抗精神病药物 Antipsychotic agents：用于治疗精神疾病的药物 Drugs Used to Treat Psychiatric Disorders

Drugs Used to Treat Psychiatric Disorders Sh- Hong Zhang(张世红),Ph.D, Associate prof shizhang713@zju.edu.cn

Drugs Used to Treat Psychiatric Disorders Shi-Hong Zhang (张世红), Ph.D, Associate Prof. shzhang713@zju.edu.cn

Psychiatric Disorders Lifetime prevalence: about 1/3-1/2 of population Mood disorder :8-10% Anxiety Disorder: 15% Substance abuse: 16% Schizophrenia: 1% Eating disorders, somatoform disorders and personality disorders Antipsychotic agents Antidepressant and antimanic agents Axiolytics

Psychiatric Disorders Lifetime prevalence: about 1/3- 1/2 of population - Mood Disorder: 8-10% - Anxiety Disorder: 15% - Substance abuse: 16% - Schizophrenia: 1% - Eating disorders, somatoform disorders, and personality disorders Antipsychotic agents Antidepressant and antimanic agents Axiolytics 2

Antipsychotic Agents Schizophrenia is a particular kind of psychosis characterized by a clear sensorium but a marked thinking disturbance

Antipsychotic Agents ----Schizophrenia is a particular kind of psychosis characterized by a clear sensorium but a marked thinking disturbance 3

Case Study W.G, 19 years old, undergraduate, member of rowing team of school, was found staying by himself, avoiding the company of friends and skipping school and athletic training. Later, he was heard speaking to himself as he sat isolated in his room mumbling and smiling then he confided to his roommate that he had uncovered a grand conspiracy to rob him of his athletic abilities and that he could hear the conspirator's voices as they planed to destroy him. Finally, he accused his roommate of being a part of the conspiracy

Case Study • W.G, 19 years old, undergraduate, member of rowing team of school, was found staying by himself, avoiding the company of friends and skipping school and athletic training. Later, he was heard speaking to himself as he sat isolated in his room, mumbling and smiling. Then he confided to his roommate that he had uncovered a grand conspiracy to rob him of his athletic abilities and that he could hear the conspirator’s voices as they planed to destroy him. Finally, he accused his roommate of being a part of the conspiracy. 4

Schizophrenia Neurological disorder-impaired ability to perceive, understand interpret the environment Impaired social and occupational function Behavioral syndrome -predictable or not

Schizophrenia • Neurological disorder - impaired ability to perceive, understand & interpret the environment • Impaired social and occupational function • Behavioral syndrome – predictable or not 5

Epidemiology Incidence consistent worldwide 1% general population - Hereditary trend 10%siblings, parents /offspring dizygotic twins 50% monozygotic twins Environmental factors implicated Prenatal stress-infection, famine, war, death of spouse Season of birth -winter> summer -Cannabis --Urban setting >rural setting ge of onset -Men17-27, Women17-37 -Childhood onset extremely rare: 1 in 10,000-100,000 Outcome 10% good-optimistic 80% remission without full recovery 10% no remission

Epidemiology • Incidence consistent worldwide --1% general population --Hereditary trend: 10% siblings , parents / offspring, dizygotic twins 50% monozygotic twins • Environmental factors implicated --Prenatal stress - infection, famine, war, death of spouse --Season of birth - winter > summer --Cannabis --Urban setting > rural setting • Age of onset --Men 17 - 27, Women 17 - 37 --Childhood onset extremely rare: 1 in 10,000-100,000 • Outcome --10% good - optimistic --80% remission without full recovery --10% no remission 6

Signs Symptoms 1. Positive symptoms Delusions(tB)-fixed false beliefs outside cultural norm (bizarre Vs. non bizarre Hallucinations(AJDE)-perceptual(usually auditory or visual, but sometimes tactile or olfactory), have no outside source Like my voice Not an illusion (f D a mistaken perception for which there is an actual external stimulus Disorganization - pattern of speech/thought/behavior, making up words without a meaning(neologisms)

Signs & Symptoms 1. Positive symptoms • Delusions (妄想)- fixed false beliefs outside cultural norm (bizarre vs. non bizarre) • Hallucinations (幻觉)- perceptual (usually auditory or visual, but sometimes tactile or olfactory), have no outside source •“Like my voice” • Not an illusion (错觉, a mistaken perception for which there is an actual external stimulus) • Disorganization – pattern of speech/thought/behavior, making up words without a meaning (neologisms) 7

Signs Symptoms 2. Negative symptoms Affective flattening(absence of emotional expressiveness) Avolition/Amotivation ( decreased motivation) Autistic behaviors(social withdrawal) Anhedonia(inability to experience pleasure Ambivalence(coexistence of opposing attitudes or feelings) Anosognosia(impaired awareness of illness

2. Negative symptoms • Affective flattening (absence of emotional expressiveness) • Avolition/Amotivation (decreased motivation) • Autistic behaviors (social withdrawal) • Anhedonia (inability to experience pleasure ) • Ambivalence (coexistence of opposing attitudes or feelings) • Anosognosia (impaired awareness of illness ) Signs & Symptoms 8

Historical Perspective Chlorpromazine(氯丙嗪) made in1950 in france, used to treat pre-operative anxiety 1952 Delay and deniker published the first report of Chlorpromazine's efficacy in psychosis 1963 Carlsson and lindqvist reported that haloperidol and Chlorpromazine result in accumulation of da metabolites D2 hypothesis(excessive dopaminergic activity plays a role in the disorder)-supported by increased dopamine receptor density and"potency'of Da antagonism at D2 related to efficacy Refs:http://www.bedrugfree.net/schizOphrenia.pdf Film: One Flew Over the Cuckoo's Nest (1975)

Historical Perspective • Chlorpromazine (氯丙嗪) made in 1950 in France, used to treat pre-operative anxiety • 1952 Delay and Deniker published the first report of Chlorpromazine's efficacy in psychosis • 1963 Carlsson and Lindqvist reported that Haloperidol and Chlorpromazine result in accumulation of DA metabolites • D2 hypothesis (excessive dopaminergic activity plays a role in the disorder) – supported by increased dopamine receptor density and “potency” of DA antagonism at D2 related to efficacy. • Refs: http://www.bedrugfree.net/Schizophrenia.pdf Film: One Flew Over the Cuckoo’s Nest (1975) 9

Classification of antipsychotics Typical Phenothiazines(吩噻嗪类): chlorpromazine,etc Thioxanthenes(硫杂蔥类): chlorprothixene,etc Butyrophenones(丁酰苯类): haloperidol,etc Atypical Clozapine, olanzapine, risperidone, aripiprazole, etc 10

Classification of antipsychotics Typical: • Phenothiazines (吩噻嗪类): chlorpromazine, etc • Thioxanthenes (硫杂蒽类): chlorprothixene, etc • Butyrophenones (丁酰苯类): haloperidol, etc Atypical: • Clozapine, olanzapine, risperidone, aripiprazole, etc 10