Faculty Bibliography

Drugs that affect neurotransmitter release can induce changes in neuroregulation during chronic administration. Thus, in addition to recurrence of symptoms of the illness, discontinuation of treatment can be associated with clinical signs and symptoms related to these changes. Atomoxetine, a new drug approved in the United States for treatment of attention deficit/hyperactivity disorder (ADHD), is associated with blockade of the presynaptic norepinephrine transporter. Because treatment of ADHD typically involves chronic treatment, the potential for production of a discontinuation syndrome as well as recurrence of symptoms upon drug discontinuation were assessed as part of the clinical development process. The effects of discontinuation of atomoxetine were assessed in children and adults with ADHD following 9 to 10 weeks of continuous therapy in 4 large studies. Symptoms of ADHD worsened following drug discontinuation but did not return to pretreatment levels. The incidence of discontinuation-emergent adverse events was low and there were no statistically significant differences between the patients abruptly discontinuing from atomoxetine and those continuing on placebo. Discontinuation of atomoxetine did not result in the development of an acute discontinuation syndrome and was well tolerated. It appears that atomoxetine may be discontinued without risk for symptom rebound or discontinuation-emergent adverse effects. Tapering of doses is not necessary when atomoxetine is discontinued

Attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in an increasingly recognized number of individuals with childhood onset. The symptoms of adult ADHD are similar to the restlessness, distractibility, and impulsivity central to childhood ADHD, but expression of symptoms changes as the individual matures. A childhood history of ADHD is requisite for a diagnosis of adult ADHD, although full DSM-IV criteria for the childhood disorder need not be met as long as significant symptoms and impairment occurred. Three case reports described here illustrate the migration of symptoms and the use of retrospective reporting and rating scales to determine a diagnosis of adult ADHD. These reports also stress the high probability of comorbid disorders and family aggregation of ADHD, as well as the likelihood that the adult with ADHD has developed coping mechanisms to compensate for his or her impairment

The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults can be a challenging process because it includes making judgments based on clinical interviews, rating scale results, informant ratings, and objective supporting evidence. The patient evaluation should gather information on the severity and frequency of symptoms, the establishment of childhood onset of symptoms, the chronicity and pervasiveness of symptoms, and the impact of symptoms on major life activities. Some of the rating scales being used in the adult population are the Conners' Adult ADHD Rating Scales, the Brown Attention-Deficit Disorder Scale for Adults, the Wender Utah Rating Scale, the ADHD Rating Scale and ADHD Rating Scale-IV, the Current Symptoms Scale, and the recently-developed Adult ADHD Self-Report Scale-v1.1 Symptom Checklist. More research is needed to establish the usefulness of self-administered rating scales compared with investigator-administered scales in the assessment and diagnosis of adult ADHD

Attention-deficit/hyperactivity disorder (ADHD) remains underdiagnosed in adults. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ADHD symptom criteria anchor the diagnosis but require interpretation that is sensitive to symptom expression in adults. For example, hyperactive symptoms may become more subjective and hidden in adults. Inattentive symptoms may involve so-called executive functions, such as planning, multitasking, and time management. While collateral reports from significant others are helpful, often the afflicted adults can report meaningfully about their lifelong condition. In addition to symptoms of ADHD, other diagnostic indicators include specific educational, occupational, and psychosocial difficulties. A number of rating scales and diagnostic interviews are available to assist in the diagnostic process

BACKGRAUND: Attention-deficit/hyperactivity disorder (ADHD) has been less studied in adults than in children, and the treatment studies reported to date have been small, single-center trials. To assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, we conducted two large, multicenter treatment trials. METHODS: Two identical studies using randomized, double-blind, placebo-controlled designs and a 10-week treatment period were conducted in adults with DSM-IV-defined ADHD as assessed by clinical history and confirmed by a structured interview (study I, n = 280; study II, n = 256). The primary outcome measure was a comparison of atomoxetine and placebo using repeated measures mixed model analysis of postbaseline values of the Conners' Adult ADHD Rating Scale. RESULTS: In each study, atomoxetine was statistically superior to placebo in reducing both inattentive and hyperactive and impulsive symptoms as assessed by primary and secondary measures. Discontinuations for adverse events among atomoxetine patients were under 10% in both studies. CONCLUSION: Atomoxetine appears to be an efficacious treatment for adult ADHD. Its lack of abuse potential may be an advantage for many patients

Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD

Although first identified in children in the 19th century, attention-deficit/hyperactivity disorder (ADHD) in adults was not described in the literature until 1976. The symptoms of adult ADHD resemble the symptoms of childhood ADHD, but symptom intensity, especially hyperactivity, may decrease over time. However, due to the challenges and responsibilities of adulthood, a normal day is extremely complicated for the ADHD adult. Molecular genetics and neuroimaging studies confirm that ADHD is a heterogeneous, neurobiological disorder, mainly of dopaminergic and noradrenergic pathways. Trials of pharmacologic treatments in adults with ADHD have produced mixed results due to considerable variability in diagnostic criteria, dosing, and response. This article reviews the history, neurobiology, and pharmacologic management of adult ADHD

Akathisia has previously been reported to exacerbate psychopathology and to be associated with noncompliance, suicidality, and violence. One previous study found brisk decrements in psychopathology after acute treatment of akathisia with intramuscular biperiden. This study assessed changes in akathisia and psychopathology in 19 patients after separate one-day treatments with intramuscular benztropine and oral propranolol. Benztropine and propranolol led to clinically meaningful and statistically significant decrements in ratings of subjective and objective measures of akathisia and in psychopathology scores. Changes in psychopathology correlated significantly with changes in subjective measures of akathisia after benztropine and with subjective and objective measures of akathisia after propranolol. Changes in akathisia accounted for 9%-42% of the variance in changes in psychopathology. After treatment, statistically significant decrements in Brief Psychiatric Rating Scale (BPRS) positive symptoms were noted, and individual items not directly related to the akathisia syndrome, such as conceptual disorganization, hallucinatory behavior, and unusual thought content declined, although not significantly. These findings, taken together with the results of a similar previous study, indicate that the effect of akathisia in exacerbating psychopathology is large. If suspected, akathisia should be treated promptly