Attention deficit hyperactivity disorder: A disease or a symptom complex?
1997; Elsevier BV; Volume: 130; Issue: 4 Linguagem: Inglês
10.1016/s0022-3476(97)70257-9
ISSN1097-6833
AutoresWarren A. Weinberg, Caryn R. Harper, Caitlin D. Schraufnagel, Roger A. Brumback,
Tópico(s)Neurological disorders and treatments
ResumoSee related article, Epilepsy and attention deficit hyperactivity disorder: Is methylphenidate safe and effective .The discoverer of a substantial thing, such as a bacillus, an extract or a disease, achieves more certain immortality than one who discovers a principle, for permanently valid principles soon become part of current thought, and in time become so obvious as to have needed no discovery (Brain, 1Brain WR Postgrad Med J. 1935; 11: 145Crossref PubMed Google Scholar 1935).In historical context, our modern understanding of epilepsy has progressed vastly during the past two centuries from the ancient ideas of possession by demons or supernatural influences. We now can identify and classify seizures on clinical, electrical, and biochemical grounds and understand some of the bases for the neuronal misfiring. No one would now question the concept that a seizure disorder is symptomatic of a variety of underlying conditions with diverse causes such as genetic, infectious, traumatic, vascular, or neoplastic, which must be identified by the clinician.In contrast, the understanding of behavioral problems is still in the dark ages. Normally intelligent children with behavioral disturbances involving inattention, poor impulse control, moodiness, and conduct problems have been given a variety of labels, but etiology has been difficult to understand. One of the problems is that all such children tend to be lumped together in a single group and labeled variously as having organic brain syndrome, Strauss syndrome, syndromes of cerebral dysfunction, hyperkinetic behavior syndrome, hyperkinetic impulse disorder, minimal brain dysfunction, hyperactive child syndrome, attention deficit disorder with or without hyperactivity, and now attention deficit hyperactivity disorder. 2American Psychiatric Association Diagnostic and statistical manual of mental disorders.4th ed. American Psychiatric Association, Washington (DC)1994Google Scholar, 3Weinberg WA Brumback RA The myth of attention deficit–hyperactivity disorder: symptoms resulting from multiple causes.J Child Neurol. 1992; 7: 431-445Crossref PubMed Scopus (47) Google Scholar, 4Weinberg WA Emslie GJ Attention deficit hyperactivity disorder: the differential diagnosis.J Child Neurol. 1991; 6: S21-S34Google Scholar A large number of biologic studies have been undertaken to characterize ADHD as a disease entity, but results have been inconsistent and not reproducible because the major features of ADHD are merely the symptoms of a variety of disorders. 3Weinberg WA Brumback RA The myth of attention deficit–hyperactivity disorder: symptoms resulting from multiple causes.J Child Neurol. 1992; 7: 431-445Crossref PubMed Scopus (47) Google Scholar Just as each form of seizure disorder (or epileptic syndrome 5Commission of Classification and Terminology of the International League Against Epilepsy: Proposal for revised classification of epilepsies and epileptic syndromes.Epilepsia. 1989; 30: 389-399Crossref PubMed Scopus (5812) Google Scholar) has unique electrophysiologic, behavioral, neuroanatomic, and therapeutic implications, so, too, do the variety of disorders (Table I) that have in common the symptoms of ADHD.6Biederman J Faraone SV Keenan K Tsuang MT Evidenceof familial association between attention deficit disorder and major affective disorders.Arch Gen Psychiatry. 1991; 48: 633-642Crossref PubMed Scopus (178) Google Scholar, 7Biederman J Newcorn J Sprich S Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders.Am J Psychiatry. 1991; 148: 564-577PubMed Google Scholar, 8Biederman J Faraone S Milberger S et al.A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders.Arch Gen Psychiatry. 1996; 53: 437-446Crossref PubMed Scopus (593) Google Scholar These overlapping symptoms can be readily evident in a comparison of the features of depression, 9Weinberg WA Rutman J Sullivan L et al.Depression in children referred to an educational diagnostic center: diagnosis and treatment.J Pediatr. 1973; 3: 1065-1072Abstract Full Text PDF Scopus (176) Google Scholar, 10Poznanski E Mokros HB Grossman J Freeman L Diagnostic criteria in childhood depression.Am J Psychiatry. 1976; 15: 491-501Google Scholar mania, 11Weinberg WA Brumback RA Mania in childhood: case studies and literature review.Arch Pediatr Adolesc Med [Am J Dis Child]. 1976; 130: 380-385Google Scholar, 12DeLong GR Lithium carbonate treatment of select behavior disorders in children suggesting manic-depressive illness.J Pediatr. 1978; 26: 389-394Google Scholar, 13Nieman GW DeLong GR Use of the personality inventory for children as an aid in differentiating children with mania from children with attention deficit disorder.J Am Acad Child Adolesc Psychiatry. 1987; 26: 381-388Abstract Full Text PDF PubMed Scopus (8) Google Scholar and primary disorder of vigilance 14Weinberg WA Brumback RA Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness.J Pediatr. 1990; 116: 720-725Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 15Weinberg WA Harper CR Vigilance and its disorders.Neurol Clin. 1993; 11: 59-78PubMed Google Scholar with ADHD (Table II) . Table ISelected causes of disturbed attention (and vigilance)Primary disorder of vigilanceAffective illnessLearning disabilitiesNarcolepsySleep deprivation (inclusing obstructive sleep apnea syndrome)EpilepsyDrugs Medications ToxinssStuctural brain lesions (midbrain or right cerebral hemisphere)Hormonal or metabolic disordersModified from Weinberg WA, Harper CR. Vigilance and its disorders.Neurol Clin 1993;11:59-78. Open table in a new tab Table 2Comparison of criteria for common behaviior disorders of children and adolescentsAttention-deficit hyperactivity disorder*Primary disorder of vigilanceMajor depressive disorder*Manic episode*A. Either (1) or (2): (1) Six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level: Inattention (a) Often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities (b) Often has difficulty sustaining attention in tasks or play activities (c) Often does not seem to listen when spoken to directly (d) Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions) (e) Often has difficulty organizing tasks and activities (f) Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework) (g) Often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools (h) Is often easily distracted by extraneous stimuli (i) Is often forgetful in daily activities (2) Six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level: Hyperactivity (a) Often fidgets with hands or feet or squirms in seat (b) Often leaves seat in classroom or in other situations in which remaining seated is expected (c) Often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness) (d) Often has difficulty playing or engaging in leisure activities quietly (e) Is often "on the go" or often acts as if "driven by a motor" (f) Often talks excessively Impulsivity (g) Often blurts out answers before questions have been completed (h) Often has difficulty awaiting turn (i) Often interrupts or intrudes on others (e.g., butts into conversations or games) B.Some hyperactive-impulsive or inattentive symptoms that caused impairment present before age 7 years C.Some impairment from symptoms present in two or more settings (e.g., at school [or work] and at homeA. A disorder of at least 1 year's duration with symptoms from all five major symptom categories 1. Decreasing ability to sustain alertness, wakefulness, arousal, and watchfulness during continuous mental (or other tasks) performance a. Complaint of tiredness, drowsiness, sleepiness, lethargy b. Yawning, stretching, sleepy-eyed (glassy-eyed) appearance c. Falling asleep; excessive napping 2. Decreasing attention to present activities a. Daydreaming b. Difficulty focusing attention; loses place in activities and conversation c. Poor performance d. Slow, delayed, or incomplete tasks e. Disorganized 3. Avoidance of structured or repetitive activities a. Loss of interest in or complaint that structured activities are dull, boring, monotonous, tedious, uninteresting (or no longer interesting) b. Preference for shifting activities that have random or irregular changes in schedule or activity (orderly randomization) 4. Motor restlessness and behaviors to improve alertness a.Fidgeting b. Talkativeness c. Moving about d. Busyness 5. Caring, compassionate, affectionate, kind temperament B.Major symptom category accepted as positive when the symptom or one or more of its behaviors is identified in a semistructured, closed-end interview of patient and primary caretakers (historians) C.Necessary that the symptom complex precede the onset of other medical disorders (including depression, narcolepsy, various medications, alcohol and drug abuse, hypothyroidism) that can cause secondary hypothyroidism D.Although symptoms may be identified at any age, the disorder generally becomes more symptomatic with schooling and aging and can result in increasing maladaptationA.Five (or more) of the following symptoms present during the same 2-week period, representing a change from previous functioning; at least one of the symptoms either (1) depressed mood or (2) loss of interest or pleasure 1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful); note: in children and adolescents, can be irritable mood 2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) 3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5\% of body weight in a month), or decrease or increase in appetite nearly every day; note: in children, consider failure to make expected weight gains 4. Insomnia or hypersomnia nearly every day 5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) 6. Fatigue or loss of energy nearly every day 7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) 8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. Symptoms do not meet criteria for a mixed episode (mania) C. Symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D. Symptoms are not due to direct physiologic effects of substance (e.g., drug of abuse, medication) or general medical condition (e.g., hypothyroidism) E. Symptoms are not better accounted for by bereavement (i.e., after loss of loved one, symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation)A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary) B. During the period of mood disturbance, three (or more) of the following symptoms persisting (four if the mood is only irritable) and present to a significant degree. 1. Inflated self-esteem or grandiosity 2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep) 3. More talkative than usual or pressure to keep talking 4. Flight of ideas or subjective experience that thoughts are racing 5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli) 6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretion, or foolish business investments) C. Symptoms do not meet criteria for mixed episode D. Mood disturbance sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or presence of psychotic features E. Symptoms are not due to direct physiologic effects of substance (e.g., drug of abuse, medication, or other treatment) or to general medical condition (e.g., hyperthyroidism)*From the American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed—revised (DSM-IV). Washington (DC): American Psychiatric Association, 1994. Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Copyright © 1994 American Psychiatric Association.†From Weinberg WA, Brumback RA. J Pediatr 1990;116:720-5. Open table in a new tab In this issue of The Journal of Pediatrics , Gross-Tsur and colleagues 16Gross-Tsur V Manor O van der Meere J Joseph A Shalev RS Epilepsy and attention deficit hyperactivity disorder: is methylphendiate safe and effective?.J Pediatr. 1997; 130: 40-44Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar provide evidence that methylphenidate can be safely administered to children with a variety of forms of epilepsy who also have attentional problems. Though the authors carefully define the various forms of epilepsy, the attentional problems were all lumped together as ADHD.There is no question that methylphenidate can relieve problems of inattention in some of the underlying disorders often defined as ADHD. The primary disorder of vigilance 14Weinberg WA Brumback RA Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness.J Pediatr. 1990; 116: 720-725Abstract Full Text PDF PubMed Scopus (82) Google Scholar is a common cause of the inattention form of ADHD symptoms. Vigilance (tonic arousal; steady-state wakefulness) is required for sustained attention. 15Weinberg WA Harper CR Vigilance and its disorders.Neurol Clin. 1993; 11: 59-78PubMed Google Scholar Multiple studies have demonstrated that the various stimulant medications (such as methylphenidate, pemoline, dextroamphetamine, caffeine, or nicotine) improve sustained attention in both healthy and clinical populations. 17Koelega HS Stimulant drugs and vigilance performance: a review.Psychopharmacology. 1993; 111: 1-16Crossref PubMed Scopus (240) Google Scholar, 18Mackworth NH Effect of amphetamine on the detectabilityof signals in a vigilance task.Can J Psychol. 1965; 19: 104-110Crossref PubMed Scopus (32) Google Scholar, 19Mackworth NH Vigilance, arousal, and habituation.Psychol Rev. 1968; 75: 308-322Crossref PubMed Scopus (92) Google Scholar Persistent improvement in performance provided by stimulant medications in children without mood disorder often is the result of successful treatment of the hypovigilance in those with underlying primary disorder of vigilance. Stimulant medications may also be beneficial in the treatment of mania. However, the stimulant medications can promote the dysphoric and vegetative symptoms of depression. 20Brumback RA Weinberg WA Pediatric behavioral neurology: an update on the neurologic aspects of depression, hyper-activity, and learning disabilities.Neurol Clin. 1990; 8: 677-703PubMed Google ScholarOf interest is the fact that only 70% of the authors' patient population had improvement of ADHD symptoms as a result of methylphenidate therapy. This finding would correlate with previous reports suggesting that 45% to 75% of children fulfilling criteria for ADHD have primary disorder of vigilance, which often responds readily to methylphenidate. 3Weinberg WA Brumback RA The myth of attention deficit–hyperactivity disorder: symptoms resulting from multiple causes.J Child Neurol. 1992; 7: 431-445Crossref PubMed Scopus (47) Google Scholar, 4Weinberg WA Emslie GJ Attention deficit hyperactivity disorder: the differential diagnosis.J Child Neurol. 1991; 6: S21-S34Google Scholar Because drowsiness is known to trigger seizures in susceptible individuals, it could be speculated that seizure frequency might decrease with relief of the vigilance problem by methylphenidate.In the 30% of children whose condition did not improve during therapy with methylphenidate, the authors do not identify the symptoms. Methylphenidate can induce depression, particularly in those children with genetic vulnerability to depression. 14Weinberg WA Brumback RA Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness.J Pediatr. 1990; 116: 720-725Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 15Weinberg WA Harper CR Vigilance and its disorders.Neurol Clin. 1993; 11: 59-78PubMed Google Scholar Did any of these children have depression as the underlying cause of their attentional problem?The neurobiologic substrates that underlie depression, mania, primary disorder of vigilance, and other pediatric behavioral conditions have yet to be fully understood. 21Weinberg WA Harper CR Brumback RA Neuroanatomic substrate of developmental specific learning disabilities and select behavioral syndromes.J Child Neurol. 1995; 10: S78-S80PubMed Google Scholar Nonetheless, it is probable that each will be unique, and there is no reason to believe that individuals with one brain abnormality (e.g., epilepsy) could not simultaneously have another neurobiologic disturbance. Thus, in any patient with epilepsy, there can be a variety of competing interactions. For example, a child with epilepsy who also has juvenile rapid-cycling manic-depressive disorder and is treated with phenobarbital could achieve control of the epilepsy but have the affective illness promoted, with symptoms of dysphoria, poor appetite, insomnia, inattentiveness, and psychomotor agitation. 22Brent DA Crumrine PK Varma RR et al.Phenobarbital treatment and major depressive disorder in children with epilepsy.Pediatrics. 1987; 80: 909-917PubMed Google Scholar, 23Brent DA Crumrine PK Varma RR et al.Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up.Pediatrics. 1990; 85: 1086-1091PubMed Google Scholar On the other hand, treatment of the same patient with valproate might alleviate both the mood disorder and the epilepsy, but if the patient had, in addition, the primary disorder of vigilance, stimulant medication would also be necessary to overcome the hypovigilance. However, stimulant medication exacerbating the neurochemical abnormality of depression 20Brumback RA Weinberg WA Pediatric behavioral neurology: an update on the neurologic aspects of depression, hyper-activity, and learning disabilities.Neurol Clin. 1990; 8: 677-703PubMed Google Scholar, 24Brumback RA Is depression a neurologic disease?.Neurol Clin. 1993; 11: 79-104PubMed Google Scholar could potentially worsen seizure control. Gross-Tsur and colleagues 16Gross-Tsur V Manor O van der Meere J Joseph A Shalev RS Epilepsy and attention deficit hyperactivity disorder: is methylphendiate safe and effective?.J Pediatr. 1997; 130: 40-44Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar describe five patients whose seizures were not controlled, three of whom had worsened control with methylphenidate. Were those children depressed? If so, specific treatment for depression in children might not only improve the ADHD symptoms but also improve seizure control. 25Ojemann LM Baugh-Bookman C Dudly DL Effect of psychotropic medications of seizure control in patients with epilepsy.Neurology. 1987; 37: 1525-1527Crossref PubMed Google ScholarThese scenarios indicate that much more research, like that of Gross-Tsur and colleagues, is necessary, but such studies should include a detailed characterization of the behavioral problem to understand the most appropriate treatment. See related article, Epilepsy and attention deficit hyperactivity disorder: Is methylphenidate safe and effective . The discoverer of a substantial thing, such as a bacillus, an extract or a disease, achieves more certain immortality than one who discovers a principle, for permanently valid principles soon become part of current thought, and in time become so obvious as to have needed no discovery (Brain, 1Brain WR Postgrad Med J. 1935; 11: 145Crossref PubMed Google Scholar 1935). In historical context, our modern understanding of epilepsy has progressed vastly during the past two centuries from the ancient ideas of possession by demons or supernatural influences. We now can identify and classify seizures on clinical, electrical, and biochemical grounds and understand some of the bases for the neuronal misfiring. No one would now question the concept that a seizure disorder is symptomatic of a variety of underlying conditions with diverse causes such as genetic, infectious, traumatic, vascular, or neoplastic, which must be identified by the clinician. In contrast, the understanding of behavioral problems is still in the dark ages. Normally intelligent children with behavioral disturbances involving inattention, poor impulse control, moodiness, and conduct problems have been given a variety of labels, but etiology has been difficult to understand. One of the problems is that all such children tend to be lumped together in a single group and labeled variously as having organic brain syndrome, Strauss syndrome, syndromes of cerebral dysfunction, hyperkinetic behavior syndrome, hyperkinetic impulse disorder, minimal brain dysfunction, hyperactive child syndrome, attention deficit disorder with or without hyperactivity, and now attention deficit hyperactivity disorder. 2American Psychiatric Association Diagnostic and statistical manual of mental disorders.4th ed. American Psychiatric Association, Washington (DC)1994Google Scholar, 3Weinberg WA Brumback RA The myth of attention deficit–hyperactivity disorder: symptoms resulting from multiple causes.J Child Neurol. 1992; 7: 431-445Crossref PubMed Scopus (47) Google Scholar, 4Weinberg WA Emslie GJ Attention deficit hyperactivity disorder: the differential diagnosis.J Child Neurol. 1991; 6: S21-S34Google Scholar A large number of biologic studies have been undertaken to characterize ADHD as a disease entity, but results have been inconsistent and not reproducible because the major features of ADHD are merely the symptoms of a variety of disorders. 3Weinberg WA Brumback RA The myth of attention deficit–hyperactivity disorder: symptoms resulting from multiple causes.J Child Neurol. 1992; 7: 431-445Crossref PubMed Scopus (47) Google Scholar Just as each form of seizure disorder (or epileptic syndrome 5Commission of Classification and Terminology of the International League Against Epilepsy: Proposal for revised classification of epilepsies and epileptic syndromes.Epilepsia. 1989; 30: 389-399Crossref PubMed Scopus (5812) Google Scholar) has unique electrophysiologic, behavioral, neuroanatomic, and therapeutic implications, so, too, do the variety of disorders (Table I) that have in common the symptoms of ADHD.6Biederman J Faraone SV Keenan K Tsuang MT Evidenceof familial association between attention deficit disorder and major affective disorders.Arch Gen Psychiatry. 1991; 48: 633-642Crossref PubMed Scopus (178) Google Scholar, 7Biederman J Newcorn J Sprich S Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders.Am J Psychiatry. 1991; 148: 564-577PubMed Google Scholar, 8Biederman J Faraone S Milberger S et al.A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders.Arch Gen Psychiatry. 1996; 53: 437-446Crossref PubMed Scopus (593) Google Scholar These overlapping symptoms can be readily evident in a comparison of the features of depression, 9Weinberg WA Rutman J Sullivan L et al.Depression in children referred to an educational diagnostic center: diagnosis and treatment.J Pediatr. 1973; 3: 1065-1072Abstract Full Text PDF Scopus (176) Google Scholar, 10Poznanski E Mokros HB Grossman J Freeman L Diagnostic criteria in childhood depression.Am J Psychiatry. 1976; 15: 491-501Google Scholar mania, 11Weinberg WA Brumback RA Mania in childhood: case studies and literature review.Arch Pediatr Adolesc Med [Am J Dis Child]. 1976; 130: 380-385Google Scholar, 12DeLong GR Lithium carbonate treatment of select behavior disorders in children suggesting manic-depressive illness.J Pediatr. 1978; 26: 389-394Google Scholar, 13Nieman GW DeLong GR Use of the personality inventory for children as an aid in differentiating children with mania from children with attention deficit disorder.J Am Acad Child Adolesc Psychiatry. 1987; 26: 381-388Abstract Full Text PDF PubMed Scopus (8) Google Scholar and primary disorder of vigilance 14Weinberg WA Brumback RA Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness.J Pediatr. 1990; 116: 720-725Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 15Weinberg WA Harper CR Vigilance and its disorders.Neurol Clin. 1993; 11: 59-78PubMed Google Scholar with ADHD (Table II) . Modified from Weinberg WA, Harper CR. Vigilance and its disorders. Neurol Clin 1993;11:59-78. *From the American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed—revised (DSM-IV). Washington (DC): American Psychiatric Association, 1994. Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Copyright © 1994 American Psychiatric Association. †From Weinberg WA, Brumback RA. J Pediatr 1990;116:720-5. In this issue of The Journal of Pediatrics , Gross-Tsur and colleagues 16Gross-Tsur V Manor O van der Meere J Joseph A Shalev RS Epilepsy and attention deficit hyperactivity disorder: is methylphendiate safe and effective?.J Pediatr. 1997; 130: 40-44Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar provide evidence that methylphenidate can be safely administered to children with a variety of forms of epilepsy who also have attentional problems. Though the authors carefully define the various forms of epilepsy, the attentional problems were all lumped together as ADHD. There is no question that methylphenidate can relieve problems of inattention in some of the underlying disorders often defined as ADHD. The primary disorder of vigilance 14Weinberg WA Brumback RA Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness.J Pediatr. 1990; 116: 720-725Abstract Full Text PDF PubMed Scopus (82) Google Scholar is a common cause of the inattention form of ADHD symptoms. Vigilance (tonic arousal; steady-state wakefulness) is required for sustained attention. 15Weinberg WA Harper CR Vigilance and its disorders.Neurol Clin. 1993; 11: 59-78PubMed Google Scholar Multiple studies have demonstrated that the various stimulant medications (such as methylphenidate, pemoline, dextroamphetamine, caffeine, or nicotine) improve sustained attention in both healthy and clinical populations. 17Koelega HS Stimulant drugs and vigilance performance: a review.Psychopharmacology. 1993; 111: 1-16Crossref PubMed Scopus (240) Google Scholar, 18Mackworth NH Effect of amphetamine on the detectabilityof signals in a vigilance task.Can J Psychol. 1965; 19: 104-110Crossref PubMed Scopus (32) Google Scholar, 19Mackworth NH Vigilance, arousal, and habituation.Psychol Rev. 1968; 75: 308-322Crossref PubMed Scopus (92) Google Scholar Persistent improvement in performance provided by stimulant medications in children without mood disorder often is the result of successful treatment of the hypovigilance in those with underlying primary disorder of vigilance. Stimulant medications may also be beneficial in the treatment of mania. However, the stimulant medications can promote the dysphoric and vegetative symptoms of depression. 20Brumback RA Weinberg WA Pediatric behavioral neurology: an update on the neurologic aspects of depression, hyper-activity, and learning disabilities.Neurol Clin. 1990; 8: 677-703PubMed Google Scholar Of interest is the fact that only 70% of the authors' patient population had improvement of ADHD symptoms as a result of methylphenidate therapy. This finding would correlate with previous reports suggesting that 45% to 75% of children fulfilling criteria for ADHD have primary disorder of vigilance, which often responds readily to methylphenidate. 3Weinberg WA Brumback RA The myth of attention deficit–hyperactivity disorder: symptoms resulting from multiple causes.J Child Neurol. 1992; 7: 431-445Crossref PubMed Scopus (47) Google Scholar, 4Weinberg WA Emslie GJ Attention deficit hyperactivity disorder: the differential diagnosis.J Child Neurol. 1991; 6: S21-S34Google Scholar Because drowsiness is known to trigger seizures in susceptible individuals, it could be speculated that seizure frequency might decrease with relief of the vigilance problem by methylphenidate. In the 30% of children whose condition did not improve during therapy with methylphenidate, the authors do not identify the symptoms. Methylphenidate can induce depression, particularly in those children with genetic vulnerability to depression. 14Weinberg WA Brumback RA Primary disorder of vigilance: a novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness.J Pediatr. 1990; 116: 720-725Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 15Weinberg WA Harper CR Vigilance and its disorders.Neurol Clin. 1993; 11: 59-78PubMed Google Scholar Did any of these children have depression as the underlying cause of their attentional problem? The neurobiologic substrates that underlie depression, mania, primary disorder of vigilance, and other pediatric behavioral conditions have yet to be fully understood. 21Weinberg WA Harper CR Brumback RA Neuroanatomic substrate of developmental specific learning disabilities and select behavioral syndromes.J Child Neurol. 1995; 10: S78-S80PubMed Google Scholar Nonetheless, it is probable that each will be unique, and there is no reason to believe that individuals with one brain abnormality (e.g., epilepsy) could not simultaneously have another neurobiologic disturbance. Thus, in any patient with epilepsy, there can be a variety of competing interactions. For example, a child with epilepsy who also has juvenile rapid-cycling manic-depressive disorder and is treated with phenobarbital could achieve control of the epilepsy but have the affective illness promoted, with symptoms of dysphoria, poor appetite, insomnia, inattentiveness, and psychomotor agitation. 22Brent DA Crumrine PK Varma RR et al.Phenobarbital treatment and major depressive disorder in children with epilepsy.Pediatrics. 1987; 80: 909-917PubMed Google Scholar, 23Brent DA Crumrine PK Varma RR et al.Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up.Pediatrics. 1990; 85: 1086-1091PubMed Google Scholar On the other hand, treatment of the same patient with valproate might alleviate both the mood disorder and the epilepsy, but if the patient had, in addition, the primary disorder of vigilance, stimulant medication would also be necessary to overcome the hypovigilance. However, stimulant medication exacerbating the neurochemical abnormality of depression 20Brumback RA Weinberg WA Pediatric behavioral neurology: an update on the neurologic aspects of depression, hyper-activity, and learning disabilities.Neurol Clin. 1990; 8: 677-703PubMed Google Scholar, 24Brumback RA Is depression a neurologic disease?.Neurol Clin. 1993; 11: 79-104PubMed Google Scholar could potentially worsen seizure control. Gross-Tsur and colleagues 16Gross-Tsur V Manor O van der Meere J Joseph A Shalev RS Epilepsy and attention deficit hyperactivity disorder: is methylphendiate safe and effective?.J Pediatr. 1997; 130: 40-44Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar describe five patients whose seizures were not controlled, three of whom had worsened control with methylphenidate. Were those children depressed? If so, specific treatment for depression in children might not only improve the ADHD symptoms but also improve seizure control. 25Ojemann LM Baugh-Bookman C Dudly DL Effect of psychotropic medications of seizure control in patients with epilepsy.Neurology. 1987; 37: 1525-1527Crossref PubMed Google Scholar These scenarios indicate that much more research, like that of Gross-Tsur and colleagues, is necessary, but such studies should include a detailed characterization of the behavioral problem to understand the most appropriate treatment.
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