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1 22 * * Drug Surveillance DSM-IV Anxious depression 4 Drug Surveillance GPRD A. (TCA) (SSRI) (SNRI)

2 SSRI 1999 SNRI SSRI , Drug Surveillance B. Pubmed (APA) 2 NICE 3 US Preventive Services Task Force 4 level II-2 US Preventive Services Task Force Level I. 1 RCT > Level II-1. > Level II-2. > Level II-3. > Level III. C. 1 National Institute for Clinical Excellence (NICE) NICE 5, 6 HDRS> (2009) , 8,

3 10, 11 NICE 6-8 (Treatment Resistant Depression: TRD) 2 Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) 12, SSRI 28% % 2 / 12-25% % / 70% STAR*D SSRI 2 3, 14 Bollini mg mg mg/ 50% 1 SSRI SSRI 16 NICE mg/day, 125mg/day 140mg/day SSRI 50mg/day 20mg/day 50mg/day 50mg/day 60mg/day 30mg/day 150 mg/day SSRI STAR*D Licht 17 (100mg/ 200mg/ )

4 RCT Angst 19 I II NOS I (Anxious depression) (Non-anxious depression) Anxious depression STAR*D 20 NICE SSRI Drug Surveillance The General Practice Research Database (GPRD: ) 500 GPRD Jick 22 D

5 E DSM-IV Anxious depression 4 Drug Surveillance GPRD F. 1. Nakagawa A, Grunebaum MF, Ellis SP, et al. Association of suicide and antidepressant prescription rates in Japan, J Clin Psychiatry 2007 Jun;68(6): APA. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. Washington, DC American Psychiatric Association; NICE. Depression: the treatment and management of depression in adults, Clinical Guideline 90 London: National Institute for Clinical Excellence; Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001 Apr;20(3 Suppl): Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008 Feb;5(2):e Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010 Jan 6;303(1): Stone M, Laughren T, Jones ML, et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 2009;339:b Anderson IM, Ferrier IN, Baldwin RC, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 2008 Jun;22(4): APA. Practice guideline for the treatment of

6 patients with major depressive disorder. 2nd ed. Washington, DC: American Psychiatric Association; Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-xr after failure of SSRIs for depression. N Engl J Med 2006 Mar 23;354(12): Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry 2009 Mar;70(3): Rush AJ, Warden D, Wisniewski SR, et al. STAR*D: revising conventional wisdom. CNS Drugs 2009 Aug 1;23(8): Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006 Mar 23;354(12): Furukawa TA. Review: placebo is better than no treatment for subjective continuous outcomes and for treatment of pain. Evid Based Ment Health 2002 Feb;5(1): Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C. Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry 1999 Apr;174: Adli M, Baethge C, Heinz A, Langlitz N, Bauer M. Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review. Eur Arch Psychiatry Clin Neurosci 2005 Dec;255(6): Licht RW, Qvitzau S. Treatment strategies in patients with major depression not responding to first-line sertraline treatment. A randomised study of extended duration of treatment, dose increase or mianserin augmentation. Psychopharmacology (Berl) 2002 May;161(2): Rothschild AJ, Williamson DJ, Tohen MF, et al. A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features. J Clin Psychopharmacol 2004 Aug;24(4): Angst J, Cui L, Swendsen J, et al. Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication. Am J Psychiatry 2010 Oct;167(10): Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008 Mar;165(3): Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003 Nov;60(11): Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA 2004 Jul 21;292(3):

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