Download Depression and anxiety Lou haiyan（娄海燕）

Depression and anxiety
Lou haiyan（娄海燕）
Institute of Pharmacology
School of Medicine
Shandong University
[email protected]
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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
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人很烦？爱发脾气或对
你的亲友漠不关心？
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
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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
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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:
 Psychotherapy
 Medication
 Electroconvulsive Therapy (ECT,电休克治疗)
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Antidepressant drugs
 Tricyclic antidepressants(TCAs)
 Monoamine oxidase inhibitors(MAOIs)
 Norepinephrine reuptake inhibitors(NARIs)
 Selective serotonin reuptake inhibitors( SSRIs)
 Serotonin and norepinephrine reuptake
inhibitors(SNRIs)
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Ⅰ.Tricyclic antidepressants (TCA)
丙米嗪（imipramine）
氯米帕明（ clomipramine ）
三环类：
阿米替林（amitriptyline）
多塞平（doxepin）
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Imipramine (丙米嗪，米帕明）
【Pharmacological effects and mechanism】
1.CNS：
produce inhibition on normal person,
elevating the mood that is depressed
slow onset:2-3w
Mechanisms：
block the uptake of NA and 5-HT
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【Pharmacological effects and mechanism】
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
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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
口干、视力模糊、
便秘、尿潴留
抑制突触前膜对5HT和NA的重摄取
突触间隙5HT和NA
抗抑郁
心肌内NA
阻断M-R
血压
阻断1-R
心律失常
过度镇静
奎尼丁样心
肌抑制作用
阻断H1-R
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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) ：
异烟肼（isoniazid）
异卡波肼（isocarboxazid）
吗氯贝胺（moclobemide）
Adverse reaction:
hypertensive crisis, liver injury
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 【Pharmacological effects and
mechanism】
 Inhibit MAO, and reduce the degradation of
monoamine.
 【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)
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TCA
Selectively reduce reuptake of NA
Weak sedation and anticholinergic activity
 Onset rapid
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Ⅳ Selective 5-HT reuptake
inhibitors (SSRIs)
Fluoxetine (Prozac,氟西汀, 百忧解)
First line
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 )
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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 SSRIs
Faster 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(Manicdepressive 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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Manic-depressive disorder (躁狂抑郁症)
—bipolar affective disorder
repeated episodes of mania or depression,
alternating mania and depression
Mechanisms:
5-HT↓ NA↑
5-HT↓ NA↓
mania
depression
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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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【Adverse reactions】
Lithium toxicity
therapeutic concentration: 0.8-1.5mmol/L
toxic concentration: >2mmol/L
monitor blood drug concentration,
withdrawal at 1.6mmol/L
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 nausea, vomit, abdominal pain, profuse
diarrhea, and ataxia, mental confusion,
hyper-reflexia, tremor, convulsion
 Intoxication can be usually reversed by
osmotic 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
 Benzodiaepines
 First-line drugs
 Mechanism: 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:
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Rapidly absorbed orally.
Rapid first-pass effect.
Elimination half-life = 2-4 hrs.
Metabolism is primarily hepatic.
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Thank you!
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