ADHD: Recent Updates and Treatment Review

Childhood ADHD: Recent Updates and Treatment ReviewRushiraj C. LaiwalaAttention-Deficit/Hyperactivity DisorderThe most common childhood behavioral disorder diagnosed in outpatient setting in United States. ADHD has been the focus of a great deal scientific- clinical research and controversy. Overall, ADHD is one of the best researched disorders in medicine and overall data on its validity are far more compelling than many other medical conditions- American Medical Associations Council on Scientific Affairs ( Goldman et al., 1998)History1902 George Still wrote about children with restless, impulsive and inattentive, intense affective responses and conduct problems. 1919 & 1920- Influenza pandemic and encephalitis lethargica epidemic- Children who survived the flu developed similar behavioral symptoms-Hypothesis of brain damage- Minimal Brain Damage Syndrome1937- C.Bradley- d,l- amphetamine reduced restlessness and improved concentration in children with behavioral problems in residential treatment center. 30 years later Keith Conners and Leon Isenberg evaluated efficacy of dextroamphetamine for children with learning disability and behavioral problems. HistoryEarly 1960s- Minimal Brain Dysfunction Late 1960s- ICD-9 & DSM- II adopted- Hyperkinetic Syndrome of Childhood.1970- Further research suggested that the main disability- impaired attention and impulsivity- gross motor overactivity was secondary. 1980- DSM III- Attention-Deficit Disorder ADD. With HyperactivityWithout HyperactivityResidual Type. DSM IV- ADHDDefinition: (DSM-IV)ADHD is a behavioral and neurocognitive condition characterized by developmentally inappropriate and impairing levels of gross motor overactivity, inattention, and impulsivity.There are five main diagnostic criteria: (1) an onset before age 7 years (2) duration greater than 6 months (3) an 18-item symptom list of which 6 of 9 inattention or 6 of 9 hyperactive/impulsive symptoms have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level; (4) some impairment in two or more settings (5) symptoms that do not occur exclusively during the course of a pervasive developmental disorder, schizophrenia, or other psychotic disorder and are not better accounted for by another mental disorder, such as depression.

Definition: (DSM-IV)ADHD, Predominately Inattentive Type - 6 of 9 symptoms of inattention,

ADHD, Predominately Hyperactive-Impulsive Type-6 of 9 symptoms of hyperactivity/impulsivity

ADHD, Combined Type- 6 of 9 symptoms in both areas.

Proposed Revision for DSM V http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=383#Comparative NosologyICD-10 DSM-IV-TRHyperkinetic Disorder (HD)ADHDMinimum criteria: 6 of 9 Inattentive and 3 of 5 Hyperactivity and 1 of 4 impulsiveCriteria: 6 of 9 Inattentive or 6 of 9 Hyperactivity/impulsive or Both. Can not diagnose HD if criteria for emotional disorder are met (Depression or Anxiety) Can diagnose ADHD even if criteria for emotional disorder metCases not meeting HD criteria- Must be managed psychologically before medication can be started. Out of 579 children with DSM-IV ADHD, Combined Subtype, from Multimodal Treatment Study (MTA trial), only 25% met the diagnostic criteria for HD. EPIDEMIOLOGYPolanczyk and colleagues estimated worldwide prevalence to be 5.2 percent. (meta-analysis that included hundreds of articles and more than 100,000 patients). Significant geographical variability and local variability among studies. Prevalence in N. America is higher than Africa, Europe and Middle East. According to CDC data,Approximately 9.5% or 5.4 million children 4-17 years of age have ever been diagnosed with ADHD (2007) The percentage of children with a parent-reported ADHD diagnosis increased by 22% between 2003 and 2007.Boys (13.2%) were more likely than girls (5.6%) to have ever been diagnosed with ADHDPrevalence of parent-reported ADHD diagnosis varied substantially by state State-based Prevalence Data of ADHD Diagnosis20032007

Stimulant Use - Steady Rise. National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ): Use of Stimulant Medication, 1987- 0.6 % 1997- 2.7 % 2008- 3.5 % Use among 6-12-year-olds was highest, going from 4.2 percent in 1996 to 5.1 percent in 2008. Fastest growth of use among 13-18-year-olds, going from 2.3 percent in 1996 to 4.9 percent in 2008.

What Causes ADHD?Exact cause unknownMeta-analysis of 83 studies with more than 6,000 subjects showed that patients with ADHD have impairments in the executive functioning domains of response inhibition, vigilance, working memory, and some measures of planning (Willcutt et al., 2005). A growing consensus that the condition involves functional and anatomical dysfunction in the brain's frontal cortex and basal ganglia segments of the cortico-basal ganglia-thalamo-cortical circuitry.So what causes this dysfunction- Genetics Neuroanatomical Neurotransmitter Environment Brain Injuries

Genetics Twin, sibling, adoption, and family studies, have all suggested that genetic factors play an important role in ADHD.Thyroid Receptor B GeneDopamine Type D2 Receptor GeneDopamine Transporter GeneDopamine 4 Receptor GeneDopamine -hydroxylase (DBH)LPHN3 gene (Arcos-Burgos M, et al.)(ADHD cases where LPHN3 gene (9%) is present are particularly responsive to stimulant medication.)Neurotransmitters in ADHDDopamine SystemMolecular genetic studies have targeted genes involved in Dopamine Regulation. Stimulant drugs bind strongly to dopamine transporter to prevent reuptake of dopamine back into the presynaptic axon for metabolism. Noradrenergic SystemDysfunction in norepinephrine systems can explain- inattention and higher levels of gross motor activity. TCAs and Atomoxetine (potent norepinephrine reuptake inhibitors) have shown clinical improvement. Neuroanatomical (Neuroimaging Research)Children with ADHD have reduced cortical white and gray matter volume. Volume deficits are more pronounced in treatment-naive children (Castellanos et al., 2002).Decreased frontal and temporal lobe volume in children with ADHD relative to controls (Sowell et al. 2003).NIMH intramural researchers found that cortex is thinner in children with ADHD and remains thin in those with less improvement. In teens who showed improvement, the cortex thickened on the right side( Drs. Philip Shaw and Judith Rapoport, NIMH Child Psychiatry Branch, and colleagues ) Neuroimaging ResearchBrain matures in a normal pattern but is delayed three years in some regions, on average, compared to control. (Philip Shaw, M.D., NIMH Child Psychiatry Branch) Frontal and temporal lobe showed the greatest maturational delay in youth with ADHD. The motor cortex emerged as the only area that matured faster than normal in the youth with ADHD, in contrast to the late-maturing frontal cortex areas that direct it. This mismatch might account for the restlessness and fidgety symptoms. The delayed pattern of maturation observed in ADHD is the opposite of that seen in other developmental brain disorders like autism, in which the volume of brain structures peak at a much earlier-than-normal age. Neuroimaging Research

Environmental Factors.Studies suggest a potential link between cigarette smoking and alcohol use during pregnancy and ADHD in children.Preschoolers who are exposed to high levels of lead, may have a higher risk of developing ADHD.Sugar: The idea that refined sugar causes ADHD or makes symptoms worse is popular, but more research discounts this theory than supports it.Food additives: Recent British research indicates a possible link between consumption of certain food additives like artificial colors or preservatives, and an increase in activity. Research is under way to confirm the findings and to learn more about how food additives may affect hyperactivity.

Brain injuriesChildren suffering a severe head injury may develop symptoms of ADHD, usually of the inattentive subtype.

However, only a small percentage of children with ADHD have suffered a traumatic brain injury.

Encephalopathies can cause inattention but generally produce other neurological symptoms (language or motor impairment) in addition to inattention.

ComorbiditiesOppositional defiant disorder (ODD)- 50% Some of these patients will develop conduct disorder. Anxiety Disorder- 30-35 % Learning Disorder and Language Problem- 25-35 % Substance Abuse- 15-19 % Mood Disorder- contentious issue- with various studies indicating 0-33%

Screening: In any mental health assessment, ask questions regarding major symptoms ( inattention, impulsivity and hyperactivity) regardless of chief complaint.

Rating scales and specific questionnaires can be included during office/clinic registration or before the interview.

If a parent reports that the patient suffers from any symptoms of ADHD that induce impairment or if the patient scores in the clinical range for ADHD symptoms on a rating scale, then a full evaluation for ADHD should be done. EvaluationThree Major Components: Interview with the parents. Interview with the child/adolescent.Investigation & psychological testing.

Interview with the parents A detail interview about each 18 symptoms. For each symptomsAge of Onset ( Childhood ) Duration ( Chronic ) Frequency ( More days than not ) Impairment ( Do not confuse with symptom) Interview parent regarding common psychiatric disorders ( ODD, CD, Depression, Anxiety, tic disorder, Substance Abuse, Psychosis) Family history: psychiatric illness. ( ADHD, Anxiety, Tic, CD) Social history: Structured Vs DisorganizedPerinatal history, development history, milestones, medical history and mental health history. Interview with the parentsParent should complete one of many standardized behavior rating scales. Request release of information- obtain similar rating scale from school teacher. Common rating scales: Academic Performance Rating Scale (APRS)ADHD Rating Scale-IVChild Behavior Checklist (CBCL)Conners Parent Rating Scale RevisedConners Teacher Rating Scale-Revised Conners Wells Adolescent Self-Report ScaleVanderbilt ADHD Diagnostic Parent and Teacher Scales and others These scales also provide information about other psychiatric symptoms which could be comorbid with ADHD or would suggest alternative diagnosis.

Interview with the child or adolescentPreschool or young school-age child (5-8 years old), interview may be done concurrently with the parent interview.Older children and adolescents should be interviewed separately from parents, as they may not reveal significant symptoms (depression, suicidal ideations, drug or alcohol abuse) in the presence of a parent. The interview with the child or adolescent is not to confirm or rule out the diagnosis of ADHD. ( Young child may not be aware of symptoms and teenage may under report symptoms) Specific emphasis to objective features to assess vocabulary, thought processes, and content of thought. Investigation & Psychological Testing For unremarkable medical history- no investigation required. Psychological Testing: Not mandatory To differentiate between ADHD and learning disorder. Academic impairment can be from ADHD or learning disorder or both. 1:1 Supervision- if child can perform at grade level or above- likely from ADHD- first treat ADHDChild engages in leisure activity that require a skill but would avoid reading a book for examination, first treat ADHDPresence of symptoms not from ADHD like impairment in expressive receptive language, poor phonological processing, poor motor co-ordination, difficulty grasping fundamental mathematics.

TreatmentSeveral interventions are effective in treating children with ADHD, including medications and behavior therapy.To examine how intensive treatment with medications compares with intensive behavior therapy, or with the combination of the two, NIMH sponsoredthe Multimodal Treatment of ADHD (MTA) study.The study included nearly 579 children, ages 7-9, who were randomly assigned to one of four treatment modes:Intensive medication management alone;Intensive behavioral treatment alone;A combination of both; orRoutine community care (the control group).

Multimodal Treatment of ADHD (MTA) studyAt the end of the 14 months, all groups showed improvement. The medication management and combined treatment groups showed significantly greater reduction in core ADHD symptoms and impairment.Combined treatment, but not medication management, was superior to community care and intensive behavioral treatment for oppositional and aggressive symptoms, internalizing symptoms, teacher-rated social skills, parentchild relationships, and reading achievement.

Multimodal Treatment of ADHD (MTA) studyMTA treatment lasted for 14 months only, after which the children were referred back to their community providers.All participants, were invited to return to the MTA clinics every one to two years for an assessment of their ADHD symptoms and level of functioning.At the end of three year follow up, Sustained improvement after three years. Initial advantages of medication management alone or in combination with behavioral treatment over purely behavioral or routine community care started to wane.Ratings from families and teachers favored the combination treatment, which allowed for lower medication doses. The careful management of medication by MTA physicians produced better outcomes than medication provided through usual community care sources.Multimodal Treatment of ADHD (MTA) study8 year follow-up, The eight-year follow-up revealed no differences in symptoms or functioning among the youths assigned to the different treatment groups as children. Youths with ADHD still had significantly more academic and social problems compared with peers who did not have ADHD. Youths who had responded well to treatment and maintained their gains for two more years after the end of the trial tended to be functioning the best at eight years.

Multimodal Treatment of ADHD (MTA) study8 year follow-up ( Continued) A majority (61.5 percent) of the children who were medicated at the end of the 14-month trial had stopped taking medication by the eight-year follow-up, suggesting that medication treatment may lose appeal with families over time. The reasons for this decline are under investigation, but they nevertheless signal the need for alternative treatments.Children who were no longer taking medication at the eight-year follow-up were generally functioning as well as children who were still medicated, raising questions about whether medication treatment beyond two years continues to be beneficial or needed by all.

Treatment Begins with psychoeducationInvolves educating the parent and child about ADHD and its various treatment options (medication and behavior therapy), linkage with community supports and additional school resources. Take into account the most recent evidence concerning effective therapies as well as family preferences and concerns.Use books, articles, videos, and some noncommercial web sites on ADHD to educate parents and patients. http://www.adhdawarenessweek.org/,http://www.nimh.nih.govhttp://www.cdc.gov and many more.

Medication (Stimulants) The short-term efficacy of psychopharmacological intervention for ADHD is well established. Methylphenidate (MPH) or amphetamine the two are equally efficacious. Long-acting formulations (Offers convenience and confidentiality) are equally efficacious as the immediate-release forms in both adolescents as well as children. (Spencer et al., 2006; Wilens et al., 2006) Medication (Stimulants)Careful titration Teacher and parent rating scales at end of one week of increase in dose Equal response to both MPH and Amphetamine - 41 % Preferential response to MPH or Amphetamine - 44 %Initial response rate- 85% if both stimulants are tried (65% -75% response when only one stimulant is tried). Regular monitoring. Look for side effects, Most common: appetite decrease, weight loss, insomnia, headache Less common: tics and emotional lability/irritability Medication- Monitoring Height and Weight:Serial plotting of on growth charts. Change in height or weight that shows aberrant growth trajectory- consider drug holidays or switching medication.

Blood Pressure and Pulse: MTA at 14th Month- higher heart rates but no tachycardia.10 year follow-up- Did not appear to increase the risk for abnormal elevations in blood pressure or heart rate. Epidemiological studies have indicated that even modest elevations in heart rate may increase a persons lifetime risk for cardiovascular problems. Persistent effect of continuous stimulant treatment on heart rate should not be dismissed. Medication- MonitoringEKG: Cases of sudden death have been reported. MPH: 0.2/100,000 & Amphetamine: 0.2/100,000 (exposure period January1, 1992 to December 31, 2004) (Villalaba-2006) Package insert- generally not be used in children and adolescents with preexisting heart disease or symptoms suggesting significant cardiovascular disease. No evidence currently indicates a need for routine cardiac evaluation (i.e., electrocardiography, echocardiography) before starting any stimulant treatment in otherwise healthy individuals (Biederman et al., 2006). Adding ECG to the current standard of care may identify more children at risk for SCD prior to starting them on stimulants for treating ADHD but it is borderline cost-effective. (Dr. Peter Denchev, and colleagues, 2010)The American Heart Association currently recommends that doctors consider obtaining an ECG prior to prescribing stimulants if they believe it is warranted.Medication- MonitoringTics: Stimulant induced tics- less clearChildren with comorbid ADHD and tic disorders, on average, show a decline in tics when treated with a stimulant but clinicians have noticed stimulant induced tics, too. Treatment-emergent tics during a trial- consider an alternative stimulant or a non stimulant Symptoms respond adequately only to a stimulant medication that induces tics- consider clonidine or guanfacine (Tourettes Syndrome Study Group, 2002)Medication- MonitoringAggression and Mood Lability: Aggressive acts and antisocial behavior may decline with stimulants (Connor et al., 2002 [rct]). Stimulant induced vs ReboundFor rebound hyperactivity- small dose of immediate release stimulant in the late afternoon. Rare cases of aggressive behavior, psychosis and manic symptoms reported (black box warning)If stimulant induced agression, mood lability, psychosis are evident- stop stimulant. Adjunctive therapy with neuroleptics or mood stabilizers is not recommended. Medication- AtomoxetineNoradrenergic reuptake inhibitor.Less pronounced effects on appetite and sleep.Relatively more nausea or sedation.Full therapeutic dose for at least several weeks to obtain full effect. Indicated for ADHD comorbid with substance abuse. RCT showed a reduction in ratings of symptoms of both ADHD and anxiety, when used in patient with ADHD and co-morbid anxiety. (Sumner et al., 2005 ). Black Box Warnings for suicidality and not approved for major depression. Treatment Failure with stimulantIf the patient fails to respond to trials after an adequate length of time at appropriate doses, Review diagnosis of ADHD again. Consider behavioral therapy. Consider alternative medications like bupropion, tricyclic antidepressants (TCAs), and alpha-agonists. Psychosocial TreatmentIncludes different modalities, such as psychoeducation, academic organization skill teaching and remediation, parent training, behavior modification, cognitivebehavioral therapy (CBT), social skills training, and individual therapy.Parent training, intensive behavior modification, and social skills training have shown most efficacy for children with ADHD in controlled trials.

Intensive Behavioral InterventionsPsychoeducation about the course, risk factors, and long-term outcomes of ADHDThe parents are encouraged to attend more carefully to their child's behaviorParents are trained to use time out effectively.Parents are instructed how to establish a contingency management or token economy system at home.Parents learn how to manage noncompliant behaviors in public settings.Finally, advances in prosocial behavior in school are supported by use of a daily report card. Psychosocial TreatmentExamples of social skills training, how to wait for their turn, share toys, ask for help, or respond to teasing. Learning to read facial expressions and the tone of voice in others, and how to respond appropriately can also be part of social skills training. It is crucial to evaluate the parents and family for dysfunction related to the child's ADHD. Parental ADHD may interfere with behavioral modification programs, indicating that treatment of the affected parent may be necessary before the child's intervention can be successful.Medications versus Psychosocial Management If a patient with ADHD has a robust response to psychopharmacological treatment and subsequently shows normative functioning in academic, family, and social functioning, then psychopharmacological treatment of the ADHD alone is satisfactory. If a patient with ADHD has a less than optimal response to medication, has a comorbid disorder, or experiences stressors in family life, then psychosocial treatment in conjunction with medication treatment is often beneficial. [(A A C A P) Practice Parameter] Referenceslaiwalar@mail.etsu.eduAmerican Academy of Child and Adolescent Psychiatry (1997), Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. American Academy of Child and Adolescent Psychiatry (2002), Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. American Academy of Child and Adolescent Psychiatry (2007), Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. Arnold LE (2000), Methylphenidate vs. amphetamine: comparative review. J Atten Disord 3:200211*The MTA Cooperative Group: A 14-month randomized clinical trial of treatment strategies for attention deficit/ hyperactivity disorder (ADHD). Arch Gen Psychiatry. 1999;56:1073.Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stephanos GA: Etiologic subtypes of attention-deficit/hyperactivity disorder: Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev. 2007;17(1):39.Shaw P, Lerch J, Greenstein D, Sharp W, Clasen L, Evans A, Giedd J, Castellanos FX, Rapoport J. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2006 May;63(5):540-9.Plessen KJ, Bansal R, Zhu H, Whiteman R, Amat J, Quackenbush GA, Martin L, Durkin K, Blair C, Royal J, Hugdahl K, Peterson BS. Hippocampus and Amygdala Morphology in Attention-Deficit/Hyperactivity Disorder. Arch Gen Psychiatry. 2006 Jul;63(7):795-807. MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: changes in effectiveness and growth after the end of treatment. Pediatrics 2004;113:762-769.Swanson JM, Elliott GR, Greenhill LL, Wigal T, Arnold LE, Vitiello B, Hechtman L, Epstein J, Pelham W, Abikoff HB, Newcorn J, Molina B, Hinshaw S, Wells K, Hoza B, Severe JB, Jensen PS, Gibbons R, Hur K, Stehli A, Davies M, March J, Caron M, Volkow ND, Posner MI, for the MTA Cooperative Group: Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. J Am Acad Child Adolesc Psychiatry 2007;46:1014-1026.Molina BSG, Hinshaw S.P., Swanson J.M., Arnold, L.E., Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L., Abikoff, H.B., Elliott GR, Greenhill LL, Newcorn, JH, Wells KC, Wigal TL, Severe JB, Gibbons RD, Hur K, Houck PR, and the MTA Cooperative Group: The MTA at 8 years: prospective follow-up of children treated for combined type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry 2009;48:484-500.Kaplan & Sadock's Comprehensive Textbook of Psychiatry Zuvekas S and Vitiello B. Stimulant medication use in children: a 12-year perspective. American Journal of Psychiatry. Online ahead of print September 28, 2011.Molina BSG, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L, Abikoff HB, Elliott GR, Greenhill LL, Newcorn JH, Wells KC, Wigal T, Severe JB, Gibbons RD, Hur K, Houck PR, and the MTA Cooperative Group.The MTA at 8 years: Prospective follow-up of children treated for combined type ADHD in the multisite study. Journal of the American Academy of Child and Adolescent Psychiatry. Online ahead of print March 2009.Other MTA references,

http://www.nimh.nih.gov/http://www.cdc.gov/en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder

Referenceshttp://www.nimh.nih.gov/http://www.cdc.gov/en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorderOther MTA referencesThe MTA Cooperative Group:A 14-Month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder (ADHD).Arch Gen Psychiatry1999;56:1073-1086.The MTA Cooperative Group: Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder (ADHD).Arch Gen Psychiatry1999;56:1088-1096.Swanson JM, Kraemer HC, Hinshaw SP, Arnold LE, Conners CK, Abikoff HB, Clevenger W, Davies M, Elliott GR, Greenhill LL, Hechtman L, Hoza, B, Jensen PS, March JS, Newcorn JH, Owens EB, Pelham WE, Schiller E, Severe JB, Simpson S, Vitiello B, Wells K, Wigal T, Wu M: Clinical relevance of the primary findings of the MTA: success rate based on severity of ADHD and ODD symptoms at the end of treatment.J Am Acad Child Adolesc Psychiatry2001; 40:168-179.Greenhill LL, Swanson JM, Vitiello B, Davies M, Clevenger W, Wu M, Arnold LE, Abikoff HB, Bukstein OG, Conners CK, Elliott GR, Hechtman L, Hinshaw SP, Hoza B, Jensen PS, Kraemer HC, March JS, Newcorn JH, Severe JB, Wells K, WigalT: Impairment and deportment responses to different methylphenidate doses in children with ADHD: the MTA titration trial.J Am Acad Child Adolesc Psychiatry2001; 40:180-187.Vitiello B, Severe JB, Greenhill LL, Arnold LE, Abikoff HB, Bukstein O, Elliott GR, Hechtman L, Jensen PS, Hinshaw SP, March JS, Newcorn JH, Swanson JM, Cantwell DP: Methylphenidate Dosage for Children with ADHD over Time under Controlled Conditions: Lessons from the MTA.J Am Acad Child Adolesc Psychiatry2001; 40:188-196.Owens EB, Hinshaw SP, Kraemer HC, Arnold LE, Abikoff HB, Cantwell DP, Conners CK, Elliot G, Greenhill LL, Hechtman L, Hoza B, Jensen PS, March JS, Newcorn JH, Pelham WE, Richters JE, Schiller EP, Severe JB, Swanson JM, Vereen D, Vitiello B, Wells KC, Wigal T: What treatment for whom for ADHD: Moderators of treatment response in the MTA.J Consult Clin Psychol2003;71:540-552.MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit/hyperactivity disorder.Pediatrics2004;113:754-761.MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: changes in effectiveness and growth after the end of treatment.Pediatrics2004;113:762-769.Swanson JM, Elliott GR, Greenhill LL, Wigal T, Arnold LE, Vitiello B, Hechtman L, Epstein J, Pelham W, Abikoff HB, Newcorn J, Molina B, Hinshaw S, Wells K, Hoza B, Severe JB, Jensen PS, Gibbons R, Hur K, Stehli A, Davies M, March J, Caron M, Volkow ND, Posner MI, for the MTA Cooperative Group: Effects of stimulant medication on growth rates across 3 years in the MTA follow-up.J Am Acad Child Adolesc Psychiatry2007;46:1014-1026.Molina BSG, Hinshaw S.P., Swanson J.M., Arnold, L.E., Vitiello B, Jensen PS, Epstein JN, Hoza B, Hechtman L., Abikoff, H.B., Elliott GR, Greenhill LL, Newcorn, JH, Wells KC, Wigal TL, Severe JB, Gibbons RD, Hur K, Houck PR, and the MTA Cooperative Group: The MTA at 8 years: prospective follow-up of children treated for combined type ADHD in a multisite study.J Am Acad Child Adolesc Psychiatry2009;48:484-500.

Thank You and Merry Christmas!!Special Thanks to Dr. Bird, Dr. McCarley, Dr. Shulruff