ADHD-Guidelines for Clinical Practice PowerPoint Presentation

Slide 1 -

Practice Parameters for the Assessment and Treatment of ADHD (2007) James H. Johnson, Ph.D. University of Florida Journal of the American Academy of Child and Adolescent Psychiatry, 46, 7, 894 - 911

Slide 2 -

AACAP Practice Parameters: Assessment and Treatment for ADHD These practice parameters describe the assessment and treatment of children and adolescents with ADHD. They are based on the current scientific evidence and clinical consensus of experts in the field. They consider the clinical evaluation for ADHD, comorbid conditions associated with ADHD, and evidence based psychopharmacological and psychosocial interventions for ADHD. These guidelines seek to lay out evidence-based guidelines for the effective diagnosis and treatment of ADHD. AACAP ©2007

Slide 3 -

AACAP Practice Parameters: Assessment and Treatment for ADHD Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric conditions. It has been the focus of a great deal of scientific and clinical study over the last century and “Overall, ADHD is one of the best-researched disorders in medicine (Goldman et al., 1998) . The overall data on its validity are far more compelling than for many medical conditions.” While scientists and clinicians debate the best way to diagnose and treat ADHD, there is no debate among competent and well-informed health care professionals that ADHD is a valid neurobiological condition that causes significant impairment in those whom it afflicts.

Slide 4 -

EVIDENCE BASE FOR PRACTICE PARAMETERS Recommendations for best treatment practices are stated in accordance with the strength of the underlying empirical and/or clinical support, as follows: • Minimal Standard [MS] is applied to recommendations that are based on rigorous empirical evidence (such as randomized, controlled trials) and/or overwhelming clinical consensus. Minimal standards apply more than 95% of the time; i.e., in almost all cases. • Clinical Guideline [CG] is applied to recommendations that are based on strong empirical evidence (such as non-randomized controlled trials) and/or strong clinical consensus. Clinical guidelines apply approximately 75% of the time; i.e., in most cases.

Slide 5 -

EVIDENCE BASE FOR PRACTICE PARAMETERS Option [OP] is applied to recommendations that are acceptable based on emerging empirical evidence (such as uncontrolled trials or case series/reports) or clinical opinion, but lack strong empirical evidence and/or strong clinical consensus. • Not Endorsed [NE] is applied to practices that are known to be ineffective or contraindicated.

Slide 6 -

EVIDENCE BASE FOR PRACTICE PARAMETERS The strength of the empirical evidence is rated in descending order as follows: • Randomized, controlled trial {rct} is applied to studies where subjects are randomly assigned to two or more treatment conditions • Controlled trial {ct} is applied to studies where subjects are non-randomly assigned to two or more treatment conditions • Uncontrolled trial {ut} is applied to studies where subjects are assigned to one treatment condition • Case series/report {cs} is applied to a case series or a case report

Slide 7 -

Screening Recommendation 1. Screening for ADHD should be part of every patient’s mental health assessment [MS]. In any mental health assessment, the clinician should screen for ADHD by specifically asking questions regarding the major symptom domains of ADHD) and asking whether such symptoms cause impairment. Screening questions should be asked regardless of the nature of the chief complaint. Rating scales or specific questionnaires containing the DSM symptoms of ADHD can also be included in clinic/office registration materials to be filled out by parents before visits or in the waiting room before the evaluation. If a parent reports the patient suffers from ADHD that induce impairment, or the patient scores in the clinical range for ADHD symptoms on a rating scale, then a full evaluation for ADHD as set out in the next recommendation is indicated.

Slide 8 -

Evaluation Recommendation 2. Evaluation of the Preschooler, Child, or Adolescent for ADHD should consist of clinical interviews with the parent and patient, obtaining information about the patient’s school or day care functioning, evaluation for comorbid psychiatric disorders, and review of the patient’s medical, social, and family histories (MS)

Slide 9 -

Evaluation Evaluation should consist of: Detailed interview with parent about each of the 18 ADHD symptoms (Presence, duration, severity, frequency, age of onset) Patient must have required number of symptoms, a chronic course, and onset during childhood. Determine in which settings symptoms and evidence of impairment occur Impairment must be differentiated from symptoms Ask questions about academic progress to determine the potential for learning disabilities.

Slide 10 -

Evaluation After reviewing ADHD symptoms, interview parents regarding other common psychiatric disorder. Gather data from parents about ODD and CD. Explore for symptoms of depression (and associated neurovegetative signs), mania, anxiety disorders, tic disorders, substance abuse and psychosis, and evidence of a learning disability. Parent should complete one of the many standardized rating scales that have well established norms for children. (Broad Band measures that assess ADHD symptoms plus symptoms of other possibly comorbid conditions.

Slide 11 -

Evaluation Family history and family functioning should also be assessed As ADHD is highly heritable, a high prevalence is likely to be found among the patients parents and siblings. Family history of other disorders may be helpful in determining the nature of any comorbid disorder – although a comorbid disorder should not be diagnosed solely on the basis of family history. Information regarding significant psychosocial stressors or trauma should be assessed.

Slide 12 -

Evaluation The clinical should obtain information about the patients history. Included here would be: Information about perinatal history Medical history mental health history, delays in reaching developmental milestones (suggestive of MR, PDD, Language Disorders).

Slide 13 -

Evaluation The clinician should also interview the child or adolescent For children 5 – 8 interview may be done with parent. Older children and adolescents should be interviewed separately from parents as they may not reveal problems in the presence of a parent. The child interview is not to confirm or refute ADHD. It allows the clinician to identify signs/symptoms inconsistent with ADHD or suggestive of comorbidity The interview also allows the clinician to assess the patient’s vocabulary, thought processes, and thought content which may suggest serious psychopathology.

Slide 14 -

Need for Lab and Neurological Evaluations Recommendation 3 : If the patients medical history is unremarkable, laboratory or neurological testing is not indicated (NE) There are few medical conditions that “Masquerade” as ADHD. And the majority of patients with ADHD have an unremarkable medical history. Significant laboratory or neurological testing is usually not indicated.

Slide 15 -

Need for Lab and Neurological Evaluations Medical conditions that could result in or be confused with ADHD symptoms (under some circumstances). History of severe head injury (usually inattentative) Encephalopathies (but usually also show other neurological signs) Hyperthyroidism (with hyperactivity & agitation); rarely has ADHD symptoms alone and seldom without other thyroid symptoms) Lead exposure Fetal Alcohol Syndrome or exposure to other toxic agents.

Slide 16 -

Need for Lab and Neurological Evaluations Unless there is strong evidence of such factors in the medical history, neurological studies (EEG, MRI, SPECT, or PET scans are not indicated for the evaluation of ADHD. The American Psychiatric Association has warned against the exposure of children to IV radioactive nucleotides as part of the diagnosis or treatment or diagnosis of child psychiatric disorders, citing lack of evidence of validity and safety issues.

Slide 17 -

Psychological and Neuropsychological Testing Recommendation 4: Psychological and Neuropsychological testing are not mandatory for the diagnosis of ADHD. They should be performed if the patients history suggests low general cognitive ability or relative to intellectual ability (OP) low achievement in language or mathematics

Slide 18 -

Psychological and Neuropsychological Testing Low scores on standardized testing of academic achievement frequently characterize ADHD patients. The clinician must determine if the academic impairment: is secondary to the ADHD, if the patient has ADHD and a learning disorder, or if the patient has only a learning disorder and the patient’s inattentiveness is secondary to the learning disorder.

Slide 19 -

Psychological and Neuropsychological Testing Academic impairment is commonly due to the ADHD itself. Many months or years of not listening in class, not mastering material in an organized fashion, and not practicing academic skills (not doing homework, etc.) leads to a decline in achievement relative to the patient’s intellectual ability. In other cases, symptoms of learning/language disorders are present which cannot be accounted for by ADHD. These include deficits in expressive and receptive language, poor phonological processing, poor motor coordination, or difficulty grasping fundamental mathematical concepts. In such cases psychological testing will be needed to identify whether these deficits are related to a specific learning disorder.

Slide 20 -

Psychological and Neuropsychological Testing In the vast majority of cases, these learning disorders will be comorbid with the ADHD. It is recommended strongly that the patient’s ADHD be optimally treated before such testing. Purely learning-disordered patients are often inattentive when struggling with material in the area of their disability (a reading-disordered patient is inattentive when he/she must read) but do not have problems outside such a restricted academic setting. Patients with learning disorders alone do not show symptoms of impulsivity or hyperactivity.

Slide 21 -

Psychological and Neuropsychological Testing Psychological testing of the ADHD patient usually consists of a standardized assessment of intellectual ability (IQ), to determine any contribution of low general cognitive ability to the academic impairment and academic achievement. Neuropsychological testing, speech/language assessments, and computerized testing of attention or inhibitory control are not required as part of a routine assessment for ADHD. They may be indicated by the findings of the standard psychological assessment.

Slide 22 -

Assessing for Comorbidities Recommendation 5. The clinician must evaluate the patient with ADHD for the presence of comorbid psychiatric disorders [MS]. The clinician must integrate the data obtained with regard to comorbid symptoms to determine: 1) whether the patient meets criteria for a separate comorbid disorder in addition to ADHD, 2) whether the comorbid disorder is the primary disorder and the patient’s inattention or hyperactivity/impulsivity is directly caused by it, or 3) whether the comorbid symptoms do not meet criteria for a separate disorder but represent secondary symptoms stemming from the ADHD.

Slide 23 -

Assessing for Comorbidities When patients with ADHD meet full DSM-IV criteria for a second disorder, the clinician should generally assume the patient has two or more disorders and develop a treatment plan to address each comorbid disorder in addition to the ADHD. Children with ADHD commonly meet criteria for ODD or CD. In young children, these disorders are nearly always comorbid. Similarly, if a patient meets full DSM-IV criteria for major depressive disorder or a specific anxiety disorder, the clinician is most likely dealing with a comorbid disorder. Most often, the onset of the depressive disorder occurs several years after the onset of ADHD (Spencer et al., 1999), while anxiety disorders have an earlier onset concurrent with the ADHD (Kovacs and Devlin, 1998).

Slide 24 -

Assessing for Comorbidities A comorbid diagnosis of mania should be considered in ADHD patients who exhibit severe mood lability/elation/irritability, thought disturbances (grandiosity, flight of ideas), severe aggressive outbursts (“affective storms”), and decreased need for sleep or age-inappropriate levels of sexual interest. Mania should not be diagnosed solely on the basis of the severity of the ADHD symptoms or aggressive behavior. Acutely manic ADHD patients generally require mood stabilization before treatment of the ADHD. The choice of a treatment regimen, particularly pharmacological intervention, is often influenced by the nature of the patient’s comorbid disorder and which disorder is currently the most impairing of major life activities. Older adolescents with ADHD should be screened for substance abuse disorders (Biederman et al., 1997; Wilens et al., 1997).

Slide 25 -

Other Psychological Disorders and ADHD Other primary psychiatric disorders can produce impairment of attention or impulse control. Impaired attention is caused by primary depressive/anxiety disorders, and those with primary mania have impaired impulse control and judgment. If a patient has no history of ADHD symptoms during childhood, but develops inattentiveness and poor concentration only after the onset of depression or mania, then the affective disorder is most likely primary. Patients with adolescent-onset ODD or CD are often described as impulsive or inattentive, but often do not meet full criteria for ADHD or had few ADHD symptoms in early childhood.

Slide 26 -

Difficulties Resulting From ADHD Some associated problems may stem from the ADHD itself and not a separate disorder. Patients with ADHD may develop associated symptoms of dysphoria or low self- esteem secondary to the frustrations of living with ADHD. In such cases, the dysphoria is related specifically to the ADHD symptoms and there is an absence of pervasive depression, neurovegetative signs, or suicidal ideation. If such dysphoria is a result of the ADHD, then it should respond to successful treatment of the ADHD.

Slide 27 -

Difficulties Resulting From ADHD The distractibility or impulsivity of ADHD patients may often be interpreted as oppositional behavior by caretakers or children. Mild mood lability (shouting out, crying easily, quick temper) is also common in ADHD. It is important to note that such associated symptoms do not reach the level of a separate DSM disorder, are temporally related to the onset of the ADHD, are often consistent with, though somewhat excessive, for the social context, and dissipate once the ADHD is successfully treated

Slide 28 -

Treatment Planning Recommendation 6. A well thought-out and comprehensive treatment plan should be developed for the patient with ADHD [MS]. The patient’s treatment plan should take into account that ADHD is a chronic disorder and treatment may consist of psychopharmacological and/or behavior therapy. This plan should take into account the most recent evidence concerning effective therapies, as well as family preferences and concerns. The plan should include parental and child psychoeducation about ADHD and its various treatment options (medication and behavior therapy), linkage with community supports, and additional school resources as appropriate.

Slide 29 -

Treatment Planning Psychoeducation is distinguished from psychosocial interventions such as behavior therapy. Psychoeducation is generally performed by the physician in the context of medication management and involves educating the parent and child about ADHD, helping parents anticipate developmental challenges that are difficult for ADHD children, and providing general advice to the parent and child to help improve the child’s academic and behavioral functioning. The treatment plan should be reviewed regularly and modified if the patient’s symptoms do not respond. Trade books, videos, and some noncommercial websites on ADHD may be useful adjunctive material to facilitate this step of treatment.

Slide 30 -

Treatment Planning The previous practice parameter (American Academy of Child and Adolescent Psychiatry, 1997) extensively reviewed a variety of non-pharmacological interventions for ADHD other than behavior therapy, including cognitive-behavioral therapy and dietary modification. No evidence was found at that time to support these interventions in patients with ADHD, and no studies have appeared since then that would justify their use. While there has been aggressive marketing of its use, the efficacy of EEG feedback, either as a primary treatment for ADHD or as an adjunct to medication treatment, has not been established (Loo, 2003). Formal social skills training for children with ADHD has not been shown to be effective (Antshel and Remer, 2003).

Slide 31 -

Pharmacological Treatment Recommendation 7. The initial psychopharmacological treatment of ADHD should be a trial with an agent approved by the Food and Drug Administration (FDA) for the treatment of ADHD [MS]. The following medications are approved by the FDA for the treatment of ADHD: dextroamphetamine (DEX), d- and d,l-methylphenidate (MPH), mixed salts amphetamine (MSA), and Atomoxetine (Strattera)

Slide 32 -

Stimulants Many randomized clinical trials of stimulant medications have been performed in patients with ADHD over the past three decades. Stimulants are highly efficacious in the treatment of ADHD. In double-blind, placebo-controlled trials in both children and adults, 65% to 75% of subjects with ADHD have been determined to be clinical responders to stimulants, compared with 4% to 30% of subjects treated with placebo, depending on the response criteria used (Greenhill, 2002). When clinical response is assessed quantitatively via rating scales, the effect size of stimulant treatment relative to placebo is quite large, averaging about 1.0, one of the largest effects for any psychotropic medication. In the MTA study, subjects who responded to short-term placebo treatment did not maintain such gains and 90% of these subjects were subsequently treated with stimulants in the 14-month time frame of the study (Vitiello et al., 2001).

Slide 33 -

Stimulants The physician is free to choose any of the two stimulant types (MPH or amphetamine), as evidence suggests the two are equally efficacious in the treatment of ADHD. Immediate-release stimulant medications have the disadvantage that they must be taken two to three times a day to control ADHD symptoms throughout the day. In the past 5 years, extensive trials have been carried out with long-acting forms of both stimulant drug types. These long-acting formulations are equally efficacious as the immediate-release forms and have been shown to be efficacious in adolescents as well as children (Spencer et al., 2006; Wilens et al., 2006). They offer greater convenience for the patient and family and enhance confidentiality, as the school-age patient need not report to the school nurse for medication administration.

Slide 34 -

Stimulants Single daily dosing is associated with greater compliance for all types of medication, Long-acting MPH may improve driving performance in adolescents relative to short-acting MPH (Cox et al., 2004 {rct}). Physicians may use long-acting forms as initial treatment; there is no need to titrate to the appropriate dose on short-acting forms and then “transfer” children to a long-acting form. Short-acting stimulants are often used as initial treatment in very small children (<16 kg in weight), for whom there are no long-acting forms in a sufficiently low dose.

Slide 35 -

Titrating Stimulant Drugs After selecting the starting dose, the physician may titrate upward every 1 to 3 weeks until the maximum dose for the stimulant is reached, symptoms of ADHD remit, or side effects prevent further titration, whichever occurs first. Patient/parent contact with physician or trained office staff during titrations is recommended. It is helpful to obtain teacher and parent rating scales after the patient has been observed by the adult on a selected dose for at least a week. The parent and the patient should be queried about side effects. An office visit should then be scheduled after the first month of treatment to review overall progress and determine whether the stimulant trial was a success and long-term maintenance on the particular stimulant should commence.

Slide 36 -

Comparing Stimulant Drugs Arnold (2000) reviewed studies in which subjects underwent a trial of both amphetamine and MPH. Approximately 41% of subjects with ADHD responded equally to both MPH and amphetamine. Some 44% responded preferentially to one of the classes of stimulants. This suggests the initial response rate to stimulants may be as high as 85% if both stimulants are tried (in contrast to the finding of 65-75% response when only one stimulant is tried). At present there is no method to predict which stimulant will produce the best response.

Slide 37 -

Straterra (Atomoxetine) Straterra (atomoxetine) is a noradrenergic reuptake inhibitor that is superior to placebo in the treatment of ADHD in children/ adolescents, and adults It can be given daily or twice a day, with the second dose given in the evening; It may have less pronounced effects on appetite and sleep than stimulants, although it may produce relatively more nausea or sedation

Slide 38 -

Straterra (Atomoxetine) Michelson et al. (2002) showed that while Straterra was superior to placebo at week 1 of the trial, the greatest effects were observed at week 6, suggesting the patient should be maintained at the full therapeutic dose for at least several weeks in order to obtain the drug’s full effect. Straterra has been studied in the treatment of patients with ADHD and comorbid anxiety (Sumner et al., 2005 {rct}). Here, patients with ADHD or an anxiety disorder (generalized anxiety, separation anxiety, or social phobia) were randomized to either Straterra or placebo (in a double-blind, placebo-controlled manner for 12 weeks of treatment. At the end of the treatment period, Straterra led to a significant reduction in ratings of symptoms of both ADHD and anxiety relative to placebo, showing the drug to be efficacious in the treatment of both conditions. The above results suggest that using Straterra for the treatment of ADHD with comorbid anxiety is a viable approach. Such findings have not been obtained with depression.

Slide 39 -

Drug Selection: Initial Treament The clinician and family face the choice of which agent to use for the initial treatment of the patient with ADHD. The American Academy of Pediatrics an international consensus statement (Kutcher et al., 2004), and the Texas Children’s Medication Project (Pliszka et al., 2006a) have all recommended stimulants as the first line of treatment for ADHD, particularly when no comorbidity is present.

Slide 40 -

Drug Selection Direct comparisons of the efficacy of Straterra to that of MPH (Michelson, 2004) and amphetamine (Wigal et al., 2004) have shown a greater treatment effect of the stimulants In a meta-analysis of Straterra and stimulant studies, the effect size for Straterra was 0.62 compared with 0.91 and 0.95 for immediate-release and long-acting stimulants, respectively (Faraone et al., 2003).

Slide 41 -

Drug Selection Straterra may be considered as the first medication for ADHD in persons with an active substance abuse problem, comorbid anxiety, or tics. It is preferred if the patient experiences severe side effects to stimulants such as mood lability or tics (Biederman et al., 2004). When dosed twice a day, effects on late evening behavior may be seen. It is the sole choice of the family and the clinician as to which agent should be used for the patient’s treatment and each patient’s treatment must be individualized. Nothing in these guidelines should be construed by third-party payers as justification for requiring a patient to be a treatment failure (or experience side effects) to one agent before allowing the trial of another.

Slide 42 -

Treatment Non-Responders Recommendation 8. If none of the above agents results in satisfactory treatment of the patient with ADHD, the clinician should undertake a careful review of the diagnosis and then consider behavior therapy and/or the use of medications not approved by the FDA for the treatment of ADHD [CG].

Slide 43 -

Treatment Non-Responders Wellbutrin, tricyclic antidepressants (Imipramine) and alpha-agonists (clonidine, Tenex) are often used in the treatment of ADHD even though they are not approved by the FDA for this purpose. Although there is at least one double blind, randomized controlled trial for Wellbutrin, TCAs and clonidine, the evidence base for these medications is far weaker than for the FDA-approved agents

Slide 44 -

Treatment Non-Responders These agents may have effect sizes considerably less than that of the approved agents, and comparable with the effectiveness of behavior therapy (Pelham et al., 1998). Thus it may be prudent for the clinician to recommend a trial of behavior therapy at this point, before moving to these second-line agents. In other cases, the patient may have had a partial response to one of the FDA-approved agents, wherein there is definite improvement over baseline symptoms but impairment at home or school still is present. Addition of behavior therapy along with treatment with the FDA-approved agent may provide added benefit in such cases.

Slide 45 -

Treatment Non-Responders In recent years, clinical consensus has led to the use of clonidine as adjunctive therapy to treat tics or stimulant-induced insomnia rather than as a primary treatment for ADHD If the alpha-agonist is deemed ineffective after an adequate trial, the medication should be tapered gradually over 1 to 2 weeks to avoid a sudden increase in blood pressure. Currently Melatonin is being widely used with sleep problems of children with ADHD.

Slide 46 -

Assessing for Side Effects Recommendation 9. During a psychopharmacological intervention for ADHD, the patient should be monitored for treatment-emergent side effects [MS]. For stimulant medications, the most common side effects are appetite decrease, weight loss, insomnia, or headache. Less common side effects of stimulants include tics and emotional lability/irritability. Treating physicians should be familiar with the precautions and reported adverse events contained in product labeling. Strategies for dealing with side effects include monitoring, dose adjustment of the stimulant, switching to another stimulant, and adjunctive pharmacotherapy to treat the side effects. If one of these side effects emerges, the physician should first assess the severity of the symptom and the burden it imposes on the patient.

Slide 47 -

Dealing With Side Effects It is prudent to monitor side effects which do not compromise the patient’s health or cause discomfort that interferes with functioning, as many side effects to stimulants are transient in nature and may resolve without treatment. This approach is particularly valuable if the patient has had a robust behavioral response to the particular stimulant medication. If the side effect persists, reduction of dosage should be considered, although the physician may find that the dose which does not produce the side effect is not effective in the treatment of the ADHD. In this case, the physician should initiate a trial of a different stimulant or a nonstimulant medication.

Slide 48 -

Dealing With Side Effects After such trials, the physician, family, and patient may find that the one particular stimulant most efficacious in the treatment of that patient’s ADHD also produces a troublesome side effect. Adjunctive pharmacotherapy may be considered. Low doses of clonidine, trazodone, or an antihistamine are often helpful for stimulant-induced insomnia.

Slide 49 -

Dealing with Side Effects Side effects of Straterra that occur more often than placebo include gastrointestinal distress, sedation, and decreased appetite. These can generally be managed by dose adjustment, and while some attenuate with time, others such as headaches may persist (Greenhill et al., 2006c). If discomfort persists, the Straterra should be tapered off and a trial of a different medication initiated. On December 17, 2004, the FDA required a warning be added to Straterra because of reports that two patients (an adult and child) developed severe liver disease (both patients recovered). In the clinical trials of 6,000 patients, no evidence of hepatotoxicity was found. Patients who develop jaundice, dark urine, or other symptoms of hepatic disease should discontinue Straterra.

Slide 50 -

Aggression, Mood Lability and Suicidal Ideation Controlled trials of stimulants do not support the widespread belief that stimulant medications induce aggression; Indeed, overall aggressive acts and antisocial behavior decline when treated with stimulants A rate of emotional lability of 8.6% was reported in patients taking Adderall XR® compared with a rate of 1.9% in the placebo group (Biederman et al., 2002). . The physician must distinguish between aggression/emotional lability that is present when the stimulant is active (i.e., during the day) and increased hyperactivity/impulsivity in the evening when the stimulant is no longer effective. The latter phenomenon (commonly referred to as “rebound”) is more prevalent than the former, and it has been shown in laboratory classroom settings that even on placebo, the behavior of children with ADHD is worse in the late afternoon and evening than in the morning (Swanson et al., 1998a {rct})

Slide 51 -

Aggression, mood lability and suicidal ideation In September of 2005, the FDA also issued an alert regarding suicidal thinking with Straterra in children and adolescents (Food and Drug Administration, 2005). In twelve controlled trials involving 1,357 patients on Straterra and 851 on placebo, the average risk of suicidal thinking was 4 per 1,000 in the Straterra-treated group vs. none in those on placebo. There was one suicide attempt in the Straterra group but no completed suicides. A boxed warning was added to the Straterra labeling. This risk is quite small, but it should be discussed with patients and family, and children should be monitored for the onset of suicidal thinking, particularly in the first few months of treatment.

Slide 52 -

Aggression, mood lability and suicidal ideation If after starting an ADHD medication the patient clearly is more aggressive, emotionally labile or experiences psychotic symptoms, the physician should discontinue that medication and consider a different agent. Adjunctive therapy with neuroleptics or mood stabilizers is not recommended if the aggressive/labile behavior was not present at baseline and is clearly a side effect of the stimulant.

Slide 53 -

Cardiovascular Issues In March 2006 the Pediatric Advisory Committee addressed the risk of sudden death occurring with agents used for the treatment of ADHD (Villalaba,2006). The FDA review revealed 20 sudden death cases with amphetamine or dextroamphetamine (14 children, 6 adults) There were 14 pediatric and four adults cases of sudden death with MPH. It is important to note that the rate of sudden death in the general pediatric population has been estimated at 1.3 -8.5/100,000 patient-years (Liberthson, 1996). The rate of sudden death among those with a history of congenital heart disease can be as high as 6% by age 20 (Liberthson, 1996).

Slide 54 -

Cardiovascular Issues Villalaba (2006) estimated the rate of sudden death in treated children with ADHD for the period January 1, 1992 to December 31, 2004 to be 0.2/100,000 patient-years for MPH, 0.3/100,000 patient-years for amphetamine, and 0.5/100,000 patient-years for atomoxetine The differences between the agents were not clinically meaningful Thus, the rate of sudden death of children taking ADHD medications do not appear to exceed the base rate of sudden death in the general population.

Slide 55 -

Cardiovascular Issues Although an advisory committee 1 month earlier had recommended a boxed warning be issued for cardiovascular events, including stroke and myocardial infarction (Nissen, 2006), the Pediatric Advisory Committee did not support this recommendation. 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).

Slide 56 -

Cardiovascular Issues The package insert for stimulants states that these medications should generally not be used in children and adolescents with preexisting heart disease or symptoms suggesting significant cardiovascular disease. Before a stimulant trial, such patients should be referred for consultation with a cardiologist for possible electrocardiography and/or echocardiography. If stimulants are initiated, then the patient should also be monitored by the cardiologists during the course of treatment.

Slide 57 -

Side Effects of Non-FDA - Approved Agents Bupropion (Wellbutrin) may cause mild insomnia or loss of appetite. Extremely high single doses (>400 mg) may induce seizures even in patients without epilepsy. TCAs frequently cause anticholinergic side effects such as dry mouth, sedation, constipation, changes in vision, or tachycardia. Reduction in dose or discontinuation of the TCA is often required if these side effects induce mpairment. Side effects of drugs like Clonidine and Tenex include sedation, dizziness, and possible hypotension.

Slide 58 -

Side Effects of Non-FDA - Approved Agents In the previous decade there was controversy over the safety of the use of drugs clonidine, in children. Swanson and colleagues (1995) noted about 20 case reports of children suffering significant changes in heart rate and blood pressure, particularly after clonidine dose adjustment. Four cases of death were reported in children taking a combination of MPH and clonidine. There were many atypical aspects of these cases and a causal relationship between the stimulant-agonist combination and the patients’ deaths was not supported

Slide 59 -

Side Effects: Non FDA Approved Drugs There have been no further reports of severe cardiovascular adverse events associated with clonidine use in ADHD patients. Nonetheless, physicians must be cautious. The patient’s blood pressure and pulse should be assessed periodically (Gutgesell et al., 1999), and abrupt discontinuations of the agonist are to be avoided. The patient and family should be advised to report any cardiac symptoms such as dizziness, fainting, or unexplained change in heart rate.

Slide 60 -

Drug Treatment Alone Recommendation 10. 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 [OP]. Note that this assumes the absence of comorbid conditions that might respond to psychosocial treatments/behavior therapy

Slide 61 -

Psychosocial Treatment Recommendation 11. 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 [CG]. Note the range of psychosocial treatments (largely behavioral or cognitive behavioral that are applicable to various comorbid conditions. See Required EBP article by Pelham (2008)

Slide 62 -

Follow-up Assessment Recommendation 12. Patients should be assessed periodically to determine if there is continued need for treatment or if symptoms have remitted. Treatment of ADHD should continue as long as symptoms remain present and cause impairment [MS].

Slide 63 -

Monitoring Height and Weight Recommendation 13. Patients treated with medication for ADHD should have their height and weight monitored throughout treatment [MS]. The effect of stimulant treatment on growth has been a concern for many years as some findings have noted that stimulants were associated with small decreases in expected height and weight gain, although they were rarely clinically significant

Slide 64 -

Monitoring Height and Weight Recently, two major reviews (Faraone et al., unpublished data, 2006; Poulton, 2005) examined all of the available data and concluded that stimulant treatment may be associated with a reduction in expected height gain, at least in the first 1 to 3 years of treatment. For example, The MTA study showed reduced growth rates in ADHD patients after 2 years of stimulant treatment compared with those patients who received no medication (MTA Cooperative Group, 2004b [rct]), and these deficits persisted at 36 months (MTA Cooperative Group, 2006 [rct])

Slide 65 -

Monitoring Height and Weight An additional study followed a group of 140 preschoolers who received MPH for up to 1 year for ADHD (Swanson et al., 2006 [rct]). The subjects had less than expected mean gains in height (-1.38 cm) and weight (-1.3 kg). In a review and analysis of cross-sectional data, Spencer et al. (1996) compared the heights of ADHD patients with those of controls in three separate age samples. They found no height deficits relative to controls in childhood, a small but statistically significant reduction in height relative to controls at puberty, but no difference in height in adulthood. There was no relationship between stimulant treatment and height measures. Spencer et al. (1996) hypothesized that ADHD itself was associated with a slower tempo of growth, which resolved by adulthood, and the shorter stature was unrelated to medication effects.

Slide 66 -

Monitoring Height and Weight In assessing for clinically significant growth reduction, it is recommended that serial plotting of height and weight on growth charts labeled with lines showing the major percentiles (5th, 10th, 25th, 50th, 75th, 90th, and 95th) be used (Mei et al., 2004). This should occur one to two times per year, and more frequently if practical. If the patient has a change in height or weight that crosses two percentile lines, then this suggests an aberrant growth trajectory. In these cases a drug holiday should be considered if return of symptoms during weekends or summers does not lead to marked impairment of functioning.

Slide 67 -

Monitoring Height and Weight The clinician should also consider switching the patient to another ADHD medication. It is important for the clinician to carefully balance the benefits of medication treatment with the risks of small reductions in height gain, which as of yet have not been shown to be related to reductions in adult height (Gittelman-Klein and Mannuzza, 1988; Kramer et al., 2000; Weiss and Hechtman, 2003).

Slide 68 -

PARAMETER LIMITATIONS AACAP practice parameters are developed to assist clinicians in psychiatric decision-making. These parameters are not intended to define the standard of care; nor should they be deemed inclusive of all proper methods of care or exclusive of other methods of care directed at obtaining the desired results. The ultimate judgment regarding the care of a particular patient must be made by the clinician in light of all the circumstances presented by the patient and his/her family, the diagnostic and treatment options available, and available resources.