FDA Hearing on Suicide and Antidepressants Presentation by Charles F. Reynolds, III, MD UPMC Professor of Geriatric Psychiatry University of Pittsburgh School of Medicine On behalf of the American Association for Geriatric Psychiatry December 13, 2006

2003 U.S. Suicide Rates by Age and Sex CDC, National Center for Injury Prevention and Control.

Reducing Suicidal Ideation and Depressive Symptoms in Depressed Older Primary Care Patients:  A Randomized Controlled Trial Utilizing Citalopram and Depression Care Management (n = 598)  Rates of suicidal ideation declined faster (p =.01) in intervention patients compared with usual care patients.  Among patients reporting suicidal ideation, resolution was faster among intervention patients (p =.03); differences peaked at 8 months (70.7% versus 43.9% resolution; p =.005)  PROSPECT (Prevention of Suicide in Primary Care Elderly: Collabortive Trial). Bruce M, Tenhave T, Reynolds CF et al: JAMA 291 (9):

Suicidal Thinking during Sertraline Treatment in Late Life Depression  Largest placebo controlled trial performed  8 week randomized, double-blind trial  Sertraline mg/d vs placebo  752 patients enrolled, 728 with at least one post treatment assessment Nelson et al. submitted

Suicidal Thinking during Sertraline Treatment in Late Life Depression Nelson et al. submitted MMRM analysis, SERT vs PLBO, p=0.02

Emergent Suicidal Thinking during Treatment in Patients with Baseline Item 3 = 0 Nelson JC, Delucchi K, Schneider LS. submitted Treatment Group Item 3 Rating Wk 0Wk 2Wk 4Wk 6Wk 8 Sertraline Placebo Treatment Group Item 3 Rating Wk 2Wk 4Wk 6Wk 8 Sertraline Placebo In 248 patients with a HAMD Item 3 score of 0 at baseline, the number of patients who reported any positive Item 3 rating during treatment did not differ in the two groups (22.4% vs 25.8%, for sertraline and placebo respectively.)

Time to Recurrence from Randomization: MTLD-II Reynolds, Dew, Pollock, et al. NEJM, 354(11): , 2006

Conclusions:  Suicide rates are highest among the elderly, especially in white men. The majority of older adults who die by suicide have seen a primary care physician in preceding month.  Depression is the strongest risk factor for late-life suicide and for suicide’s precursor, suicidal ideation.  Depression treatment guidelines tailored for the elderly in primary care and involving the use of SSRI (citalopram) pharmacotherapy bring about faster rates of decline in suicidal ideation than usual care (PROSPECT; n = 598).  SSRI pharmacotherapy with sertraline brings about reduction of suicidal ideation more rapidly than placebo in old-age depression (Nelson, Schneider et al., n = 728) and is not associated with incident suicidal ideation different from placebo.  Maintenance pharmacotherapy with the SSRI paroxetine reduces recurrence risk over 2 years by 60% in late life depression.

Sources of support for research conducted by Charles F. Reynolds, III, MD:  National Institute of Mental Health  For pharmaceutical supplies only:  Forest Laboratories, Inc.  Pfizer, Inc.  GlaxoSmithKline  Bristol-Myers Squibb Company  Eli Lilly and Company