anxiety X & W - お勉強のお部屋

1. 発作が見られるようになったのはいつからか.発作の時間帯は. 発作時に痛みを伴うか. 痛みがあるならその性状と部位は. 食事, サプリメント, 薬などが関係していないか. 誘引となりうる物質やイベントはないか.

2. 心疾患, 呼吸器, 内分泌, 薬剤, 代謝, 神経, 精神.

FacultyComments

The differential diagnosis list foranxiety should include the following broad categories:

• medicalillness
  
• medication use(including prescription, over-the-counter and herbalsupplements)
  
• medicationabuse
  
• substance use(including alcohol, nicotine, caffeine and illegalsubstances)
  
• substanceabuse
  
• primarypsychiatric
  

3. FacultyComments

1.　　　　review thepatients problem list could any of the patients medical diagnoses eitherprecipitate or exaggerate symptoms of anxiety?

2.　　　　review thepatients family history are there any patterns of medical conditionsthat could induce anxious feelings?

3.　　　　review thepatients list of medications including prescription, over-the-counterand herbal supplements - could any of these drugs either precipitate or worsensymptoms of anxiety?

4.　　　　assess the useand/or abuse of substances

5.　　　　determine if thepatient meets the criteria for one of the primary psychiatric anxietydisorders - is there a family history of psychiatricdiagnoses?

4. 甲状腺ホルモンとb刺激薬

FacultyComments

Included in the differential for Dr.Johnson are:

�　 unnecessarily high dose ofSynthroid causing an iatrogenic hyperthyroidism

�　 onset of asthma attack withassociated apprehension

�　 overuse of albuterolinducing restless, nervousness or anxiety

�　 onset of menopause withassociated fluctuations in body temperature and mood

5.

A)　　　上記の診察で見つからない器質性疾患 (可能性は低いが, 異型狭心症や喘息など) が実在し不安の原因となる.

B)　　　パニック障害.

FacultyComments

Endocrine

• thyroiddysfunction (note that 2/3 of patients with Graves Disease meet the criteriafor Generalized Anxiety Disorder)
  
• adrenaldysfunction such as Cushings disease
  
• pituitarydysfunction
  
• parathyroiddysfunction
  
• pheochromocytoma
  
• menopause
  
• acuteintermittent porphyria
  

Cardiovascular

• angina/myocardial infarction
  
• cardiacarrhythmias
  
• mitral valveprolapse
  
• cardiomyopathy(increased noradrenergic tone may be the precipitatingfactor)
  
• anemia
  

Respiratory

• hypoxia
  
• asthma
  
• COPD
  
• pneumothorax
  
• pulmonaryembolism
  

Immunologic

• lupuserythematosus
  
• rheumatoidarthritis
  

Metabolic

• hypoglycemia
  

Neurologic

• epilepsy
  
• migraine
  
• CVA
  

InfectiousDisease

• HIV
  
• cerebralsyphilis
  

Dietary

• vitamin B12deficiency
  
• monosodiumglutamate excess
  
• pellagra
  

6. FacultyComments

The following medications include anxietyas a side effect:

• anticholinergics
  
• chemotherapyagents
  
• decongestants
  
• dietpills
  
• digitalis
  
• neurolepticsproducing the extrapyramidal side effect of akathesia, or motorrestless
  
• SSRIs
  
• steroids
  
• sympathomimetics
  
• theophylline
  
• thyroidsupplements, such as thyroxine
  

7. Intoxication with the followingsubstances and illicit drugs often produces feelings ofanxiousness:

• caffeine
  
• cocaine
  
• hallucinogens
  
• tobacco
  

8. Withdrawal of alcohol, narcotics andsedative-hypnotics such as benzodiazepines and barbituates often inducesanxiety in a patient.

9.

神経症性障害 --- パニック障害など

気分障害 --- うつ病

FacultyComments

The primary psychiatric anxiety disordersinclude:

�　 PanicDisorder characterized byrecurrent panic attacks

�　 Phobiasan intense fear of specific objectsor situations

�　 Generalized AnxietyDisorder (GAD) a six-month(or longer) history of anxious symptoms without panicattacks

�　 Posttraumatic StressDisorder (PTSD) follows atraumatic, often life-threatening event

�　 Obsessive CompulsiveDisorder (OCD) recurrentintrusive unwanted thoughts and compulsive behaviors

�　 Adjustment Disorder withAnxious Mood pooradaptation to a new situation manifested as anxiety

10. FacultyComments

Anxiety is manifested in a number ofareas. Patients experience physical symptoms of autonomic arousal,including anorexia, chest tightness, diaphoresis, diarrhea, dizziness, drymouth, dyspnea, headache, muscle tension, nausea, palpitations, paresthesia,shortness of breath, and tremulousness. Patients also experience a change inaffect, ranging from edginess to panic. Anxiety also manifestscognitively as worry and apprehension and behaviorally asavoidance of the perceived stressor.

11. FacultyComments

The following neurotransmitters areassociated with anxiety:

-norepinephrine cell bodies of thenoradrenergic system are located in the locus ceruleus of the rostral pons andaxons project to cerebral cortex, limbic system, brain stem and spinalcord

-serotonin- cell bodies arelocated in the raphe nuclei of the rostral brainstem and project to thecerebral cortex, limbic system and hypothalamus

-G-aminobutyric acid (GABA) therole of GABA is supported by the beneficial effect seen with benzodiazepineuse, which enhances the avtivity of GABA

12. FacultyComments

�　 These brain structures areinvolved in the production of anxiety:

�　　　　the locusceruleus in the rostral pons, the primary source of the brainsnorepinephrine (NE):

�　　　　when stimulatedin monkeys, an acute fear response is produced

�　　　　when destroyedin monkeys, abnormal complacency in the face of danger isexhibited

�　 the limbic system,which receives noradrenergic and serotonergic innervation and contains a highconcentration of GABA receptors: the limbic system monitors the environment forlife-threatening cues

13. FacultyComments

One in four people have met the criteriafor an anxiety disorder. Lifetime prevalence for an anxiety disorder in womenis about 30% and lifetime prevalence for an anxiety disorder in men isapproximately 20%.

14. FacultyComments

An estimated 60% of psychiatricconditions are treated by primary care physicians. In fact, studies haveimplicated anxiety as the fifth most common diagnosis overall among primarycare physicians. This is not surprising as anxiety is the chief complaint ofover 10% of patients presenting in primary care settings.

Specialist practices also see a highpercentage of patients with anxiety disorders. Up to 15% of patients incardiology practices suffer from Panic Disorder, compared to 1% of the generalpopulation.

15.

DSM-IV-TR 300.02全般性不安障害

A: (仕事や学業など) 多数の出来事または活動についての過剰な不安と心配(予期配慮) が, 少なくとも6ヶ月間, 起こる日の方が起こらない日よりも多い.
B: その人は, その心配を制御することが難しいと感じている.
C: 不安と心配は, 以下の６つの症状のうち3つ(またはそれ以上) を伴っている (過去6ヶ月間, 少なくとも数個の症状が, ある日の方が無い日より多い)

注: 子供の場合は1項目だけが必要.
(1) 落ち着きのなさ, または緊張感, または過敏.
(2) 疲労しやすいこと.
(3) 集中困難, または心が空白になること.
(4) 刺激に敏感.
(5) 筋肉の緊張.
(6) 睡眠障害 (入眠または睡眠を続けることが困難, 又は落ち着かず熟睡感のない睡眠).

D: 不安と心配の対象が, 他の障害の特徴に限られていない. 例えば, 不安または心配が, (パニック障害のように) パニック発作が起こること (社会恐怖のように) 人前で恥ずかしくなること, (強迫性障害のように) 汚染されること, (分離不安障害のように) 家庭または身近な家族から離れること, (神経性無食欲症のように) 重大な疾患があること, によるものではない. また, その不安と心配は外傷後ストレス障害の期間中にのみ起こるものでもない.
E: 不安, 心配, または身体症状が臨床的に明らかな苦痛, または社会的職業的な重要な領域における機能の障害を引き起こしている.
F: 不安障害が, 物質 (例: 乱用薬物・投薬) または一般的な身体疾患の直接的な生理学的作用によるものではなく, 気分障害, 精神病性障害, 広汎性発達障害の期間中にのみ起こるものではない.

ICD-10 F41.1全般性不安障害Generalizedanxiety disorder

本質的な病像は全般的かつ持続的であるが,きわめて優勢であっても, いかなる特殊な周囲の状況にも限定されない (すなわち「自由に浮動する」) 不安である. 他の不安障害と同様に, 主要症状はきわめてさまざまであるが, たえずいらいらしている, 振戦, 筋緊張, 発汗, 頭のふらつき, 動悸, めまいと心窩部の不快などの訴えがよく認められる. 患者か身内がすぐにでも病気になるのではないか, あるいは事故にあうのではないかという恐怖がさまざまな他の心配事や不吉な予感とともに, しばしば口にされる. この障害は女性により一般的で, しばしば慢性の環境的ストレスと関連している. その経過はさまざまであるが, 動揺し, 慢性化する傾向を示す.

診断ガイドライン

患者は, 少なくとも数週, 通常は数カ月, 連続してほとんど毎日, 不安の一次症状を示さなければならない. それらの症状は通常, 以下の要素を含んでいなければならない.

(a) 心配 (将来の不幸に関する気がかり,「いらいら感」, 集中困難など).

(b) 運動性緊張 (そわそわした落着きのなさ, 筋緊張性頭痛, 振戦, 身震い, くつろげないこと).

(c) 自律神経性過活動 (頭のふらつき, 発汗, 頻脈あるいは呼吸促迫, 心窩部不快, めまい, 口渇など).

小児では頻回に安心させる必要があったり,繰り返し身体的訴えをすることがあったりするかもしれない. 他の症状, とりわけ抑うつが一過性に (一度につき2, 3日間) 出現しても, 主診断として全般性不安障害を除外することにはならないが, 患者はうつ病エピソード(F32.-), 恐怖症性障害 (F40.-), パニック障害 (F41.0), あるいは強迫性障害 (F42.-) の診断基準を完全に満たしてはならない.

9含: 不安神経症, 不安反応, 不安状態

9除: 神経衰弱 (F48.0)

16. FacultyComments

GAD has a lifetime prevalence of 5%. TheFemale to Male ratio is 2:1. The age of onset is usually in the 20s, with thegradual appearance of symptoms. One third of patients with GAD seek psychiatrichelp - most patients see their primary care physician, cardiologists orpulmonologists, gastroenterologists with somaticcomplaints.

17. 孤立状態にある. 一人にされるのではないかという恐れが強く,世話好きであることが多い. 怒ると人を遠ざけてしまうのでめったに怒らない. 不正や不公平には敏感.

絶えず緊張し, 表情は不安そうで, 手指の震えや精神的発汗あり, 心悸亢進, 不眠に悩まされる. 浮動性不安. 浮動性の身体症状. 経過とともに慢性化する傾向にあり, パーソナリティ化することもある.

Faculty Comments

Most patients with GAD report feelinganxious and nervous most of their lives. Many patients present by their earlytwenties, but patient may present at any age. The course is chronic, withsymptoms waxing and waning. Stressful life situations naturally worsen thesymptoms of GAD.

Nonpharmacologic treatment should betried if the anxiety is mild and does not significantly interfere withfunctioning. Relaxation techniques and biofeedback are often very effective.Cognitive therapy has also proven successful in patients, as they are taught toview their worries more realistically.

If the patients anxiety is causing asignificant impairment in daily functioning, pharmacologic treatment isindicated.

Benzodiazepines are beneficial intreating patients with GAD, particularly if combined with cognitive or behaviortherapy. During the worsening of GAD symptoms five years ago, Dr. Johnsonbenefited from a trial of diazepam(Valium^�).

Some patients with GAD will significantlyimprove with 2-6 weeks of treatment with benzodiazepines. However, mostpatients require treatment longer than six months in order to prevent a relapseof symptoms. The long term use of a benzodiazepine is safe and beneficial formany patients. However, it is a good idea to taper medication periodically toevaluate if continued use is necessary. The benefits and risks ofbenzodiazepine use will be discussed in the follow-upcase.

Buspirone (BuSpar^�) is another medication used to treat GADthis will also be discussed later.

18. パニック発作.

19.

パニック発作: (DSM-IV) 強い恐怖または不快を感じるはっきりと他と区別できる期間でその時, 以下の症状のうち4つ(またはそれ以上) が突然に発現し, 10分以内にその頂点に達する。

(1)動悸, 心悸亢進, または心拍数の増加

(2)発汗

(3)身震いまたは震え

(4)息切れ感または息苦しさ

(5)窒息感

(6)胸痛または胸部の不快感

(7)嘔気または腹部の不快感

(8) めまい感, ふらつく感じ, 頭が軽くなる感じ, または気が遠くなる感じ

(9) 現実感消失 (現実でない感じ), または離人症状 (自分自身から離れている)

(10) コントロールを失うことに対する, または気が狂うことに対する恐怖

(11)死ぬことに対する恐怖

(12)異常感覚（感覚麻痺またはうずき感）

(13)冷感または熱感

S. Freudは,最初性生活の不全に, その後, 人格内部の葛藤に由来すると考えて不安発作と呼んだが, この発作にイミプラミンが有効なこと, 乳酸ナトリウムで引き起こすことのできることが判明して, 生物学的基盤を有すると考えられるようになり, 呼び名もパニック発作となった.

パニック障害: 特別な状況や環境的背景に限定されず, したがって予期できずに起こる反復性の重篤な不安発作(パニック発作) を主な病像とする障害.

(DSM-IV)

(1) と (2) の両方を満たす.

(1) 予期しないパニック発作が繰り返しおこる.

(2) 少なくとも一回の発作の後 ,約1か月間(またはそれ以上), 以下のうち1つ(またはそれ以上) が続いていたこと.

(a) もっと発作が起こるのではないかという心配の継続

(b) 発作またはその結果が持つ意味についての心配

(c) 発作と関連した行動の大きな変化

20. FacultyComments

The age of onset for Panic Disorder isusually between the late-teens and mid-30s. A bimodal distribution exists, withone peak in late adolescence and a smaller peak in the mid-30s. However,isolated Panic Attacks and Panic Disorder may present at anyage.

21. FacultyComments

Patients with Panic Disorder may presentwith attacks occurring once a week over many weeks to months. Patients may alsodisplay symptoms of attacks daily for one to two weeks followed by months beingsymptom free. The course is typically chronic, but waxing andwaning.

Because the symptoms of panic attacks areoften seen in other medical conditions, patients seen in the emergency room areoften evaluated for the following conditions: cardiac (arrhythmias, SVT),pulmonary (asthma attacks), endocrine (hyperthyroidism, hyperparathyroidism),neurological (seizures), and substance abuse. Frequent Emergency Room visitscan drain finances and put a strain on work or schoolresponsibilities.

22. FacultyComments

The lifetime prevalence of Panic Disorderhas been determined to be between 1.5% and 3.5% by epidemiological studiesthroughout the world.

23. FacultyComments

Anxiety in general seems to have afamilial association.

Twin studies implicate a geneticcomponent to Panic Disorder, and first degree relatives of patients have a fourto seven times greater chance of developing Panic Disorder than the generalpopulation.

However, there has been no conclusivedata on familial patterns of Generalized AnxietyDisorder.

24. #9 を参照.

25. 抗不安薬が主. ベンゾジアゼピン誘導体を主に用いる. 抗精神病薬を併用することもある. パニック発作に対しては三環系抗うつ薬(イミプラミン, クロミプラミン), SSRI (パロキセチン) が有効. ベンゾジアゼピン系のアルプラゾラムも有効.

Faculty Comments

Up to two-thirds of patients withsymptoms of depression also have symptoms of anxiety. And research hassuggested that up to 80% of patients with Panic Disorder have had an episode ofmajor depressive disorder. The relationship between GAD and MDD is not asclear.

26. ベンゾジアゼピン誘導体はシナプス膜の特定の部位に結合し,GABA_A受容体機能を充進させる.この結合部位をベンゾジアゼピン受容体と呼び,GABA_A受容体のgサブユニットがベンゾジアゼピン結合に重要である. GABAの存在下にベンゾジアゼピン誘導体が受容体に結合するとClが細胞内へ流入し, シナプス膜に過分極が起こり,GABA_A受容体機能が克進する. ベンゾジアゼピン受容体は大脳皮質, 辺縁系および間脳に多く分布し, それらの部位の機能にベンゾジアゼピン誘導体の作用点を求めることができる. 抗不安作用は辺縁系 (扁桃, 海馬, 臭球) および大脳皮質のベンゾジアゼピン受容体と関連し,GABA_A受容体機能を克進させ, これらの部位の神経過剰活動を抑制し不安を減少させると考えられている. 海馬ではコリン性神経, セロトニン神経の過剰活動がベンゾジアゼピン誘導体により抑制される.

Faculty Comments

Isolated Panic Attacks, as is the casewith Dr. Johnsons one episode, requires no long-term pharmacological treatment- a one-time dose of a benzodiazepine may be used if the patient is seen in theoffice or ER.

If a patient presents with recurrentattacks and criteria is met for Panic Disorder, a number of medications can beused for treatment:

-benzodiazepines high-potency benzos aremost effective

-Selective Serotonin Reuptake Inhibitors(SSRIs) - includes Celexa (citalopram), Prozac (fluoxetine), Lovox(fluvoxamine), Paxil (paroxetine), Zoloft (sertraline)

-B-Blockers such as propranolol oratenolol

The optimal duration of treatmentunknown. It is recommended that benzodiazepines and SSRIs be tapered after 6months of being symptom-free in order to reassess the need for continuedmedication.

27.

29, 30.

ブスピロン：buspirone(本邦になし. 類似薬としてはタンドスピロン (セデイール^�))

クエン酸タンドスピロン: 非ベンゾジアゼピン系・セロトニン神経系に選択的に作用.

【重要な基本的注意】

(1) 神経症においては, 罹病期間が長い (3年以上) 例や重症例あるいは他剤 (ベンゾジアゼピン系誘導体) での治療効果が不十分な例等の治療抵抗性の患者に対しては効果が現れにくい. 1日60mgを投与しても効果が認められないときは, 漫然と投与することなく中止する.

(2) 使用にあたっては, 高度の不安症状を伴う患者の場合効果が現れにくいので, 慎重に症状を観察する等注意する.

(3) 眠気・めまい等が起こることがあるので, 投与中の患者には自動車の運転等危険を伴う機械の操作に従事させないように注意する.

(4) ベンゾジアゼピン系誘導体とは交差依存性がないため, ベンゾジアゼピン系誘導体から直ちに本剤に切り替えると, ベンゾジアゼピン系誘導体の退薬症候が引き起こされ, 症状が悪化することがあるので, 前薬を中止する場合は徐々に減量する等注意する.

【重大な副作用】

(a) 肝機能障害, 黄疸 (0.1%未満): AST, ALT, ALP,G-GTの上昇等を伴う肝機能障害や黄疸が現れることがあるので, 観察を十分に行い, 異常が認められた場合には中止するなど, 適切な処置を行う.

(b) セロトニン症候群 (頻度不明): 興奮, ミオクロヌス, 発汗, 振戦, 発熱等を主症状とするセロトニン症候群が現れることがあるので, これらの症状が出現した場合には, 中止し, 水分補給等の全身管理とともに適切な処置を行う.

====================================

1. 消化管からよく吸収される. 代謝は主に脱メチル化, 脱アミノ, および水酸化反応により不活性かされ尿中へ排出. 肝・腎機能が低下すると排泄が遅れ体内に蓄積される(グルクロン酸抱合は加齢や肝障害の影響を受けにくい).

2. Faculty Comments

It is estimated that 10% of adults havetaken a benzodiazepine for at least one month during the lastyear.

3. Faculty Comments

The benzodiazepines with a rapid changein drug level cause an initial high.　These drugs include:

• triazolam(Halcion) - high potency, short-acting
  
• diazepam(Valium) - low potency, long-acting
  

5. 腎機能

Faculty Comments

Benzodiazepine use in olderadults is associated with increased risk of falls, including falls that resultin hip fracture. Increased likelihood of automobile accidents and cognitivedysfunction are more likely in older adults using benzodiazepines. Therefore,begin with low doses of the LOT drugs.

6. 妊婦・授乳婦には慎重投与.

7, 11. バルビツレート誘導体と比較すると頻度は少ないが, 長期服用によって耐性や精神･身体依存が起こることがある. 長期投与後退薬すると, 不安, 不眠, 興奮, 痙攣などの禁断症状 (退薬症状) が現れることがある. 半減期の短い薬は蓄積を越しにくいが, 退薬症状はより急激で程度も強い. 半減期の長い薬は蓄積しやすいが退薬症状は現れても軽度である.

8. Faculty Comments

Patients with a personality disorder or aprevious history of drug or alcohol abuse. It is estimated that ten to twentypercent of alcoholics who have used prescription benzodiazepines willeventually abuse them. Surprisingly, it is estimated that up to 40% ofalcoholics receive prescription benzodiazepines.

9. Faculty Comments

Guidelines for prescribingbenzodiazepines:

1- diagnosismade of a benzodiazepine- responsive syndrome

2- use ofnon-pharmacological therapies if indicated

3- assessment ofduration of treatment -- forewarn patients that extra medication will not beprescribed unless a dose increase is recommended by the prescribing physiciandocument this in the patient chart to alert colleagues in your office who mayreceive requests from your patient when they are on-call for thepractice

4- considerrisk-benefit ratio screen patients for alcohol and drug abuse, and use inpatients with a history of abuse (a relative

contraindication) only if there isno treatment alternative and arrangements have been made for close follow-upduring treatment

5-adjust dose totreat symptoms but minimize side effects such as drowsiness--

warn patients about possiblesedation and warn patients to avoid driving or operating heavy machinery untilthey are certain their dose does not cause sedation or motorincoordination

6- monitor forabuse, suggested by unsupervised dose acceleration

7- slowly taperthe drug after an appropriate trial to see if further treatmentnecessary

8- reconsiderdiagnosis if patient responding poorly or if patient requiring doses higherthan originally anticipated

(from Handbook of Psychiatric DrugTherapy)

10. FacultyComments

Benzodiazepine intoxicationproduces:

• slurredspeech
  
• incoordination
  
• unsteadygait
  
• nystagmus
  
• impairment inattention or memory
  
• stupor orcoma
  

12. FacultyComments

In such circumstances the physician canswitch the patient from alprazolam (Xanax) to another high-potency drug that islonger-acting, such as clonazepam (Klonopin). This switch takes about one weekand is accomplished as follows:

1- Administer clonazepam at one-half thedaily alprazolam dose divided into two doses one in the early morning and onemid-afternoon.

2- Discontinue regular alprazolam doses,but allow PRN dosing of alprazolam (up to the previous does) for the firstseven days. Stop the alprazolam entirely after 7 days of clonazepamuse.

3- If more medication is requires forsymptom control, increase clonazepam 0.25 to 0.5 mg q week until symptomsabate.

4.