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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 – – – – 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 • • • • 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 • • • • • 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) • • • • • • • 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