Transcript The Use of Antipsychotics in Children and Adolescents
Mental Health Issues in Adolescents: Screening and Treatment
Lin Sikich, MD Director, ASPIRE Program Associate Professor of Psychiatry, UNC
Disclosures for Dr. Sikich
Research support from: NIMH, NIH, NICHD Eli Lilly Janssen Positscience Pfizer Bristol Meyer Squibb Participation in industry sponsored clinical trials ACTN Neuropharm Bristol Meyer Squibb Curemark Seaside
Meds w/FDA approval in adol depression
Fluoxetine (Prozac) in 8-18 yo’s with MDD Escitalopram (Lexapro) in 12-17yo’s wMDD All other medications are used off-label for the treatment of adolescent Major Depression
How common is mental illness in youth?
ADHD is about 7% overall, 3% in teens Dysthymia is about 3% in teens Major Depression is 3% in children and ~7% in teens (equal or sl higher than adults) One in five teens will experience major depression before they turn 20 Bipolar disorder is ~1%
Prevalence of Pediatric Affective Disorders
Major Depression
1 yr Point Prevalence: children ─ 0.4 - 5 % adolescents ─ 4 - 8% Cumulative Prevalence by age 18: 15-20%
Dysthymia,
3 month point prevalence: 0.3%
Depression NOS,
3 mth point prevalence: 1.5%
Bipolar Disorder
3 month point prevalence: <0.1% Cumulative Prevalence by age 18: 0.4%-1%
Point Prevalence continued
Anxiety disorders are about 10% Schizophrenia is 0.25% - 0.5% Substance Use in past month is 8% in 8 th graders, 16% in 10 th and 22% in seniors Alcohol 40%-58%-72% Marijuana 6%-14%- 19%, daily1%-2.7%-5.4% Oxycontin 2%-3.6%-4.7%
Potential Consequences of Depression
↑ risk of physical illness ↑health care costs ↑early pregnancy ↑substance abuse impairments in schooling, social relationships & poorer job outcomes as adults ↑ risk of completed suicide (8%)
Similar risks with other mental illnesses
10% risk of completed suicide with bipolar disorder and with schizophrenia Substance use increases suicide attempts by 1.4-6.2 OR Poor health or disability increases suicide attempt by 3.0 OR
But diagnosis of depression has
’d . . . Libby, A. M. et al. Arch Gen Psychiatry 2009;66:633-639.
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Many affected youth are not identified
~50% of those w/depression are not diagnosed Only 25-30% receive any treatment 90% of pediatricians feel they should diagnose but about ½ feel uncomfortable with their skills or that they don’t have time to fully evaluate Schools and Primary Care Providers have become main mental health providers
In 2009, USPSTF recommended routine screening for depression in primary care.
Accuracy of Screening tools in teens Instrument Sensitivity
PHQ-AD Beck-PC 73 91
Positive PV
56 55.6
Negative PV
97 98.8
Beck DI >11 84 10 99.5
CES 84 8 99 PHQ-AD free; Beck are proprietary; CES not culturally sensitive, longer with some reverse scoring
PHQ-Adolescent
Rates the past 2 weeks Responses are + not at all +several days +more than ½ the days +nearly every day MDD if any + response to mood or anhedonia and total of 5 items >50% of days Other depressive disorder if any + response to mood or anhedonia and 2-4 items >50% of days Takes ~ 3 min to complete Also assesses dysthymia, impairment & suicide
Acceptability of screening
(Zuckerbrot et al, (2007), Pedatrics 119: 101-108)
3 primary care practices screened 94% of all English speaking adolescents who came for visits while waiting for MD Provider burden was low Patients were felt to appreciate screening Provider comfort dx’ing depression & screening for suicidality increased in 80% 73% thought referrals to MHS ↑’d
Screening tools better than interview?
120 100 80 60 40 20 0 Self report Interview Parents Depression Depression Suicidality
If the screening tool indicates depression, what to do next . . .
Determine severity of symptoms Determine level of impairment Determine if there is suicidality Determine if there is substance abuse R/O other disorders with similar symptoms: Hypothyroidism Trauma including sexual abuse Bipolar disorder Psychosis Must
ASK directly
and
specifically
about suicide, psychosis, substances and abuse with teen alone
Suicide: Risk by Diagnosis 140 120 100 80 60 40 20 0 % w/attempts % completed OR of attempt
No DX MDD BP Schiz Subst MDD +Subst SZ +Subst SZ +sex ab
14 12 10 8 6 4 2 0
Diagnosis of Bipolar Disorder Requires at least 1Manic Episode:
A distinct, qualitatively abnormal period of irritable, expansive or elevated mood AND 3 (4 if irritable) of the following Distractibility Psychomotor Agitation Pressured Speech Racing Thoughts Grandiosity Impulsivity Decreased (< 4-6hrs) Sleep without fatigue Increased pleasurable and/or productive activities
Mixed Manic & Depressed Episode: Simultaneously meets criteria for both
Not a medication side effect If irritable mood, could easily overlap agitation, decreased sleep, poor attention Would also need one from each class: loss of energy, guilt, appetite change, thoughts of death pressured speech, racing thoughts, grandiosity, excessive negative activities
Should assess for psychotic symptoms if:
Mood disorder In Pediatric Depression 20-40% have hallucinations In youth hospitalized w/mania 80% have hallucinations and 35% have 5 or more psychotic symptoms Attentional problems don’t respond to stimulants Multiple behavioral problems (school, isolative, aggressive) New onset of unusual or very intense behaviors New onset of social withdrawal Deterioration in level of functioning or distress especially if strong family history of psychotic disorder Probably in all substance abusers
Early Warning Signs of Psychosis
Increasing withdrawal Reduction in motivation Poor hygiene Feeling picked on Inattention Becoming poorly organized Talking under one’s breath
To assess for psychosis, ask . . .
Are there ever times when you hear something and other people act like they can’t hear it? Or times when you see something and others act like they don’t?
Are there times, when you feel really mad and don’t know why or when you feel everyone is against you?
Parents for times when child has asked if they were called and they weren’t or new onset lying about things In teens, psychosis is equally likely to occur in affective illness as schizophrenia
Once you have ID’d Depression . . .
Ensure immediate safety: remove guns, hospitalize if needed Develop strategies to reduce modifiable stressors (eg. school, deadlines) If mild to moderate depression, psychotherapy alone may be effective If severe depression, comorbid problems, suicidality or psychosis, likely will need both medication and psychotherapy Develop a FU plan
Evidence treating Adolescent Depression 100 80 60 40 20 0 CB T CB T IPT Fam ily TA DS CB T Flu oxe tin e Flu oxe tin e TA DS Flu Esc oxe italo tine pra m Esc italo pra m
TADS Treatment Response
Fig. 1: % Responders Fig. 2: No. Needed to Treat
80 70 60 50 40 30 20 10 0 COMB FLX CBT PBO 12 10 8 6 4 2 0 COMB FLX CBT
CBT benefit converges in TADS
No benefit of adding CBT to SSRI for initial psychosocial nonresponders
British Primary Care study in 208 adolescents who had not responded to 6 session initial psychotherapy found no advantage of adding CBT Goodyer et al., 2008. Health Technology Assessment 12 (14).
Partners in Care Study - Asarnow
Randomly assigned 9 peds practices to usual care or quality care Quality care involved Team leader with depression expertise Care manager who could do CBT Care manager assisted with assessment, referral, both medication and psychological treatment if family & patient wished Prior to black box warning on antidepressants
Improving Pediatric Depression Care
(Asarnow et al., 2005 JAMA 293:311-319.) 45 40 35 30 25 20 15 10 5 0 Usual Quality
** ** *
PMD MH Medication Counseling Specialty Severe Deprssion Change in SA
Antidepressant Potential Adverse Effects
TCA’s: sedation, constipation, weight gain sudden cardiac death, lethal in overdose SSRI’s: Acute side effects often mild (GI distress, dreams) Withdrawal symptoms with short half-life agents Reduced sexual arousal & interest May cause activation May lead to bipolar switch May lead to apathy Suicidality
About 4% of youth treated with antidepressants versus ~ 2% of youth treated with placebo develop significant suicidality ..
TADS Suicidality
30 25 20 15 10 5 0 Baseline COMB FLX CBT PBO Week 6 Week 12
Concern about suicidality in light of questionable antidepressant efficacy
Number Needed to Treat = 9 Number Needed to Harm = 59 Further, there are high rates of emergent suicidality with psychotherapy too. (Bridge et al., (2005) AJP 162:2173-2175) 10/88 in CBT trial had SI during trial w/1attempt Higher total depression scores More cognitive distortion More likely to have endorsed SI on Beck at w0 40% revealed only by self report, 60% both .
FDA issued black box warning for all antidepressants used in pediatric patients
Does not prohibit use of antidepressants in youth Calls upon physicians and families to closely monitor child for clinical worsening, unusual behaviors suicidality Especially when treatment starts or dose changes “Ideally, such observation would include: At least weekly, face-to-face contact during 1 st 4 weeks At least biweekly face-to-face weeks 5 through 8 Then at week 12 and subsequently as clinically indicated AACAP guidelines say monitoring should be individualized based on risk on specific schedule and is a partnership between MD, patient, and family
What if there is substance abuse?
Refer for specific substance abuse treatment Strongly consider regular home monitoring by parents Stress increased risk for suicide
What if there is psychosis?
Treat with antipsychotic Refer for specialty mental health care Higher risk of bipolar disorder developing Higher risk of suicide
What if there is bipolar disorder
Refer for specialty mental health care Be very cautious about use of antidepressant Consider treatment with antipsychotic or ? Mood Stabilizer
Valproate is not efficacious in ped BP
Placebo n=70; VPA n=74 in DB; Long-term n=54 Wagner et al., JAACAP 48:519-532, 2009.
Antipsychotics have efficacy in Pediatric Bipolar Disorder 70 60 50 40 30 20 10 0 Quetiapine Olanzapine Risperidone Aripiprazole Placebo High Dose Difference
Antipsychotic Associated Weight Gain (Correll et al, JAMA 2009; 1 0 3 2 9 8 7 6 5 4 Olanzapine Quetiapine Risperidone Aripiprazole
Weight change varies within individuals
a
60 60
60 60 50 50 40 30 20 40 30 20
0 0
10 0 -10 -20 -30 10 -10 -20 -30 0
Mean Acute Wt Individual Molindone Subjects
Acute and Long-term Weight changes 4 2 0 12 10 8 6
P <0.0001
P <0.008
P <0.0001
P <0.0001
P <0.0001
Molindone Olanzapine Risperidone W0-W8M W0-W52 M
Potential strategies for SGA Weight Gain More attention to healthy lifestyle instruction Switch to lower risk agent (aripiprazole/molindone/ziprasidone) Add an adjunctive agent like orlistat, histamine 2 blockers, amantadine or metformin, which is only agent specifically tested in youth
Change in BMI z-score 0.2
Placebo
0.1
0 -0.1
Metformin
-0.2
0 4 8 Weeks of Treatment 12 16
Klein et al., AJP 2006
Summary of Studies
Any youth 3-20yrs starting an antipsychotic to monitor for weight & metabolic problems Youths 10-20yrs who have gained 10% baseline body weight on an antipsychotic to try 3 approaches to reduce weight Treatment studies for autism and bipolar Developmental monitoring for 3-17yo’s with autism who do NOT want medication trtmt
How to Refer a Patient to
Ask family if you could give their contact information to us so we can call them with more information about possible studies Call the ASPIRE Research Hotline at: Email us at
We will provide a comprehensive evaluation We will facilitate care by another provider if we are not able to accept the child into a study or family chooses not to participate.