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ADHD Update
•
•J= eff Turley, MD
•C= hild and Adolescent Psychiatrist
•<= p:onmouseclick hyperlinktype=3D"url" href=3D"http://www.jeffturley.com/"/>= www.JeffTurley.com<= span style=3D'mso-spacerun:yes'> 
Intend= ed Audience: Adults interested in Attention-Deficit Hyperactivity Disorder and associa= ted cognitive or behavioral difficulties.
Synops= is:  Dr. Turley reviews the core defi= cits of ADHD, describes executive function and dysfunctions, and discusses controversies and obstacles to accurate diagnosis and treatment.  The common medication treatments= are surveyed.  Links to more in-= depth discussions of neurobiological correlates and mechanisms of individual treatments are provided.  Re= cent developments in medication formulations are discussed.   Dr. Turley emphasizes the importance of data collection for the safe and effective management of me= dication treatments and notes some potential adverse effects of various compounds.=
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Core Deficits of ADHD
•Symptom triad:  Inattentiveness, = Impulsivity, and Restlessness •Each of these core deficits can be sub-divided.  •ADHD is almost certainly not one “illness” but rather a clu= ster of difficulties arising from different causes
ADHD i= s a syndrome of relative infirmities or abnormalities in brain functioning.  The modifier “relativeR= 21; is important because normally-functioning people vary in their abilities to focus and concentrate, stay on task, inhibit impulses, and control motor activities.  Boys differ from girls, and younger individuals from older.  All of the behaviors used to dia= gnose the syndrome are normal for all people at some times of their lives.  Behaviors become “symptoms” when they are clearly indicative of some level of impaired functioning.  When symptoms appear to hang together, their aggregate is referred to as a syndrome or disorder.
The tr= iad of deficits comprising ADHD are:
1.Inattentiveness: relative difficulty directing and sustaining mental resources on a task.
2.Impulsivity:  relative difficulty controlling actions or thinking before acting.=
3.Restlessness:  relative difficulty remaining quiet and still.

Each o= f the deficits can be subdivided into other measurable neuropsychological skills.  For instance, inattentiveness ma= y be defined as a failure to notice novel stimuli, or a failure of screening mechanisms for attaching significance to stimuli (i.e. irrelevant stimuli= are noticed to the exclusion of relative stimuli).  Impulsivity and restlessness may= arise from impairment in normal mechanisms for inhibition, the function that al= lows an individual to withhold a response if circumstances change.   Lack of inhibition amounts= to distractibility or lack of concentration and results in errors and impulsiveness.  Inhibitory t= asks activate the prefrontal cortex and basal ganglia of the brain, regions in which the dopamine system is associated with executive functioning.  Effective medications work on the dopamine transmitter systems.

Syndro= mes are clusters of symptoms that may have different causes. ADHD is almost certa= inly not one “illness” but rather a group of difficulties arising = from complex, multifactorial causes.
------=_NextPart_01C81D5E.07336840 Content-Location: file:///C:/F13392E5/ADHDUpdate_files/slide0626.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Attention-Deficit/Hyperactivity Disorder, Revisited

Executive Dysfunction
•What are executi= ve functions? <= /span>•Is executive dysfunction the = same thing as ADHD? &= #13;•What to do?  Behavior modification or = skills training?
www.Schoolbehavior.com 
Execut= ive functions (EF) are central processes that are most intimately involved in giving organization and order to our actions and behavior. They have been compar= ed to the "maestro" who conducts the orchestra. But what are these processes? The whole topic is very controversial, but there seems to be a consensus that executive functions involve (at the very least):
1.planning for the future and strategic thinking
2.the ability to inhibit or delay responding
3.initiating behavior, and
4.shifting between activities flexibly

If we = break down the skills or functions into sub-functions, we might say that executive funct= ions tap into the following abilities or skills:
1.Goal
2.Plan
3.Sequence
4.Prioritize
5.Organize
6.Initiate
7.Inhibit
8.Pace
9.Shift
10.Self-monitor
11.Emotional control
12.Completing

As you= can see, many of the deficits of ADHD appear to be “executive” in nature.  A growing body of scientific evi= dence localizes executive functioning in the connections between pre-frontal co= rtex (the part of the brain above the eyes) and other brain areas like the bas= al ganglia (deeper brain structures that control movement) and the limbic sy= stem (deeper structures that influence emotional experience).


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Executive Dysfunction
- May skip steps in multi-step task
- May have difficulty relating story chr= onologically =
- May "jump the gun" socially
Sequence
- May start project with= out necessary materials
- May not leave enough time to complete=
- May not make plans for the weekend with = pee= rs
Plan
Acts as if "future-blind" (Barkley, 2002), i.e. not wor= king towards the future.
Goal
Possible Signs or Symptoms of Dysfuncti= on
Function
Diffic= ulties setting goals, planning activities, and sequencing steps towards completion of a = task all fall under the general heading of “disorganized.”  Individuals lacking these abilit= ies may have never developed the associated skills.  Without the skills one would have great difficulty establishing organized habits.
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Executive Dysfunction
May run out of time
Pace
- May appear distractible and/or impulsive
- May pick smaller, immediate reward over larger, delayed reward
Inhibit
Difficulty getting started on tasks may ap= pear as oppositional behavior
Initiate
- May lose important papers or possessions= =
- May fail to turn in completed work =
- May create unrealistic schedule
Organize
- May waste time doing s= mall project and fail to do big project
- May have difficulty identifying what material to record in note-taking
Prioritize
Possible Signs or Symptoms of Dysfuncti= on
Function
People= with ADHD often share a frustration that they work very hard and seem to get nowhere.  Because they often= lack the relative ability to prioritize tasks and pace their time, much effort= can be expended without task completion.&nbs= p; External pressures sometimes help the person with weak executive skills to prioritize and initiate.  Without fear of failure, deadlines, and other pressure they tend to “spin their wheels.”
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Executive Dysfunction
May start tasks but not finish them=
Complete
May exhibit inappropriate or over-reactive response to situations
Emotional = Control
- Doesn’t check to insure that each step is completed
- Doesn’t monitor pace to determine = if goal will be met on time,
- Doesn’t check work before submitti= ng it= 3;
Self-Monitor
May have difficulty maki= ng transitions and/or coping with unforeseen events=
Shift
Possible Signs or Symptoms of Dysfunction<= /span>
Function
People= with weak executive skills often have a low frustration tolerance.  One would think with all that pr= actice being frustrated, they would get good at it.  Unfortunately, this is often not= the case because they lack healthy skills for self-monitoring, awareness of feelings, and emotional self-control.&nb= sp; They can become especially upset if the task at hand involves flexibility and adaptation.  Some people “hyper-focus” on an element of the task to the exclusi= on of other critical aspects necessary for completion.
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Diagnosis: caveats
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•No reliable test= s
•Indirect evidence (continuous performance tests, freedom from distractibility = index, etc.)
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Criteria are subjective
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Sex biases <= /span>
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Sleep deprivatio= n=3D ADHD
Some c= ritics think that ADHD either does not exist, that it represents a variation of normal behavior, or that it is over-diagnosed.&= nbsp; Others suspect that ADHD is used as an excuse for social immaturit= y, poor parenting, bad choices, and failures of discipline.  There is no doubt that, compared= to years past, many more children carry the diagnosis and a growing number of adults are being identified and treated.=   While the body of scientific evidence seems irrefutable, there may= be some truth to these other caveats too.

ADHD i= s diagnosed subjectively.  A diagnostici= an matches reports of core behaviors to a concept of “developmental appropriateness,” and determines whether or not the behaviors cause= a significant impairment.  If = these conditions are met, the diagnosis is made and treatment options can be considered.  There are no re= liable tests to distinguish the patient with ADHD from a “normal” person, because everyone has aspects of ADHD.  Measurable data point to relative deficits of executive functioning, but the associated tests are often expensive and may not be available.  Continuous performance tests which measure a person’s abilit= y to focus on a meaningless task over a period of perhaps 30 minutes (respond = and inhibit responses as instructed) and measures errors of omission (indicat= ing inattentiveness) and errors of commission (indicating failure of inhibition).  These tests ha= ve been validated scientifically, but their practical utility is low (in Dr. Turley’s opinion).  St= andard intelligence testing includes some measures of core ADHD deficits (a scale for freedom from distractibility, measures of working memory), and expens= ive neuropsychological testing measures several other executive functions.  An individual’s score on t= hese measures can be compared to a “normative” sample.

Younge= r children tend to look more ADHD than older children, and boys are more inattentive, impulsive, and restless than girls at the same age.  Accordingly, sex biases are diff= icult to avoid.

Sleep = deprivation, whether a result of lifestyle or a side-effect of medication treatment, results in impairments indistinguishable from ADHD.
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=

Obstacles to treatment
<= span class=3DBB style=3D'position:absolute;left:-4.14%;top:-.15em'>•Diagnostic uncertainties (lack of tests)
•Overlap of “symptoms” with normal (especially for boys)
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Limited number of treatments
•Fear (stigma, ad= verse effects, addiction/abuse, comorbidity)
Epidem= iological studies indicate that ADHD is the most common neurobehavioral disorder presenting in children, affecting 5-8% of children and 4-5% of adults in = the United States.  Studies sugg= est that less than half of these diagnosable cases are treated.  Some of the obstacles of treatme= nt are associated with detection (lack of confirmatory tests difficulties distinguishing disorder from normal) and others are associated with treat= ment or fear of treatment.  Paren= ts may be reluctant to present their child for treatment, concerned that they wo= uld be joining an unhealthy trend in society by doing so, or bowing to pressu= re from schools.  Others fear side-effects of medication or worry that it will foster dependency on medications.  Children may r= esist taking the medication, or forget.
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Available treatments
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Stimulants <= /span>
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Noradrenergic agents
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Antidepressants&= #13;
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Antihypertensive= s
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Arousal agents
Drug t= herapy remains the mainstay of treatment for ADHD.
Stimul= ant medications include various preparations of methylphenidate and amphetamines.  These drugs increase the levels of dopamine (DA), and/or norepinephrine (NE) in the central nervous system.  The= ir effectiveness is established by more than 300 controlled trials and their safety is well established.
Stratt= era (atomoxetine) is a noradrenergic medication that blocks the reuptake of N= E, selectively increasing NE in the central nervous system.  Although the medication is less predictably effective for ADHD symptoms, it may be especially useful for treatment of ADHD complicated by oppositional anxiety or tics.
Antide= pressants are second-line treatment for ADHD.  Wellbutrin (bupropion) and tricyclic antidepressants affect DA and= NE systems, though less directly than do stimulants.  Tricyclic antidepressants are dangerous in overdose and require consistent monitoring of the ECG.  Desipramine was implicated in the deaths of 4 children, but independent evaluation of these cases failed to support a causal link.
Antihy= pertensive medications (used to lower high blood pressure)  are also effective for ADHD.  These include clonidine and guanfacine.  Reports implica= ted the combination of methylphenidate and clonidine in the deaths of 4 child= ren but causal links could not be established.
Provig= il (modafinil) is a novel, non-stimulant arousal agent that seems to activate arousal systems in the brain, leading to improvements in attention.

Antide= pressants like Prozac (fluoxetine), Paxil (paroxetine), and others have no effect on ADH= D, but they may interfere with the metabolism of other medications used for = the condition.  Dosage modificat= ions may be necessary if treatments are combined.
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Does therapy help?
•Behavior therapy= is commonly recommended, but a large and well = controlled study showed that effects were minimal compared to medication •Parental supervi= sion of medication treatment is critical to success.
The la= rgest and most comprehensive study to date (the Multimodal Treatment Study of Children W= ith Attention Deficit/Hyperactivity Disorder—the MTA Cooperative Group study) indicates that intensive behavior therapy, comprising child, famil= y, and school-based interventions, adds little to the effects of long-term stimulant therapy. The MTA study also identified that the quality of supervision of medication may be an important factor in optimizing long-t= erm therapeutic benefit.

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New Developments
•Vyvanse (lisdexamfetamine dimesylate) is a pro-drug version of amphetamine which is converted to an active compound in the GI tract =
•Marketed as longer-acting
•May be the stimulant of choice for substance dependent patients
•Still a controlled substance!
New de= velopments:
Vyvans= e is a stimulant medication activated by catabolism in the GI track.  Although risks of abuse are lower compared to dextroamphetamine, the medication is still a controlled substance.
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New Developments
•Daytrana (methylphenidate) patch may reduce blood level fluctuations <= /span>
<= span class=3DBB style=3D'position:absolute;left:-3.79%;top:-.15em'>•Necessary for ki= ds who don’t swallow pills
•24 hr. drug expo= sures are higher for patch vs. oral
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Kids and patches don’t get along
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Risks of allergy= may be higher
New De= velopments:
methyl= phenidate is a familiar, well studied treatment that is now available as a transdermal patch.  This allows flexibil= ity of treatment with variability of wear-time, and may be especially useful for children who can’t swallow pills.&= nbsp; Unfortunately, the use of a skin patch for drug treatment is complicated by local skin irritation, security concerns, and difficult keeping the patch adhered.
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<= span style=3D'font-family:Tahoma;mso-ascii-font-family:Tahoma;font-size:91%'> School Data is important
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Checklists for diagnosis, monitoring
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Time of day shou= ld be recorded
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Dealing with par= ents
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Positive observa= tions essential
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Boundaries <= /span>
<= span class=3DBB style=3D'position:absolute;left:-3.7%;top:-.15em'>•Download forms f= rom = www.JeffTurley.com 
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<= span style=3D'font-family:Tahoma;mso-ascii-font-family:Tahoma;font-size:91%'> Adverse responses (stimulants)
•Commonly:  decreased appetite, insomnia, = benign elevation= s of pulse and BP
<= span class=3DBB style=3D'position:absolute;left:-3.81%;top:-.15em'>•Possibly:  agitation, anxiety, short stature=
•Rarely:  mania, rage, panic, abuse/diversion&= #13;
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Exceedingly rarely:  death<= /div>
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Adverse responses (other meds)
<= span class=3DBB style=3D'position:absolute;left:-4.43%;top:-.15em'>•Wellbutrin (bupropion):  seizures
<= span class=3DBB style=3D'position:absolute;left:-4.33%;top:-.15em'>•Tricyclics:  heart rhythm disturbance
•Clonidine, Tenex (guanfacine) : hypotension, sedation <= span class=3DBB style=3D'position:absolute;left:-3.86%;top:-.15em'>•Strattera (atomoxetine):  suicidality, = liver toxicity<= /span>
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Intended Audience: Adults inter= ested in Attention-Deficit Hyperactivity Disorder and associated cognitive or behavioral difficulties. Synopsis:&n= bsp; Dr. Turley reviews the core deficits of ADHD, describes executive f= unction and dysfunctions, and discusses controversies and obstacles to accurate diagnosis and treatment.  The common medication treatments are surveyed.  Links to more in-depth discussion= s of neurobiological correlates and mechanisms of individual treatments are provided.  Recent development= s in medication formulations are discussed.   Dr. Turley emphasizes the i= mportance of data collection for the safe and effective management of medication treatments and notes some potential adverse effects of various compounds.<= span style=3D'mso-spacerun:yes'> 
ADHD is a syndrome of = relative infirmities or abnormalities in brain functioning.  The modifier “relative̶= 1; is important because normally-functioning people vary in their abilities to f= ocus and concentrate, stay on task, inhibit impulses, and control motor activities.  Boys differ from girls, and younger individuals from older.  All of the behaviors used to diag= nose the syndrome are normal for all people at some times of their lives.  Behaviors become “symptoms&= #8221; when they are clearly indicative of some level of impaired functioning.  When symptoms appear to hang toge= ther, their aggregate is referred to as a syndrome or disorder. 
The triad of deficits com= prising ADHD are:
1.Inattentiveness: relative difficulty directing and sustaining mental resources on a task. 
2.Impulsivity:  relative difficulty controlling a= ctions or thinking before acting.
3.Restlessness:  relative difficulty remaining qui= et and still. 
Each of the deficits can = be subdivided into other measurable neuropsychological skills.  For instance, inattentiveness may= be defined as a failure to notice novel stimuli, or a failure of screening mechanisms for attaching significance to stimuli (i.e. irrelevant stimuli = are noticed to the exclusion of relative stimuli).  Impulsivity and restlessness may = arise from impairment in normal mechanisms for inhibition, the function that all= ows an individual to withhold a response if circumstances change.   Lack of inhibition amounts = to distractibility or lack of concentration and results in errors and impulsiveness.  Inhibitory ta= sks activate the prefrontal cortex and basal ganglia of the brain, regions in which the dopamine system is associated with executive functioning.  Effective medications work on the= dopamine transmitter systems. 
Syndromes are clusters of symptoms that may have different causes. ADHD is almost certainly not one “illness” but rather a group of difficulties arising from comp= lex, multifactorial causes. 
Executive functions (EF) are central processes tha= t are most intimately involved in giving organization and order to our actions and behavior. They have been compared to the "maestro" who conducts the orchestra. But what are these processes? The whole= topic is very controversial, but there seems to be a consensus that executive functions involve (at the very least): = ;
1.planning for the future and strategic thinking
2.the ability to inhibit or delay responding
3.initiating behavior, and
4.shifting between activities flexibly
If we break down the skills or functions into sub-functions, we might say that executive functions tap into the following abilities or skills:
1.Goal
2.Plan
3.Sequence
4.Prioritize
5.Organize
6.Initiate
7.Inhibit
8.Pace
9.Shift
10.Self-monitor
11.Emotional control
12.Completing
As you can see, many of the deficits of ADHD appea= r to be “executive” in nature.&nbs= p; A growing body of scientific evidence localizes executive functioning in the connections between pre-frontal cortex (the part of the b= rain above the eyes) and other brain areas like the basal ganglia (deeper brain structures that control movement) and= the limbic system (deeper structures that influence emotional experience). 
Difficulties setting goals, pla= nning activities, and sequencing steps towards completion of a task all fall und= er the general heading of “disorganized.”  Individuals lacking these abiliti= es may have never developed the associated skills.  Without the skills one would have= great difficulty establishing organized habits.  
People with ADHD often share a frustration that they work very hard and seem to get nowhere.  Because they often lack the relat= ive ability to prioritize tasks and pace their time, much effort can be expend= ed without task completion.  Ext= ernal pressures sometimes help the person with weak executive skills to prioriti= ze and initiate.  Without fear of failure, deadlines, and other pressure they tend to “spin their wheels.”
People with weak executive skil= ls often have a low frustration tolerance.  One would think with all that practice being frustrated, they would= get good at it.  Unfortunately, t= his is often not the case because they lack healthy skills for self-monitoring, awareness of feelings, and emotional self-control.  They can become especially upset = if the task at hand involves flexibility and adaptation.  Some people “hyper-focus= 221; on an element of the task to the exclusion of other critical aspects neces= sary for completion. 
Some critics think that ADHD ei= ther does not exist, that it represents a variation of normal behavior, or that= it is over-diagnosed.  Others su= spect that ADHD is used as an excuse for social immaturity, poor parenting, bad = choices, and failures of discipline.  = There is no doubt that, compared to years past, many more children carry the diagnosis and a growing number of adults are being identified and treated.  While the body of scientific evidence seems irrefutable, there may be some truth to these ot= her caveats too. 
ADHD is diagnosed subjectively.  A diagnostician matches reports of core behaviors to a concept of “developmental appropriateness,” and determines whether or not= the behaviors cause a significant impairment.=   If these conditions are met, the diagnosis is made and treatment options can be considered.  T= here are no reliable tests to distinguish the patient with ADHD from a “normal” person, because everyone has aspects of ADHD.  Measurable data point to relative deficits of executive functioning, but the associated tests are often expensive and may not be available.  Continuous performance tests which measure a person’s ability= to focus on a meaningless task over a period of perhaps 30 minutes (respond a= nd inhibit responses as instructed) and measures errors of omission (indicati= ng inattentiveness) and errors of commission (indicating failure of inhibition).  These tests hav= e been validated scientifically, but their practical utility is low (in Dr. Turley’s opinion).  Sta= ndard intelligence testing includes some measures of core ADHD deficits (a scale for freedom = from distractibility, measures of working memory), and expensive neuropsycholog= ical testing measures several other executive functions.  An individual’s score on th= ese measures can be compared to a “normative” sample. 
Younger children tend to look more ADHD than older children, and boys are = more inattentive, impulsive, and restless than girls at the same age.  Accordingly, sex biases are diffi= cult to avoid.
Sleep deprivation, whether a result of lifestyle or a side-effect of medication treatment, results in impairments indistinguishable from ADHD.<= span style=3D'mso-spacerun:yes'> 
Epidemiological studies indicat= e that ADHD is the most common neurobehavioral disorder presenting in children, affecting 5-8% of children and 4-5% of adults in the United States.  Studies suggest that less than ha= lf of these diagnosable cases are treated.  Some of the obstacles of treatment are associated with detection (l= ack of confirmatory tests difficulties distinguishing disorder from normal) and others are associated with treatment or fear of treatment.  Parents may be reluctant to prese= nt their child for treatment, concerned that they would be joining an unhealt= hy trend in society by doing so, or bowing to pressure from schools.  Others fear side-effects of medic= ation or worry that it will foster dependency on medications.  Children may resist taking the medication, or forget. 
Drug therapy remains the mainstay of treatment for ADHD. 
Stimulant medications include various preparations of methylphenidate and = amphetamines.  These drugs increase the levels of dopamine (DA), and/or norepinephrine (NE) in the central nervous system.  Their effectiveness is establishe= d by more than 300 controlled trials and their safety is well established.  Strattera (atomoxetine) is a noradrenergic medication that blocks the reuptake of NE, selectively increasing NE in the central nervous system.  Although the medication is less predictably effective for ADHD symptoms, it may be especially useful for treatment of ADHD complicated by oppositional anxiety or tics.  Antidepressants are second-l= ine treatment for ADHD.  Wellbutr= in (bupropion) and tricyclic antidepressants affect DA and NE systems, though less directly than do stimulants.  Tricyclic antidepressants are dangerous in overdose and require consistent monitoring of the ECG.  Desipramine was implicated in the deaths of 4 children, but indepen= dent evaluation of these cases failed to support a causal link.  Antihypertensive medications= (used to lower high blood pressure)  are also effective for ADHD.  The= se include clonidine and guanfacine.  Reports implicated the combination of methylphenidate and clonidine= in the deaths of 4 children but causal links could not be established. P= rovigil (modafinil) is a novel, non-stimulant arousal agent that seems to activate arousal systems in the brain, leading to improvements in attention. 
Antidepressants like Prozac (fluoxetine), Paxil (paroxetine), and others h= ave no effect on ADHD, but they may interfere with the metabolism of other medica= tions used for the condition.  Dosa= ge modifications may be necessary if treatments are combined. 
The largest and most comprehens= ive study to date (the Multimodal Treatment Study of Children With Attention Deficit/Hyperactivity Disorder—the MTA Cooperative Group study) indicates that intensive behavior therapy, comprising child, family, and school-based interventions, adds little to the effects of long-term stimul= ant therapy. The MTA study also identified that the quality of supervision of medication may be an important factor in optimizing long-term therapeutic benefit.
New developments:
Vyvanse is a stimulant medication activated by catabolism in the GI track.  Although risks of abu= se are lower compared to dextroamphetamine, the medication is still a controlled substance. 
New Developments:
methylphenidate is a familiar, well studied treatment that is now availabl= e as a transdermal patch.  This al= lows flexibility of treatment with variability of wear-time, and may be especia= lly useful for children who can’t swallow pills.  Unfortunately, the use of a skin = patch for drug treatment is complicated by local skin irritation, security conce= rns, and difficult keeping the patch adhered.&= nbsp;
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if( IsWin("PPTSld") && parent.IsFullScrMode() ) FullScrInit(); =09 MakeSldVis(); ChkAutoAdv() if( runAnimations ) { if( document.all("NSPlay") ) document.all("NSPlay").autoStart =3D false; if( sld.filters && sld.filters.revealtrans ) setTimeout( "document.body.start()", sld.filters.revealtrans.duration * = 1000 ); else document.body.start(); } } function MakeSldVis()=20 { var fTrans=3Dg_showAnimation && SldHasTrans() if( fTrans )=09 { if( g_bgSound ) { idx=3Dg_bgSound.indexOf(","); pptSound.src=3Dg_bgSound.substr( 0, idx ); pptSound.loop=3D -(parseInt(g_bgSound.substr(idx+1))); } SlideObj.filters.revealtrans.Apply()=09 } SlideObj.style.visibility=3D"visible" if( fTrans ) SlideObj.filters.revealtrans.Play() } function MakeNotesVis()=20 { if( !IsNts() ) return false=20 SlideObj.style.display=3D"none" nObj =3D document.all.item("NotesObj") parent.SetHasNts(0) if( nObj ) {=20 nObj.style.display=3D"" parent.SetHasNts(1) } return 1 } function ChkAutoAdv() { if(SldHasTrans()) SlideObj.onfilterchange=3DAutoAdv else AutoAdv() } function AutoAdv() { if(!IsWin("PPTSld") || !gUseSldTimings )return var sld=3DGetCurSld() if( (sld.mAdvDelay>0) && !parent.IsFramesMode() ) setTimeout("parent.GoToNextSld()",sld.mAdvDelay) } function GetObj(id) { if(g_supportsPPTHTML) return document.all(id); else return document.getElementById(id); } function SldHasTrans() { return SlideObj.style.filter !=3D ""; } function GetSldId()=20 { var regExp =3D /file:\/\/\//i var pos =3D location.href.search(regExp) if (MHTMLPrefix !=3D "" && pos !=3D -1) sId =3D location.href.substring(pos) else { sId =3D RemoveFilePrefixFromHref(location.href); var regExp =3D /\// var fixedHref =3D sId var pos =3D -1 =09 pos =3D fixedHref.search(regExp) while (pos !=3D -1) { fixedHref =3D fixedHref.replace(regExp, "\\") pos =3D fixedHref.search(regExp) } =09 if (g_fBaseHyperlink =3D=3D true) sId =3D "file:///" + fixedHref; else sId =3D fixedHref.substring(fixedHref.lastIndexOf('\\') + 1) } =09 return sId } function HideMenu() { if( frames["PPTSld"] && PPTSld.document.all.item("ctx= tmenu") && PPTSld.ctxtmenu.style.display!=3D"none" ) { PPTSld.ctxtmenu.styl= e.display=3D'none'; return true } return false } function IsWin( name ) { return window.name =3D=3D name } function IsNts() { return IsWin("PPTNts") } function IsSldOrNts() { return( IsWin("PPTSld")||IsWin("PPTNts") ) } function SupportsPPTAnimation() { return( navigator.platform =3D=3D "Win32"= && navigator.appVersion.indexOf("Windows")>0 ) } function SupportsPPTHTML() { var appVer=3Dnavigator.appVersion, msie=3DappVer.indexOf("MSIE "), ver=3D0 if( msie >=3D 0 ) ver=3DparseFloat( appVer.substring( msie+5, appVer.indexOf(";",msie) ) ) else ver=3DparseInt(appVer) return( ver >=3D 4 && msie >=3D 0 ) } function _RSW() { if( !g_supportsPPTHTML || IsNts() || ( !g_scaleInFrame && (!IsWin("PPTSld") || !parent.IsFullScrMode()) ) ) return var padding=3D0; if( IsWin("PPTSld") && parent.IsFramesMode() ) padding=3D6 cltWidth=3Ddocument.body.clientWidth-padding cltHeight=3Ddocument.body.clientHeight-padding factor=3D(1.0*cltWidth)/g_origW if( cltHeight < g_origH*factor ) factor=3D(1.0*cltHeight)/g_origH newSize =3D g_origSz * factor if( newSize < 1 ) newSize=3D1 s=3DSlideObj.style s.fontSize=3DnewSize+"px" s.posWidth=3Dg_origW*factor s.posHeight=3Dg_origH*factor s.posLeft=3D(cltWidth-s.posWidth+padding)/2 s.posTop=3D(cltHeight-s.posHeight+padding)/2 if( g_scaleHyperlinks ) ScaleHyperlinks( factor ) } function _InitAnimations() { animRuntimeInstalled =3D ''+document.body.localTime !=3D 'undefined'; isFullScreen =3D (window.name =3D=3D "PPTSld") && !parent.IsFramesMode(); g_animUseRuntime =3D g_showAnimation && animRuntimeInstalled && !(isFullSc= reen && parent.IsSldVisited()); if( g_animUseRuntime ) { collSeq =3D document.all.tags("seq"); if( collSeq !=3D null ) { for(ii=3D0;ii numSlds ) gSldJumpIdx =3D numSlds; if ( gSldJumpIdx >=3D 0 ) { if ( gSldJumpIdx =3D=3D 0 ) gSldJumpIdx =3D 1; var jumpTo 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