PSYCHOPHARMACOLOGIC APPROACHES TO DEPRESSION IN CHILDREN AND - - PowerPoint PPT Presentation
PSYCHOPHARMACOLOGIC APPROACHES TO DEPRESSION IN CHILDREN AND ADOLESCENTS Learning Objectives Describe the evidence for selective serotonin reuptake inhibitors (SSRIs) in youth with depressive disorders List predictors of treatment
inhibitors (SSRIs) in youth with depressive disorders
SSRI-resistant major depressive disorder
selection in adolescents with major depressive disorder
Adolescence Preschool School-Age Age 7 Age 4 Puberty Irritability3 Moodiness3 Loss of interest3 Depressed mood, lack of concentration, insomnia, suicidal ideation Somatic complaints Increase in suicide attempts and suicide completion Hypersomnia (increases with age)2
Ryan et al. The Clinical Picture of Major Depression in Children & Adolescents. Arch Gen Psychiatry 1987;44:854-61; Luby et
Lewinsohn et al. Major depression in community adolescents: age at onset, episode duration, and time to recurrence. J Am Acad Child Adolesc Psychiatry 1994;33:809-18.
Weight loss (increases with age)1
Delusions
Beesdo et al. Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. Arch Gen Psychiatry 2010;67:47-57.
Strawn and Walkup. The quest to identify the best treatment for pediatric depression. Lancet Psychiatry 2020 (in press); Birmahar et al. Practice Parameter for the Assessment and Treatment of Children and Adolescents with Depressive Disorders. J Am Acad. Child Adolesc Psychiatry 2007;46:1503-26.
psychopharmacologic treatment for children with depression
many clinicians, but data are limited
Treatment Week Adjusted Mean Children’s Depression Rating Scale Score 45 60 30 6 12 Placebo CBT Alone Fluoxetine alone Fluoxetine + CBT
March et al. JAMA 2004;292:807-20; Emslie et al. J Am Acad Child Adolesc Psychiatry 2006;45:1440–55.
Tao et al. J Child and Adolesc Psychopharmacology 2010.
Fluoxetine Treatment Week Mean Scale Score 1 2 6 8 10 12 0 1 2 Morbid Thoughts Anhedonia Observed Depression Reported Depression 3 4 3 4
Duration of antidepressant treatment
Weight gain (if applicable) Monoamine levels
activation
Symptoms Receptor sensitivity
Varigonda et al. JAACAP 2015;54(7):557-64; Strawn et al. JAACAP 2018;57(4):235-44.
Improvement in Depressive Symptoms
2 4 6 8 10
Week
Initial 5 mg 25 mg 5 mg Week 1 10 mg 50 mg 20 mg Week 2 10 mg 50 mg 20 mg Week 3 10 mg 100 mg 20 mg Week 4 10 mg 100 mg 20 mg Optional increases Week 5 15 mg 100 mg 40 mg Week 6 15 mg 150 mg 40 mg Week 7 20 mg 150 mg 40 mg Week 8 20 mg 150 mg 40 mg Week 9 20 mg 150 mg 40 mg Week 10 20 mg 150 mg 40 mg fluoxetine escitalopram sertraline Age 7–11
Initial 5 mg 25 mg 10 mg Week 1 5 mg 50 mg 10 mg Week 2 10 mg 50 mg 20 mg Week 3 10 mg 50 mg 20 mg Week 4 15 mg 75 mg 20 mg Optional increases Week 5 15 mg 100 mg 20 mg Week 6 20 mg 100 mg 20 mg Week 7 20 mg 150 mg 40 mg Week 8 20 mg 150 mg 40 mg Week 9 20 mg 200 mg 60 mg Week 10 20 mg 200 mg 60 mg fluoxetine escitalopram sertraline Age 12–17
morbidity and development of chronic depression
resistant depression in adolescents
Brent et al. Treatment of Resistant Depression In Adolescents. JAMA 2008;299(8):901-13. Strawn and Walkup. The quest to identify the best treatment for pediatric
Strawn et al. Treatment Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance. J Child Adolesc.Psychopharm 2020 (in press).
fluoxetine
tolerate higher dose
Fluoxetine 20 mg Fluoxetine 40 mg
Brent D et al. JAMA 2008;299(8):901-13.
Fluoxetine 40 mg
SSRI Non-responders (>2 mos of tx) Week Week 12 Wk
Brent D et al. JAMA 2008;299(8):901-13.
N=334 Age: 12–18 years Dx: MDD + no response to 2-month initial SSRI Primary Outcome: CGI-I <2 + >50% decrease in CDRS-R and dCDRS-R. SNRI + CBT Venlafaxine XR SNRI Venlafaxine XR SSRI + CBT Citalopram + CBT Paroxetine + CBT Fluoxetine + CBT SSRI Citalopram Paroxetine Fluoxetine
Treatment Week 4 6 2 6 12 SSRI Venlafaxine 3 5 CDRS Score Treatment Week 2 4 6 12 1 3 Antidepressant without CBT Antidepressant + CBT Clinical Global Impression Scale—Severity 5
Brent D et al. JAMA 2008;299(8):901-13.
Improvement in Depressive Symptoms
Mills, Croarkin Strawn. Under review 2020.
Improvement in Depressive Symptoms
Mills, Croarkin Strawn. Under review 2020.
p=0.01
remission when controlling for others
days
1.5 sessions of behavioral activation)
activation
anhedonia
Goldstein BI et al. J Am Acad Child Adolesc Psychiatry 2009;48(12):1182-92. No response Response Substance Use Severity Time (weeks)
Sakolsky DJ et al. J Clin Psychopharmacol 2011;31(1):92-7.
10 20 30 40 50 60 70 80 VEN FLX/CIT FLX CIT PAR ≥ GM <GM
P= .04
P=.07 P=.005
Ramsey et al. Gene-Based Dose Optimization in Children. Annu Rev Pharmacol Toxicol 2020;60:4.1–4.21. 16-year-old female 14-year-old female
Ramsey et al. Annu Rev Pharmacol Toxicol 2020;60:4.1–4.21.
Strawn, Poweleit, Ramsey. CYP2C19-guided escitalopram and sertraline dosing in pediatric patients: a pharmacokinetic modeling study. J Child Adol Psychop 2019;29(5):340-7.
Intermediate metabolizer Poor metabolizer Normal metabolizer Rapid metabolizer Ultrarapid metabolizer
Phenotype Equivalent dose Poor metabolizer 10 mg Intermediate metabolizer 15 mg Normal metabolizer 20 mg Rapid metabolizer 25 mg Ultrarapid metabolizer 30 mg
Strawn JR et al. J Child Adol Psychop 2019;29(5):340-7.
Intermediate metabolizer Poor metabolizer Normal metabolizer Rapid metabolizer Ultrarapid metabolizer
Phenotype Equivalent dose Poor metabolizer 50 mg Intermediate metabolizer 125 mg Normal metabolizer 150 mg Rapid metabolizer 175 mg Ultrarapid metabolizer 225 mg
0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% SSRI VLX Low High
p=0.75 p=0.02
Adapted from G. Emslie. Annual Meeting of the American Academy of Child & Adolescent Psychiatry 2012.
Brent DA et al. Am J Psychiatry 2009;166:418–26.
20 25 30 35 40 45 50 55 60 65
Emslie GJ et al. Am J Psychiatry. 2010;167(7):782-91.
20 25 30 35 40 45 50 55 60 65
Emslie GJ et al. Am J Psychiatry 2010;167(7):782-91.
to respond than patients who did not receive any soporific (p=0.001)
likely to self-harm (OR=3, p=0.03)
paroxetine or fluoxetine responded (0/13)
responded similarly to those who received no sleep medication (60% vs. 50%)
Shamseddeen W et al. J Child Adolesc Psychopharmacol 2012;22(1):29-36.
Trazodone mCPP
to respond than patients who did not receive any soporific (p=0.001)
likely to self-harm (OR=3, p=0.03)
paroxetine or fluoxetine responded (0/13)
responded similarly to those who received no sleep medication (60% vs. 50%).
Paroxetine Fluoxetine 2D6 Trazodone mCPP mCPP
Shamseddeen W et al. J Child Adolesc Psychopharmacol 2012;22(1):29-36.
Gunlicks-stoessel M et al. J Am Acad Child Adolesc Psychiatry 2019;58(1):80-91.
IPT-A Early decision
>20% reduction <20% reduction
IPT-A Early decision
>20% reduction
Continue IPT-A IPT-A Frequency
<20% reduction Fluoxetine
Gunlicks-stoessel M et al. J Am Acad Child Adolesc Psychiatry. 2019;58(1):80-91.
IPT-A Early decision
>20% reduction
Continue IPT-A IPT-A Frequency
<20% reduction Fluoxetine
IPT-A Late decision
>40% reduction <40% reduction
Gunlicks-stoessel M et al. J Am Acad Child Adolesc Psychiatry. 2019;58(1):80-91.
IPT-A Early decision
>20% reduction
Continue IPT-A IPT-A Frequency
<20% reduction Fluoxetine
IPT-A Late decision
>40% reduction
Continue IPT-A IPT-A Frequency
<40% reduction Fluoxetine
Gunlicks-stoessel M et al. J Am Acad Child Adolesc Psychiatry. 2019;58(1):80-91.
Croarkin et al. In preparation.
Left dorsolateral prefrontal cortex stimulation, 5 days/week
trial
less functional impairment)
concerns
tolerated
initial agent (>25% improvement)
response (e.g., more functional impairment)
and start new antidepressant
Keks N et al. Aust Prescr 2016;39(3):76-83;
and start new antidepressant
gradually taper the first antidepressant and start the new antidepressant immediately after discontinuation
Keks N et al. Aust Prescr 2016;39(3):76-83;
and start new antidepressant
gradually taper the first antidepressant and start the new antidepressant immediately after discontinuation
gradually withdraw the first antidepressant then start the new antidepressant after a wash out period
Keks N et al. Aust Prescr 2016;39(3):76-83;
Keks N et al. Aust Prescr 2016;39(3):76-83;
and start new antidepressant
gradually taper the first antidepressant and start the new antidepressant immediately after discontinuation
gradually withdraw the first antidepressant then start the new antidepressant after a wash out period
first antidepressant while beginning the new antidepressant
Following unsuccessful treatment with paroxetine and fluoxetine, a 15-year-old girl, who meets DSM-5 criteria for major depressive disorder, is prescribed extended-release venlafaxine which is initiated at 37.5 mg daily and titrated to 150 mg daily for 8 weeks. She has had minimal improvement in depressive
consideration? 1. Venlafaxine treatment may increase her likelihood of treatment-emergent suicidality 2. Addition of cognitive-behavioral therapy is unlikely to confer any significant benefit 3. Her likelihood of clinical improvement is directly related to her serum venlafaxine concentration 4. Addition of trazodone to manage her initial insomnia may increase her likelihood of remission
A 13-year-old boy meets DSM-5 criteria for major depressive disorder and has been treated with paroxetine 40 mg daily for 8
treatment option? 1. Continue for an additional 4 weeks at the current dose. 2. Discontinue paroxetine and begin duloxetine 30 mg qAM 3. Discontinue paroxetine and begin citalopram 10 mg qAM 4. Augment with buspirone 10 mg BID
Higher blood levels of which of the following medications have been associated with a greater likelihood of improving in adolescents with treatment-resistant depression? 1. Venlafaxine 2. Citalopram 3. Fluvoxamine 4. Duloxetine