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Depression and anxiety

Lou haiyanLou haiyan （娄海燕）（娄海燕）Institute of PharmacologyInstitute of Pharmacology

School of MedicineSchool of MedicineShandong UniversityShandong University

louhaiyan@sdu.edu.cnlouhaiyan@sdu.edu.cn

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Depression 　 Common psychiatric disease, 11% WHO ， Depression will become the main killer to people in 21th century

BLUE FLU

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Depression is an illness that is characterized by a series of changes that gradually cause

significant impairment of the activity of people concerned.

It is more than feeling blue, down in the dumps or sad about a particular issue or situation.

It is a medical condition that requires diagnosis and treatment

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Symptoms of Depression

FIVE OR MORE OF THE FOLLOWING FOR AT LEAST TWO WEEKS:

Feelings of sadness, depressed mood and/or irritability

Loss of interest or pleasure in activities Changes in weight or appetite Changes in sleep pattern-not enough or too much

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Symptoms of Depression

Feelings of guilt, hopelessness or worthlessness Inability to concentrate, remember things or make

decisions Constant fatigue or loss of energy Restlessness or decreased activity Recurrent thoughts of suicide or death

6人很烦？爱发脾气或对你的亲友漠不关心？ 　　　　　　　　　　　　　　

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Hamilton rating scale for depression

（汉密尔顿抑郁量表 )

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Epidemiology

The most common psychiatric disorder Depression incidence

Men: 13%Women: 21%

Bipolar disorder: 1.3-1.8% Age of onset: 25-35 year Major risk factor: stress

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Etiology

Biological factors Social factors Psychological factors

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Biological factors

Genetic High prevalence in first degree relatives High concordance with monozygotic twins Short allele of serotonin transported gene,2003

Medical illness: Parkinson's, Alzheimer's, cancer, diabetes or stroke

Vascular changes in the brain Chronic or severe pain Previous history of depression Substance abuse

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Social factors

Loneliness, isolation Recent bereavement Lack of a supportive social network

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Psychological factors

Traumatic experiences Damage to body image Fear of death Frustration with memory loss Role transitions

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Neurobiology of depression

The monoamine deficiency theory Decreased levels or activity of

nor-epinephrine and/or serotonin

Abnormality in HPA axis Hippocampus volume ↓

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Treatment for Depression

Approximately 80% of people who receive treatment for Depression improve.

There are three types of treatment:PsychotherapyMedicationElectroconvulsive Therapy (ECT, 电休克治疗 )

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Tricyclic antidepressants(TCAs) Monoamine oxidase inhibitors(MAOIs) Norepinephrine reuptake inhibitors(NARIs) Selective serotonin reuptake inhibitors( SSRIs) Serotonin and norepinephrine reuptake

inhibitors(SNRIs)

Antidepressant drugs

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丙米嗪（ imipramine ）

氯米帕明（ clomipramine ）

阿米替林（ amitriptyline）

多塞平（ doxepin ）

三环类：

ⅠⅠ.Tricyclic antidepressants (TCA).Tricyclic antidepressants (TCA)

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1.CNS ： produce inhibition on normal person,

elevating the mood that is depressed

　 slow onset:2-3w

Imipramine (丙米嗪，米帕明）

Mechanisms ： block the uptake of NA and 5-HT

【 Pharmacological effects and mechanism 】

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2. autonomic nervous system

block M-R

3. cardiovascular system

hypotension: block α1 –R

arrhythmias,tachycardia: NA↑

quinidine-like inhibitory action on heart

used with caution in patients with cardiovascular

disease

2. autonomic nervous system

block M-R

3. cardiovascular system

hypotension: block α1 –R

arrhythmias,tachycardia: NA↑

quinidine-like inhibitory action on heart

used with caution in patients with cardiovascular

disease

【 Pharmacological effects and mechanism 】

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【 Clinical uses 】 1. depressions caused by all kinds of reasons

2. enuresis( 遗尿症 ) in children

3. anxiety and phobia ( 恐怖症 )

【 Adverse reactions 】 1. atropine-like action

2. cardiovascular reaction

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三环类抗抑郁药的作用及机制

抑制突触前膜对 5-HT 和 NA 的重摄取 阻断 M-R 阻断 1-R

阻断 H1-R奎尼丁样心肌抑制作用

抗抑郁

心律失常

口干、视力模糊、便秘、尿潴留 血压

过度镇静心肌内 NA突触间隙 5-HT 和 NA

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doxepin （多塞平，多虑平）

抗焦虑作用强，对伴有焦虑症状的抑郁 症疗效最佳。

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Ⅱ Monoamine oxidase inhibitors(MAOIs) ：Ⅱ Monoamine oxidase inhibitors(MAOIs) ：

异烟肼（ isoniazid ）

异卡波肼（ isocarboxazid ）

吗氯贝胺（ moclobemide ）

Adverse reaction: Adverse reaction:

hypertensive crisis, liver injuryhypertensive crisis, liver injury

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【 Pharmacological effects and mechanism 】 Inhibit MAO, and reduce the degradation of m

onoamine. 【 Clincal uses 】 : atypical depression not first choice 【 Adverse reactions 】

Severe: hypertension crisis

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Ⅲ NA reuptake inhibitors

Desipramine ( 地昔帕明 )

Maprotiline ( 马普替林 )

Nortriptyline ( 去甲替林 )

TCATCA Selectively reduce reuptake of NASelectively reduce reuptake of NA Weak sedation and anticholinergic activityWeak sedation and anticholinergic activity Onset rapidOnset rapid

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Ⅳ Selective 5-HT reuptake inhibitors (SSRIs)

Fluoxetine (Prozac, 氟西汀 , 百忧解 )

Paroxetine (Paxil, 帕罗西汀 , 赛洛特 )

Sertraline (Zoloft, 舍曲林 , 郁乐复 )

Fluvoxamine (Luvox, 氟伏沙明 , 兰释 )

Citalopram (Celexa, 西酞普兰 , 喜普妙 )

First line

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氟西汀（ fluoxetine, 百忧解）

selectively inhibit 5-HT reuptake

no affinity to the receptors in CNS and

periphery ， less adverse reactions

better tolerance and security than TCAs

take effects after 2-6 weeks

used for depression , compulsion( 强迫症 )

polyphagia( 贪食症 )

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Ⅴ 5-HT and NA reuptake inhibitors (SNRIs)

Venlafaxine ( 文拉法辛 , 怡诺思） Duloxetine ( 度洛西汀）

Have advantages over SSRIsFaster onset of action (< 2 weeks)Used for depression and anxiety

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Electroconvulsive Therapy (ECT)

Second-line treatment Faster acting than most medications Is used in life threatening situations to achieve

fast relief Can be used in combination with medication Side effects: short-term memory loss

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Section 2

Anti-manic Drugs

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Bipolar Disorder(Manic-depressive disorder)

People with this type of illness change back and forth between periods of depression and periods of mania (an extreme high).

Symptoms of mania may include: Less need for sleep Overconfidence Racing thoughts Reckless behavior( 行为鲁莽） Increased energy

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repeated episodes of mania or depression,

alternating mania and depression

Mechanisms:

5-HT↓ NA↑ mania

5-HT↓ NA↓ depression

Manic-depressive disorder ( 躁狂抑郁症 ) —bipolar affective disorderbipolar affective disorder

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Antimanic drug (mode stabilizing agents)

Lithium carbonate Antipsychotic agents

( 氯丙嗪、氟哌啶醇、氯氮平、利培酮 ) Antiepileptic agents

( 卡马西平、丙戊酸钠 ) Calcium blockers ( 维拉帕米 )

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Lithium carbonate( 碳酸锂 ) —“Mood-stabilizing” agent

【 Pharmacological effects and mechanism 】

little impact on normal person,

anti-mania, sometimes also effective for

depression

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碳酸锂的可能作用机制

1. 抑制脑内神经末　梢对 NA 、 DA 的释放

突触间隙单胺类递质减少2. 促进 NA 、 DA 的

重摄取及灭活

3. 抑制 AC 及 PLC 介导的反应

4. 影响 Na+ 、 Ca2+ 、Mg2+ 转运

影响神经功能

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【 Clinical uses 】

manic-depressive psychosis especially for

acute and mild mania (80%)

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Lithium toxicity therapeutic concentration: 0.8-1.5mmol/L

toxic concentration: >2mmol/L

monitor blood drug concentration,

withdrawal at 1.6mmol/L

【 Adverse reactions 】

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nausea, vomit, abdominal pain, profuse diarr

hea, and ataxia, mental confusion, hyper-refl

exia, tremor, convulsion

Intoxication can be usually reversed by osm

otic diuresis or by dialysis ( 透析 )

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Section 3

Anti-anxiety Drugs

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Anxiety

Anxiety is an unpleasant emotional experience characterized by fear disproportionate to the severity of stressful factors in the environment, or fear without cause.

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Anti-anxiety drugs

BenzodiaepinesFirst-line drugsMechanism: binds to GABAA receptor and act

as positive allosteric modulators.

Buspirone( 丁螺环酮） Psychotherapy

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Buspirone (BuSpar®) Partial agonist at the serotonin 1a receptor.

Relieves anxiety without producing sedation, impairment of motor skills, or memory loss.

Does not induce withdrawal symptoms upon discontinuation.

Does not act immediately. Can take up to 1 week to become effective. Used for chronic anxiety states.

Pharmacokinetics: Rapidly absorbed orally. Rapid first-pass effect. Elimination half-life = 2-4 hrs. Metabolism is primarily hepatic.

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Thank you!