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Current Management of Depression and Anxiety in Children and Adolescents


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This presentation was offered in 2009 as part of a CME conference at Fairview Hospital/CCF Health System in the summer of 2009.

Published in: Health & Medicine
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Current Management of Depression and Anxiety in Children and Adolescents

  1. 1. The Current Management of Depression and Anxiety in Children and Adolescents Stephen Grcevich, M.D. Child and Adolescent Psychiatry The Family Center by the Falls Chagrin Falls, Ohio President, Board of Directors Key Ministry Foundation Presented at Fairview Hospital/CCF Health System Cleveland, Ohio June 12, 2009 <ul><li>E-mail: Web: </li></ul><ul><li>Phone: (440) 543-3400 Special Needs Ministry: </li></ul>
  2. 2. Educational Objectives: <ul><li>Review complexities involved with accurately diagnosing depression and anxiety disorders in children and teens </li></ul><ul><li>Discuss recent large scale, publicly-funded studies examining the benefits of psychotherapy and serotonin reuptake inhibitors in children and teens with depression or anxiety </li></ul><ul><li>Provide an update on the risks of suicidal thoughts and behavior in youth prescribed antidepressants </li></ul><ul><li>Review the relative benefits and limitations of available medications used to treat depression and anxiety in kids </li></ul><ul><li>Outline the benefits and limitations of psychotherapeutic interventions in this population </li></ul>
  3. 3. Potential Conflicts of Interest 2008-09: (Complete disclosure as % of annual income available upon request) Pharmaceutical Industry Consulting: Shire US (100% of compensation donated to charity in 2008) Grant/Research Support Child and Adolescent Psychiatry Trials (CAPTN) Network-ASK, NOTA studies funded through NIMH Speakers’ Bureaus None since 2006 Other Financial/Material Support Web MD/Medscape Leerink-Swann Major Shareholder None
  4. 4. Age-appropriate fears in children: <ul><li>Infants: fear of loud noises, fear of being startled, fear of strangers </li></ul><ul><li>Toddlers: fear of imaginary creatures, fear of the dark, separation anxiety </li></ul><ul><li>School-age children: worries about injury, natural events (storms) </li></ul><ul><li>Older children, adolescents: fears related to school performance, social competence, health issues </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(2):267-283
  5. 5. Specific Anxiety Disorders in Children, Adolescents: <ul><li>Separation Anxiety Disorder </li></ul><ul><li>Specific Phobia </li></ul><ul><li>Generalized Anxiety Disorder </li></ul><ul><li>Social Phobia </li></ul><ul><li>Selective Mutism </li></ul><ul><li>Panic Disorder </li></ul><ul><li>Obsessive-Compulsive Disorder </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(2):267-283
  6. 6. Anxiety: Red Flag Signs and Signals <ul><li>“ What If” Questions </li></ul><ul><li>Avoidance </li></ul><ul><li>Repeatedly seeking reassurance </li></ul><ul><li>Physical complaints </li></ul><ul><li>Sleep problems (sleep latency) </li></ul><ul><li>Poor concentration, attention </li></ul><ul><li>Perfectionism </li></ul><ul><li>School attendance problems </li></ul><ul><li>Easily distressed </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(2):267-283
  7. 7. Epidemiology of Anxiety Disorders: <ul><li>Prevalence of at least one anxiety disorder: 6-20% </li></ul><ul><li>Girls>Boys (especially phobias, panic disorder, agoraphobia, separation anxiety) </li></ul><ul><li>Severity=persistence </li></ul><ul><li>Kids often develop new anxiety disorders over time </li></ul><ul><li>Greater risk of depression, substance abuse </li></ul><ul><li>Genetics, parent-child interactions, parental modeling, temperament are risk factors </li></ul><ul><li>Coping skills may be considered as protective factors </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(2):267-283
  8. 8. MDD Diagnostic Criteria: DSM-IV <ul><li>At least 2 weeks of pervasive change in mood manifest by either depressed or irritable mood and/or loss of interest and pleasure. </li></ul><ul><li>Other symptoms: changes in appetite, weight, sleep, activity, concentration or indecisiveness, energy, self-esteem (worthless, excessive guilt), motivation, recurrent suicidal ideation or acts. </li></ul><ul><li>Symptoms represent change from prior functioning and produce impairment </li></ul><ul><li>Symptoms may be attributable to substance abuse, medications, other psychiatric illness, bereavement, medical illness </li></ul>DSM IV-TR, American Psychiatric Association
  9. 9. Epidemiology <ul><li>MDD prevalence: 2% children, 4%-8% adolesc. </li></ul><ul><li>Male:female ratio: childhood 1:1, adolesc 1:2 </li></ul><ul><li>Cumulative incidence by age 18 years: 20% </li></ul><ul><li>Since 1940, each successive generation at higher risk for MDD </li></ul><ul><li>Dysthymia prevalence: 0.6%-1.7% children, 1.6%-8% adolesc. </li></ul><ul><li>Often under-recognized </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(11):1503-1526
  10. 10. Need to Recognize Developmental Variations of MDD <ul><li>CHILDREN: </li></ul><ul><li>More symptoms of anxiety (i.e. phobias, separation anxiety), somatic complaints, auditory hallucinations </li></ul><ul><li>Express irritability with temper tantrums & behavior problems, have fewer delusions and serious suicide attempts </li></ul><ul><li>ADOLESCENTS: </li></ul><ul><li>More sleep and appetite disturbances, delusions, suicidal ideation & acts, impairment of functioning </li></ul><ul><li>Compared to adults, more behavioral problems, fewer neurovegative symptoms </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(11):1523-1546
  11. 11. Comorbidity and Depression in Children and Adolescents: <ul><li>40-90% have one or more additional psychiatric diagnoses </li></ul><ul><li>20-50% have two or more comorbid diagnoses </li></ul><ul><li>Most common comorbidities: dysthymia, ADHD, oppositional defiant disorder, substance use disorders </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(11):1523-1546
  12. 12. Time Course of Depression in Kids: <ul><li>Median duration in clinically referred kids is 7-9 months </li></ul><ul><li>Duration in community based samples is on average, two months </li></ul><ul><li>90% remit within 1-2 years </li></ul><ul><li>40-60% will relapse after acute treatment </li></ul><ul><li>70% rate of recurrence within five years </li></ul><ul><li>20-40% may eventually develop bipolar disorder </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(11):1523-1546
  13. 13. Differential Diagnosis of Depression: <ul><li>Anxiety disorders </li></ul><ul><li>Bipolar disorder </li></ul><ul><li>Learning disabilities </li></ul><ul><li>ADHD, disruptive behavior disorders </li></ul><ul><li>Personality disorders (Borderline) </li></ul><ul><li>Substance use disorders </li></ul><ul><li>Adjustment disorder with depressed mood </li></ul><ul><li>Bereavement </li></ul><ul><li>Medical causes (including medication) </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(11):1523-1546
  14. 14. Conditions associated with/mistaken for anxiety disorders in kids: <ul><li>ADHD (treatment may exacerbate anxiety) </li></ul><ul><li>Asperger’s disorder </li></ul><ul><li>Learning disabilities </li></ul><ul><li>Depression </li></ul><ul><li>Psychotic disorders </li></ul><ul><li>Medication-induced anxiety </li></ul>J Am Acad Child Adolesc Psychiatry, 2007;46(2):267-283
  15. 15. Treatment options for depression: <ul><li>Antidepressant medication </li></ul><ul><li>Cognitive-Behavioral Therapy (CBT) </li></ul><ul><li>Family Therapy </li></ul><ul><li>Other therapies ( interpersonal therapy , group therapy, supportive psychotherapy) (Evidence-based interventions in green) </li></ul>J Am Acad Child Adolesc Psychiatry, 2007; 46(11):1503-1526
  16. 16. Treatment of anxiety disorders in children, adolescents: <ul><li>Cognitive-behavioral therapy (with modifications for specific anxiety disorders) </li></ul><ul><li>SSRIs, other medications </li></ul><ul><li>Parent-child, family interventions </li></ul><ul><li>Classroom-based accommodations, interventions Evidence-based interventions in green </li></ul>J Am Acad Child Adolesc Psychiatry , 2007; 46(2):267-283
  17. 17. Medications Used in Kids With Anxiety Disorders <ul><li>SSRIs (Sertraline, Fluvoxamine, Fluoxetine) </li></ul><ul><li>Clomipramine </li></ul><ul><li>Venlafaxine </li></ul><ul><li>Tricyclic antidepressants (imipramine) </li></ul><ul><li>Buspirone </li></ul><ul><li>Benzodiazepines </li></ul>J Am Acad Child Adolesc Psychiatry 2007; 46(2) 267-283
  18. 18. CAMS (Child-Adolescent Anxiety Multimodal Study): <ul><li>NIMH-funded, RCT comparing placebo, sertraline, CBT and combination treatment (CBT+sertraline) for treatment of separation anxiety disorder, social anxiety disorder, generalized anxiety disorder </li></ul><ul><li>Children, ages 7-17, N=488 </li></ul><ul><li>CBT: 14 sessions, using “Coping Cat” curriculum </li></ul><ul><li>Sertraline: started at 25 mg/day, increased by fixed-flexible titration (mean dose:133 mg/day) </li></ul>Walkup JT et al, N Engl J Med, 2008;359:2753-2766
  19. 19. CAMS (Child-Adolescent Anxiety Multimodal Study): <ul><li>Response rates: COMB: 80.7%, CBT: 59.7%, SER: 54.9%, PBO: 23.7% </li></ul><ul><li>COMB>CBT=SER>PBO </li></ul><ul><li>Effect Sizes: COMB: 0.86, SER: 0.45, CBT: 0.31 </li></ul><ul><li>No adverse effects>PBO in medication groups </li></ul><ul><li>Beneficial effects of COMB vs. SER evident after week 8 </li></ul>Walkup JT et al, N Engl J Med, 2008;359:2753-2766
  20. 20. Indications for Pharmacotherapy in AACAP Practice Parameters for Depression: <ul><li>Children and teens with moderate to severe depression </li></ul><ul><li>More severe depressive episodes will generally require antidepressant treatment </li></ul><ul><li>Medication may be administered alone until the child is amenable to psychotherapy, or combined with therapy from the beginning </li></ul><ul><li>Youth who don’t respond to monotherapy (medication or psychotherapy) require a combination of medication and psychotherapy </li></ul>J Am Acad Child Adolesc Psychiatry , 2007; 46(11):1503-1526
  21. 21. Published double-blind, placebo-controlled studies: SSRI efficacy for MDD in youth <ul><li>Emslie et al (1997): modest fluoxetine efficacy: fluoxetine 58%, placebo 32% </li></ul><ul><li>Keller et al (2001): paroxetine efficacy: paroxetine 63%, imipramine 50%, placebo 46%, 1 of 2 primary outcome measures was significant; 2 other studies were negative </li></ul><ul><li>Emslie et al (2002): fluoxetine efficacy: effects modest (fluoxetine 41%, placebo 20%) & not all outcome measures were significantly different than placebo </li></ul><ul><li>Wagner et al (2003): sertraline efficacy: sertraline 69%, placebo 59% </li></ul><ul><li>Emslie et al (2009): escitalopram efficacy: 64.3%, placebo 52.9%, effect size 0.27 </li></ul>Emslie GJ et al, J Am Acad Child Adolesc Psychiatry 2009;48(7):721-729
  22. 22. Metanalysis of Randomized Trials of SSRIs: <ul><li>Pooled response rates (13 trials, N=2910) 61% response rate on active drug, 50% placebo NNT=10, NNH=112 (NNT=6 for OCD, NNT=3 for anxiety) </li></ul><ul><li>Pooled risk differences for suicidal ideation (27 trials, N=5310), increased risk of suicidal ideation=0.7% (0.9% MDD, 0.5% OCD, 0.7% ANX) </li></ul><ul><li>No completed suicides </li></ul><ul><li>For children ages 12 and under with MDD, only fluoxetine demonstrated efficacy </li></ul>Bridge JA et al, JAMA 2007; 297(15):1683-1696
  23. 23. Metanalysis of Randomized Trials of SSRIs: <ul><li>Effect size of SSRIs in MDD: 0.25 </li></ul><ul><li>Effect size in OCD: 0.48 </li></ul><ul><li>Effect size in non-OCD anxiety: 0.69 </li></ul><ul><li>Adolescents respond better than school-age children for both MDD and Anxiety </li></ul><ul><li>Better response to antidepressants in more severe illness </li></ul>Bridge JA et al, JAMA 2007; 297(15):1683-1696
  24. 24. Why does fluoxetine perform better than other SSRIs in MDD?: <ul><li>Long half life makes inconsistent adherence less of a concern </li></ul><ul><li>Unique pharmacokinetic, pharmacodynamic properties? </li></ul><ul><li>Lower rates of discontinuation from withdrawal symptoms </li></ul><ul><li>Fluoxetine studies involved fewer sites, more experienced investigators </li></ul>Bridge JA et al, JAMA 2007; 297(15):1683-1696
  25. 25. Combination Treatment of MDD <ul><li>NIMH sponsored “The Treatment of Adolescents with Depression Study” (TADS): </li></ul><ul><li>Multicenter controlled clinical trial </li></ul><ul><li>12-17 year olds with MDD </li></ul><ul><li>Aims to compare efficacy of fluoxetine, CBT, combination, & placebo in 36 weeks with 1 year follow-up. </li></ul>March J et al. J Am Acad Child Adolesc Psychiatry, 2006;45(12):1393-1403
  26. 28. Treatment Resistant Study <ul><li>NIMH funded multicenter study “Treatment of Resistant Depression in Adolescents (TORDIA) </li></ul><ul><li>Aims to benefit treatment resistant adolescents, age 12-18 years old </li></ul><ul><li>Compare fluoxetine, paroxetine, or venlafaxine, either alone or in combination with CBT for 24 weeks with 1 year follow-up </li></ul>Brent D et al, JAMA, 2008;299(8):901-913
  27. 29. TORDIA Results: <ul><li>Response rate to CBT+2 nd antidepressant=54%, antidepressant alone 41% (significant) </li></ul><ul><li>2 nd SSRI and Venlafaxine equally effective </li></ul><ul><li>2 nd SSRI better tolerated than venlafaxine </li></ul>Brent D et al, JAMA, 2008;299(8):901-913
  28. 30. The FDA and Antidepressants for Kids: <ul><li>Boxed warning regarding increased risk of suicidality issued 10/15/04 </li></ul><ul><li>Antidepressants were not contraindicated in children and adolescents! </li></ul><ul><li>Website for more info: </li></ul>
  29. 31. Slide courtesy of David Fassler, MD
  30. 32. Current FDA position <ul><li>The risk of suicidality for these drugs was identified in a combined analysis of short-term (up to 4 months) placebo-controlled trials of nine antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs) and others, in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. A total of 24 trials involving over 4400 patients were included. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4%, twice the placebo risk of 2%. No suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: </li></ul><ul><li>* Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders. </li></ul><ul><li>* Anyone considering the use of an antidepressant in a child or adolescent for any clinical use must balance the risk of increased suicidality with the clinical need. </li></ul><ul><li>* Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. </li></ul><ul><li>* Families and caregivers should be advised to closely observe the patient and to communicate with the prescriber. </li></ul><ul><li>* A statement regarding whether the particular drug is approved for any pediatric indication(s) and, if so, which one(s). </li></ul><ul><li>Among the antidepressants, fluoxetine and escitalopram are approved for use in treating MDD in pediatric patients. Fluoxetine, Sertraline, Fluvoxamine, and Clomipramine are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children. </li></ul>
  31. 33. Cognitive Behavioral Therapy (CBT) <ul><li>Three Components: </li></ul><ul><li>Cognitive (Changing Thoughts) </li></ul><ul><li>Behavioral (Changing Behaviors) </li></ul><ul><li>Emotional/Physiological (Changing Feelings) </li></ul>
  32. 34. Challenges affecting response to CBT: <ul><li>Research studies employ highly manualized treatment interventions </li></ul><ul><li>Does the clinician have formal training in CBT? </li></ul><ul><li>Is the clinician actually doing CBT? </li></ul><ul><li>Some evidence (in kids being treated for anxiety) that exposure phase of treatment is critical, may not see benefits until 9 or more visits </li></ul>
  33. 35. Classroom-based accommodations, interventions: <ul><li>Case management support to coordinate planning, communication between school, treatment providers </li></ul><ul><li>Education of school personnel (threats of truancy complicate treatment) </li></ul><ul><li>Identification of adults in school who can assist in problem-solving, anxiety management strategies </li></ul><ul><li>Shortened assignments for kids with OCD, GAD </li></ul><ul><li>Extended test-taking time, testing in private room for kids with performance anxiety </li></ul>
  34. 36. Conclusions <ul><li>Anxiety and depression are common conditions in the pediatric population, and similarities exist in the differential diagnosis and treatment of patients presenting with such symptoms. </li></ul><ul><li>In general, anxiety appears more responsive to treatment with cognitive-behavioral therapy and/or medication than Major Depression. </li></ul><ul><li>A slightly increased risk of suicidal thoughts/behavior early in the course of treatment is present with SSRIs are used in the treatment of depression (0.9%), OCD (0.5%) and anxiety disorders (0.7%) </li></ul><ul><li>Combination therapy (CBT plus SSRI) has been demonstrated to be more effective than medication alone or CBT alone in youth with anxiety or depression </li></ul>
  35. 37. Additional Resources: <ul><li>Parent Medication Guide for Depression: </li></ul><ul><li> </li></ul><ul><li>(also available is med guide for ADHD) </li></ul><ul><li>AACAP Practice Parameters (free download): </li></ul><ul><li> </li></ul><ul><li>Antidepressant metanalysis (Bridge et al, 2007) </li></ul><ul><li> </li></ul><ul><li>Today’s Power Point with bonus material: </li></ul><ul><li> </li></ul>
  36. 38. Question 1: Which of the following steps would not be appropriate for a PCP evaluating a 12 year old with insomnia and school refusal: <ul><li>A: Perform a comprehensive physical exam and order labs based upon the findings of the PE </li></ul><ul><li>B: Inquiring about the child’s academic performance and asking the child’s parents and teachers to complete standardized rating scales </li></ul><ul><li>C: Initiating treatment with fluoxetine after the disclosure that the child had been bullied at school ten days before, in the absence of a history of preexisting anxiety </li></ul><ul><li>D: Asking lots of questions about the child’s eating habits, energy level, concentration, daily fluctuations in mood, friendships, interests, and asking the patient if he/she has experienced any thoughts about committing suicide </li></ul>
  37. 39. Question 2: Which of the following medications are approved for use in the pediatric population by the FDA? <ul><li>A: Paroxetine (Paxil) for depression in teens </li></ul><ul><li>B: Venlafaxine XR (Effexor XR) for treatment of anxiety in teens </li></ul><ul><li>C: Fluvoxamine (Luvox) for treatment of Obsessive-Compulsive Disorder in children and teens </li></ul><ul><li>D: Citalopram (Celexa) for treatment of anxiety in children and teens </li></ul>
  38. 40. Question 3: Which of the following statements about the TADS study is true ? <ul><li>A: CBT appeared to provide significant benefit to depressed teens after twelve weeks compared to placebo </li></ul><ul><li>B: Teens treated with fluoxetine demonstrated an increase in suicidal thoughts during the acute phase of treatment </li></ul><ul><li>C: Fluoxetine as a stand-alone treatment for depression was more effective than CBT in acute treatment </li></ul><ul><li>D: There was no significant benefit from combining CBT with fluoxetine in acute treatment </li></ul>
  39. 41. Question 4: Which of the following statements is false : <ul><li>A: Most randomized studies of SSRIs in youth with depression have demonstrated medication more effective than placebo </li></ul><ul><li>B: SSRIs tend to demonstrate far more robust effect size for treatment of anxiety in children and adolescents than for depression </li></ul><ul><li>C: The occurrence of increased suicidal thoughts in response to treatment with SSRIs is greater in youth with depression than anxiety </li></ul><ul><li>D: Differences in delivery of cognitive-behavioral therapy in the community may limit the ability to generalize results of treatment in large scale studies of youth with depression or anxiety </li></ul>
  40. 42. Question 5: All of the following statements about the CAMS study for anxiety in children and teens are true except : <ul><li>A: CBT and sertraline were equally effective as stand alone treatments for anxiety and superior to placebo. </li></ul><ul><li>B: Full benefits of combination therapy were evident within the first eight weeks of treatment </li></ul><ul><li>C: Rates of insomnia, fatigue, sedation and restlessness were lower in the CBT group compared to the medication group </li></ul><ul><li>D: No differences were noted in rates of suicidal or homicidal ideation between kids in the sertraline group and kids in the placebo group </li></ul>
  41. 43. Answers <ul><li>1-C </li></ul><ul><li>2-C </li></ul><ul><li>3-C </li></ul><ul><li>4-A </li></ul><ul><li>5-B </li></ul>