FDA Hearing on Suicide and FDA Hearing on Suicide and AntidepressantsAntidepressants

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

PsychiatryDecember 13, 2006

2003 U.S. Suicide Rates by Age and Sex2003 U.S. Suicide Rates by Age and Sex

0

10

20

30

40

50

60

15-1

9

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

485

+

Age Group

Rat

e p

er 1

00,0

00 Men Women

CDC, National Center for Injury Prevention and Control.CDC, National Center for Injury Prevention and Control.

http://webapp.cdc.gov/cgi-bin/broker.exehttp://webapp.cdc.gov/cgi-bin/broker.exe

Reducing Suicidal Ideation and Depressive Reducing Suicidal Ideation and Depressive Symptoms in Depressed Older Primary Care Symptoms in Depressed Older Primary Care

Patients: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):1081-1091

Suicidal Thinking during Sertraline Suicidal Thinking during Sertraline Treatment in Late Life DepressionTreatment in Late Life Depression

Largest placebo controlled trial performed

8 week randomized, double-blind trial

Sertraline 50-100 mg/d vs placebo

752 patients enrolled, 728 with at least one post treatment assessment

Nelson et al. submittedNelson et al. submitted

Suicidal Thinking during Sertraline Suicidal Thinking during Sertraline Treatment in Late Life DepressionTreatment in Late Life Depression

0

0.2

0.4

0.6

0.8

1

0 2 4 6 8

Week

Item

3 S

core

Sertraline Placebo

Nelson et al. submittedNelson et al. submitted

MMRM analysis, SERT vs PLBO, p=0.02MMRM analysis, SERT vs PLBO, p=0.02

Emergent Suicidal Thinking during Treatment Emergent Suicidal Thinking during Treatment in Patients with Baseline Item 3 = 0in Patients with Baseline Item 3 = 0

Nelson JC, Delucchi K, Schneider LS. submittedNelson JC, Delucchi K, Schneider LS. submitted

Treatment Group

Item 3 Rating

Wk 0 Wk 2 Wk 4 Wk 6 Wk 8

Sertraline 3 0 0 0 0 0

2 0 1 2 2 2

1 0 12 10 9 9

0 116 97 90 85 103

Placebo 3 0 1 0 0 0

2 0 3 3 2 1

1 0 11 14 14 11

0 132 116 110 108 112

Treatment Group

Item 3 Rating

Wk 2 Wk 4 Wk 6 Wk 8

Sertraline 3 0 0 0 0

2 1 2 2 2

1 12 10 9 9

0 97 90 85 103

Placebo 3 1 0 0 0

2 3 3 2 1

1 11 14 14 11

0 116 110 108 112

In 248 patients with a HAMD Item 3 score In 248 patients with a HAMD Item 3 score of 0 at baseline, the number of patients who of 0 at baseline, the number of patients who reported any positive Item 3 rating during reported any positive Item 3 rating during treatment did not differ in the two groups treatment did not differ in the two groups (22.4% vs 25.8%, for sertraline and placebo (22.4% vs 25.8%, for sertraline and placebo respectively.)respectively.)

Time to Recurrence from Randomization: MTLD-II

Reynolds, Dew, Pollock, et al. NEJM, 354(11):1130-1138, 2006

Weeks since randomization

0 10 20 30 40 50 60 70 80 90 100 110 120

% f

ree

from

rec

urre

nce

0.0

0.2

0.4

0.6

0.8

1.0

Paroxetine + IPT (n=28)Paroxetine + Clinical Management (n=35)IPT + Placebo (n=35)Clinical Management + Placebo (n=18)

Log rank X2=9.77, df=3, p=.0206

Conclusions: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 Sources of support for research conducted by Charles F. Reynolds, III, MD: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