抗抑郁治疗的遗传药理学教材教学课件.pptVIP

抗抑郁治疗的遗传药理学; 抑郁症的终身患病率为10%~20%，时点患病率为2%~5%，在世界十大常见疾病中该病排行第四。 预计在2020年，抑郁障碍在疾病总负担中位居第二。 ;Diagnostic Criteria for Major depression (DSM-IV);Drug type;Relapse rate with drug vs. placebo in continuation studies (Dunner DL. 2001 J Clin Psychiatry);(Geddes JR et al. 2003 Lancet);治疗失败 30-40%;About 30-40% of MDD patients do not respond sufficiently to SSRIs (Tsai SJ et al. Current pharmacogenomics 2003). Approximately 30% of people suffering from clinically significant depressive illness do not respond to the usually recommended dose of antidepressants (Stimpson et al. the Cochrane Database Review 2003). ;The history of good response to that agent by a person or a family member (Synopsis of Psychiatry. 8th). A familial tendency to respond to specific antidepressants or antidepressant groups. (O’Reilly RL et al. 1994 Biol Psychiatry) Genetic factors play a substantial role in antidepressant response (Tsai SJ et al. Current pharmacogenomics 2003)(O’Reilly RL et al. 1994 Biol Psychiatry) ;;;Serotonin transporter promoter function in human JAR placental choriocarcinoma cell ;Serotonin transporter promoter function in human lymphoblast cell;Smeraldi et al., Mol. Psychiatry. 1998 102 (age: 30-60, M/F = 32/67) patients with major depressive disorder, baseline HDRS-2121 Randomly assigned to Fluvoxamine + Placebo or Fluvoxamine + Pindolol Measuring 21-item Hamilton Depression Rating Scale (HDRS-21) weekly for 6 weeks ; ;Copyright restrictions may apply.;;;;;;MAOA-VNTR in promotor: DRD2 Ser311Cys, DRD4 exon 4 VNTR 5HT1A C-1018G, 5HT2A T102C, 5HT2A G-1438A, 5HT2C, 5HT6 T267C* ACE I/D* G-protein ?3 C825T ADRB1 G1165C NOS1 C276T* IL-1? C-511T* BDNF V66M* （脑源神经营养因子 ） Phase-II enzymes CYP1A2, CYP2B6, CYP3A4, CYP2D6, CYP2C19, CYP2C9;; F . Dose Clearance. T ;Amitriptyline 阿米替林 Citalopram 西酞普兰 Desipramine 地昔帕明 Doxepin 多虑平 Duloxetine 度洛西汀 Fluoxetine 氟西汀 Fluvoxamine 氟伏沙明 Imipramine 丙咪嗪 Maprotiline 马普替林 Mianserin 米安色林 Mirtazapine 米氮平 Moclobemide 吗氯贝