handouts to send: moodcheck, hcl-32 props: load internet: set up google on hcl-32

Handouts to send: MoodCheck, HCL-32

Props:

Load Internet:

Set up Google on HCL-32

President

Antidepressants & Kids:Suicide & the

Risk/Benefit of Treatment

• Rick Bingham, MDSalem, OR

6/6/08

No Financial Conflicts of Interest

Outline• Antidepressants are needed, valuable tools

– Biology of antidepressant action– Untreated anxiety and depression is devastating – Antidepressants work

• Antidepressants & Suicide Risk– FDA– Subsequent research

• The Future– Research underway (including CAPTN)– Primary Care & Mental Health Collaboration

• Take Home – Prescribing antidepressants– Tools & Resources

Finding balance

• Do no harm

• Prevent secondary

• Make effective use of the tools we have

Antidepressant suicidality

Risks of untreated

depression

?

AntidepressantsAntidepressants

Treated Treated

DepressionDepression

Suicidality

Suicidality


Treated Treated


•Untreated depression:

Recurrence School performance↓ Job failure Relationship failure Health consequences

Suicidality

Suicidality


Treated Treated


•Untreated depression: Suicide Recurrence School performance↓ Job failure Relationship failure Health consequences

Suicidality

Suicidality

Suicide death

Suicide death


Treated Treated


•Untreated depression: Suicide Recurrence School performance↓ Job failure Relationship failure Health consequences

Suicidality

Suicidality

Suicide death

Suicide death


Treated Treated


Antidepressant Suicidality

Depression Consequences

Confound and Confusion

Other issues- make visual

• Corporate Greed (E Spitzer law suit GlaxoSmith Kline

• Triumph of public health over Big Pharma?

TIME 8/2002

Too hot to touch-visual

Psychiatry has other obstacles

• Something about the difference with psychiatry

• Continuing questions

• Continuing stigma and misunderstanding

• Affect of lay media (get visual = drugging kids)

• Concerns about developing brain

Carving Nature at it’s Joints

DSM at ~400 diagnoses:Carving Nature at its Feathers?!

Medications risk to brain development-visual

Suicide 101

• In rank order, a common cause of death

• Almost all have psychiatric disorders

• The majority have a mood disorder

• The majority are not in treatment

• A very small fraction are on antidepressants at the time of death by suicide (3%)

Psychiatrically Ill

Deaths

Mood Disorders

Suicide 101

On Antidepressants

Antidepressant suicidality

Risks of untreated

depression

?

• Pooled analysis, short-term placebo controlled

• Total of 24 trials

• Nine antidepressants

• 4400 patients

• MDD, OCD, anxiety

October 15, 2004

• Suicidal thinking and behavior increased on antidepressants

• No suicide deaths occurred

• Absolute Risk on Placebo = 2%

• Absoulte Risk on Antidepressant = 4%

• Relative Risk Difference = 2%

October 15, 2004

October 15, 2004

Antidepressants per Antidepressants per 1000 medication 1000 medication

usersusers

Suicides / 100,000 Suicides / 100,000 populationpopulation

11.5

73.1

0

10

20

30

40

50

60

70

80

1 25.7

5.8

5.9

6

6.1

6.2

6.3

6.4

6.5

6.6

1 21990 2000 1990 2000

[You’ll have to comment about the scale, the small change, but relative to the other graphs we made, same ballpark and significant

Olfson et al, Arch Gen Psych 2003

Gibbons et al, Am J Psych 2007

1988 1992 1996 2000 2004

Su

icid

e r

ate

pe

r 10

0,0

00

2.5

3.0

3.5

4.0

4.5

U.S. Suicide Rates, <20 years old

Warnings:UK Health CanadaFDA

Decreasing Antidepressants (teens)Unchanged Suicide Rate

Wheeler. BMJ 2008; 336: 542-

Katz et al, Can Med Assoc J, 2008

Canadian Suicide Rates, 8-17 year olds

Warnings:UK Health CanadaFDA

• Black box changed some

• 19-24

What is the mechanism?

Do antidepressants work?

• If not, this is a “No brainer”

Efficacy of Antidepressants in Kids

Placebo Antidepressant Difference

Depression 50% 61% 11%

OCD 32% 52% 20%

Non-OCD Anxiety

39% 69% 30%

Bridge, J et. al. JAMA. 2007; 297:1683-1696

Efficacy of Fluoxetine in Kids

Placebo Fluoxetine Difference

Depression 42% 62% 20%

OCD 28% 51% 23%

Non-OCD Anxiety

35% 61% 26%


Epidemiology

• Common

• Start early

• devestating

• Undertreated

• Brain: a different organ

Risk vs. Benefit for Kids

NNT NNH

• Non-OCD Anxiety 3 200

• OCD 6 143

• Depression 10 112


Compare to Asthma

LABA Parallel Example

• Two columns with checks for similarities and no checks for differences

Summarize the LABA story

Salpeter, S. R. et. al. Ann Intern Med 2006;144:904-912

Effect of long-acting {beta}-agonists compared with placebo on odds ratio of life-threatening asthma exacerbations

From “Suicidality” to Suicide Death

Suicide Death NNH: 1/280,000

Suicidality NNH: 1/143

Suicide Suicide AttemptAttempt NNH: NNH: 1/2801/280

Attempt / Death : 1 / 1000

Translating “Suicidality” to Suicide Death

Suicidality or suicide attempt is a proxy for SuicideA rough proxy, since attempts are much less common

~1000 attempts for every suicideSO

With “suicidality” NNH = 143but only ~half were attempts, thus NNH ~ 280

Translating attempts to suicide deaths (x 1000) = 280,000OR

~1 per one quarter million

Intracellular Tug-of-War

Atrophic Factors: glutamate, cortisol

Trophic Factors: Trophic Factors: BDNF, bcl-2BDNF, bcl-2

Courtesy Jim Phelps, MD

Neuroplasticity andCellular ResilienceBDNF

BDNF

anti-depressants

PI-3(inositol-lipid pathway)

GSK-3

BAD

GR

Bcl-2exercise (!)

omega-3’s(fish oil)

?

lithium

CREB

valproate

Stress/Depression

glutamate

calcium

cortisol

lamotrigine(?)

Courtesy Jim Phelps, MD

Take Home Messages

• Screen for bipolar disorder

• Collect family history

• Use antidepressants with appropriate monitoring

• Refer kids to evidence-based psychotherapy

Bipolar Disorder

…patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

October 2004

http://www.hhs.gov/

"Health care providers should instruct patients, their families and their caregivers to be alert for the emergence of agitation, irritability, and the other symptoms described above, as well as the emergence of suicidality and worsening depression".

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania, and mania have been reported…[w/ AD’s]

March 22, 2004

http://www.hhs.gov/

Because antidepressants are believed to have the potential for inducing manic episodes in patients with bipolar disorder, there is a concern about using antidepressants alone in this population [bipolar]. Therefore, patients should be adequately screened to determine if they are at risk for bipolar disorder before initiating antidepressant treatment so that they can be appropriately monitored during treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

March 22, 2004

http://www.hhs.gov/

GENERAL BEHAVIOR INVENTORYMania-Parent Version (GBI-P-M)

Which antidepressants?

What to Monitor

• Worsening depression

• Agitation/Irritability

• Activation (speeded up movements & mind)

• Sleeplessness

• Intense anxiety

When to Monitor?

• Thoughts about suicide or dying• Attempts to commit suicide• New or worse depression• New or worse anxiety• Feeling very agitated or restless• Panic attacks• Difficulty sleeping (insomnia)• New or worse irritability• Acting aggressive, being angry, or violent• Acting on dangerous impulses• An extreme increase in activity and talking• Other unusual changes in behavior or mood

• Thoughts about suicide or dying• • Attempts to commit suicide• • New or worse depression• • New or worse anxiety• • Feeling very agitated or restless• • Panic attacks• • Difficulty sleeping (insomnia)• • New or worse irritability• • Acting aggressive, being angry, or violent• • Acting on dangerous impulses• • An extreme increase in activity and talking• • Other unusual changes in behavior or mood

Combined Treatment of OCD: CBT + Sertraline 54%CBT 39%Sertraline 21%Placebo 4%

POTS Study (adolescent OCD): JAMA. 2004; 292:1969-1976

Combined Treatment of Depression: CBT + Fluoxetine 71%CBT 61%Fluoxetine 43%Placebo 35%

TADS Study (adolescent depression): JAMA. 2004; 292:807-820

Combined Treatment of OCD: CBT + Sertraline 54%CBT 39%Sertraline 21%Placebo 4%

POTS Study (adolescent OCD): JAMA. 2004; 292:1969-1976

Combined Treatment of Depression: CBT + Fluoxetine 71%CBT 61%Fluoxetine 43%Placebo 35%

TADS Study (adolescent depression): JAMA. 2004; 292:807-820

BMJ march 2008

0

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1 2 3 4 5 6 7 8 9 10 11 12 13

Series1

1993 1997 2001 2005

Fluoxetine Associated with Birth of New Hippocampal Cells

• New neurons born in human hippocampus• Study in mice

– Fluoxetine known to show specific behavioral effects linked to its antidepressant effects

– Focused x-rays blocked neurogenesis in hippocampus– With the the birth of new cells blocked, the

behavioral/antidepressant effects of fluoxetine were rendered ineffective suggesting that this is the mechanism of action

Science 2003 301: 805

• Things like new or more intense suicidal thoughts, anxiety, agitation, irritability, or markedly increased physical or mental activity.

The Future

• Current Studies In Progress

• CAPTN

• Primary Care / Mental Health Collaboration– OOCAP / OPS Collaboration

CAPTN ASK WEEKLY ENROLLMENT

(AS OF 5/30/08)

ENROLLMENT GOAL 2,420

Site # Principal Investigator Location Total Enrolled

AL520 Nelson Handal Dothan, AL 28

IL226 Phillip Helding Hinsdale, IL 27

OH124 Stephen Grcevich Chagrin Falls, OH 24

NC509 Allan Chrisman Durham, NC 16

OR701 Rick Bingham Salem, OR 15

SITES ENROLLING 41 SUBJECTS ENROLLED 278

Hippocampus

Hippocampal Volume Loss

Sheline et al Am J Psychiatry. 2003

Early-Onset Depression

MacMaster and Kusumakar BioMedCentral (BMC) Medicine 2004

age: 13-18 years old

illness duration: 2.89 yrs avg

mean onset: 14 yrs old

Left: 17% decrease vs. controls

Thanks: Jim Phelps, M.D.

www.PsychEducation.org

Objectives

1. Learn a little about the current scientific framework of how antidepressants work.

2. Understand the importance of actively identifying and treating anxiety and depression in children and adolescents.

3. Know the current status of research on the negative and positive affect of antidepressants on suicidal thoughts, behavior, and suicide death.

4. Understand how primary care clinicians should rationally include antidepressants in the treatment of anxiety and depression in kids even in the context of concerns about suicide risk.

handouts to send: moodcheck, hcl-32 props: load internet: set up google on hcl-32

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