Transcript 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]
1
Depression
 Common psychiatric disease, 11%
 WHO，Depression will become the
main killer to people in 21th century
BLUE FLU
2
 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
3
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
4
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
5
6
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)
7
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
8
Etiology
 Biological factors
 Social factors
 Psychological factors
9
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
10
Social factors
 Loneliness, isolation
 Recent bereavement
 Lack of a supportive social network
11
Psychological factors





Traumatic experiences
Damage to body image
Fear of death
Frustration with memory loss
Role transitions
12
Neurobiology of depression
 The monoamine deficiency theory
 Decreased levels or activity of
nor-epinephrine and/or serotonin
 Abnormality in HPA axis
 Hippocampus volume ↓
13
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)
14
Antidepressant drugs
 Tricyclic antidepressants(TCAs)
 Monoamine oxidase inhibitors(MAOIs)
 Norepinephrine reuptake inhibitors(NARIs)
 Selective serotonin reuptake inhibitors( SSRIs)
 Serotonin and norepinephrine reuptake
inhibitors(SNRIs)
15
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）
16
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
17
【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
18
【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
19
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
20
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。
21
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
22
 【Pharmacological effects and
mechanism】
 Inhibit MAO, and reduce the degradation of
monoamine.
 【Clincal uses】: atypical depression
not first choice
 【Adverse reactions】
Severe: hypertension crisis
23
Ⅲ NA reuptake inhibitors
Desipramine (地昔帕明)
Maprotiline (马普替林)
Nortriptyline (去甲替林)



TCA
Selectively reduce reuptake of NA
Weak sedation and anticholinergic activity
 Onset rapid
24
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 )
25
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)
26
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
27
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
28
Section 2
Anti-manic Drugs
29
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
30
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
31
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)
32
Lithium carbonate(碳酸锂)
—“Mood-stabilizing” agent
【Pharmacological effects and mechanism】
little impact on normal person,
anti-mania, sometimes also effective for
depression
33
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
34
【Clinical uses】
manic-depressive psychosis especially for
acute and mild mania (80%)
35
【Adverse reactions】
Lithium toxicity
therapeutic concentration: 0.8-1.5mmol/L
toxic concentration: >2mmol/L
monitor blood drug concentration,
withdrawal at 1.6mmol/L
36
 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)
37
Section 3
Anti-anxiety Drugs
38
Anxiety
 Anxiety is an unpleasant emotional
experience characterized by fear
disproportionate to the severity of stressful
factors in the environment, or fear without
cause.
39
Anti-anxiety drugs
 Benzodiaepines
 First-line drugs
 Mechanism: binds to GABAA receptor and act
as positive allosteric modulators.
 Buspirone(丁螺环酮）
 Psychotherapy
40
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.
41
Thank you!
42