Transcript IBD and the Brain Eva Szigethy MD, PHD Associate Professor

Psychopharmacology for the IBD
pediatric caregiver
Eva Szigethy MD, PHD
Associate Professor of Psychiatry, University of Pittsburgh
Director, Medical Coping Clinic, Children’s Hospital of Pittsburgh
Director, Visceral Inflammation and Pain (VIP) Center
Division of Gastroenterology, Hepatology, and Nutrition
December 14, 2013
Disclosure
• Sources of Funding
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CCFA Senior Investigator Award
NIMH R01 Grants
American Psychiatric Press Inc., Book Editor
Merck- Consultant, Advisory Board
• All medication suggestions in this
presentation are off-label uses unless
noted otherwise.
Targets for Psychotropic Medications
Mood
LIFE STRESS
EARLY
ADVERSITY
ILLNESS
PERCEPTION
Pain
INFLAMMATION
Sleep
STEROIDS
Anxiety
GENETICS
Case # 1
• 12 year old female with inactive IBD on biologics
present with:
– Anxiety
– Depression
with impaired daily functioning
– Pain
WHAT WOULD YOU DO?
Psychotherapy!
Psychotherapy!
Psychotherapy!
Antidepressant considerations
TCA
SSRI
SNRI
Pain
Depression
Anxiety
Adverse effects Sedation
Constipation
Hypotension
Dry mouth
Arrhythmia
Weight gain
Depression
Anxiety
Pain
Depression
Agitation
Diarrhea
Night sweats
Headache
Sexual
dysfunction
Nausea
Agitation
Dizziness
Sleep
disturbance
Fatigue
Liver
dysfunction
Overdose Risk
Cost/month
Minimal
$40-80
Minimal
$60-100
Potential
benefits
Moderate
$5-30
Anxiety disorders- common complaints not
always captured in anxiety disorder
definitions
• Excessive interpersonal
sensitivity
• Fear
• Apprehension
• Dread
• Shyness
• Worry
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Physical complaints
Sleep problems
Eating problems
Excessive need for
reassurance
• Explosive outbursts
• Avoidance
Antidepressants in patients with IBD
• Clinical reports and case series support for SSRIs,
SNRIs and bupropion for depression and anxiety in
adults
• No randomized trials in adults or children
• Recent review of EMR of 1000 IBD patients- most
common antidepressants prescribed by GI and PCPs
• SSRIs
• SNRIs
• Bupropion
Serotonin Reuptake Inhibitors FDA
approved for children
• Approved for OCD
– Clomipramine > 10 years
– Fluvoxamine > 8 years
– Sertraline > 6 years
– Fluoxetine > 7 years
• Approved for depression
– Fluoxetine > 12 years
– Escitalopram > 12 years
• Approved for non-OCD anxiety
– none
SSRI Efficacy for non-OCD anxiety
disorders
• Separation anxiety disorder, generalized anxiety
disorder, social phobia
– Fluvoxamine
– Fluoxetine
• Specific phobia
– Paroxetine
– Fluoxetine
– Venlafaxine
• Generalized anxiety disorder
– Sertraline
– Venlafaxine
RUPP 2001; Birmaher 2003; Walkup 2009; Wagner 2004, Beckel 2007; March 2007; Rynn 2007
Anxiety Disorders
• Antidepressants work well
– SSRIs is medication of choice
– Some data for augmentation strategies
– Limited data for benzodiazepines
• All psychopharmacology enhanced with
psychotherapy by trained professional
Dosing of SSRIs based on clinical trials
• Fluoxetine up to 40 mg
by week 12
• Fluvoxamine 100-150
mg by week 10
• Sertraline 100-150mg
by week 8
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Side Effects
Activation common 1015%
Bipolar switch
uncommon (< 1%)
GI side effects early
Easy bruising and
bloody noses
Suicidality ??
Citalopram Dosing
• FDA: citalopram should not be used > 40
mg/day
• Concern about prolongation of QT interval
CITALOPRAM DOSE
INCREASE IN QT INTERVAL, milliseconds
20 mg
8.5
40 mg
12.6
60 mg
18.5
What to do about SSRI activation?
• Education- early in treatment (24-72 hours post dose
change) and usually subsides
• Switch to second SSRI or non-activating antidepressant
– Mirtazapine (use if + anorexia, nausea, diarrhea)
– Duloxetine (use if + pain)
– TCAs
• Amitriptyline (3 ◦) more sedating
• Nortriptyline (2◦) less sedating
• Desipramine (2◦) least sedating
Case #2
• 16 year old male with IBD x 4 years and
depression
– Active inflammation +/– Comorbid anxiety +/– Abdominal pain +/-
Depressive Subtypes in Pediatric IBD
Fever
Diarrhea
INFLAMMATORY
BOWEL DISEASE
Inflammation
Pain
Fatigue
Sleep
Depressed Mood
Concentration
Anhedonia
Hopelessness
Suicide
DEPRESSION
Despair
Worthlessness
Decisions for depression in pediatric
IBD
• If inactive IBD.......then SSRI first line
• If active IBD………then bupropion first line
• If severe comorbid anxiety….then SSRI alone
or added to bupropion
• If comorbid pain….then SNRI or low dose TCA
added
Pediatric Depressive Disorders (No IBD)
• SSRI- first line (60% response rate)
• Alternate SSRI-second line (50% response rates)
• Different class of antidepressant- third line
– SNRI- duloxetine (20-40 mg)
– Bupropion- open trials promising; no randomized
trials (150- 300mg)
– Selegine (transdermal) 6mg, 9mg or 12 mg/24h
• Newer antidepressants- no efficacy data in
children
– vilazadone, desvenlafaxine, l-methylfolate, ketamine
Pediatric Depression
• Early response (12 weeks) predicts remission
at 24 weeks
• Predictors of poor response:
– More severe depression
– Baseline suicidality
– Anhedonia
– Hopelessness
– Comorbid disorders (anxiety, substance abuse)
– Family conflict
Emslie 2011; Goldstein 2007; Asarnow 2009; Mcmalkin 2012
The Black Box Warning
• October 2004: Black Box warning for suicidality in
adolescents and children
– 24 Trials examined, containing 4400 children and
adolescents
– 9 Antidepressants included
– No completed suicides in these trials
– More youth on a med spontaneously reported suicidality
vs. youth on placebo (4/100 vs. 2/100)
• This included suicidal thoughts and behaviors but again, none of
these studies had any completed suicides.
• A more recent trial has shown that a decrease in the
amount of SSRI use has led to an increase in the suicide
rates in children and adolescents.
Gibbons, R. American J. Psychiatry 163:11, November 2006; Bridge, J. JAMA (2007) 297:15:
1683-96.
Suicide Prevention in Depressed
Children and Adolescents
• Encourage home safety
– Adolescents are much more likely to kill themselves with
firearms
– Children are much more likely to kill themselves by
strangulation
– Ask about suicide and watch for suicidal behavior
• Monitor and ask about drug/alcohol use
• Monitoring after starting antidepressant:
– Weeks 1-4: weekly
– Weeks 5-12: every other week
– After Week 12: as clinically indicated (Q4wks?)
– Bottom line is any child on an SSRI, monitor carefully
especially in the beginning.
SSRI Treatment Choices for Depression
SSRI
Forms
Start Dose
+/- by
Max Dose
+RCT
Evid.
FDA Approval
Fluoxetine
Tab,
liquid
10 mg
5-10mg
60mg
Y
8-17
Sertraline
Tab,
liquid
25mg
12.525mg
200mg
Y
N
Citalopram
Tab,
liquid
10mg
10mg
40mg
Y
N
Escitalopram
Tab,
liquid
5mg
5mg
20mg
Y
12-17
Paroxetine
Tab,
liquid
10mg
10mg
60mg
N
N
Fluvoxamine
Tab,
liquid
25mg BID
25mg
300mg
N
N
Patient put on high dose steroids with changes
in mood (irritable, depressed)…..
IBD
(Auto)immune
Inflammation
Surge of cytokines
(TNFα, IL-2, IL-6, IL-12/23,IFN-γ)
Steroids
Treatment
Systemic corticosteroids
What will you do?
It depends…..
• If sleep disrupted……treat sleep disturbance
• If irritable/depressed…..SSRI, mood stabilizer
• If concentration impaired/fatigue….
bupropion, stimulants
When to consult a psychiatrist?
• If suicidal/suicide plan/suicide attempt
• If psychotic (steroids, delirium)
• If post-traumatic stress disorder- requires
intensive behavioral interventions….no magic pill.
• If multiple comorbid psychiatric disorders present
Comorbid psychiatric diagnoses in
depressed youth with IBD (n=217)
(Szigethy et al., 2013)
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Generalized anxiety disorder 22%
Phobias 15%
Attention Deficit Hyperactivity disorder 16%
Oppositional Defiant Disorder 9%
Separation Anxiety Disorder 9%
Post-traumatic stress disorder 1.5%
Eating disorder 1%
Augmentation Strategies…time to call
a psychiatrist
• Clonazepam (dose up to 4-6mg/daily)
• Neuroleptics (good for OCD, comorbid tics but severe
side effects)
• IV clomipramine (HR, BP, EKG) IV route bypasses liver
• Buspirone (though negative trial for GAD)
• Lithium ( Serotonergic sensitization of brain); good for
comorbid depression
• Stimulants- good for SSRI induced apathy and
comorbid ADHD or depression
• Atomoxetine…comorbid anxiety and ADHD or if
stimulants not tolerated
Biopsychosocial Treatment
BIOLOGICAL
PSYCHOLOGICAL
SOCIAL
Treat underlying
organic problem
Cognitive
restructuring/
Education
Exercise
Monitoring symptoms
BehavioralEnable/expect return
activation/distraction to life
Medications
Conflict resolution
Family/Parent therapy
Alternativeacupuncture
Hypnosis/Meditation
School/ work
modification
Sleep
Activity scheduling
Social network