Diagnosis & Assessment in Pediatric Psychopharmacology

Transcription

1 Diagnosis & Assessment in Pediatric Psychopharmacology Joseph Biederman, MD Professor of Psychiatry Harvard Medical School Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD Massachusetts General Hospital

2 Disclosures My spouse/partner and I have the following relevant financial relationship with a commercial interest to disclose: Research Support: The Department of Defense, Food Drug Administration, Ironshore, Lundbeck, Magceutics Inc., Merck, PamLab, Pfizer, Shire Pharmaceuticals Inc., SPRITES, Sunovion, Vaya Pharma/Enzymotec, and NIH.

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6 Insel s JAMA Editorial May 2014 Mental and SUDs account for 23% of global morbidity, more than any other group of medical disorders 50% of adults with a mental disorder reported onset by 14 years or younger In terms of burden of illness, mental and substance abuse disorders are, in fact, the predominant noncommunicable disorders of young people

7 2013 CDC Major Report on Mental Illness in Youth 1 in 5 youth has a mental illness Estimated total cost $247 billion Because of their high prevalence, early onset, their impact on the child, family, and community, and its associated enormous cost Mental and behavioral disorders of the young represent a major public-health issue in the US (and across the world)

8 Most Prevalent Mental Illnesses in Youth ADHD (6.8%) Conduct disorder (3.5%) Anxiety (3.0%) Depression (2.1%) ASD (1.1%) SUD (in prior yr 4.7%) Alcohol abuse (in prior yr 4.2%) Cigarette Dependence (prior month 2.8%) Suicide was the second leading cause of death in youth

9 JAMA Psychiatry. Published online July 15, doi: /jamapsychiatry

10 Olfson et al. N Engl J Med 2015;372:

11 Olfson et al. N Engl J Med 2015;372:

12 Walker et al. JAMA Psychiatry. 2015;72(4):

13 Bufferd et al. Am J Psychiatry 2012;169:

14 Problem: Limited Manpower There are less than 7000 fully trained child and adolescent psychiatrists currently practicing in the US, despite estimates that over 30,000 would be required to meet the current demand. The need for services is projected to increase 100% by the year 2020, highlighting a growing mental health crisis. Increasing importance of the PCP in the management of children s mental health problems Center for Mental Health Services

15 Problem: Prejudices and Misconceptions Pervasiveness of psychosocial and psychological hypotheses to explain childhood mental disorders Poor public acceptance for using pharmacotherapy in children Bad Press Frequent alarming statistics on the use of psychotropics in children Diagnostic Conundrums (i.e., DSM-V Temper Dysregulation Disorder) Diagnostic biases in the medical community (mental illnesses do not exist; they are accounted by other conditions; their treatment not necessary; cosmetic pharmacotherapy)

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17 Akinbami et al. NCHS Data Brief No. 70, August 2011

18 Zuvekas al. Am J Psychiatry 2012; 169:

19 Groopman, J. (2007, April 9). What s Normal? Diagnosing bipolar disorder in children. The New Yorker, p. 28

20 Parens et al. N Engl J Med May 20;362(20):1853-5

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22 June 19, 2006 'Off-Label' Antipsychotics for Kids The statistics are staggering: a sixfold spike, between 1993 and 2002, in the number of doctor visits in which kids and adolescents were prescribed antipsychotic drugs. Total tally in '02: 1.2 million. Antipsychotics are powerful drugs, typically used to treat severe mental illnesses like schizophrenia in adults and they're not FDA-approved for children. But increasingly, doctors are prescribing newer generations of antipsychotics "off label" for a range of conditions in young people, from mood disorders to behavioral problems and ADHD. Kalb, C. (2006, June 19). 'Off-Label' Antipsychotics for Kids. Newsweek Health.

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25 Mean Change from Baseline Mean Change in YMRS from Baseline by Medication Class Pharmacotherapy of Pediatric Bipolar Disorder: YMRS Mean Change from Baseline by Drug Class 0 Traditional Mood Stabilizers* Other Anticonvulsants Atypical Neuroleptics Naturopathic Treatments *Monotherapy Only

26 Problem: Lack of FDA Approval for the Use of Many Psychotropics in Youth Absence of FDA approval is not synonymous with proscription of use Lack of FDA approval only denotes that the drug was not adequately studied for the particular condition, at a particular dose or for a particular age group When used off-label, risks, potential benefits and informed consent should be carefully documented

27 Black Box Fatigue Cardiovascular risk/sudden death for stimulants Suicidality/activation for antidepressants and anticonvulsants Metabolic syndrome/ TD for neuroleptics General uncertainties about long-term effects of psychotropics

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29 Cooper et al. N Engl J Med 2011

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31 FDA issues Black Box Warning: Suicide Risk with Antidepressant 78 out of 4,400 cases in controlled clinical trials on all antidepressants in pediatric patients suffered increases in suicidal ideation and/or self-harm 52 patients (3.8%) randomized to medications 26 patients (2.1%) randomized to placebo No patients committed suicide or seriously harmed self AACAP Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee September 28, 2004

32 % of high school students who felt sad or hopeless, who seriously considered attempting suicide, who made a suicide plan, and who attempted suicide Seriously considered attempting suicide Made a suicide plan Grade Attempted suicide SOURCE: United States, Youth Risk Behavior Survey, Suicide attempt required medical attention

33 Antidepressant Medication and Suicide in Adolescents (t=5.14, P<.001) AD AD= Antidepressant rate per 1000 Medication Users Suicide Olfson et al., (2003) AGP 60 (10):

34 Rates of Suicide Attempts During the 3 Months Before and the 6 Months After Initial Antidepressant Prescription Simon et al. (2006) Am J Psychiatry (163):41-47

35 Am J Psychiatry 164:38A, June 2007

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37 Trends in the prescribing of psychotropics medications to preschoolers Main Findings Psychotropic medications prescribed for preschoolers increased dramatically from with the preponderance of medications with off-label (unlabeled) indications. <2% of preschoolers receive various psychotropics Zito et al JAMA. Feb 23;283(8):

38 Percent of Sample MGH Study of Preschoolers 100 Types of Psychiatric Disorders in Preschoolers (N=200) 75 86% 50 61% 25 28% 43% 0 Multiple Anxiety Mood Diagnostic Categories Disruptive ADHD Wilens et al. J Dev Behav Pediatr Feb;23(1 Suppl):S31-6

39 Mean Age of Onset MGH Study of Preschoolers: Preliminary Study of Psychopathology Age of Onset of Psychopathology Mean age at referral = 5.2 years ADHD Mood Disruptive Multiple Diagnostic Categories Anxiety Wilens et al. J Dev Behav Pediatr Feb;23(1 Suppl):S31-6

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41 AAP News Release, October 16 th 2011

42 General Principles A successful pharmacotherapeutic intervention requires realistic expectations and initial diagnostic hypotheses with careful definition of target symptoms i.e., the treatment of insomnia is very different if driven by existential concerns, mania, psychosis or depression While psychotropics can be highly beneficial, their use is not universally successful

43 General Principles The use of psychotropics should follow a careful evaluation of the child and the family Before beginning treatment, the family and the child need to be familiarized with the risks and benefits of such an intervention

44 General Principles Treatment should be started at the lowest possible dose with frequent reevaluation during the initial phase of treatment Following a sufficient period of clinical stabilization (i.e months) it is prudent to reevaluate the need for continued psychopharmacologic intervention This approach need to be considered when the clinical picture has fully stabilized

45 General Issues: Adverse Effects Certain adverse effects can be anticipated based on known pharmacologic properties of the drug (i.e.., the anticholinergic effects of tricyclic antidepressants), while others, generally rare, are unexpected (idiosyncratic) and are difficult to anticipate

46 Components of the Diagnostic Process Psychiatric Assessment Cognitive Assessment Assessment of School Functioning Psychosocial Assessment Laboratory Assessments (when indicated)

47 Diagnostic Process: Cognitive Assessment Estimates of IQ Estimates of EFDs (i.e, working memory, processing speed) Estimates of academic performance: Achievement in math and reading Search for discrepancies between expected and actual functioning Distinguish Low achievement from Underachievement Example: a brilliant child that is performing averagely in school may be underachieving

48 Diagnostic Process: Psychosocial Evaluation Evaluation of the family environment Marital discord Parenting difficulties Separation and divorce Custodial parent Guardianship Potential issues of abuse and neglect

49 Psychosocial Adversity Low SES (poverty) Family conflict Single parent homes Parental psychopathology

50 Odds Ratio Findings from Rutter Study 12 Risk for Childhood Mental Disturbance Number of Indicators of Adversity Biederman et al. Am J Psychiatry Sep;159(9):

51 The Challenge of Psychopathology vs. Stress Reaction Normal Reaction Stress Adjustment Disorder Major Psychiatric Disorders (such as Major Depressive Disorder or Anxiety Disorder)

52 Diagnostic Process: Psychosocial Evaluation Social Functioning Relationship with peers Relationship with parents Use of leisure time

53 Diagnostic Process: Psychosocial Evaluation Social Functioning Assessment Anamnesis Questionnaires and Rating Scales

54 Diagnostic Process: School Functioning School Functioning School and grade placement Teacher information Parent-based school information

55 Diagnostic Process: School Functioning Indices of school dysfunction Repeated grades Placement in special classes Need for Tutoring

56 Diagnostic Process: School Functioning Parent-based school information Parent-teacher conferences Teacher reports Teacher complaints Observation

57 Diagnostic Process: Laboratory Assessment Blood Chemistries CBC LFTs Renal screening tests Thyroid screening tests Drug screening Therapeutic drug monitoring Cardiovascular Assessments ECG, BP, HR Other Assessments HT WT

58 Indications for Major Drug Classes Stimulants Antidepressants Antipsychotics Mood stabilizers Anxiolytics Alpha adrenergic compounds Beta blockers

59 Indications for Major Drug Classes Stimulants ADHD Narcolepsy Tx resistant depression

60 Indications for Major Drug Classes Antidepressants Depressive disorders Anxiety disorders OCD (serotonergic) ADHD (noradrenergic, dopaminergic) Enuresis (TCAs)

61 Percentage of Youth Antidepressants Best for Anxiety Disorders Antidepressants Placebo Major Depressive Disorder Obsessive Compulsive Disorder Anxiety Disorders Source: Journal of the American Medical Association. April 18, 2007.

62 Treatment of Adolescent Depression Effect Size for CDRS (ITT) COMB FLX CBT March et al. JAMA. (2004) 292 (7):

63 Indications for Major Drug Classes Antipsychotics (atypical) Psychotic disorders Tourette s disorder Bipolar disorder Dysphoric dyscontrol Augmentation of antidepressants

64 Indications for Major Drug Classes Mood stabilizers Bipolar disorder Tx refectory depression Dysphoric dyscontrol

65 Indications for Major Drug Classes Anxiolytics Anxiety disorders Augmentation of treatments for other disorders (BPD, depression, TS) Severe situational anxiety Tourette s syndrome (high potency BZDs) Stimulant induced anxiety Insomnia

66 Indications for Major Drug Classes Alpha Adrenergic Compounds (clonidine, guanfacine) TS/Tics ADHD Dyscontrol SIB Augmentation Treatment emergent adverse effects (I.e., stimulant-induced insomnia

67 Indications for Major Drug Classes Beta Blockers Akathisia Stage fright Tremor Dyscontrol SIB

68 Indications for Combined Pharmacotherapy Comorbidity Treatment resistant cases: Augmentation Treatment emergent adverse effects Poor tolerability with therapeutic doses of individual medicines Wilens et al. JAACAP Jan;34(1):110-2

69 Combined Pharmacotherapy Treatment resistant cases Augmentation Less than satisfactory response to a single agent Potential synergy of combined agents for certain disorders Combined Tx may permit the use of lower doses of two agents reducing the adverse effect profile associated with higher doses of a single agent

70 Combined Pharmacotherapy Comorbidity High rates of psychiatric comorbidity in childhood psychiatric disorders Irrespective of etiology, different disorders require different treatments

71 Combined Pharmacotherapy Vast array of potential combinations Clinicians should become familiar with potential psychopharmacological combination regimens adverse effects [i.e., excessive sedation] drug-drug interactions [i.e.,fluoxetine plus TCAs]

72 Combined Pharmacotherapy Simple cases: monotherapy could be sufficient and should be preferred Complex cases: monotherapy may be insufficient and combined pharmacotherapy needs to be considered

73 Yet, the FDA did not provide any guidance for dosing limitations in pediatric patients If children were to be at the same or higher risk for Citalopram associated QTc prolongations as adults, such risk would require EKG monitoring in children prescribed doses >0.5 mg/kg 940 mg for an 80 kg adult).

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76 Percent with Abnormal or High QTc by Medication 20.0% 18.0% 16.0% 14.0% 12.0% 10.0% 8.0% 6.0% 4.0% 2.0% 0.0%

77 Summary In this study using an electronic medical record, mean QTc intervals were in the normal range for all medications No single medication was associated with a significantly greater QTc than others

78 Conclusion Results suggest that: Most antidepressants do not meaningfully and consistently prolong QTc at doses typically prescribed for children Citalopram is not associated with significantly prolonged QTc at doses typically prescribed in children