Psychiatric medication treatment in children and adolescents: The good, the bad and the ugly Gabrielle A. Carlson, MD Professor of Psychiatry and Pediatrics Director, Child and Adolescent Psychiatry Stony Brook University School of Medicine Gabrielle.Carlson@StonyBrook.edu
What ADHD is ADHD is a heterogeneous, clinical condition If appropriately defined (with symptoms, pervasiveness and impairment) it may constitute a difference of degree and possibly kind from normal ; symptoms in >2 settings Deficit does not mean None. It means that attention cannot be sustained when the child or adult is not interested. It occurs in children all over the world (i.e. it is not a US invention); rates ~5-8%
MOTHER S RATING FOR STEVE TEACHER RATING FOR STEVE
Lifetime Impairments of ADHD Disruptive behavior Low self-esteem esteem Smoking Substance use Crime Car accidents Relationship failures Poor work history Chronic substance abuse and dependence Incarceration Preschool Adolescent Adult School-age College-age Academic failure Poor socialization Self-esteem issues Injuries Academic failure Occupational failure Substance abuse Slide courtesy of Joseph Biederman, MD.
Medication Treatment for ADHD in USA Stimulant Non-Stimulant Short-acting Ritalin Focalin MPH-based Intermediate Ritalin SR Metadate ER Dextro- amphetamine based Long acting Concerta Metadate CD Ritalin LA Focalin LA Daytrana Short-acting Approved Strattera Intuniv Kapvay Intermediate Dextrostat Dexedrine Dexedrine tabs Spansules Adderall Not approved modafanil TCAs Wellbutrin Clonidine Tenex Effexor Long-acting Adderall XR Vyvanse
Meta-analysis analysis of 29 controlled studies over 25 years, encompassing 4465 children, adolescents) with some added information Drug ( Effect Size Amphetamine 0.92 Methylphenidate 080 0.80 Atomoxetine 0.73 Guanfacine ER 0.73 Neurofeedback 0.6 Clonidine 0.58* Modafinil 0.49 Bupropion 0.32 Diet without additives 0.2 Faraone SV, Spencer TJ: Presented at: American Psychiatric Association Annual Meeting, Toronto, Canada, May 2006. * Connor et al., JAACAP, 1999; Gevensleben et al., 2009
% Normalized at 14-month Endpoint MTA Groups vs. Classroom Controls 100 88% 80 68% 56% Class Cntrls 60 Comb 34% MedMgt 40 25% Beh 13.5% 20 ComCare PATS 0 Endpoint MTA N = 579 Classroom Controls N = 288 Swanson et al. for the MTA Cooperative Group
Stimulants and Side effects They MAY cause loss of appetite, delayed sleep, crankiness when the drug wears off For kids on chronic, high doses who don t eat, there may be a slowing of growth that couple be up to about an inch Rates of sudden death probably no higher than unmedicated kids unless there is a family history of sudden and unexplained death. Stimulants do NOT cause problems with the liver, the kidneys, fertility, puberty Cases of psychosis and mania are VERY rare They don t cause or increase rates of drug addiction; the jury is out as to whether they prevent it.
DEPRESSION REMEMBER D*U*M*P*S D = DEFINITE PERSONALITY CHANGE - A YOUTH WHO HAS PREVIOUSLY BEEN A GOOD STUDENT OR A NICE KID, SUDDENLY OR EVEN GRADUALLY BECOMES DEFIANT, DISAGREEABLE, DISTANT, DISORGANIZED U = UNDENIABLE DROP IN GRADES - A YOUTH WHOSE GRADES GO FROM As TO Cs OVER A SEMESTER OR WHO STARTS TO AVOID SCHOOL ALTOGETHER OR DEVELOPS "SCHOOL PHOBIA" M = MORBID PREOCCUPATION - A YOUTH WHOSE COMPOSITIONS DWELL ON DEATH AND DISASTER OR WHO VOICES SUICIDAL THOUGHTS OR WHO ENGAGES IN SELF DESTRUCTIVE BEHAVIOR P = PESSIMISM / PSYCHOSIS A YOUTH WHO IS GRIM, DEPRESSED, DEMORALIZED AND SEES NO JOY IN ANYTHING ACUTE ONSET OF DEPRESSIVE HALLUCINATIONS AND/OR DELUSIONS S = SOMATIC COMPLAINTS WITHOUT PHYSICAL BASIS - A YOUTH WHO SPENDS MORE TIME IN THE NURSES OFFICE THAN THE CLASSROOM
Rise of DSM IV MDD at puberty (A ld t l 1998) (Angold et al., 1998) GIRLS BOYS
Outcome Episodes last 7-9 months 90% remit by 1.5-2 years 40% recur by 2 years Persists from adolescence to adulthood in 60-70% of cases c. 20% develop Bipolar Disorder over the next 5 years associated with acute, severe depression family history of manic-depression or MDD Adverse outcomes: suicide, drug and alcohol problems, social impairment, school drop-out, adult depression
Antidepressants - SSRIs Selective serotonin reuptake inhibitors increase serotonin available in synapse Prozac/fluoxetine, Zoloft/sertraline, Celexa/citalopram, Lexapro/escatalopram have the most data in kids They take 2-4 weeks to begin to work Used for depression and anxiety disorders (e.g. OCD, social phobia, separation anxiety disorder, generalized anxiety disorder, panic disorder )
Age related Antidepressant response in MDD; Bridge et al., JAMA 297:1683, 2007 Safer, Pediatrics, 2007.08 <.001 <.001 P values 70 60 50 40 30 20 10 0 Tee ens Chil hildren Adu dults AD PBO
Antidepressants and Suicide in Children In 2004, the FDA looked at 24 clinical trial involving 4,400400 children and adolescents taking antidepressants for depression and anxiety disorders. Children taking active meds 4% developed suicidal thoughts/behaviors Children taking placebo 2% No children in studies committed suicide. Putting effectiveness next to side effects: antidepressants help 1/10 depressed children, 1/3 anxious children. Making suicidal threats occurs in 1/112 depressed kids, 1/143 anxious ones
Atypical Antipsychotics Risperidone/Risperdal Olanzapine/Zyprexa Quetiapine/Seroquel Ziprasidone/Geodon Aripiprazole/Abilify Clozapine/Clozaril not much in kids GCarlson, MD
Atypical Antipsychotics Indications/Uses Psychosis (Schizophrenia)-approved for teens Irritability in autism-aripiprazole/abilify and risperidone/risperdal approved Mania-risperidone, aripiprazole, quetipine approved for ages 10-17; olanzapine age 13-17 17 Also used for Tourettes/Tics Also used for volatile aggression GCarlson, MD
Short term risperidone Vs placebo for irritability in behavior disorders and autism 70 60 % res sponse 50 40 drug drug 30 drug Placebo 20 placebo placebo 10 0 CGI-I >/=2 50% drop
Atypical Antipsychotics Adverse Effects Weight gain/obesity Increase blood sugar (diabetes) Increase lipids (cholesterol/triglyceride levels) Sedation Increase prolactin levels amenorrhea, galactorrhea, breast enlargement (males) Cardiovascular - arrhythmias GCarlson, MD
Weight Gain on Risperidone by Age 18 16 14 Percent 12 Increase in 10 Body Weight8 Over 6 Baseline 4 2 0 5-11 12-17 33-44 71-83 yrs yrs yrs yrs Treatment Duration 0 wks 4-8 wks 9-16 wks 17-56 wks Age Group Safer DJ, et al., J Clin Psychopharmacol 24: 429-436, 2004
Mood Stabilizers Used a fair amount in kids as part of the bipolar epidemic; little in the way of data showing efficacy Lithium sodium valproate/ Depakote Carbamazepine/ Tegretol topirimate/ Topimax Lamotrigine/ Lamictal Oxcarbazepine/Trileptal GCarlson, MD
UNFORTUNATELY WE DON T HAVE SMART BOMBS We try to use meds systematically But it remains trial and error We need feedback from parents and teachers re: efficacy Meds help some; rarely normality