentation
 DDx
 Workup
 Treatment
 Medication
Updated: Apr 19, 2011
 Background
 Anatomy
 Pathophysiology
 Etiology
 Epidemiology
 Prevalence of anxiety disorders by race
 Sex ratio for anxiety disorders
 Age distribution for anxiety disorders
 Prognosis
 Patient Education
 Show All
Background
Anxiety disorders are common psychiatric disorders. Many patients with anxiety disorders experience
physical symptoms related to anxiety and subsequently visit their primary care providers. Despite the high
prevalence rates of these anxiety disorders, they often are underrecognized and undertreated clinical
problems. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-
IV-TR) classifies the anxiety disorders into the following categories:
 Anxiety due to a general medical condition
 Substance-induced anxiety disorder
 Generalized anxiety disorder
 Panic disorder
 Acute stress disorder
 Posttraumatic stress disorder (PTSD)
 Adjustment disorder with anxious features
 Obsessive-compulsive disorder (OCD)
 Social phobia , also referred to as social anxiety disorder
 Specific phobia, also referred to as simple phobia - Specific phobias have been further broken down by the
DSM-IV-TR to include animal type, such as fear of dogs (cynophobia), cats (ailurophobia), bees (apiphobia),
10
spiders (arachnophobia), snakes (ophidiophobia); natural environment type, such as fear of heights
(acrophobia), water (hydrophobia), or thunderstorms (astraphobia); blood injection/injury type, such as fear
of pain (algophobia) or of being beaten (rhabdophobia); situational type, such as fear of flying
(pteromerhanophobia), elevators, or enclosed spaces; and other type
Anxiety disorders appear to be caused by an interaction of biopsychosocial factors, including genetic
vulnerability, which interact with situations, stress, or trauma to produce clinically significant syndromes.
(See Pathophysiology and Etiology.)
Symptoms vary depending on the specific anxiety disorder. (See Clinical Presentation.)
Treatment usually consists of a combination of pharmacotherapy (see Medication) and/or psychotherapy.
(See Treatment Strategies and Management.)
Anatomy
The brain circuits and regions associated with anxiety disorders are beginning to be understood with the
development of functional and structural imaging. The brain amygdala appears key in modulating fear and
anxiety. Patients with anxiety disorders often show heightened amygdala response to anxiety cues. The
amygdala and other limbic system structures are connected to prefrontal cortex regions.
Hyperresponsiveness of the amygdala may relate to reduced activation thresholds when responding to
perceived social threat. [1, 2] Prefrontal-limbic activation abnormalities have been shown to reverse with
clinical response to psychologic or pharmacologic interventions.
Pathophysiology
In the central nervous system (CNS), the major mediators of the symptoms of anxiety disorders appear to be
norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA). Other neurotransmitters and
peptides, such as corticotropin-releasing factor, may be involved. Peripherally, the autonomic nervous
system, especially the sympathetic nervous system, mediates many of the symptoms. [3]
Positron emission tomography (PET) scanning has demonstrated increased flow in the right
parahippocampal region and reduced serotonin type 1A receptor binding in the anterior and posterior
cingulate and raphe of patients with panic disorder. [4] MRI has demonstrated smaller temporal lobe volume
despite normal hippocampal volume in these patients. [5] The CSF in studies in humans shows elevated
levels of orexin, also known as hypocretin, which is thought to play an important role in the pathogenesis of
panic in rat models. [6]
Research and treatment trials suggest that abnormalities in serotonin neurotransmission in the brain are
meaningfully involved in obsessive-compulsive disorder (OCD). This is strongly supported by the efficacy
of serotonin reuptake inhibitors in the treatment of OCD. [7, 8]
Evidence also suggests abnormalities in dopaminergic transmission in at least some cases of OCD. In some
cohorts, Tourette disorder (also known as Tourette syndrome) and multiple chronic tics genetically co-vary
11
with OCD in an autosomal dominant pattern. OCD symptoms in this group of patients show a preferential
response to a combination of selective serotonin reuptake inhibitors (SSRIs) and antipsychotics. [9]
Functional imaging studies in OCD have demonstrated some reproducible patterns of abnormality.
Specifically, magnetic resonance imaging (MRI) and PET scanning have shown increases in blood flow and
metabolic activity in the orbitofrontal cortex, limbic structures, caudate, and thalamus, with a trend toward
right-sided predominance. In some studies, these areas of overactivity have been shown to normalize
following successful treatment with either SSRIs or cognitive-behavioral therapy (CBT). [10]
These findings suggest the hypothesis that the symptoms of OCD are driven by impaired intracortical
inhibition of specific orbitofrontal-subcortical circuitry that mediates strong emotions and the autonomic
responses to those emotions. (Similar abnormalities of inhibition are observed in Tourette disorder, with a
postulated abnormal modulation of basal ganglia activation.) Cingulotomy, a neurosurgical intervention
sometimes used for severe and treatment-resistant OCD, interrupts this circuit (see Treatment).
More recently, attention has focused on glutamatergic abnormalities in OCD. [11] Although modulated by
serotonin and other neurotransmitters, the synapses in the cortico-striato-thalamo-cortical circuits thought to
be centrally involved in the pathology of OCD principally employ the neurotransmitters glutamate and
GABA.
The fact that obsessive-compulsive symptoms seem to often take very stereotypic forms has led some to
hypothesize that the pathologic disturbance causing OCD may be disinhibiting and exaggerating some built-
in behavioral potential that we have, which under other circumstances might have an adaptive function (eg,
primate grooming rituals).
Etiology
Anxiety disorders in general
The first consideration is the possibility that anxiety is due to a known or unrecognized medical condition.
Substance-induced anxiety disorder (over-the-counter medications, herbal medications, substances of abuse)
is a diagnosis that often is missed.
Genetic factors significantly influence risk for many anxiety disorders. Environmental factors such as early
childhood trauma can also contribute to risk for later anxiety disorders. The debate whether gene or
environment is primary in anxiety disorders has evolved to a better understanding of the important role of
the interaction between genes and environment. [12] Some individuals appear resilient to stress, while others
are vulnerable to stress, which precipitates an anxiety disorder.
Most presenting anxiety disorders are functional psychiatric disorders. Psychological theories range from
explaining anxiety as a displacement of an intrapsychic conflict (psychodynamic models) to conditioning
(learned) paradigms (cognitive-behavioral models). Many of these theories capture portions of the disorder.
The psychodynamic theory has explained anxiety as a conflict between the id and ego. Aggressive and
impulsive drives may be experienced as unacceptable resulting in repression. These repressed drives may
12
break through repression, producing automatic anxiety. The treatment uses exploration with the goal of
understanding the underlying conflict. Cognitive theory has explained anxiety as the tendency to
overestimate the potential for danger. Patients with anxiety disorder tend to imagine the worst possible
scenario and avoid situations they think are dangerous, such as crowds, heights, or social interaction.
Panic disorder
Panic disorder appears to be a genetically inherited neurochemical dysfunction that may involve autonomic
imbalance; decreased GABA-ergic tone [13] ; allelic polymorphism of the catechol-O-methyltransferase
(COMT) gene; increased adenosine receptor function; increased cortisol [14] ; diminished benzodiazepine
receptor function; and disturbances in serotonin, [15] serotonin transporter (5-HTTLPR) [16] and promoter
(SLC6A4) genes, [17] norepinephrine, dopamine, cholecystokinin, and interleukin-1-beta. [18] Some theorize
that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor
hypersensitivity. [7] Some epileptic patients have panic as a manifestation of their seizures. Genetic studies
suggest that the chromosomal regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 may be associated with
the heritability of panic disorder phenotype. [19]
The cognitive theory regarding panic is that patients with panic disorder have a heightened sensitivity to
internal autonomic cues (eg, tachycardia).
Triggers of panic can include the following:
 Injury (eg, accidents, surgery)
 Illness
 Interpersonal conflict or loss
 Use of cannabis (can be associated with panic attacks, perhaps because of breath-holding) [20]
 Use of stimulants, such as caffeine, decongestants, cocaine, and sympathomimetics (eg, amphetamine,
MDMA [“ecstasy”]) [21]
 Certain settings, such as stores and public transportation (especially in patients with agoraphobia)
 Sertraline can induce panic in previously asymptomatic patients. [22]
 The SSRI discontinuation syndrome can induce symptoms similar to those experienced by panic patients.
In experimental settings, symptoms can be elicited in people with panic disorder by hyperventilation,
inhalation of carbon dioxide, caffeine consumption, or intravenous infusions of hypertonic sodium lactate or
hypertonic saline, [23] cholecystokinin, isoproterenol, flumazenil [24] , or naltrexone. [25] The carbon dioxide
inhalation challenge is especially provocative of panic symptoms in smokers. [26]
Posttraumatic stress disorder
PTSD is caused by experiencing, witnessing, or being confronted with an event involving serious injury,
death, or threat to the physical integrity of an individual, along with a response involving helplessness and/or
intense fear or horror. The more severe the trauma and the more intense the acute stress symptoms, the
higher the risk for PTSD. When these events involve an individual with a physiologic vulnerability based on
genetic (inherited) contributions and other personal characteristics, PTSD results.
13
Researchers have identified factors that interact to influence vulnerability to developing PTSD. [27] [28] These
factors include the following:
 The characteristics of the trauma exposure itself, such as proximity to, severity of, and duration of exposure
to the trauma
 The characteristics of the individual, such as prior exposure to trauma, childhood adversity (eg, separation
from parents), preexisting anxiety or depression, and sex (women are at greatest risk for many of the most
common assertive traumas)
 Posttrauma factors, such as availability of social support, emergence of avoidance or numbing, hyperarousal,
and reexperiencing symptoms (for reexperiencing symptoms specifically, a pilot monozygotal twin study
shows that patients with PTSD have impaired extinction of novel conditioned fear stimuli [29] )
Obsessive-compulsive disorder
The cause of OCD is not known; however, genetic factors, infections, other neurologic conditions, stress,
and interpersonal relationships have all been shown to be relevant.
Twin studies have supported strong heritability for OCD, with a genetic influence of 45-65% in studies in
children, and 27-47% in adults. [30] Monozygotic twins may be strikingly concordant for OCD (80-87%),
compared with 47-50% concordance in dizygotic twins. [31] Several genetic studies have supported linkages
to a variety of serotonergic, dopaminergic, and glutamatergic genes. [32, 33, 34, 35, 36] Other genes putatively
linked to OCD have included those coding for catechol-O-methyltransferase (COMT), monoamine oxidase-
A (MAO-A), brain-derived neurotrophic factor (BDNF), myelin oligodendrocyte glycoprotein (MOG),
GABA-type B-receptor 1, and the mu opioid receptor, but these must be considered provisional associations
at this time. In some cohorts, OCD, attention deficit hyperactivity disorder (ADHD), and Tourette
disorder/tic disorders co-vary in an autosomal dominant fashion with variable penetrance.
Case reports have been published of OCD with and without tics arising in children and young adults
following acute group A streptococcal infections. Fewer reports cite herpes simplex virus as the apparent
precipitating infectious event. It has been hypothesized that these infections trigger a CNS autoimmune
response that results in neuropsychiatric symptoms (pediatric autoimmune neuropsychiatric disorders
associated with streptococcal infections [PANDAS]). A number of the poststreptococcal cases have
reportedly improved following treatment with antibiotics.
Rare reports exist of OCD presenting as a manifestation of neurologic insults such as brain trauma, stimulant
abuse, and carbon monoxide poisoning.
OCD symptoms can worsen with stress; however, stress does not appear to be an etiologic factor.
OCD symptoms can interact negatively with interpersonal relationships, and families can become involved
with the illness in a counterproductive way (eg, a patient with severe doubting obsessions may constantly
ask reassurance for irrational fears from family members or significant others; constantly providing this can
inhibit the patient from making attempts to work on their behavioral disturbances). Parenting style or
upbringing does not appear to be a causative factor in OCD.
14
Social phobia (social anxiety disorder)
Genetic factors seem to play a role in social phobia. Based on family and twin studies, the risk for social
phobia appears to be moderately heritable. [37, 38]
Social phobia can be initiated by traumatic social experience (eg, embarrassment) or by social skills deficits
that produce recurring negative experiences. A hypersensitivity to rejection, perhaps related to serotonergic
or dopaminergic dysfunction, is present. Current thought is that social phobia appears to be an interaction
between biological and genetic factors and environmental events.
A psychoanalyst would likely conceptualize social anxiety as a symptom of a deeper conflict—for instance,
low self-esteem or unresolved conflicts with internal objects. A behaviorist would see phobia as a learned,
conditioned response resulting from a past association with a situation with negative emotional valence at
the time of association (eg, social situations are avoided because intense anxiety was originally experienced
in that setting). Even if no danger is posed in most social encounters, an avoidance response has been linked
to these situations. Treatment from this perspective aims to weaken and eventually separate the specific
response from the stimulus.
Specific (simple) phobia
Genetic factors seem to play a role in specific phobia as well (eg, in blood-injury phobia), and the risk for
such phobias also seems to be moderately heritable. [37] In addition, specific phobia can be acquired by
conditioning, modeling, or traumatic experience.
Agoraphobia may be the result of repeat, unexpected panic attacks, which, in turn, may be linked to
cognitive distortions, conditioned responses, and/or abnormalities in noradrenergic, serotonergic, or GABA-
related neurotransmission.
Epidemiology
United States statistics
Social phobia is the most common anxiety disorder; it has an early age of onset—by age 11 years in about
50% and by age 20 years in about 80% of individuals that have the diagnosis—and it is a risk factor for
subsequent depressive illness and substance abuse. [39]
Once believed to be rare, OCD was found to have a lifetime prevalence in the range of 1.7-4%. Discovery of
effective treatments and education of patients and health care providers have significantly increased the
identification of individuals with OCD over the past decade.
According to 2 major studies in the United States—the Epidemiological Catchment Area (ECA) study [40]
and the National Comorbidity Survey (NCS) study [41] —in conjunction with other studies, the estimated
lifetime prevalence rates for individual anxiety disorders are 2.3-2.7% for panic disorder, 4.1-6.6% for
generalized anxiety disorder, 2.3-2.6% for OCD, 1-9.3% for PTSD, and 2.6-13.3% for social phobia.
15
Further, the NCS reported the following lifetime (and 30-day) prevalence estimates: 6.7% (and 2.3%) for
agoraphobia, 11.3% (and 5.5%) for simple (ie, specific) phobia, and 13.3% (and 4.5%) for social phobia. [42,
43]
International statistics
The prevalence of specific anxiety disorders appears to vary between countries and cultures. A cross-
national study of the prevalence of panic disorder found lifetime prevalence rates ranging from 0.4% in
Taiwan to 2.9% in Italy. A cross-cultural study of the prevalence of OCD found lifetime prevalence rates
ranging from 0.7% in Taiwan to 2.5% in Puerto Rico.
In some Far East cultures, individuals with social phobia may develop fears of being offensive to others
rather than fears of being embarrassed.
Prevalence of anxiety disorders by race

The ECA study found no difference in rates of panic disorder among white, African American, or Hispanic
populations in the United States. Some studies have found higher rates of PTSD in minority populations.
Some of this association may be due to higher rates of specific traumatic events (ie, assault) in minority
populations.
Sex ratio for anxiety disorders

The female-to-male ratio for any lifetime anxiety disorder is 3:2 (see the image below).
Anxiety. Chart showing the female-to-male sex ratio for anxiety disorders. Adapted
from Kessler et al, 1994.
Age distribution for anxiety disorders

Most anxiety disorders begin in childhood, adolescence, and early adulthood (see the image below).
Separation anxiety is an anxiety disorder of childhood that often includes anxiety related to going to school.
This disorder may be a precursor for adult anxiety disorders.
16
Anxiety. Age of onset for anxiety disorders based on specific anxiety disorder type.
Panic disorder demonstrates a bimodal age of onset in the NCS study in the age groups of 15-24 years and
45-54 years. The age of onset for OCD appears to be in the mid 20s to early 30s.
Most social phobias begin before age 20 years (median age at illness onset, 16 years. [42] )
Agoraphobia usually begins in late adolescence to early adulthood (median age at illness onset, 29 years. [42]
)
In general, specific phobia appears earlier than social phobia or agoraphobia. The age of onset depends on
the particular phobia. For example, animal phobia is most common at the elementary school level and
appears at a mean age of 7 years; blood phobia appears at a mean age of 9 years; dental phobia appears at a
mean age of 12 years; and claustrophobia appears at a mean age of 20 years. Most simple (specific) phobias
develop during childhood (median age at illness onset, 15 y). [42] ) and eventually disappear. Those that
persist into adulthood rarely go away without treatment.
New-onset anxiety symptoms in older adults should prompt a search for an unrecognized general medical
condition, a substance abuse disorder, or major depression with secondary anxiety symptoms.
Prognosis
Anxiety disorders have high rates of comorbidity with major depression and alcohol and drug abuse. Some
of the increased morbidity and mortality associated with anxiety disorders may be related to this high rate of
comorbidity. Anxiety disorders may contribute to morbidity and mortality through neuroendocrine and
neuroimmune mechanisms or by direct neural stimulation, (eg, hypertension or cardiac arrhythmia). Chronic
anxiety may be associated with increased risk for cardiovascular morbidity and mortality.
Considerable evidence shows that social phobia (social anxiety disorder) results in significant functional
impairment and decreased quality of life. [44, 45]
Severe anxiety disorders may be complicated by suicide, with or without secondary mood disorders (eg,
depression). The Epidemiological Catchment Area study found that panic disorder was associated with
suicide attempts (odds ratio = 18 compared with populations without psychiatric disorders). How much of
the association of panic disorder with suicide is mediated through the association of panic disorder with
mood and substance abuse disorders is unclear. Acute stress may play a role in producing suicidal behavior.
The presence of any anxiety disorder, phobias included, in combination with a mood disorder appears to
increase likelihood of suicide attempts compared with a mood disorder alone. [46] Suicide attempts can be
precipitated by adverse life events such as divorce or financial disaster. The effects of acute stress in
17
producing suicidal behavior are increased in those with underlying mood, anxiety, and substance abuse
problems.
Phobias are highly comorbid. Most comorbid simple (specific) and social phobias are temporally primary,
while most comorbid agoraphobia is temporally secondary. Comorbid phobias are generally more severe
than pure phobias. Social phobia is also frequently comorbid with major depressive disorder and atypical
depression, which results in increased disability. [45, 47] Despite evidence of impairment, only a minority of
individuals with simple (specific) phobia ever seek professional treatment.
Interestingly, in clinical samples, over 95% of the patients reporting agoraphobia also present with panic
disorder , while in epidemiologic samples, simple agoraphobia appears to be more prevalent than panic
disorder with agoraphobia. [48]
Patient Education
Education can be obtained through books, newsletters, support groups, and the Internet. Some useful Web
sites are as follows:
 National Institute of Mental Health, Anxiety Disorders
 SAMHSA's National Mental Health Information Center, Anxiety Disorders
 MentalHelp.net
 eMedicineHealth, Mental Health and Behavior Center and Anxiety Center
 eMedicineHealth, Stress , Anxiety , Panic Attacks , and Hyperventilation
Family members should receive information about the effect of anxiety disorders on mood, behavior, and
relationships. Family members can assist in care by reinforcing the need for medical treatment and
supervision. Family members may also assist by providing a collaborative resource for monitoring the
severity of the patient's anxiety symptoms and response to treatment interventions.
Anxiety Disorders Clinical Presentation

 Overview
 Presentation
 DDx
 Workup
 Treatment
 Medication
 History
18
 Mental Status Examination
 Physical Examination
 Show All
History
To rule out anxiety disorders secondary to general medical or substance abuse conditions, a detailed history
and review of symptoms is essential. Review use of caffeine-containing beverages (coffee, tea, colas,
Mountain Dew), over-the-counter medications (aspirin with caffeine, sympathomimetics), herbal
“medications,” or street drugs. Ask the patient’s sleep partner about apneic episodes or myoclonic limb
jerks. Concurrent depressive symptoms are common in all of the anxiety disorders. Severe anxiety disorders
may produce agitation, suicidal ideation, and increased risk of completed suicide. Always ask about suicidal
ideation or suicidal intent. (See Mental Status Examination)
Generalized anxiety disorder
This disorder is characterized by excessive anxiety and worry. Worrying is difficult to control. Anxiety and
worry are associated with at least 3 of the following symptoms:
 Restlessness or feeling keyed-up or on edge
 Being easily fatigued
 Difficulty concentrating or mind going blank
 Irritability
 Muscle tension
 Sleep disturbance
 Although not a diagnostic feature, suicidal ideation and completed suicide have been associated with
generalized anxiety disorder
Panic disorder
Patients with panic disorder frequently present to the emergency department (ED) with chest pain or
dyspnea, fearing that they are dying of myocardial infarction. They typically report a spontaneous sudden
onset of fear or discomfort, typically reaching a peak within 10 minutes. Attacks are associated with a
constellation of systemic symptoms, including the following (4 or more of these are needed for DSM-IV-TR
criteria):
 Palpitations, pounding heart, or accelerated heart rate
 Sweating
 Trembling or shaking
 Shortness of breath or feeling of smothering
 Choking sensation
 Chest pain or discomfort
 Nausea or abdominal distress
 Feeling dizzy, unsteady, lightheaded, or faint
19
 Derealization (ie, feeling of unreality) or depersonalization (ie, being detached from oneself)
 Fear of losing control or going crazy
 Fear of dying
 Paresthesias (ie, numbness or tingling sensations)
 Chills or hot flashes
During the episode, patients have the urge to flee or escape and have a sense of impending doom (as though
they are dying from a heart attack or suffocation). Other symptoms may include headache, cold hands,
diarrhea, insomnia, fatigue, intrusive thoughts, and ruminations.
Patients with panic disorder have recurring episodes of panic, with the fear of recurrent attack resulting in
significant behavioral changes (eg, avoiding situations or locations) and worry about the implications of the
attack or its consequences (eg, losing control, going crazy, dying).
Panic disorder may result in changes in personality traits, characterized by the patient becoming more
passive, dependent, or withdrawn. DSM-IV-TR criteria include 4 or more attacks in a 4-week period or 1 or
more attacks followed by at least 1 month of fear of another. Agoraphobia, present in 30% of persons with
PD, establishes the diagnosis.
Assess precipitating events, suicidal ideation or plan, phobias, agoraphobia, and obsessive-compulsive
behavior. Exclude involvement of alcohol, illicit drugs (eg, cocaine, amphetamine, phencyclidine, amyl
nitrate, lysergic acid diethylamide [LSD], yohimbine, 3,4-methylenedioxymethamphetamine [MDMA, or
ecstasy]), cannabis, and medications (eg, caffeine, theophylline, sympathomimetics, anticholinergics).
Consider symptomatology of other medical disorders, which may manifest with anxiety as a primary
symptom.
 Angina and myocardial infarction (eg, dyspnea, chest pain, palpitations, diaphoresis)
 Cardiac dysrhythmias (eg, palpitations, dyspnea, syncope)
 Mitral valve prolapse
 Pulmonary embolus (eg, dyspnea, hyperpnea, chest pain)
 Asthma (eg, dyspnea, wheezing)
 Hyperthyroidism (eg, palpitations, diaphoresis, tachycardia, heat intolerance)
 Hypoglycemia
 Pheochromocytoma (eg, headache, diaphoresis, hypertension)
 Hypoparathyroidism (eg, muscle cramps, paresthesias)
 Transient ischemic attacks (TIAs)
 Seizure disorders
Consider other mental illnesses that may result in panic attacks, including schizophrenia, manic disorder,
depressive disorder, posttraumatic stress disorder, phobic disorders, and somatization disorder. Assess
family history of panic or other psychiatric illness.
20
The information elicited from the interview with the patient must satisfy certain diagnostic criteria to make
the formal diagnosis. As with many diagnoses, PTSD can be subclinical, in which the criteria are almost but
not fully met. Diagnosis is based on criteria from the DSM-IV-TR. The mental status examination should
routinely consist of questions about exposure to trauma or abuse.
The first criterion has 2 components: (1) experiencing, witnessing, or being confronted with an event
involving serious injury, death, or a threat to a person’s physical integrity and (2) a response involving
helplessness, intense fear, or horror (sometimes expressed in children as agitation or disorganized behavior).
The second major criterion involves the persistent reexperiencing of the event in one of several ways. This
may involve thoughts or perception, images, dreams, illusions, hallucinations, dissociative flashback
episodes, or intense psychological distress or reactivity to cues that symbolize some aspect of the event.
However, children reexperience the event through repetitive play, not through perception like adults.
The third diagnostic criterion involves avoidance of stimuli that are associated with the trauma and numbing
of general responsiveness; this is determined by the presence of 3 or more of the following:
 Avoidance of thoughts, feelings, or conversations that are associated with the event
 Avoidance of people, places, or activities that may trigger recollections of the event
 Inability to recall important aspects of the event
 Significantly diminished interest or participation in important activities
 Feeling of detachment from others
 Narrowed range of affect
 Sense of having a foreshortened future
The fourth criterion is symptoms of hyperarousal, and 2 or more of the following symptoms are required to
fulfill this criterion:
 Difficulty sleeping or falling asleep
 Decreased concentration
 Hypervigilance
 Outbursts of anger or irritable mood
 Exaggerated startle response
Fifth, the duration of the relevant criteria symptoms should be more than 1 month, as opposed to acute stress
disorder, for which the criterion is a duration of less than 1 month.
Finally, the disturbance is a cause of clinically significant distress or impairment in functioning.
Children may have different reactions to trauma than adults. For children aged 5 years or younger, typical
reactions can include a fear of being separated from a parent, crying, whimpering, screaming, immobility
and/or aimless motion, trembling, frightened facial expressions, and excessive clinging. Parents may also
notice regressive behaviors. Children of this age tend to be strongly affected by their parents’ reactions to
the traumatic event.[49]
21
Children aged 6-11 years may show extreme withdrawal, disruptive behavior, and/or an inability to pay
attention. Regressive behaviors, nightmares, sleep problems, irrational fears, irritability, refusal to attend
school, outbursts of anger, and fighting are also common. The child may have somatic complaints with no
medical basis. Schoolwork often suffers. Also, depression, anxiety, feelings of guilt, and emotional numbing
are often present. Adolescents aged 12-17 years may have responses similar to adults.[49]
OCD is diagnosed primarily by presentation and history. Common obsessions include contamination, safety,
doubting one’s memory or perception, scrupulosity (need to do the right thing, fear of committing a
transgression, often religious), need for order or symmetry, and unwanted and intrusive sexual/aggressive
thought. Common compulsions include cleaning/washing, checking (checking locks, stove, iron, safety of
children), counting/repeating actions a certain number of times or until it “feels right,” arranging objects,
touching/tapping objects, hoarding, confessing/seeking reassurance, and list making.
Once the diagnosis is suspected, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)[50] is an important
tool in defining the range and severity of symptoms and monitoring the response to treatment. The Y-BOCS
is comprised of 10 items, 5 for obsessions and 5 for compulsions, each scored 0-4 (total score 0-40). For
both obsessions and compulsions, these items rate the time spent, interference with functioning, distress,
resistance, and control.
The following elements should be covered when obtaining the history; some suggestions for typical
interview questions are included.[51]
The first element concerns the nature and severity of obsessive symptoms. The following questions may be
asked:
 Have you ever been bothered by thoughts that do not make any sense and keep coming back to you even
when you try not to have them?
 When you had these thoughts, did you try to get them out of your head? What would you try to do?
 Where do you think these thoughts were coming from?
The second element concerns the nature and severity of compulsive symptoms. The following questions
may be asked:
 Has there ever been anything that you had to do over and over again and could not resist doing, such as
repeatedly washing your hands, counting up to a certain number, or checking something several times to
make sure you have done it right?
 What behavior did you have to do?
 Why did you have to do the repetitive behavior?
 How many times would you do it and how long would it take?
 Do these thoughts or actions take more time than you think makes sense?
 What effect do they have on your life?
22
The information appropriate for a full evaluation includes age of onset; a history of tics, either current or
past; and a psychiatric review of systems and comorbidities. With regard to the last, OCD is frequently
attended by other psychiatric comorbid diagnoses, prominently including major depressive disorder, alcohol
and/or substance use disorders, other anxiety disorders, impulse control disorders (eg, trichotillomania, skin-
picking), and Tourette and tic disorders (perhaps 40% of individuals with Tourette disorder will have OCD).
Therefore, in taking a psychiatric history, the focus should be on identifying such comorbidities, seeking
evidence of the following:
 Mood and anxiety symptoms
 Somatoform disorders, especially hypochondriasis and body dysmorphic disorder
 Eating disorders
 Impulse control disorders, especially kleptomania and trichotillomania
 ADHD.
The co-occurrence of schizophrenia and OCD is more problematic for a variety of reasons. Not infrequently,
individuals with schizophrenia do seem to have significant OC symptoms (sometimes, ironically, caused or
exacerbated by the use of the very effective antipsychotic clozapine, whereas adjunctive antipsychotics may
lessen treatment-resistant OC symptoms in those who do not have schizophrenia). When OC symptoms are
present in someone who has schizophrenia, they may meet criteria for a diagnosis of OCD, but such patients
often respond poorly to the usual OCD treatments, and perhaps OCD in schizophrenia has a different
pathophysiology.
A family history of OCD, Tourette disorder, tics, ADHD, and other psychiatric diagnoses should be inquired
into, as should any current or past substance abuse or dependence. Antecedent infections, especially
streptococcal and herpetic infection, should be asked about as well.
A person with social phobia will typically report a marked and persistent fear of social or performance
situations, to the extent that his or her ability to function at work or in school is impaired. Exposure to social
or performance situation always produces anxiety, and this fear/anxiety is recognized as excessive. Social or
performance situations are avoided or endured with intense anxiety. Avoidance behavior, anticipation, or
distress in the feared social or performance setting produces significant impairment in functioning.
Ask the patient about any difficulties in social situations, such as speaking in public, eating in a restaurant,
or using public washrooms. Fear of scrutiny by others or of being embarrassed or humiliated is described
commonly by people with social phobia.
Agoraphobia
Inquire about any intense anxiety reactions that occur when the patient is exposed to specific situations such
as heights, animals, small spaces, or storms. Other areas of inquiry should include fear of being trapped
without escape (eg, being outside the home and alone; in a crowd of unfamiliar people; on a bridge, in a
tunnel, in a moving vehicle).
23
If specific phobias are suspected, specific questions need to be asked about irrational and out of proportion
fear to specific situations (eg, animals, insects, blood, needles, flying, heights). Phobias can be disabling and
cause severe emotional distress, leading to other anxiety disorders, depression, suicidal ideation, and
substance-related disorders, especially alcohol abuse or dependence. The physician must inquire about these
areas as well.
Mental Status Examination

A complete mental status examination should be obtained for each patient with anxiety symptoms, assessing
appearance, behavior, ability to cooperate with the exam, level of activity, speech, mood and affect, thought
processes and content, insight, and judgment. Patients may exhibit physical signs of anxiety such as sweaty
palms, restlessness, and distractibility. Patients are generally oriented times 3 and cooperative. Mood may be
normal or depressed. Affect is often preserved. Psychotic symptoms are not typical of uncomplicated
anxiety disorders. Suicidal ideation should be assessed by asking about passive thoughts of death, desires to
be dead, thoughts of harming self, or plans or acts to harm self. Homicidal ideation is uncommon. Cognition
is typically intact with no impairment in memory, language, or speech. Insight and judgment are typically
intact.
Two main elements of the mental status examination should be assessed in generalized anxiety disorder. The
first involves asking about suicidal/homicidal ideation or plan, such as the following:
 Have you ever wished you were never born, thought you would be better off dead, wish to harm yourself or
others, have a plan to harm yourself or others, or ever tried to kill yourself or seriously injure yourself or
others?
The second involves formal testing of orientation/recall, such as the following:
 Does the patient respond when you call them by name (oriented to person)?
 Is the patient oriented to place and time? When you ask what place, season, day, month, year is it, does the
patient respond appropriately?
 Does the patient have intact short- or long-term recall? Ask the patient to spell the word WORLD forward
and backward, count backward from 100 by 7s, recall what he or she did to celebrate his or her birthday last
year and the name of his or her first-grade teacher.
Panic disorder
Mental status screening is essential for diagnosis. Standardized examinations include the Primary Care
Evaluation of Mental Disorders (PRIME-MD), the Mobility Inventory for Agoraphobia (MIA), the
Agoraphobia Cognitions Questionnaire (ACA), and the Body Sensations Questionnaire (BSQ).
No signs on mental status examination are specific for panic disorder. While the patient may or may not
appear anxious at the time of interview, their Mini-Mental Status Examination, including cognitive
24
performance, memory, serial-7, and proverb interpretation, should appear intact and consistent with the
patient’s educational level and apparent baseline intellectual functioning.
The mental status examination may reveal an anxious-appearing person, although this is not required for
diagnosis. Speech may reflect anxiety or urgency, or it may sound normal. Mood may be described as
similar to “anxious,” with congruent affect. Incongruent affect should raise consideration for other
diagnostic possibilities. Thought processes should be logical, linear, and goal directed. Thought content is
particularly important to specifically assess in order to ensure a patient has no suicidal or homicidal
thoughts. Acute anxiety, as a form of acute mental anguish, can lead to unsafe or self-injurious behavior.
Abnormalities in thought process or thought content (aside from impulsive suicidal thoughts) should prompt
reconsideration of other etiologies. Insight and judgment are usually present and intact.
General appearance may be affected in patients with PTSD. Patients may appear disheveled and have poor
personal hygiene. Behavior may be altered. Patients may appear agitated, and their startle reaction may be
extreme.
Orientation is sometimes affected. The patient may report episodes of not knowing the current place or time,
even though this may not have been evident during the interview. Memory is likely to be affected. Patients
may report forgetfulness, especially concerning the specific details of the traumatic event. A pilot study
suggests memory abnormalities may not be limited to the traumatic event itself.[52] Concentration is poor, as
is impulse control. Speech rate and flow may be altered.
Mood and affect may be changed. Patients may have feelings of depression, anxiety, guilt, and/or fear.
Thoughts and perception may be affected. Patients may be more concerned with the content of
hallucinations, delusions, suicidal ideation, phobias, and reliving the experience; certain patients may
become homicidal. Potential for suicide and homicide must be noted as part of the mental status.
A complete mental status examination should be performed. The patient should be evaluated for orientation,
memory, disturbances of mood and affect, presence of hallucinations, delusions, suicidal and homicidal risk,
and judgment (including whether insight into the irrational nature of their symptoms is still present).
Phobic disorders
In a situation where the patient is acutely confronted with the object of his or her phobia, the patient’s
mental status examination is significant for an anxious affect, with a restricted range. Neurovegetative signs
(such as tremor or diaphoresis) might be present. The patient also reports feeling anxious (mood) and can
clearly identify the reason for his/her anxiety (thought content). The thought content is significant for phobic
ideation (unrealistic and out of proportion fears). Insight might be impaired, especially during exposure, but
most times the patient has preserved insight and while reporting that they cannot control their feelings, they
also acknowledge that the severity of their fears is not justified.
25
At any other time, a patient with phobic disorder has a mental status within normal limits, with the exception
of thought content positive for phobic ideation. Of note, phobic ideas might remain undisclosed unless
questions about phobias are specifically asked. Phobias do not present with suicidal or homicidal ideation,
but comorbid conditions commonly associated with phobias, including depression and other anxiety
disorders, do present with suicidal or homicidal ideation. If comorbid conditions exist, a specific assessment
of the suicidal and homicidal risk should also be completed.
Physical Examination
Because anxiety manifests with a number of physical symptoms, any patient who presents with a de novo
complaint of physical symptoms suggesting an anxiety disorder should have a physical examination and
basic laboratory workup to rule out medical conditions that might present with anxiety like symptoms (see
Differentials).
For a patient who presents for a repeat visit with similar complaints, after medical contributors have been
ruled out, a careful mental status examination might be better suited than repeat physical examination and
laboratory investigations. (See Mental Status Examination.) While considering anxiety as the primary
suspect, the physician should always remember that over time patients with anxiety do develop medical
conditions at the same rate as other patients. In other words, a diagnosis of anxiety, while changing the
threshold for investigation of physical symptoms, should not deprive the patient of regular follow-up
examinations as otherwise indicated.
Common physical signs of generalized anxiety disorder include tremor, tachycardia, tachypnea, sweaty
palms, and restlessness.
Typically, children and adults with generalized anxiety disorder also experience uncomfortable physical
symptoms including rapid heartbeat, feeling short of breath, increased sweating, stomach cramping, a
feeling of a lump in the throat or inability to swallow, frequent need to urinate, dry mouth, nausea, diarrhea,
cold and/or clammy hands, headaches, or neck or backaches. A feeling of nervous tension is often
accompanied by a feeling of shaking, trembling, twitching, or body aches. Often, children especially are not
diagnosed or receive incorrect treatment and they may undergo unnecessary, invasive, or dangerous medical
testing and inappropriate medication treatment for supposed presence of physical illnesses and, as a result,
experience an increase in the intensity of fear and worry about their health status.[53, 54, 55]
Panic disorder
No signs on physical examination are specific for panic disorder. The diagnosis is made primarily by
history.
The patient may have an anxious appearance. A patient presenting in an acute state of panic can physically
manifest any anticipated sign of an increased sympathetic state. Tachycardia and tachypnea are common;
blood pressure and temperature may be within the reference range, though hypertension may occur as well.
26
Tremors may be noted. Cool clammy skin may be observed. Hyperventilation may be difficult to detect by
observing breathing because respiratory rate and tidal volume may appear normal. Patients may have
frequent sighs or difficulty with breath holding. Reproduction of symptoms with overbreathing is unreliable.
Chvostek sign, Trousseau sign, or overt carpopedal spasm may be present.
The remaining examination findings are typically normal in panic disorder. However, remember that panic
disorder is largely a diagnosis of exclusion, and attention should be focused on the exclusion of other
disorders.
A panic attack generally lasts 20-30 minutes from onset—rarely more than an hour. Somatic concerns of
death from cardiac or respiratory problems may be a major focus of patients during an attack. Patients may
end up in the ED.
Patients may present with physical injuries from the traumatic event (eg, bruises in victims of domestic
abuse). Patients with chronic PTSD may present with somatic complaints and, possibly, general medical
conditions. Special attention should be paid to the patient’s sleep hygiene. Recent studies suggest that even a
single cognitive-behavioral treatment (CBT) for sleep abnormalities can significantly improve daytime
PTSD symptoms, as can pharmacological treatments for sleep abnormalities.[56, 57]
Evaluate all patients with OCD for the presence of Tourette disorder or other tic disorders, as these
comorbid diagnoses may influence treatment strategy. The findings on neurologic and cognitive
examination should otherwise be normal. Focal neurologic signs or evidence of cognitive impairment should
prompt evaluation for other diagnoses.
Skin findings in OCD may include eczematous eruptions related to excessive washing, hair loss related to
trichotillomania or compulsive hair pulling, and excoriations related to neurodermatitis or compulsive skin
picking.
Anxiety Disorders Differential Diagnoses

 Overview
 Presentation
 DDx
 Workup
 Treatment
 Medication
27
Diagnostic Considerations
Prior to medication treatment, order testing for drugs of abuse, pregnancy, and screening tests for diabetes
mellitus.
Anxiety disorders have one of the longest differential diagnosis lists of all psychiatric disorders. Anxiety is a
nonspecific syndrome and can be due to a variety of medical or psychiatric syndromes. Additionally, a
variety of anxiety symptoms, such as panic, worry, rumination, and obsessions, can present in a variety of
psychiatric illnesses, including mood disorders, psychotic disorders, personality disorders, somatoform
disorders, and cognitive impairment disorders (eg, delirium). Anxiety also can be observed as part of a drug
withdrawal or drug intoxication effect.
Other important causes in the differential include medication-induced anxiety (ie, due to epinephrine or
other sympathomimetics, theophylline or other neurostimulant bronchodilators, analgesics containing
caffeine, corticosteroids, antivirals, others); migraine, seizure disorders, or other CNS-based disorders; and
sleep disorders such as restless legs syndrome, sleep apnea, and periodic limb movement. Heroin abuse also
should be considered in the differentials.
Differentials
 Acute Respiratory Distress Syndrome
 Addison Disease
 Adrenal Crisis
 Alcohol-Related Psychosis
 Alcoholism
 Amphetamine-Related Psychiatric Disorders
 Anaphylaxis
 Androgen Excess
 Anorexia Nervosa
 Apnea, Sleep
 Asthma
 Atrial Fibrillation
 Atrial Tachycardia
 Body Dysmorphic Disorder
 Brief Psychotic Disorder
 Bulimia
 Caffeine-Related Psychiatric Disorders
 Cannabis Compound Abuse
 Cardiogenic Shock
28
 Conversion Disorders
 Delirium
 Delirium Tremens
 Delusional Disorder
 Depression
 Diabetes Mellitus, Type 1
 Diabetic Ketoacidosis
 Digitalis Toxicity
 Dissociative Disorders
 Dysthymic Disorder
 Encephalopathy, Dialysis
 Encephalopathy, Hepatic
 Encephalopathy, Hypertensive
 Encephalopathy, Uremic
 Epilepsy Surgery
 Esophageal Motility Disorders
 Esophageal Spasm
 Euthyroid Hyperthyroxinemia
 Factitious Disorder
 Fibromyalgia
 Folic Acid Deficiency
 Food Poisoning
 Gastritis, Acute
 Gastritis, Chronic
 Goiter
 Goiter, Diffuse Toxic
 Hallucinogens
 Hyperaldosteronism, Primary
 Hypercalcemia
 Hyperparathyroidism
 Hyperprolactinemia
 Hypersensitivity Reactions, Delayed
 Hypersensitivity Reactions, Immediate
 Inhalant-Related Psychiatric Disorders
 Injecting Drug Use
 Insomnia
29
 Irritable Bowel Syndrome
 Lyme Disease
 Malingering
 Meningitis
 Multifocal Atrial Tachycardia
 Personality Disorders
 Phobic Disorders
 Premenstrual Dysphoric Disorder
 Primary Hypersomnia
 Primary Insomnia
 Schizoaffective Disorder
 Schizophrenia
 Shared Psychotic Disorder
 Sleep Disorder, Geriatric
 Sleep Disorders
 Somatoform Disorders
 Stimulants
 Syndrome of Inappropriate Secretion of Antidiuretic Hormone
 Thyroiditis, Subacute
 Tourette Syndrome
 Undifferentiated Connective-Tissue Disease
 Unstable Angina
Anxiety Disorders Workup

 Overview
 Presentation
 DDx
 Workup
 Treatment
 Medication
 Approach Considerations
 Studies to Exclude Medical Disorders
30
 Show All
Approach Considerations
When the index of suspicion for anxiety being produced by a medical disorder is low (lack of physical
findings, younger age, typical anxiety disorder presentation), initial laboratory studies might be limited to
the following:
 Complete blood cell count
 Chemistry profile
 Thyroid function tests
 Urinalysis
 Urine drug screen
Studies to Exclude Medical Disorders

For presentations with a higher index of suspicion for other medical causes of anxiety (ie, atypical anxiety
disorder presentation, older age, specific physical examination abnormalities), more detailed evaluations
may be indicated to identify or exclude underlying medical disorders.
Electroencephalography, lumbar puncture, and head/brain imaging
Rule out CNS disorder using electroencephalography (EEG), lumbar puncture, or brain computed
tomography (CT) scan, as indicated by history and associated clinical findings. EEG may be used to exclude
seizure disorder because these conditions may mimic anxiety.
Imaging studies are limited to presentations in which medical illness, such as a seizure disorder, is
suspected. If headache is a prominent feature, an EEG or MRI could be considered along with neurologic
consultation to rule out seizures or brain tumor. A head CT scan may be ordered for suspected intracranial
abnormality, or an MRI scan for intracranial abnormality.
Functional MRI and PET scanning have shown increases in blood flow and metabolic activity in the
orbitofrontal cortex, limbic structures, caudate, and thalamus, with a trend toward right-sided predominance,
in patients with obsessive-compulsive disorder. In some studies, these areas of overactivity have been shown
to normalize following successful treatment with either SSRIs or CBT.[10] These imaging modalities,
however, are of value for research, and not indicated for normal workups.
Electrocardiography
Rule out cardiac disorders (eg, myocardial infarction) using electrocardiography (ECG) or treadmill ECG.
ECG may be used to check for mitral valve prolapse or to exclude arrhythmia.
Tests for infection
Rule out infectious causes using rapid plasma reagent test, lumbar puncture (CNS infections), or HIV
testing.
31
Arterial blood gas analysis
Arterial blood gas analysis is useful in confirming hyperventilation (respiratory alkalosis) and excluding
hypoxemia or metabolic acidosis. The presence of hypoxemia with hypocapnia or a widened alveolar-
arterial (A-a) gradient should increase the suspicion of pulmonary embolus.
Electrolyte analysis
Electrolyte analysis is unnecessary, although several abnormalities may be present in the setting of
hyperventilation. Serum phosphorus and ionized calcium may be diminished in patients with
hyperventilation and carpopedal spasm, Chvostek sign, or Trousseau sign. The serum calcium level may be
within the reference range.
Chest radiography
Chest radiography is useful in excluding other causes of dyspnea with chest pain (eg, pulmonary embolism).
Thyroid function
Hyperthyroidism is one of the most common medical causes for anxiety related to a medical condition.
Serum thyroid-stimulating hormone and T4 levels should be considered for excluding a primary thyroid
abnormality.
Approach Considerations
Treatment usually consists of a combination of pharmacotherapy (see Medication) and/or psychotherapy.[58]
Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer
agents, which have a safer adverse effect profile and higher ease of use than the older tricyclic
antidepressants (TCAs), such as selective serotonin reuptake inhibitors (SSRIs). Antidepressants that are not
FDA-approved for the treatment of a given anxiety disorder, such as nefazodone and mirtazapine, still may
be beneficial. Older antidepressants, such as TCAs and monoamine oxidase inhibitors (MAOIs), also are
effective in the treatment of some anxiety disorders.
Behavioral therapy and CBT have demonstrated efficacy through controlled studies.[59] Computerized CBT
(FearFighter) has been recommended for panic and phobia by the National Institute for Health and Clinical
Excellence guidelines (NICE).[60] Psychodynamic therapy (or insight-oriented therapy) is rarely indicated as
an exclusive treatment for phobias and is now mostly used for cases of phobic disorders that overlap
personality disorders. Deciding which treatment or combination of treatments to prescribe depends on a
careful interview and assessment of the patient’s goals and level of pathology.
The outcome of treatment is determined by several factors, including the following:
 Severity of diagnosis
 level of functioning prior to onset of symptoms
 Degree of motivation for treatment
32
 level of support (eg, family, friends, work, school) Ability to comply with medication and/or
psychotherapeutic regimen
Acute Anxiety
Patients with significant discomfort from their anxiety can benefit from emergency anxiolytic treatment,
primarily with a benzodiazepine. In addition to ED treatment, patients in an acute anxious state of such
severity that they pose a danger to themselves or to others should have a psychiatric consultation.
In the best of circumstances, a calm environment and social support from family, friends, and the emergency
staff are ideal. For patients with more severe anxiety, a short course of a fast-acting anxiolytic agent is
recommended. Chronic anxiety requires a comprehensive approach; the best pharmacotherapy varies for
each individual, and outpatient follow-up with a psychiatrist is recommended. However, these patients can
be discharged on a short course of benzodiazepines until they see a psychiatrist. Patients who express
suicidal or homicidal thoughts should have an emergent psychiatric evaluation in the ED.
Generalized Anxiety Disorder

Successful treatment approaches generally involve medication combined with psychotherapy. However,
cognitive-behavioral therapy (CBT) has been proven superior in placebo-controlled trials. CBT generally
includes self-reward as well as problem solving and can be as effective as medications, especially for
children with mild generalized anxiety disorder.[61]
Combining CBT with medications is extremely helpful in resistant cases.[62, 63] Other psychotherapies, such
as relaxation therapy, supportive psychotherapy, or mindfulness therapy, have been used if CBT is not
appropriate.[64]
Indications for hospitalization include the following:
 Severe functional impairment (cannot meet own daily needs)
 Suicide or homicide risk
 Social skills deficits (eg, the person is so preoccupied that he or she is unaware that his or her actions and
behaviors have the potential to provoke others to cause harm)
Emotional intelligence is a protective factor for suicidal behavior; thus, this should be assessed as part of the
decision regarding need for a psychiatric hospitalization.[54]
Panic Disorder
Pharmacotherapy, cognitive and behavioral psychotherapy, and other psychological treatment modalities are
all used to treat panic disorder.
Reassure and calm the patient. Untreated panic attacks can subside spontaneously within 20-30 minutes,
especially with reassurance and a calming environment. Transport the patient to a medical treatment facility
to exclude medical causes for the first attack or when suspected on subsequent attacks.
Pharmacotherapy for Anxiety and Panic Disorders
33
Selective serotonin reuptake inhibitors (SSRIs) are generally used as first-line agents, followed remotely by
tricyclic antidepressants (TCAs).
Fluoxetine (Prozac) can be used (especially if panic disorder occurs with depression); however, patients may
poorly tolerate it initially because it may initially increase anxiety, except at very low starting doses.
Fluoxetine has a long half-life, making it a good choice in marginally compliant patients. It alters
metabolism of cytochrome P-450 2D6–cleared agents; this fact should be considered.
Paroxetine (Paxil) represents a partially sedating SSRI option that is also available in a controlled-release
preparation (Paxil CR), which may improve tolerability, but paroxetine still inhibits P450 2D6.
Citalopram (Celexa) and escitalopram (Lexapro) are likely to cause fewer hepatic enzyme interactions and
may be appropriate initial choices for patients with complicated medical regimens or those who are
concerned about drug interactions. Escitalopram also appears to be particularly well tolerated in preliminary
studies, although it may be restricted from some formularies due to the large difference in cost with
citalopram without a commensurate improvement in efficacy or tolerability for many patients.
Sertraline (Zoloft) represents a similar SSRI option with a slightly different pharmacodynamic profile,
including sigma receptor effects, although it has some P450 3A4 interactions.
Mirtazapine (Remeron)[65] has a much more sedating effect, generally reducing its potential to aggravate
initial anxiety. Mirtazapine acts distinctly as an alpha-2 antagonist, consequently increasing synaptic
norepinephrine and serotonin, while also blocking some postsynaptic serotonergic receptors that
conceptually mediate excessive anxiety when stimulated with serotonin.
Mirtazapine may cause residual morning sedation that often improves with continued therapy and may cause
an increase in appetite or weight gain. A study by Kim et al suggests among patients with major depressive
disorder who have high anxiety symptoms, mirtazapine (15–30 mg/d) administered in the early weeks of
treatment may have an earlier-onset action for anxiety symptoms.[66]
Sedating antidepressants such as paroxetine, mirtazapine, and other TCAs/TeCAs are usually prescribed
only at night before bed to help improve sleep but should include a warning not to operate a motor vehicle or
machinery if feeling sedated or directly after the dose.
Initiation of antidepressant agents are thought to cause early worsening of anxiety, agitation, and irritability,
particularly when used to treat anxiety. Sinclair et al use the term jitteriness/anxiety syndrome to describe
these effects and completed a systematic search of articles that describe these effects.[67]
No validated rating scales for jitteriness/anxiety syndrome were identified among 107 articles included in
the review. No evidence indicated a difference in incidence of jitteriness/anxiety syndrome between SSRIs
and TCAs, and a higher incidence was not observed in anxiety disorders. Incidence rates of
jitteriness/anxiety syndrome varied widely in the published literature (4-65%).
The authors concluded that jitteriness/anxiety syndrome is poorly characterized, but perception of this
syndrome influences clinician prescribing. They recommend more evaluation of adverse effects at early
points during antidepressant trials to more comprehensively describe this syndrome.
34
Intravenous or oral acute sedation with benzodiazepines may be used. Alprazolam (Xanax) has been widely
used for panic disorder, but it is currently discouraged because of its higher dependence potential;
alprazolam has a short half-life, which makes it particularly prone to rebound anxiety and psychological
dependence. Clonazepam (Klonopin) has become a favored replacement because it has a longer half-life and
empirically elicits fewer withdrawal reactions upon discontinuation.
Prompt use of benzodiazepines can ease the uncomfortable anxiety associated with the attack and can
provide the patient with definitive confidence that treatment can control the symptoms. This is particularly
helpful for preventing subsequent visits to emergency services while longer-term therapy is helping the
patient gain control.
Benzodiazepines act quickly but carry the liability of physiologic and psychologic dependence. They can be
reasonably used as an initial adjunct while SSRIs are titrated to an effective dose, and they can then be
tapered over 4-12 weeks while the SSRI is continued. This approach can improve short-term tolerability,
although it may increase the risk of sedation and requires warnings not to operate motor vehicles after taking
benzodiazepines or if feeling sedated.
If possible, avoid long-term benzodiazepines for chronic anxiety disorders. Benzodiazepines can achieve
long-term control but should be reserved for patients with refractory panic disorder and should generate a
psychiatric referral for pharmacologic management review and potentially a psychotherapist for any
additional nonpharmacologic treatment options.
Psychotherapy for Anxiety and Panic Disorders

Cognitive and behavioral psychotherapy can be used alone or in addition to pharmacotherapy. The
combination approach yields superior results for most patients compared to either single modality.
Cognitive therapy helps patients understand how automatic thoughts and false beliefs/distortions lead to
exaggerated emotional responses, such as anxiety, and can lead to secondary behavioral consequences.
Specific patterns of cognitive distortions (twisted thoughts) tend to respond best to specific techniques
described in cognitive behavior therapy books (eg, The Feeling Good Handbook by David Burns, MD).
While intended for use in conjunction with therapy, patients can purchase these books and complete the
course themselves.
Behavioral therapy involves sequentially greater exposure of the patient to anxiety-provoking stimuli; over
time, the patient becomes desensitized to the experience. Relaxation techniques also help control patients’
levels of anxiety. Respiratory training can help control hyperventilation during panic attacks and help
patients control anxiety with controlled breathing. Other forms of psychological treatment, including
psychodynamic psychotherapy for specific issues, are available but exceed the scope of this article.
Consultation with a psychiatrist is helpful to initiate longer-term therapy and to provide follow-up planning.
Longer-term therapy currently consists of SSRIs, often with additional psychotherapeutic techniques.
Posttraumatic Stress Disorder

35
One study found that nearly half (48%) of the patients in general medical practices with PTSD were
receiving no mental health treatment at the time of intake to the study. The most common reason patients
gave for not receiving medication was the failure of physicians to recommend such treatment.[68]
Many of the complications and disability associated with prolonged PTSD may be prevented by initiating
the assessment and treatment quickly after the traumatic event, well before a diagnosis of PTSD can be
made.
Treatment is often best accomplished with a combination of pharmacologic and nonpharmacologic
therapies. Medications may be required to control the physiologic symptoms, which can enable the patient to
tolerate and work through the highly emotional material in psychotherapy. For adolescents and children,
treatment is primarily psychotherapeutic in nature.
Treatment is often complicated by comorbid disorders. If present, alcohol or substance abuse problems
should be the initial focus of treatment. In the presence of coexisting depression, treatment should focus on
the PTSD because its course, biology, and treatment response are unlike those associated with major
depression.
Nonpharmacologic treatment consists of group therapy, individual and family therapy, CBT, play therapy,
art therapy, anxiety management, and relaxation techniques. Other specific techniques used to process
traumatic events include eye movement desensitization and reprocessing (EMDR) and hypnosis. EMDR has
been successful in helping the survivors of various traumas, such as domestic violence, sexual abuse, crime,
and combat. The method involves psychotherapy that combines various therapeutic approaches with eye
movements (or other types of rhythmic stimulation) to stimulate the brain’s information-processing
mechanisms. A recent meta-analysis of studies in adults with PTSD revealed trauma-focused CBT and
EMDR should be first-line nonpharmacologic therapies for PTSD.[69, 70]
Some patients may benefit from psychodynamic-oriented psychotherapy, especially if PTSD was caused by
early sexual or physical abuse. Flooding, a technique involving prolonged exposure to the adverse stimuli,
has been used with some success on veterans. In a recent study of service members with PTSD caused by
the traumatic events of September 11, 2001, or Operation Iraqi Freedom, self-managed, Internet-based CBT
led to a greater reduction in PTSD symptoms than Internet-based supportive counseling.[71]
Inpatient care is necessary only if the patient becomes suicidal or because of the presence of complicating
comorbid conditions that may require inpatient treatment (eg, depression, substance abuse). Hospitalization
is also indicated if the patient becomes homicidal.
Obsessive-Compulsive Disorder
The mainstays of treatment of OCD include pharmacotherapy, particular forms of behavior therapy
(exposure and response prevention and some forms of CBT), education and family interventions, and
neurosurgical treatment in extremely refractory cases. A practice guideline for the treatment of OCD has
recently been published by the American Psychiatric Association.[72]
36
Pharmacotherapy for OCD
First-line pharmacologic treatments for OCD are potent serotonin reuptake inhibitors, such as the SSRIs
(fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram) and clomipramine (Anafranil),
with possible alternatives including venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI). All
of these are commonly used to treat OCD, although not all have received a US Food and Drug
Administration (FDA) indication for this disorder. Unlike in the case of major depression, complete or near-
complete remission of OCD symptoms is rare with only serotonergic antidepressant treatment. More
typically, perhaps half of patients may experience symptom reductions of 30-50%, as measured by the Y-
BOCS, with many others failing to even achieve this degree of relief.
Several treatment studies suggest a possible role for norepinephrine in cases of OCD. A subset of patients
reportedly show greater clinical improvement with a combination of serotonin and norepinephrine reuptake
inhibition as compared to treatment with SSRIs alone. These have included patients treated with
clomipramine (a TCA that inhibits both serotonin and norepinephrine reuptake) and those whose SSRI
treatment was augmented with an agent such as desipramine (a TCA that inhibits norepinephrine reuptake to
a greater extent than serotonin reuptake).
Doses above those needed for treatment of depression may be more effective for some patients. A
therapeutic dose for 6-10 weeks may be required to observe a clinical response (see Medication). Response
tends to be slow and continue for at least 12 weeks (the common duration of OCD pharmacologic clinical
trials), unlike the use of these same antidepressants in the treatment of major depressive episodes, where
responses are more often seen somewhat earlier.
More recently, attention has focused on possible glutamatergic treatments for OCD.[11] Preclinical studies
and several case reports and small clinical trials have provided some preliminary support for the therapeutic
use of specific glutamatergic agents (eg, memantine, N-acetylcysteine, riluzole, topiramate, glycine).[73, 74]
However, these agents have varied glutamatergic and other pharmacologic effects, so if they are
demonstrated to be effective, clarifying any therapeutic mechanism of action will be important.
Other interventions that have not received an FDA indication for OCD include the addition of a
norepinephrine reuptake inhibitor (eg, desipramine) to an SSRI, or a trial of venlafaxine; addition of a
typical or atypical antipsychotic, especially in patients with a history of tics; augmentation with buspirone;
addition of inositol; and sole or augmented use of selected glutamatergic agents.[73, 74]
Psychotherapy for OCD
Behavioral therapy is a first-line treatment for OCD that should be undertaken with a psychotherapist who
has specific training and experience in such therapy (most commonly, behaviorally trained psychologists).
Some patients will not undertake behavioral therapy, with perhaps 25% rejecting it and 25% dropping out,
but it should definitely be encouraged if a competent behavioral therapist is available.
Exposure and response (or ritual) prevention (ERP) is the important and specific core element in behavior
therapy for OCD. The patient rank orders OCD situations he or she perceives as threatening, and then the
37
patient is systematically exposed to symptom triggers of gradually increasing intensity, while the patient is
to suppress his or her usual ritualized response. This is generally challenging and often quite distressing for
the patient, but when effectively done, it promotes unlearning of the strong link that has existed between
having an urge and giving into the urge. When a patient does not respond in the face of a potent trigger,
extinction of the response can take place. Significant others should be involved when possible, and they may
have to be willing to change their responses to the patient (eg, not provide requested reassurance to irrational
doubts).
ERP is now usually administered as part of a broader program of CBT, specifically designed for OCD.
Other elements of CBT that are used include identifying and challenging the cognitive distortions of OCD
symptoms (eg, intolerance of uncertainty, black and white thinking, focusing on unlikely extreme
possibilities instead of viewing the future in a balanced manner, ascribing overimportance to thoughts,
excessive concern about the importance of one’s thoughts, inflated sense of responsibility). After making the
patient aware of his or her irrational thoughts, the therapist works to have the patient counter them with
more rational thoughts and do cost/benefit analyses regarding performing his or her rituals.
Meditation and relaxation techniques may be useful, but not during active ERP, as the effectiveness of these
exercises requires that the patient experience a significant level of discomfort and then not respond with his
or her characteristic rituals. A patient may benefit from a self-help book in conducting ERP (eg, Foa and
Wilson, 2001[72] ), and workbooks are available for CBT as well. When recommending such a book, the
treating physician should be familiar with its content.
Another related approach described by Dr. Jonathan Grayson focuses on getting the patient to accept living
with uncertainty, as it relates to his or her obsessional ideas, and prepare an individualized script to reinforce
this attitude.[75]
Strategies for treatment resistance of OCD
Psychodynamic psychotherapy alone has generally not been found helpful in ameliorating OCD symptoms.
It may, however, be useful in working on a patient’s resistance to accepting recommended treatments, or in
appreciating the interpersonal effects that a patient’s OCD symptoms are having on others.[76]
Strategies for treatment resistance should always include an assessment of complicating diagnoses,
medication compliance, drug dose, and duration of therapy. The presence of a comorbid diagnosis that has
not been addressed, such as depression or panic disorder, can interfere with clinical recovery and
identification may guide the choice of interventions. Targeted interventions might include, for example,
lithium or antipsychotic augmentation or ECT for depression. Interventions for patients with treatment
resistance include a change or increase in medication (eg, increasing the dose or prescribing a different SSRI
or clomipramine) and more intensive CBT.
Some clinicians feel that individuals with comorbid Tourette disorder or with hoarding as their principal
OCD symptom may be more likely to be treatment resistant, although there is significant variation in
treatment response, regardless of the particular presenting symptomatology.
38
Surgical therapy for OCD
Neurosurgical treatment of OCD is performed at a limited number of centers and is reserved for patients
with severe and refractory symptoms. The most common small series use a specific small lesion (eg,
cingulotomy[77] ) or deep brain stimulation (DBS).[78, 79] Current clinical trials are also exploring the
application of transcranial magnetic stimulation (TMS) for OCD, a noninvasive treatment approach.
One cingulotomy technique involves the stereotactic placement of bilateral lesions in the anterior cingulate
cortex. A case series of 18 patients showed a 28% response rate, with an additional 17% showing a partial
response. No significant adverse neurologic or cognitive sequelae were noted.
A DBS technique consists of implanting a device to electrically stimulate the subthalamic nucleus. A
crossover study in 17 patients with severe, refractory OCD in which patients received 3 months of active
stimulation and 3 months of sham stimulation in randomized order found that there was significantly more
improvement during the active stimulation periods. However, serious adverse events were substantial and
included intracerebral hemorrhage and infection.[79]
In February 2009, the FDA approved the use of Reclaim Deep Brain Stimulation Therapy for individuals
with chronic, severe OCD. This device is an implanted medical device that is designed to target a region
called the ventral capsule/ventral striatum, which is in the anterior limb of the internal capsule of the brain.
Phobic Disorders
Both psychotherapy and pharmacotherapy are useful in treating social phobia. Self-exposure monotherapy is
recommended for this phobia, as it has been shown to work as well as computerized-based exposure
training, clinician-led exposure, or combinations therapies of self-exposure and CBT/self-help manual.[80]
Social phobia typically responds to either an SSRI or a monoamine oxidase inhibitor (MAOI).[81, 82, 83]
Initiate treatment with an SSRI and titrate to the minimum effective dose. SSRIs approved for social phobia
include paroxetine[84] (including SR form) and sertraline, but other SSRIs have also been shown to be
effective (eg, fluvoxamine[85] ). The SSRI dose can be increased if response is partial or nonexistent at 6
weeks—doses can be increased every 2 weeks until maximum dose is reached.
Failing this, patients sometimes respond to high-potency benzodiazepines. Long-term treatment data from
clinical studies of clonazepam are limited but support the drug’s efficacy.[86] Beta-blockers, clonidine, and
buspirone are usually not helpful for long-term treatment, although a beta-blocker such as atenolol, nadolol,
or propranolol may be useful for the circumscribed treatment of situational/performance anxiety on an as-
needed basis.
Consider tapering medications slowly after 6-12 months of full response. If symptoms reoccur following
taper, restart therapy and continue indefinitely.[86]
39
Specific phobias respond well to CBT. Gradual desensitization is the most commonly used treatment.
Randomized, controlled clinical trials indicate that specific (simple) phobias also respond to exposure
therapy.[87] A small, randomized, controlled clinical trial showed that virtual reality exposure (VRE) therapy
is as effective as standard exposure (SE) therapy for fear of flying, with gains maintained up to 1 year
following the treatment.[88]
Other treatments include cognitive approaches, relaxation, and breathing control techniques. To date, no
controlled studies demonstrate the efficacy of psychopharmacologic intervention for specific phobias.
Agoraphobia
Agoraphobia (specifically, the panic symptoms) most often responds to treatment with an SSRI.[89, 90, 91]
Treatment should be started at a low dose then titrated to the minimum effective dose for controlling the
patient’s panic. Benzodiazepines can be used either as an adjunct or as primary treatment; however,
benzodiazepines are usually not chosen as a first-line treatment because of the potential for abuse.[92] If the
patient has frequent panic attacks and no history of substance abuse, a benzodiazepine can be considered
until the SSRI takes effect. Long-acting benzodiazepines (eg, diazepam, clonazepam) prescribed on a
standing rather than on an as-needed basis are preferred due to a lower addictive potential; dose can be
increased every 2-3 days until panic symptoms are controlled or the maximum dose is reached.
Consider using the short-acting alprazolam for short-term use to control acute symptoms of panic. If
response is minimal or nonexistent after 6 weeks, the SSRI dose can be further increased every 2 weeks until
response or maximal dose is reached. Partial or no response at the highest SSRI dose warrants consideration
of the following alternatives: change to a different SSRI; change to a different class (venlafaxine,
duloxetine); change to TCAs/TeCAs or MAOIs (both TCAs/TeCAs and MAOIs have demonstrated efficacy
in controlled trials for agoraphobia).
For a patient with good response, treatment should be continued for 9-12 months before considering slowly
tapering the medications. With symptom recurrence following taper, treatment should be resumed and
continued indefinitely.
Diet
Caffeine-containing products such as coffee, tea, colas, and Mountain Dew should be discontinued (or
decreased to a low reasonable level). Over-the-counter preparations and herbal remedies should be reviewed
with special caution because ephedrine and other herbal compounds may precipitate or exacerbate anxiety
symptoms. The use of some gentle herbal preparations may be considered in persons who do not have
allergies or sensitivities to those agents.[93]
Consultations
40
Most often, psychiatrists are consulted. Psychology consultation and testing is indicated if cognitive
impairment is of concern or if the patient may be a candidate for CBT. Social work consultation may be
helpful if coping skills are markedly impaired.
In anxiety disorders secondary to a general medical condition, specialty consultation may be indicated.
Cardiology consultation is indicated when symptoms include heart rate irregularity or abnormal blood
pressure. Neurology consultation is indicated when symptoms include headaches or visual field
abnormalities, balance abnormalities, or mental status changes. Endocrinology consultation is indicated
when symptoms include heat or cold intolerance, problems with fluid balance, or mood swings due to
cortisol abnormalities.
To reduce muscle tension, manual manipulation or massage therapy can be helpful in nonpharmacologic
approaches. Treatment with a licensed practitioner is important, as there have been cases of sexual abuse or
battery with nonlicensed nonprofessionals.
Medication Summary
Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer
agents that have a safer adverse effect profile and higher ease of use than the older tricyclic antidepressants
(TCAs), such as selective serotonin reuptake inhibitors (SSRIs). Antidepressants that are not FDA-approved
for the treatment of a given anxiety disorder, such as nefazodone and mirtazapine still may be beneficial.
Older antidepressants, such as TCAs and monoamine oxidase inhibitors (MAOIs), also are effective in the
treatment of some anxiety disorders.
A Cochrane review of second-generation antipsychotic drugs found that quetiapine and risperidone were
effective when combined with antidepressants; however, adverse side effects were also reported.[94]
Benzodiazepines
Class Summary
Benzodiazepines often are used with antidepressants as adjunct treatment. They are especially useful in the
management of acute situational anxiety disorder and adjustment disorder where the duration of
pharmacotherapy is anticipated to be 6 weeks or less and for the rapid control of panic attacks. They include
lorazepam (Ativan) and clonazepam (Klonopin).
If long-term use of benzodiazepines seems necessary, obtaining a confirmatory opinion from a second
clinician may be helpful because chronic benzodiazepine use may be associated with tolerance, withdrawal,
41
and treatment-emergent anxiety. The risk of addiction with benzodiazepines should be carefully considered
before use in the anxiety disorders. Avoid use in patients with a prior history of alcohol or other drug abuse.
Closely monitor for evidence of unauthorized dose escalation or obtaining benzodiazepine prescriptions
from multiple sources.
View full drug information
Alprazolam (Xanax)
For management of anxiety attacks. Binds receptors at several sites within the central nervous system,
including the limbic system and reticular formation. Effects may be mediated through GABA receptor
system.
Lorazepam (Ativan)
Sedative hypnotic in the benzodiazepine class that has a short onset of effect and a relatively long half-life.
By increasing action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in
the brain, may depress all levels of the CNS, including limbic and reticular formation. Available for PO, IV,
or IM use.
Clonazepam (Klonopin)
Long-acting benzodiazepine that increases the presynaptic GABA inhibition and reduces the monosynaptic
and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA
neurotransmission and other inhibitory transmitters. Has multiple indications, including suppression of
myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia).
Reaches peak plasma concentration at 2-4 h after oral or rectal administration.
Diazepam (Valium)
Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition.

Appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect.
Also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor
neuron disorders.
Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration
drops to 20% of Cmax.
Individualize dosage and increase cautiously to avoid adverse effects.
42
Chlordiazepoxide (Librium)
Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing gamma-
aminobutyric acid (GABA) activity, a major inhibitory neurotransmitter. Provides rapid onset and efficacy
in sedating aggressive patients.
Oxazepam (Serax)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Serotonin And Norepinephrine Reuptake Inhibitors

Class Summary
Pharmacologic agents with reuptake inhibition of serotonin and norepinephrine such as venlafaxine (Effexor
and Effexor XR) and duloxetine (Cymbalta) may be helpful in a variety of mood and anxiety disorders.
Venlafaxine (Effexor XR)
FDA-approved for generalized anxiety disorder, panic disorder and social anxiety disorder in adults. May be
helpful for other anxiety disorders.
Duloxetine (Cymbalta)
Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Indicated for generalized anxiety
disorder.
Tricyclic Antidepressants
Class Summary
The tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic
effects, as well as sedative effects. They include imipramine (Tofranil) and clomipramine (Anafranil).
Caution is warranted in the use of TCAs because of their higher toxicity and potential lethality in overdose.
Their use should be limited to cases in which SSRIs are ineffective or cannot be afforded. Clomipramine has
an FDA indication in the treatment of OCD and is the only TCA effective in the treatment of this condition.
Indeed, it can be effective in cases refractory to treatment with SSRI agents.
Imipramine (Tofranil)
43
Tricyclic antidepressant that has norepinephrine and serotonin reuptake-inhibition properties. One of the
oldest agents available for the treatment of depression and has established efficacy in the treatment of panic
disorder. Elderly and adolescent patients may need lower dosing or slower titration.
Amitriptyline (Elavil)

Desipramine (Norpramin)
Tricyclic antidepressant that has norepinephrine and serotonin reuptake-inhibition properties. One of the
oldest agents available for the treatment of depression and has established efficacy in the treatment of panic
disorder. Elderly and adolescent patients may need lower dosing or slower titration.
Clomipramine (Anafranil)
Dibenzazepine compound belonging to family of tricyclic antidepressants. Inhibits membrane pump

mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.
Clomipramine affects serotonin uptake while it affects norepinephrine uptake when converted into its
metabolite desmethylclomipramine. Believed that these actions are responsible for its antidepressant
activity.
Nortriptyline (Pamelor)
Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin
and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration
of these neurotransmitters in the central nervous system. Pharmacodynamic effects such as the
desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors
also appear to play a role in its mechanisms of action.
Protriptyline (Vivactil)
Increases synaptic concentration of serotonin and/or norepinephrine in CNS by inhibiting their reuptake by
the presynaptic neuronal membrane.
Doxepin (Sinequan)
44
Increases concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by
presynaptic neuronal membrane. These effects are associated with a decrease in symptoms of depression.
Amoxapine
Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron.

Metabolite (7-hydroxyamoxapine) has significant dopamine receptor blocking activity similar to
haloperidol. Elicits strong anticholinergic effects.
Trimipramine (Surmontil)
Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. Elicits

strong anticholinergic effects.
Selective Serotonin Reuptake Inhibitors

Class Summary
The SSRIs include paroxetine (Paxil), escitalopram (Lexapro), sertraline (Zoloft), fluoxetine (Prozac),
fluvoxamine (Luvox), and citalopram (Celexa). SSRIs are first-line agents for long-term management of
anxiety disorders, with control gradually achieved over a 2- to 4-wk course, depending on required dosage
increases.
SSRIs are helpful for generalized anxiety disorder, panic disorder, obsessive-compulsive disorder (OCD),
and social phobia. All SSRIs may be equal in the treatment of anxiety disorders; however, higher doses may
be necessary in the treatment of OCD.
All commonly used SSRIs appear to have a role in the treatment of panic disorder. However, patients with
panic disorder may be more sensitive to treatment with antidepressants and frequently need lower initial
doses and slower titration to accomplish successful therapy.
Fluoxetine has a very long half-life, making it well suited for patients who have difficulty remembering to
take all of their medications each day. The longer half-life also minimizes the risk and severity of SSRI
withdrawal that can occur when patients exhaust or abruptly discontinue their SSRI.
Paroxetine (Paxil)
Alternative sedating SSRI. Potent selective inhibitor of neuronal serotonin reuptake. Also has weak effect on
norepinephrine and dopamine neuronal reuptake. For maintenance dosing, make dosage adjustments to
maintain patient on lowest effective dosage, and periodically reassess patient to determine need for
continued treatment.
45
Escitalopram (Lexapro)
FDA approved for generalized anxiety disorder. SSRI and S-enantiomer of citalopram. Used for the
treatment of depression. Mechanism of action is thought to be potentiation of serotonergic activity in central
nervous system resulting from inhibition of CNS neuronal reuptake of serotonin. Onset of depression relief
may be obtained after 1-2 wk, which is sooner than other antidepressants.
Sertraline (Zoloft)
FDA-approved for panic disorder, PTSD, social phobia, and OCD. May be helpful for other anxiety
disorders.
Fluoxetine (Prozac)
FDA-approved for OCD and panic disorder. May be helpful for other anxiety disorders.
Fluvoxamine (Luvox)
FDA approved for OCD in children (8-17 y) and adults. May be helpful for other anxiety disorders.
Citalopram (Celexa)
Enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. Also has the
advantage of fewer potential drug interactions. Citalopram is a 50:50 racemate of r- and s-citalopram.
Anticonvulsant
Class Summary
The drug of choice in this category is the gamma-aminobutyric acid derivative pregabalin (Lyrica).However,
caution is necessary when prescribing (prescribe the smallest amount with fewest refills), as it is a Schedule
V medication due to the possibility of drug diversion and drug dependance and has a “street value” to drug
addicts. Some anticonvulsant medications, such as divalproex (Depakote) and gabapentin (Neurontin), may
have a role in the treatment of anxiety disorders, especially in patients with high potential for abusing
benzodiazepines.
Pregabalin (Lyrica)
46
Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha2-delta site
(a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters,
possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with
diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Gabapentin (Neurontin)
Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-amino butyric acid

(GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via
the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels
Has apparent anxiolytic properties.
Divalproex (Depakote, Depakote ER)
Has proven effectiveness in treating and preventing mania. Classified as a mood stabilizer and can be used
alone or in combination with lithium. Useful in treating patients with rapid-cycling bipolar disorders and has
been used to treat aggressive or behavioral disorders. A combination of valproic acid and valproate has been
effective in treating persons in manic phase, with a success rate of 49%.
Antipsychotic Agent
Class Summary
Atypical and typical antipsychotic medications are generally used more as augmentation strategies and are
second-line treatment options in generalized anxiety disorder.[95] Mechanisms of action generally include a
combination of neuroreceptor blockade (generally dopaminergic blockade) as well as up- and
downregulation of receptor sensitivity.
All drugs in this class may increase risk of life-threatening neuroleptic malignant syndrome, acute dystonias,
tardive dyskinesia, weight gain, metabolic syndrome, and potential to cause diabetic ketoacidosis as well as
stroke, hypertension, hypotension, or sudden death from cardiac conduction or cardiac electrophysiological
abnormalities. Quetiapine has a pending application for approval by the FDA for use in generalized anxiety
disorder as well as in major depressive disorder for patients whose symptoms do not remit with other
treatments as it seems that low doses (50-300 mg range) of quetiapine may not be associated with the risk of
hyperglycemia and metabolic syndrome that potentially can occur in higher dosage ranges or with other
antipsychotic medications.
Risperidone (Risperdal)
47
Binds to dopamine D2 receptor with a 20-times lower affinity than for the 5-HT2 receptor. Improves
negative symptoms of psychoses and reduces incidence of extrapyramidal adverse effects.
Response to antipsychotics is less dramatic than in true psychotic Axis I disorders, but symptoms such as
anxiety, hostility, and sensitivity to rejection may be reduced. Antipsychotics are typically used for a short
time while the symptoms are active.
Aripiprazole (Abilify)
Improves positive and negative schizophrenic symptoms. The mechanism of action is unknown but is
hypothesized to work differently than other antipsychotics. Aripiprazole is thought to be a partial dopamine
(D2) and serotonin (5HT1A) agonist and antagonize serotonin (5HT2A). Additionally, no QTc interval
prolongation was noted in clinical trials. Available as tab, orally disintegrating tab, or oral solution.
Quetiapine (Seroquel)
May act by antagonizing dopamine and serotonin effects.

Newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include
fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia. Immediate- and
extended-release formulations available.
Haloperidol (Haldol)
DOC for patients with acute psychosis when no contraindications exist. Haloperidol and droperidol (below)
are of butyrophenone class, and are noted for high potency and low potential for causing orthostasis.
However, the potential for EPS/dystonia is high.
Parenteral dosage form may be admixed in same syringe with 2-mg lorazepam for better anxiolytic effects.
Molindone (Moban)
Dihydroindolone antipsychotic with pharmacologic profile in laboratory animals that predominantly

resembles that of major tranquilizers causing reduction of spontaneous locomotion and aggressiveness,
suppression of a conditioned response and antagonism of the bizarre stereotyped behavior and hyperactivity
induced by amphetamines.
Clozapine (Clozaril)
48
Demonstrates weak D2-receptor and D1-receptor blocking activity, but noradrenolytic, anticholinergic,
antihistaminic, and arousal reaction inhibiting effects are significant. Also possesses antiserotonergic (5-
HT1c, 5-HT2, 5-HT3) properties. Affinity for mesolimbic D4 dopamine receptor accounts for striking
effects in control of behavioral and psychiatric symptoms with low incidence of extrapyramidal symptoms.
Histamine receptor blockade accounts for increased incidence of sleep disturbances. Associated with a risk
of agranulocytosis when used at doses required for treatment of patients with schizophrenia whose
symptoms are refractory to standard neuroleptics. In US, weekly dosing and weekly CBCs are required for
clozapine to be dispensed; discontinuing therapy at first sign of leukopenia decreases but does not eliminate
risk of agranulocytosis; whether agranulocytosis is associated with low doses in treating elderly patients and
those with dementia is not clear.
Olanzapine (Zyprexa)
May inhibit serotonin, muscarinic, and dopamine effects. Response to antipsychotics is less dramatic than in
true psychotic Axis I disorders, but symptoms such as anxiety, hostility, and sensitivity to rejection may be
reduced. Antipsychotics are typically used for a short time while the symptoms are active.
Antihypertensive Agent
Class Summary
Agents in this class may have a positive effect on the physiological symptoms of anxiety. Beta-blockers
such as atenolol, nadolol, or propranolol may be useful for the circumscribed treatment of
situational/performance anxiety on an as-needed basis. A pilot study revealed propranolol is effective in
decreasing physiological signs of hyperarousal for up to 1 week when used shortly after patients with PTSD
re-experience their traumatic event.[19]
Clonidine (Catapres)
Investigational agent. Central alpha-adrenergic agonist that stimulates alpha2-adrenoreceptors in brain stem
and activates an inhibitory neuron, resulting in a decrease in vasomotor tone and heart rate. Available in tab
or transdermal skin patches. Frequently given to children. Affects alpha1-, alpha2-, and alpha3-adrenergic
receptors.
Propranolol (Inderal, Betachron E-R, InnoPran XL)
Investigational agent. Blocks the physiological symptoms of anxiety and may be helpful for decreasing the
severity of the somatic symptoms of anxiety. May cause unpleasant cardiovascular and GI adverse effects
and is not the DOC especially as hypotension and/or cardiac block can occur. Initiation of therapy should be
49
performed with close monitoring of blood pressure to prevent hypotensive crisis. Do not discontinue
abruptly as this may precipitate hypertensive crisis. Available as tablets, sustained release, and liquid
preparations.
Nadolol (Corgard)
Competitively blocks beta1 and beta2-receptors. Does not exhibit membrane stabilizing activity or intrinsic
sympathomimetic activity.
Atenolol (Tenormin)
Used to treat hypertension. Selectively blocks beta1-receptors with little or no affect on beta2 types. Beta-
adrenergic blocking agents affect blood pressure via multiple mechanisms. Actions include negative
chronotropic effect that decreases heart rate at rest and after exercise, negative inotropic effect that decreases
cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the
kidneys. Used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing
congestion, and decreasing myocardial energy expenditure.
Beta-adrenergic blockers reduce inotropic state of left ventricle, decrease diastolic dysfunction, and increase
LV compliance, thereby reducing pressure gradient across LV outflow tract. Decreases myocardial oxygen
consumption, thereby reducing myocardial ischemia potential. Decreases heart rate, thus reducing
myocardial oxygen consumption and reducing myocardial ischemia potential. During IV administration,
carefully monitor blood pressure, heart rate, and ECG
Antianxiety Agents
Class Summary
Buspirone is a nonsedating antipsychotic drug unrelated to benzodiazepines, barbiturates, and other
sedative-hypnotics. It has been found to be comparable with benzodiazepines in reducing symptoms of
anxiety in double-blind placebo-controlled clinical trials and has fewer sedative or withdrawal adverse
effects than benzodiazepines. Buspirone also has fewer cognitive and psychomotor adverse effects, which
makes its use preferable in elderly patients. Major limitations include lack of antipanic activity and reduced
anxiolytic effects in patients recently withdrawn from benzodiazepines. Also has a longer onset of action
and, thus, is of fairly limited use as a sole agent in the treatment of acute anxiety in the ED.
Buspirone is a novel antianxiety agent with no other members in its class.
Buspirone (BuSpar)
50
5-HT1A agonist affecting serotonergic neurotransmission in CNS. Has some dopaminergic activity as well.
In addition, has demonstrated anxiolytic effect but can take up to 2-3 wk for full efficacy. Also has a low
abuse potential and does not mitigate panic attacks. Not useful in benzodiazepine withdrawal but has a low
adverse-effect profile.
Atypical Antidepressants
Class Summary
Antidepressants that are not FDA-approved for the treatment of a given anxiety disorder, such as nefazodone
and mirtazapine still may be beneficial for the treatment of anxiety disorders. Mirtazapine has a much more
sedating effect, generally reducing its potential to aggravate initial anxiety. Mirtazapine acts distinctly as an
alpha-2 antagonist, consequently increasing synaptic norepinephrine and serotonin, while also blocking
some postsynaptic serotonergic receptors that conceptually mediate excessive anxiety when stimulated with
serotonin.
Nefazodone (Serzone)
Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Also has negligible affinity for
cholinergic and histaminergic receptors. Withdrawn from the US due to liver impairment.
Trazodone (Desyrel)
Useful in the treatment of panic disorders. Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-
HT. Also has negligible affinity for cholinergic and histaminergic receptors.
In animals, selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral
changes induced by the serotonin precursor 5-HTP.
Mirtazapine (Remeron)
Increases availability of serotonin and norepinephrine.

Nefazodone (Serzone)
Antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. Also has negligible affinity for
cholinergic and histaminergic receptors. Withdrawn from the US due to liver impairment.
Monoamine Oxidase Inhibitor (MAOI)
51
Class Summary
MAOIs are most commonly prescribed for patients with social phobia. They include the agents phenelzine
(Nardil), selegiline (Emsam), tranylcypromine (Parnate), and isocarboxazid (Marplan).
Advantages of MAOIs are low risk of dependence and less anticholinergic effect than TCAs. Disadvantages
are the higher number of adverse effects, including sexual difficulty, hypotension, and weight gain, and
potential lethality in overdose. A diet low in tyramine must be followed to avoid a hypertensive crisis. Over-
the-counter medications should be used with great caution.
The use of MAOIs should be limited to cases in which SSRIs are ineffective or cannot be afforded. MAOIs
may be especially indicated in treatment-refractory panic disorder and social anxiety disorder. MAOIs also
may have a role in the treatment of certain subtypes of OCD refractory to conventional treatment, such as
patients with symmetry obsessions or associated panic attacks.
Phenelzine (Nardil)
In one double-blind placebo-controlled trial, was more efficient in reducing intrusion symptoms. Has
demonstrated clear superiority over placebo in double-blind trials for treating specific symptoms of panic
disorders. Usually reserved for patients who do not tolerate or respond to traditional cyclic or second-
generation antidepressants.
Selegiline (Emsam)
Irreversible MAOI. Has greater affinity for MAO-B compared with MAO-A; however, at antidepressant
doses, inhibits both isoenzymes. MAO-A and MAO-B catabolize neurotransmitter amines in CNS (eg,
norepinephrine, dopamine, serotonin). Indicated for treating major depressive disorder. At lowest strength
(ie, 6 mg delivered over 24 h), may be used without the dietary restrictions required for oral MAOIs used to
treat depression.
Tranylcypromine (Parnate)
Treats major depression. Binds irreversibly to MAO, thereby reducing monoamine breakdown and
enhancing synaptic availability.
Isocarboxazid (Marplan)
Nonselective hydrazine MAOI demonstrated to inhibit MAO in the brain, heart, and liver. Mechanism by
which MAOIs act as antidepressants is not fully understood but is thought to involve elevation of brain
52
levels of biogenic amines. However, MAO is a complex enzyme system widely distributed throughout body,
and drugs that inhibit MAO cause a number of clinical effects. Thus, it is unknown whether MAO
inhibition, other pharmacologic actions, or interaction of both is responsible for the antidepressant effects
observed.
53

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Anxiety Disorders

Prevalensi gangguan kecemasan oleh ras

Sex rasio untuk gangguan kecemasan

Kecemasan. Bagan yang menunjukkan ke-laki-laki sex ratio-perempuan

Umur distribusi untuk gangguan kecemasan

Kecemasan. Age of onset untuk gangguan kecemasan berdasarkan jenis

Prevalence of anxiety disorders by race

Sex ratio for anxiety disorders

Age distribution for anxiety disorders

Anxiety Disorders Clinical Presentation

Mental Status Examination

Anxiety Disorders Differential Diagnoses

Anxiety Disorders Workup

Studies to Exclude Medical Disorders

Generalized Anxiety Disorder

Pharmacotherapy for Anxiety and Panic Disorders

Psychotherapy for Anxiety and Panic Disorders

Posttraumatic Stress Disorder

Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition.

Serotonin And Norepinephrine Reuptake Inhibitors

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Dibenzazepine compound belonging to family of tricyclic antidepressants. Inhibits membrane pump

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron.

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. Elicits

Selective Serotonin Reuptake Inhibitors

Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-amino butyric acid

May act by antagonizing dopamine and serotonin effects.

Dihydroindolone antipsychotic with pharmacologic profile in laboratory animals that predominantly

Increases availability of serotonin and norepinephrine.

Monoamine Oxidase Inhibitor (MAOI)

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